Fourth year

 

Common conditions

26 December 2020

22:57

Common Procedures and examples

A patient undergoing an orthopaedic procedure

Arthroscopy

Joint replacement

A patient undergoing an abdominal/gastrointestinal tract procedure

Cholecystectomy

Hernia repair

Colonoscopy

Colectomy

A patient undergoing a breast procedure

Lumpectomy

Mastectomy

A patient undergoing an opthalmic procedure

Cataract surgery

A patient undergoing a urological procedure

Cystoscopy

 

 

Common Conditions and Examples

A patient with cancer

Colorectal cancer

Breast cancer

Lung cancer

Prostate cancer

A patient with musculoskeletal disease

    Osteoarthritis

Rheumatoid arthritis

Neck or back pain

Osteoporosis

A patient with chronic kidney disease

A patient with diabetes mellitus

A patient with lung disease

Chronic obstructive pulmonary disease

Asthma

A patient with chronic liver disease

Alcoholic liver disease

Nonalcoholic steatohepatitis

Chronic viral hepatitis

A patient with hearing loss

Presbyacusis

A patient with visual loss

Macular degeneration

Glaucoma

Cataract

A patient with vascular disease

Hypertension

Ischaemic heart disease

Heart failure

A patient with skin disease

Eczema

Psoriasis

Acne

A patient with chronic neurological disease

Epilepsy

Stroke

Migraine

A patient with persistent unexplained physical symptoms

 

 

 

Stroke

24 December 2020

23:10

The clinical features of stroke are of a “sudden onset of focal or global cerebral dysfunction due to a vascular cause”.

 “a sudden onset of focal or global cerebral dysfunction, persisting for more than 24 hours, for which the cause is vascular”

It includes cerebral infarction, intracerebral haemorrhage and subarachnoid haemorrhage

 

LACI

TACI

PACI

POCI

30 days

 

 

 

 

 

 

 

Dead

2%

39%

4%

7%

Dependent

36%

56%

39%

31%

Independent

62%

4%

56%

62%

1 Year

 

 

 

 

 

 

 

Dead

11%

60%

16%

19%

Dependent

28%

36%

29%

19%

Independent

60%

4%

55%

62%

 

 

From <https://mle.ncl.ac.uk/cases/page/8650/>

 

Antiplatelet-

 These reduce the risk of further ischaemic stroke (and of myocardial infarction and other vascular events) by a relative risk reduction of 20-30%.  In absolute terms that means a reduction of risk of about 1% over the first month, 2-3 % over the first year, and 1% per year thereafter.

 

They work by interfering in platelet function and therefore reducing the risk that unstable atherosclerotic plaque will cause an occlusive thrombus or embolus.

 

The most commonly used after stroke would include aspirin (used in a 300mg or 75 mg daily dose predominantly in the first fortnight after stroke where the evidence is strongest for it’s effect) or clopidogrel (which appears to be more effective in longer term prevention and is used at a 75mg daily dose).

 

An inevitable consequence of reducing blood clotting capacity is to increase the risk of bleeding.  Many patients have minor bleeding or easy bruising as a result of these medications.  More rarely serious bleeding will be caused or significantly exacerbated (in 1-2% of patients per year).  Serious bleeding is more common in patients who have a recent history of bleeding from for example a peptic ulcer.  For patients over 50 it is usually recommended that a proton pump inhibitor (PPI) be prescribed at the same time to reduce the risk of bleeding from peptic ulcers – but that obviously exposes the patient to the risk of further side effects (e.g. diarrhoea) from the PPI.

 

Statins-

These also reduce the risk of further ischaemic stroke (and of myocardial infarction and other vascular events) by a relative risk reduction of 20-30%.  In absolute terms that means a reduction of risk of about 1% over the first month, 2-3 % over the first year, and 1% per year thereafter.  This risk reduction holds regardless of the patients’ actual cholesterol level – risk is reduced even in patients with relatively low cholesterol levels at the time of stroke.  Likewise there is no specific cholesterol target to be aimed for – just being on the drugs appears to be effective.

 

The strongest evidence is for high potency statins at maximal doses – particularly for atorvastatin at 80 mg per day.  The evidence for effectiveness for other “cholesterol lowering” drugs is poor and they are not recommended.

 

Around 10% of patients started on statin treatments will develop unpleasant usually localised muscle aches.  This is probably more common in patients with lower muscle mass – but is largely unpredictable.   Happily this side effect almost always resolves promptly with reducing the dose of the statin, changing to a statin with a different mode of action (pravastatin or rosuvastatin) or stopping treatment.  There is a much smaller risk of severe muscle problems (myositis) which also present with muscle pain, but where there is associated muscle damage evidenced by a raised serum creatine kinase level) or of hepatotoxicity.  NICE guidelines suggest checking cholesterol levels 2-3 months after starting statin treatment (these should drop by at least 20-30% over this time, and if they don’t then the patient may not be taking or absorbing the tablets for some reason), along with liver function tests to detect hepatotoxicity.  Minor rises in the liver enzyme ALT are common, and only rises to 3 times the upper limit of normal are considered a reason to stop therapy.

 

 

Anti hypertensive-

Unlike statin therapy, where there is no threshold level where treatment should start and no target to achieve, treatment for hypertension is target driven.  Optimal reduction in the risk of further events – and this holds for intracerebral haemorrhage as well as for cerebral infarction – is achieved with reduction of blood pressure to levels consistently lower than 130/80.  Antihypertensive therapy is the only treatment that reduces the long term risk of recurrent intracerebral haemorrhage – antiplatelet agents and statins are not effective, and may slightly increase risk.

 

Achieving this blood pressure again reduces the risk of further events by 20-30% in relative risk reduction terms, and in absolute terms this equates to a long-term risk reduction of around 1% per year.

 

There are many drugs that can be used to achieve this.  Clinicians usually follow the NICE recommendations for choice of antihypertensive therapy (referenced in Case 1 in years ½ MBBS).

 

Each drug has specific potential side effects (e.g. persistent dry cough with angiotensin converting enzyme (ACE) inhibitors).  All have the frequent side effect of causing or exacerbating orthostatic hypotension and therefore of making patients feel dizzy or light headed, potentially causing syncope and falls.

 

Anticoagulants-

Anticoagulants (e.g. warfarin or direct oral anticoagulants like apixaban) have a specific role in reducing the risk of ischaemic stroke in patients with atrial fibrillation, which could be either permanent or paroxysmal.  In this specific situation the risk of recurrent ischaemic stroke is much higher than in other patients with stroke (probably 15-20% in the first year and persisting at greater than 10% per annum long term).

 

Strokes in the context of atrial fibrillation have an additional potential mechanism, as they can arise from emboli of thrombin rich thrombus which form in the left atrium of the heart.  The risk of forming these thrombin rich (red) thrombi is greatly reduced by anticoagulant drugs (but not by antiplatelet drugs).

 

For these patients anticoagulant drugs reduce risk of stroke by a relative risk reduction of 60-70%.  In absolute terms this equates to a risk reduction of more than 10% in the first year and 7-8% every year thereafter.

 

These drugs also carry an inevitable risk of causing serious bleeding complications which is probably around 3-4 % per year, and minor bleeding problems with bruising are very common.  Bleeding complications, and particularly intracranial bleeding complications, are significantly less frequent with the direct oral anticoagulants than with warfarin.

 

Warfarin also has a disadvantage compared with the direct oral anticoagulants in that the required dose varies between people and over time, so that frequent (usually monthly) blood tests and dose adjustments are necessary to maintain anticoagulation at levels that are high enough to be effective but not so high as to further increase bleeding risk.  It has a modest advantage over the direct agents in that warfarin is easily reversible with intravenous clotting factors should serious bleeding occur, whilst direct anticoagulants are not reliably reversible.  It’s worth pointing out that despite this the risk of serious bleeding is higher with warfarin.

 

Decision making around starting anticoagulants in atrial fibrillation is an area which has been studied extensively.  There are many decision aids to support this.  These include scores to estimate the risk of stroke in individual patients (e.g. the CHADS2VASC score) and to estimate an individual patients risk of bleeding side effects (e.g. HASBLED score).  They also include many videos and written materials including pictorial aids to help clinicians explain these risks to their patients.  It is one of the areas where shared decision making has been most frequently used, and it would be worth your while to spend some time considering how you might discuss these risks and benefits in a clinical consultation.

 

It’s fair to say that as anticoagulation has become safer the balance of risks even for primary prevention of stroke is almost always in favour of anticoagulant drugs, and in secondary prevention (where the stroke risk and the effectiveness of treatment is higher) there are very few situations where the hard logic of statistical risk/benefit balance would not strongly suggest using anticoagulants.

 

Carotid Endarterectomy-

In terms of reducing the risk of further ischaemic stroke, there is good evidence that carotid endarterectomy reduces the long term risk of recurrent stroke in patients who have a >50% stenosis in the internal carotid artery on the same side as they had their stroke.  The effectiveness of this treatment declines rapidly with time – so that by a point 3 months after stroke the risks of the procedure almost balance those of avoiding treatment.  The treatment has only been studied in patients who have made a good recovery with minimal persistent deficit after stroke (practically defined as being able to walk independently into the outpatient consulting room and have a reasonable discussion with the vascular surgery team).

 

The benefit of surgery increases with the severity of carotid stenosis.  In those with 70-99% stenosis, endarterectomy reduced the risk of stroke by an absolute 15% over 5 years.  In those with 50-60% stenosis the risk was reduced by 5% at 5 years.  These reported benefits may be overestimates as trials of surgery took place compared with standard treatment that at that time did not include modern antiplatelet drugs or statins.  Further it takes 6 months to a year for the benefit of surgery to become apparent, because although the long term risk of stroke is reduced, the operation itself causes a 3-4% additional risk of stroke at the time of operation or within 30 days.

 

For patients with a lower life expectancy (older patients or those with comorbidities) the potential for benefit is lower as this only accrues many months after operation.  Even if their life expectancy is longer most people value their current health (and wealth) much more highly than their health in the future (economists term this “discounting”), so for many patients the prospect of increasing their immediate risk of stroke outweighs the potential longer term benefits when considering operation.  This effect is probably magnified by a perhaps illogical but certainly real human perception that if they had a stroke as a result of operation then this would be an unnatural event that they precipitated – whereas a stroke occurring without operation would feel more like an act of fate beyond their control and be more bearable as a result.

 

There are several risk and benefit calculation tools that can help in supporting patients with these decisions including one from the Department of Clinical Neuroscience in Oxford https://www.ndcn.ox.ac.uk/divisions/cpsd/carotid-stenosis-tool.

 

 

 

 

Migraines

26 December 2020

19:08

Commonly reported features of migrainous aura include:

 

Visual disturbances e.g. blind spots (scotoma), 'zig zags' (fortification spectra)

Numbness and tingling

Difficulty talking (aphasia)

Balance problems

And, very rarely, motor weakness

The frequency of migraine can vary from  every few months to daily headaches. The severity may also fluctuate with 'typical' migraine headaches that are worse than usual or better than usual.

 

Chronic Migraine

Patients with previously sporadic or regular but infrequent migraines can convert into chronic migraine which is defined by headaches that occur at least 15 days out of the month, where 8 of these 15 headaches are migrainous in nature.

 

From <https://mle.ncl.ac.uk/cases/page/8744/>

 

 

 

Status Migrainosus

Status migrainosus describes migraine attacks that are more severe and more prolonged than a patients typical episodes. This is often defined as >72 hours in duration.

These severe episodes can be reduced by good acute management of migraine in the earlier stages of an attack.  They are however also associated with overuse of medication.

 

From <https://mle.ncl.ac.uk/cases/page/8744/>

 

Medication Overuse Headache

We considered Medication Overuse Headache as a differential diagnosis for migraine, but it is also a potential complication and consequence of migraine.

Recap: Headaches associated with the overuse of certain medications. 

Defined as:

·         Present 15 or more days per month

·         Developed or worsened during medication overuse

·         Resolves or reverts to previous pattern within two months of discontinuing medication overuse

·         Regular use for 3 months or more of one of the following drugs for headache:

·         Triptans, opioids, ergots or combinations of these on 10 or more days per month

·         Paracetamol, aspirin, NSAIDs or combinations or combinations of these on 15 or more days per month.

 

From <https://mle.ncl.ac.uk/cases/page/8744/>

 

Migrainous Infarction

Migrainous infarction is a rare complication where a migraine attack is associated with a neurological lesion on imaging.

Features of migrainous infarction are:

1.       One or more features of migraine aura

2.       Migraine aura must be typical of previous attacks

3.       Ischaemic brain lesions demonstrated

4.       Focal neurological deficit(s) must persist longer than 60 minutes

5.       Episode must be associated with a pain crisis

 

From <https://mle.ncl.ac.uk/cases/page/8744/>

 

 

Acute Management

The aim of acute management is the termination or significant relief of the symptoms of migraine. These include pain, nausea and vomiting. When considering acute management, factors such as the reliability of the patient keeping medication down due to vomiting is important.

Acute management should be taken at the start of headache whilst the pain is mild.

Simple analgesia

Ibruprofen

Aspirin

Paracetamol

Triptans

5HT agonists

Oral preparations 

Intranasal or subcutaneous preparations can be used if vomitus prevents oral preparations

Patients should be advised to only take triptans at the start of the headache not the start of the aura.

Anti-Emetic medications

Metoclopramide

Prochloperazine

All patients should be followed up to track the effectiveness of acute management and escalate if necessary. 

Prophylaxis

For many patients migraine is an intermittent problem, best managed acutely when it arises.  For others however migraine is so frequent, severe and disruptive that they would consider daily medication to prevent attacks.

Prophylactic treatment for migraine should be considered in the following circumstances:

·         Significant impact on the patients quality of life and daily function

·         Frequent occurrence

·         Prolonged or severe despite optimum acute management

·         Acute treatments are contraindicated or ineffective

·         Patient is at high risk of medication overuse due to frequent use of acute medication.

 

Pharmacological Options

·         Propranolol 

·         Topiramate

·         Amitriptyline 

·         Botulinium A toxin injections (where 3 prophylactic agents have failed)

 

Other options

·         Cognitive behavioural therapy

·         Mindfulness therapy

·         Acupuncture - 10 sessions over 5-8 weeks

·         Riboflavin supplementation - 400mg once daily

 

Follow up for patients on prophylaxis:

Patients should be advised to keep a headache diary where they track the incidence and severity of their headaches. This allows both the patient and the clinician to track the effectiveness of therapy and titrate medication as needed.

Patients also need to be reviewed often during the titration process (2-3 weeks) for side effects. Once on stable treatment patients can be reviewed every 6-12 months.

Patients should be counselled that migraine relief on prophylaxis often takes 4-8 weeks from the onset of treatment. This is to manage expectations.

Failure to respond to max tolerated dose of prophylaxis for 3 months is a failure of treatment and these patients should be referred to neurology.

 

From <https://mle.ncl.ac.uk/cases/page/9322/>

 

Interventional Treatments

The intention for all of these is relief but not cure of migraine

Transcutaneous electrical stimulation of supra-orbital nerve

Involves wearing a headband that uses small currents to stimulate the nerves of the forehead to reduce pain. Has also been shown to reduce migraine. Indications: Distressing symptoms where medical therapy has failed.

Transcutaneous stimulation of the cervical branch of vagus nerve

Involves using a small handheld device to deliver low voltage currents to stimulate the cervical branch of vagus nerve. The aim is to relieve pain and reduce the frequency of episodic headaches. It can be used for cluster headache and migraine that are distressing where medical treatment has failed.

Transcranial magnetic stimulation 

Involves placing a device on the scalp and delivering single or repeated magnetic pulses.

Percutaneous closure of the foramen ovale

Involves closure of an abnormal remnant of the fetal heart where there is a persistent communication between the left and right atrium. This has been shown in some patients to be a  cause of recurrent migraine.

Occipital nerve stimulation

Involves implanting electrodes to deliver electrical impulses to the occipital nerve to mask migraine pain.

 

From <https://mle.ncl.ac.uk/cases/page/9325/>

Other options in migraine

In addition to clinician-led management, there are several self management strategies that patients can employ themselves that may improve symptoms.

Nutrition

Regular meals seem to reduce the frequency and severity of migraine attacks. Common food triggers for migraine include caffeine, chocolate and alcohol. 

Triggers vary greatly between patients however, so there is no single dietary regime that will apply to all patients.  Patients can use their headache diaries to attempt to identify and restrict any additional dietary factors that may trigger headaches. 

1  Resources

Specific Diets

Whilst regular meals are generally agreed to be preventative of migraine, there is relatively little high quality evidence that specific diets consistently improve the frequency and severity of migraine.

Ketogenic diet: Involves restriction of carbohydrate and sugar with dietary emphasis on protein and fat intake. The notion is to enter a state of ketosis.

Low glycaemic index diet: Involves switching to consumption of low glycaemic index foods, which are metabolised over a longer period of time and cause slower rises in blood sugar rather than causing peaks and troughs in blood sugar. The notion is to maintain blood glucose at a relative steady state.

3  Resources

Stress Management

Psychological stressors can trigger migraine.  Avoiding or minimising stressful situations and practicing effective stress management can reduce migraine.  

It's worth considering that migraine (and it's effect on relationships and work for example) can cause stress, producing a vicious cycle.  

Sleep Quality and Hygiene

Disordered sleep is a common trigger for migraine.  Many patients find they can reduce attacks by improving their sleep quality and hygiene; aiming to sleep at the same time each night, followed by a predictable period of sleep and a predictable waking time.

Disturbed sleep may also be a consequence of prolonged severe migraine, either directly, or because of associated stress.  Again, breaking this cycle may lead to significant benefits.

 

From <https://mle.ncl.ac.uk/cases/page/9324/>

 

NICE would recommend escalating to use of a triptan if ibuprofen or paracetamol or aspirin ineffecdtive.

·         Depending on the severity of attacks, associated symptoms, contraindications and comorbidities:

o    Offer simple analgesia such as:

·         Ibuprofen (400mg) — if ineffective, consider increasing to 600 mg or

·         Aspirin (900 mg) or

·         Paracetamol (1000mg).

o    Offer a triptan, alone or in combination with, paracetamol or an NSAID:

·         Oral sumatriptan (50–100 mg) is first choice — other triptans should be offered if sumatriptan fails.

·         If vomiting restricts oral treatment, consider a non-oral formulation (such as intra-nasal or subcutaneous).

o    Consider offering an anti-emetic (such as metoclopramide 10mg or prochlorperazine 10mg) in addition to other acute medication even in the absence of nausea and vomiting.

·         Metoclopramide should not be used regularly due to the risk of extrapyramidal side effects.

·         Advise the person that:

o    Acute medication should be taken early while pain is mild.

o    If they have aura, triptans should be taken at the start of the headache and not at the start of the aura (unless the aura and headache start simultaneously).

·         Do NOT offer ergots or opioids.

 

From <https://mle.ncl.ac.uk/cases/page/9342/>

 

2) NICE guidelines state that topiramate, propranolol and amitriptyline are indicated for medical prophylaxis of migraine. Riboflavin supplementation and acupuncture can also be used as preventative measures.

 

From <https://mle.ncl.ac.uk/cases/page/9342/>

 

 

3) Topiramate should not be used in pregnancy as it is actively teratogenic. Propranolol and Amitriptyline are considered safer if prophylaxis is a requirement. Seek specialist advice if unsure.

 

teratogenic effects of beta blockers (propranolol) and anti-epileptics (topiromate) and the implications if she were to fall pregnant. 

 

 

 

prophylaxis in this instance as his migraines as:

·         Significant impact on quality of life and daily function (this is subjective)

·         Prolonged or severe despite optimum acute management

 

 

 

Back and Neck pain

26 December 2020

21:58

red flag symptoms of back pain

 

T            Trauma

U        Unexplained weight loss

N        Neurologic symptoms

A        Age >50

F        Fever

I        IV drug use

S        Steroid use

H        History of cancer

 

 

 

·         Cauda equina syndrome (CES). Red flags include:

o    Severe or progressive bilateral neurological deficit of the legs (such as major motor weakness with knee extension, ankle eversion, or foot dorsiflexion.

o    Recent-onset urinary retention and/or urinary incontinence

o    Recent-onset faecal incontinence

o    Perianal or perineal sensory loss (saddle anaesthesia or paraesthesia)

o    Unexpected laxity of the anal sphincter.

·         Spinal fracture. Red flags include:

o    Sudden onset of severe central spinal pain which is relieved by lying down.

o    A history of major trauma (such as road traffic collision or fall from a height), minor trauma, or even just strenuous lifting in people with osteoporosis or those who are taking corticosteroids.

o    Structural deformity of the spine

o    There may be point tenderness over a vertebral body.

·         Cancer. Red flags include:

o    The person being over 50 years of age.

o    Gradual onset of symptoms

o    Severe unremitting pain that remains when the person is supine

o    Aching night pain that prevents or disturbs sleep

o    Pain aggravated by straining

o    Thoracic pain

o    Localised spinal tenderness

o    No symptomatic improvement after 4-6 weeks of conservative low back pain therapy.

o    Unexplained weight loss.

o    Past history of cancer – breast, lung, gastrointestinal, prostate, renal, and thyroid cancers are more likely to metastasise to the spine.

o    Back pain could also point towards multiple myeloma, or lymphoma.

·         Infection (such as discitis, vertebral osteomyelitis, or spinal epidural abscess). Red flags include:

o    Fever

o    Tuberculosis, or recent urinary tract infection

o    Diabetes

o    History of IV drug use

o    Immunocompromised patients (for example due to HIV infection, or the use of immunosuppressants).

This list isn’t inclusive. There are other serious causes of back pain that aren’t related to the spine, such as an Abdominal Aortic Aneurysm (Triple A) rupture, or pathology in the kidneys.

 

From <https://mle.ncl.ac.uk/cases/page/9879/>

is it Could if of an will in Pagers of the Ne h 'Olithiasis m red cells in urine. Useful f CES. A residÄ Wume of •200mls is of CES. If inf=tion. or inflammation is Imaging in s dip FBC, ESR, CRP Thyr&d tests Plain Note: if then a stmding X." of the sane is %eferob'e A fi/m offers bmited o nd affæts a —d "n e 'm aging phasphatase an be in diæase, and Pagers dimse of th ærticulartyin of the prostate Could useful f Could useful f ancer is the of the hck *in. Used if fracture is Can det=t Sgcndylol an detuted with standing lumbar X.ay Vertebral collapse from Pagers diÆaæ of the Ofte, stres the Ofte, best in detail. Gives good tissues, including di"s and anything impinging on the spinal cord Disc leions e by MRI MRI is most the 1Æful in digits, and lutic diæase Whæn other are suspected. wide of further may bere uired Chest Mainly if the is displaying sym May show or May show pulmona"/ tutÆ€osis_ Used if turnur is found In primary QTinoma is WII renal stones to visualiæ the a picture of an it to accurately to detæ May a postæ& uQr for helicobacter pylori or

NICE suggests should be done:

·         If there are red flag symptoms and signs that may suggest a serious underlying cause, admit of refer urgently for specialist assessment, or imaging, using clinical judgement.

·         If an underlying cause for the low back pain has been identified, manage according to the specific diagnosis.

 

From <https://mle.ncl.ac.uk/cases/page/9888/>

 

 

Yellow Flag Symptoms

There will be psychosocial barriers to active rehabilitation, and these should be spotted to reduce the risk of chronicity.

These barriers are called “Yellow Flags”. They include:

·         Sickness behaviours, such as extended rest.

·         Belief that pain and activity are harmful

·         Social withdrawal

·         Emotional problems such as low mood, depression, anxiety, and stress.

·         Problems and/or dissatisfaction at work

·         Problems with claims or compensation, or time off work

·         Overprotective or unsupportive family/friends.

·         Inappropriate expectations or engagement in treatment

 

From <https://mle.ncl.ac.uk/cases/page/9905/>

Risk stratification tools such as STarT Back are a useful way of stratifying patient’s risk of a poor prognosis, and matching the treatment option that is best for them.

Testing for the presence of Waddell’s signs is also a suggested method of identifying whether there are non-organic or psychological components to the patient’s pain.

 

From <https://mle.ncl.ac.uk/cases/page/9905/>

 

 

Management of Non-Specific Lower Back Pain

Since non-specific low back pain does not have a known patho-anatomical cause, treatment focuses on reducing pain and its consequences.

Here are a few tips:

·         Give information, reassurance and advice.

·         Address issues that may predispose to further episodes (yellow flags).

·         Do not prescribe bed rest – advise the patient to stay as active as possible.

·         Consider regular pain relief; lowest dose, short course of non-steroidal anti-inflammatory drugs. Consider also a short course of muscle relaxants.

·         Only offer weak opioids if non-steroidal anti-inflammatories are ineffective, contraindicated, or not tolerated.

·         Paracetamol mono-therapy has been shown to be ineffective, contraindicated or not tolerated.

 

Pain Management Services

·         Multidisciplinary approaches by Pain Management teams are an invaluable service aimed at providing individualised care packages to help people live with their chronic pain.

·         Referral should be considered if not resuming normal activities or off work.

·         The Living Well with Pain Team provide this service in the Northumbria Trust.

o    GPs or advanced practitioner physiotherapists from the area can make referrals.

o    The team offers workshops on pain management, psychological therapy, and physiotherapy.

·         If you’re interested, you can find out more information about the team here: https://www.northumbria.nhs.uk/our-services/living-well-with-pain/

Chronic pain Non-malignant pain Cancer pain erve block Epidurals PCA pump Neurolytic block herapy Pinal stimulators Pain persisting / increasing Step 1 Non-opioid analgesics NSAlDs Pain persisting / Increasing Step 2 Weak opioids Eg. Codeine, tramadol Acute Chronic pain wi Pain persisting / Increasing Step 3 Strong opioids Eg. Morphine Methadone Oral administration Transdermal patch ut control IC pain NSAlDs (with or without adjuvants at each step)

From <https://mle.ncl

made for free at coggle.it Biological impact The Bio-psycho-social Impacts of Chronic Pain Impact on where you live Impact on relationships Impact on family life Social impact Impact on friendships Impact on work Risks associated with surgical treatments for chronic back pan Sleep disturbance Lack of mobility due to pain could lead to weight gain, therefore increasing risk of many other illnesses Coping with side effects of medications "Diagnostic momentum" - chronic pain could mask symptoms of other health problems Psychological impact Increase in daily stress levels Anger surrounding pain and A feeling of loss of identity A loss of cognitive function medication Constant fatigue Anxiety (é Impact on mental health Depressic Not being able to afford rent due to unemployment Having to make adaptations to your home so it can accommodate your needs Having to move house to a home that can accommodate your needs Adapting to a potential change of roles in the relationship (eg. changing primary earner Becoming more bad tempered with partners Worrying about whether pain will affect intimacy Not being as able to go out and meet potential partners Not being able to care for dependent relatives Becoming more bad tempered with family members Not being able to do the activities you want with loved ones Having to consider the affect of your pain if wanting to start a new family Personality changes due to constant pain could affect friendships Becoming tired more easily might reduce the amount of socialising you can do Feeling you have less to contribute during social situations since your life is engulfed by your pain Undergoing a stressful litigation process for a claim against an employer The sense of loss if you have to give up your career Feeling guilty for taking sick leave The difficulty of focussing on work despite pain

.ac.uk/cases/page/9906/>

 

 

 

 

 

 

Rheumatoid Arthritis 

26 December 2020

22:15

·          Boutonniere deformity. There is DIP hyperextension and PIP flexion

 

·         swan neck deformity. There is DIP flexion and PIP hyperextension

 

·          Z thumb deformity or sometimes called Hitchhiker's thumb.

·         There is hyperextension of the interphalangeal joint, and fixed flexion and subluxation of the metacarpophalangeal joint.

 

·         Ulnar deviation

 

 

Rheumatoid Arthritis in a nutshell...

 

· RA is the commonest cause of chronic inflammatory arthritis in the UK. It is much less common in Malaysia and in this context the main differential diagnosis is Systemic Lupus Erythematosus (SLE).

 

· Clinical features include joint pain, joint swelling, morning stiffness, difficulty in moving and ability to perform motor tasks. The presentations however can be variable and patients often describe a fluctuation in symptoms from day to day and week to week. There is often a chronic relapsing / remitting course which may be progressive and indolent but acute presentations occur. There are often systemic symptoms – again variable – including fatigue, loss of energy and even weight loss.

 

· The differential diagnosis is wide and includes other causes of inflammatory arthritis (including SLE and other connective tissue diseases), infection related arthritis, crystal arthritis, hypothyroidism, and malignancy.

 

· The clinical assessment is most important in making a diagnosis – taking an MSK history and performing a competent joint examination are essential. The diagnosis of RA is essentially clinical with investigations to exclude differential diagnoses. Radiographs can be normal in early RA. US is a highly sensitive way to detect synovitis. Rheumatoid factor can be negative in RA. Anti CCP antibodies are highly specific for RA.

 

· RA can have a dramatic impact on activities of daily living and the variability in symptoms make it difficult to plan ahead.

 

· Being able to stay in work is important to maintain an income and concern about work is often a cause of anxiety.

 

· The approach to management of RA includes medical and biopsychosocial aspects. The multidisciplinary team (MDT) is essential and includes the nurse, allied health (physiotherapy and occupational therapy).

 

· Management of RA includes pharmacologic and non-pharmacologic options.

 

· The aim of management is to achieve disease control as soon as possible, mitigate / avoid side effects of treatment, optimise function and enable patients to lead a fulfilling independent life.

 

· The medical management includes treatment to manage symptoms, prevent joint damage and disability, and prevent / reduce the risk of complications of the disease and or side effects of treatment.

 

· The emphasis is on early diagnosis and prompt access to immunosuppressive treatments with escalation of treatment to achieve rapid disease control.

 

· Early remission is the goal of management and is achievable for many patients although patients have to take treatments long term - a curative treatment is not currently available.

 

· Early RA clinics aim for all suspected RA patients to have a prompt first assessment and access to highly effective treatment options that are now available has led to clinical outcomes being much improved.

 

· Comorbidities are common in patients with RA and may influence the treatment options. Increased mortality is reported in RA. The main cause of death is cardiovascular disease.

 

· RA is a serious disease and prior to the emergence of highly effective DMARDS and biologics, high morbidity with disability was common along with marked increased mortality from cardiovascular disease in particular. The outcome has markedly improved in recent decades.

 

 

 

 

 

 

 

Differentials

The differential diagnosis must include other causes of inflammatory arthritis (including SLE and other connective tissue diseases), infection related arthritis, crystal arthritis, hypothyroidism, and malignancy. This list is not exhaustive. 

 

The clinical assessment is most important in making a diagnosis – taking an MSK history to come up with a differential diagnosis and performing a competent joint examination is essential. 

 

 

 

Comparison Of features Of musculoskeletal disease in systemic lupus erythematosus or rheumatoid arthritis Feat re *rtrophy SyrWviaI M Omi ng stiffness Swan Systemic lupus erythematosus PI P MCP Rheumatoid arthritis PI CPS knee Corn ruin , not reduci&e proximal interphala.al; MCP: "*tacarpophalangee.

 

 

Investigations

The diagnosis of RA is essentially clinical with investigations to exclude differential diagnoses.

1. Bedside 

·         Urinalysis as a baseline and to exclude other differentials.

2. Bloods - baseline before treatment and to exclude other differentials.

·         FBC, ESR, CRP, U&Es, LFTs, Autoantibodies (including Rheumatoid factor / anti-CCP), TFTs.

Other tests depending on the presentation to exclude other differentials. Remember that Rheumatoid factor (RF) may be negative in RA and also a positive RF is not diagnostic of RA. Anti CCP antibodies are highly specific for RA. Positive RF and anti-CCP antibodies are prognostic indicators of a more severe course in the context of a diagnosis of RA.

3. Imaging - as a baseline before treatment and to exclude other differentials.

·         US joints are the most sensitive imaging modality to detect synovitis.

·         Joint radiographs helpful as a baseline and to exclude other differentials but are often normal in early RA.  

·         Chest XR - helpful as a baseline (prior to starting methotrexate or other treatments) and to    exclude other differentials including latent TB.

4. Special tests

·         Blood tests – latent TB, Hep B, Hep C, HIV status (pending clinical context) – before starting    immunosuppressives.

·         Lung Function - helpful as a baseline (prior to starting methotrexate or other treatments)

·         Synovial fluid assessment – joint aspiration is essential to exclude septic arthritis and crystal  arthropathies

 

 

Risks of investigations: 

There are no particular risks of the investigations although joint aspiration must be done using sterile technique and by a competent operator. The blood tests may be negative or normal so can be falsely reassuring – for example RF can be negative in RA

 

From <https://mle.ncl.ac.uk/cases/page/13278/>

 

Patients suspected to have RA should be referred to a rheumatologist as soon as possible to confirm the diagnosis, establish the severity of the disease and develop a care plan. Early referral and ongoing rheumatology input has bee shown to improve disease outcomes.

 

A combination of therapies is used: 

1. Anti- inflammatory medication ( e.g NSAIDs and systemic/intraarticular glucocortoids)

 These medications are used to temporarily control the disease in patients commencing DMARDs or during disease flares. They are useful at reducing inflammation but do not provide long term control or prevent joint injury. Glucocorticoids are often not used for long periods of time due to their side effects. 

2. Disease Modifying Anti-rheumatic Drug (DMARDs)

These include nonbiological and biological DMARDs which can reduce or prevent joint damage and preserve function. Patients should therefore be started on DMARDs as soon as possible. 

Examples of nonbiological DMARDs include Methotrexate, hydroxychloroquine and sulfasalazine. 

Biological DMARDs work by targeting cytokines or their receptors. They can therefore be subclassifed into TNF-alpha inhibitors e.g infliximab, adalimumab; IL-1 receptor antagonists e.g anakinra and IL-6 receptor antagonists  e.g tocilizumab etc.

 

Typically patients are commended on Methotrexate first line.

Patients unable to take methotrexate will require an alternative such as hydroxychloroquine or sulfasalazine. 

If patients are resistant to initial DMARD therapy then a combination of DMARDs can be used e.g  methotrexate +TNF inhibitor. 

 

From <https://mle.ncl.ac.uk/cases/page/13281/>

 

1. Pregnancy/ women of child bearing age- methotrexate is teratogenic. If used in women of child bearing age effective contraception should be used and continued for 6 months after treatment. Hepatic impairment

 

The emphasis is on early diagnosis and access to immunosuppressive treatments with escalation of treatment to achieve rapid disease control (so called ‘treat to target’). Regular monitoring patient is important to assess the response to treatment and any side effects.

 

Disease activity and severity is assessed clinically (history and examination), bloods tests (acute phase reactants) and imaging of joints (usually by US). There are various outcome measures and the Disease Activity Score (DAS28) is a composite score to assess indication and response to biologics. Patient Reported outcomes measures (PROMS) are important and relate to the impact on the individual. Active RA  and systemic effects are usually easily recognized by the presence of actively inflamed joints, fever, anaemia, an elevated erythrocyte sedimentation rate (ESR), or an elevated serum C-reactive protein (CRP).

The management of RA is complex and the MDT approach is important to enable patients to understand the rationale for treatments and make appropriate choice for them. A shared decision making approach is important.

 

 

Non-pharmacologic options. Briefly, these measures include:

 

●Patient education

 

●Psychosocial interventions

 

●Rest, exercise, and physical and occupational therapy

 

●Nutritional and dietary counselling

 

●Interventions to reduce risks of cardiovascular disease, including smoking cessation and lipid control

 

●Screening for and treatment of osteoporosis

 

●Immunizations to decrease risk of infectious complications of immunosuppressive therapies.

 

 

02QO Ire. affiliatß. R•ts Natural history and prognosis Of rheumatoid arthritis 70 percent detecta* x-ray of feet occur first two years of At 20 years, over 60 percent of patients with RA to class ser-caring. using aids, mt replacemer%s) or class IV (bss of requiring daily care) Increased inedence of: Life of RA then control —pedelty •n with one or of the folbwinq: dim persistent disease activity thigh ESR, CRP) rt.toid md "LA-DR epitoß, • if GQphic 82537 2.0

 

 

 

Joint failure

 

Patients with RA are at risk of secondary osteoarthritis even with therapeutic interventions. Some patients progress to disabling, destructive joint disease. Patients may present with mechanical symptoms (pain on weight bearing and walking) and in the case of knee or ankle involvement, with locking and or giving way. The accurate evaluation of such patients is essential, since deterioration associated with mechanical problems of the muscle or joint is treated much differently from ongoing inflammation or systemic manifestations of rheumatoid arthritis (RA).  Osteoporosis can lead to avascular necrosis of the hip and secondary osteoarthritis.

 

The goals of therapy in the patient with end-stage disease are:

 

●Pain relief

 

●Protection of remaining articular structures

 

●Maintenance of function

 

●Relief from fatigue and weakness

 

The indications for surgical intervention in patients with RA include severe pain or functional disability due to joint destruction. The timing of surgery is important -  waiting too long has the risk of much muscle atrophy from disuse resulting in postoperative rehabilitation being unsuccessful.

 

 

Treatment during pregnacy:

- Pre-conception counselling should be offered involving a rheumatologist and obstetrician. 

- Ideally pregnancy should be planned for when their disease is under good control on medications compatible with pregnancy e.g TNF inhibitors, sulfasalazine

-Commence folic acid prior to pregnancy 

- If RA becomes active in pregnancy, NSAIDs can be used until the 3rd trimester or low dose prednisolone. Or the patient can be commenced on a safe DMARD. 

 

From <https://mle.ncl.ac.uk/cases/page/13294/>

 

Infection

 

●Serious infection – In patients with an active serious infection, conventional and biologic disease-modifying antirheumatic drugs (DMARDs) and tofacitinib should be temporarily held until resolution of infection and completion of antimicrobial therapy. In patients with a history of a serious infection, we recommend conventional DMARDs over biologic agents. Medications administered more frequently are preferred in patients in whom there is heightened concern regarding infection or with recurrent infections because of the relative greater ease of discontinuing the therapy and its immunomodulatory effect if needed.

 

●Hepatitis B – In patients with natural immunity to hepatitis B virus (HBV; HBV core antibody [HBc]-positive, normal liver chemistries, HBV surface antibody [HBs]-positive, and HBV surface antigen [HBsAg]-negative), treatment for RA should be the same as for HBV-unexposed RA patients, but viral loads should be monitored every 6 to 12 months to ensure there is no reactivation. For patients with active untreated hepatitis, referral for antiviral therapy should be obtained before immunosuppressive therapy, and patients should be treated in collaboration with their hepatologist. In the absence of additional harms, RA treatment may proceed for patients with active HBV on concomitant antiviral treatment. (See "Hepatitis B virus: Screening and diagnosis" and "Hepatitis B virus: Overview of management".)

 

●Hepatitis C – Patients with active hepatitis C virus (HCV) and normal liver function should not be treated differently than RA patients without HCV. If underlying liver disease is present, non-hepatotoxic DMARDs (sulfasalazine [SSZ] or hydroxychloroquine [HCQ]) are preferred initially. Patients with HCV infection should be managed in collaboration with their hepatologist. (See "Overview of the management of chronic hepatitis C virus infection".)

 

●Tuberculosis – Prior to initiation of immunomodulatory therapy, patients with risk factors for tuberculosis (TB) should be screened for latent TB and treated if indicated (see 'Pre-treatment evaluation' above). In patients in whom latent TB is diagnosed, at least one month of treatment should be completed prior to the initiation of immunosuppressive agents.

 

In patients with latent TB who are unable to complete anti-TB therapy, we prefer to use nonbiologic DMARDs as monotherapy or in combinations. In patients with persistent disease activity despite such intervention, it may be necessary to use a biologic DMARD, in which case we prefer agents other than tumour necrosis factor (TNF) inhibitors. We also review the risks of such intervention in detail with the patient when deciding upon therapy and consult with a specialist in infectious disease for additional assistance in management.

 

Malignancy

 

Management of RA in patients with malignancy or a history of malignancy is based upon findings from observational studies including registries together with expert opinion.

 

●Non-melanoma skin cancer (basal cell and squamous cell carcinoma) – In patients with a history of non-melanoma skin cancer, conventional DMARDs are preferred over biologic DMARDs or tofacitinib. There is no contraindication to escalation of therapy to include biologics, but routine skin cancer surveillance is indicated.

 

●Melanoma skin cancer – In patients with a history of melanoma conventional DMARDs are preferred over biologic DMARDs or tofacitinib. Approaches including monoclonal antibody treatments that activate T cells have shown benefit in treating melanoma; therefore, some clinicians avoid the use of abatacept in patients with a prior history of melanoma. Routine skin cancer surveillance is indicated.

 

●History of lymphoproliferative disorder – In patients with a history of a lymphoproliferative disorder, we prefer conventional DMARDs, and if a biologic agent is needed, the first choice would be rituximab, given its use in the treatment of lymphoproliferative disorders and a lack of evidence for increased cancer risk with its use.

 

●Solid organ malignancy – In patients with a treated solid organ malignancy within the past five years, we use conventional DMARDs over biologic DMARDs. If a biologic agent is needed, the first choice would be rituximab, given the lack of evidence for increased cancer risk with its use. In patients who are more than five years out from a treated solid organ malignancy, excluding melanoma, RA treatment is no different than from those without malignancy.

 

Lung disease - Comorbid pulmonary disease is common in patients with RA and may also be a complication of therapy or of the disease; adverse effects from methotrexate include a pneumonitis especially in smokers. There is an increased risk of opportunistic infection including TB with immunosuppressive treatments.

 

Diabetes — in patients with both diabetes and RA, glucocorticoids should be used with particular caution because they may worsen control of the diabetes.

 

Infections - Covid-19 pandemic and implications for patients on immunosuppressive treatment – new guidance is available

 

https://www.nice.org.uk/guidance/ng167.

 

Vaccines – vaccines are encouraged although live vaccines are contra-indicated. Annual influenza vaccine is recommended.

 

Osteoporosis – patients with RA are at risk of osteoporosis for a number of reasons – chronic inflammation, less weight bearing and systemic use of glucocorticoids are risk factors. Good disease control, weight bearing exercise and diet supplementation with calcium and vitamin D are important.

 

Increased mortality is reported in RA. The main cause of death is cardiovascular disease. The increased risk of cardiovascular disease is multi-factorial and control of chronic inflammation is key as it may lead to the development of atherosclerosis. Medications used to treat RA such as steroids and NSAIDs can also increase the risk of CVD.

 

The QRISK  assessment (a prediction algorithm for CVD) includes RA as a risk factor. An important aspect of management of RA therefore is to establish and manage cardiovascular risk (control of BP, lipids) and lifestyle factors (smoking, diet and exercise) also need to be addressed.

 

From <https://mle.ncl.ac.uk/cases/page/13291/>

 

Some patients may develop destructive joint disease despite maximal therapy. This can be without the presence of any active inflammation.

 

Goals of treatment in these patients are:

 

1. Adequate pain relief

 

2. Maintain fucntion

 

3. Relief of other symptoms such as fatigue and weakness.

 

4. Protect remaining joints

 

If there is no ongoing inflammation, treatments should be focussed instead on non-pharmacological treatments e.g physical therapy and occupational therapy.

 

 

 

 

 

 

 

Osteoarthritis

26 December 2020

23:21

 

It is difficult to estimate the prevalence of OA as it is asymptomatic in many people, but the WHO estimate that worldwide, approximately 10% of men and 20% of women over 60 have symptomatic OA. In England, between 2000 and 2018, 3.1 million patients presented with OA. Involvement of the knee or hip each accounted for almost 40% of presentations. Generally, regardless of the principal joint, OA incidence tends to start rising rapidly from the age of 40 years and peaks in the mid-60s.

 

 

 

Distal Interphalangeal joints and thumb carpometacarpal joints (OA)

Distal Interphalangeal joints (OA, PsA) Proximal interphalangeal joints (RhA, OA) Proximal interphalangeal joints, metacarpophalangeal joints (RA) Index and middle finger metacarpophalangeal joints (haemochromatosis) 

 

From <https://mle.ncl.ac.uk/cases/page/13099/>

 

 

 

Bony (OA) or soft tissue (Inflammatory)

Red, warm (RA, PsA, gout, pseudogout) Variable (inflammatory arthritis or Inflammatory OA 

 

From <https://mle.ncl.ac.uk/cases/page/13099/>

 

Morning stiffness of >30minutes increases the likelihood of inflammatory arthritis

 

From <https://mle.ncl.ac.uk/cases/page/13099/>

 

 

 

 

 

Risk factors include

·         Age

·         Gender (females gender is associated with higher prevalence and severity)

·         Genetic predisposition

·         Previous injury to a joint

·         Anatomic features (eg Developmental Dysplasia of the Hip)

·         Obesity (which surprisingly is associated even with hand OA)

·         Occupation (e.g. heavy manual work, whole-body vibration – such as heavy goods vehicle drivers)

 

From <https://mle.ncl.ac.uk/cases/page/13101/>

 

 

 

Physiotherapist (Exercise regime and pain relieving modalities)

Occupational therapist (Joint protection, aids and adaptations, coping strategies)

Podiatrist (splinting, insoles, footwear advice, minor foot surgery)

Social worker (financial implications of disability, housing)

Appliance officer (splints, braces, walking aids)

Psychologist (coping strategies, chronic pain management)

 

 

 

 

 

This may be a useful adjunct to therapy by relieving the pain. In hand OA, it is often used to relieve pain from the carpometacarpal joint of the thumb. However it is not without risk. You may remember the following from last year’s EoCP:

·         Main indication for injection is relief of symptoms

·         Complications – infection (very rare <1/15,000), pain, bruising, failure, complications of steroid

·         Rest for at least 24 hours after

·         US guidance – especially hip

·         Equipment – gloves, antiseptic spray, needles, syringes, swabs, plaster, steroid and lidocaine

·         Aseptic non-touch technique (ASNTT)

·         Knee slightly flexed (10-15 degrees)

·         Medial or lateral approach

 

From <https://mle.ncl.ac.uk/cases/page/13110/>

 

Arthroplasty (joint replacement) in OA:

·         Indicated in patients with severe pain when conservative measures have failed

·         A risk-benefit balance assessment is required when deciding to operate on patients who have OA and are obese due to the increased risk of complications from surgery given the patients are obese

·         Patients who are obese may be at higher risk of requiring revisions

·         96% of total knee replacements have a 10 year survival rate (i.e., survival of the joint replacement)

·         OA is the most common indication for hip replacements with pain relief being one of the principal driving factors

·         Severity of X-ray changes in and of themselves do not pose a sufficient indication for hip replacements

·         NICE guidelines advise that obesity should not prevent a patient being referred for consideration for hip replacement surgery

 

From <https://mle.ncl.ac.uk/cases/page/13111/>

 

 

 

 

 

Acne

26 December 2020

23:54

Acne vulgaris: Summary

·         Acne vulgaris is a chronic inflammatory skin condition affecting mainly the face, back and chest - it is characterised by blockage and inflammation of the pilosebaceous unit (the hair follicle, hair shaft and sebaceous gland). It presents with lesions which can be non-inflammatory (comedones), inflammatory (papules, pustules and nodules) or a mixture of both.

·         Up to 95% of adolescents in Western industrialized countries are affected by acne to some extent — 20 to 35% develop moderate or severe acne.

·         Complications of acne include skin changes such as scarring, post-inflammatory hyperpigmentation or depigmentation and psychosocial problems such as depression and anxiety.

·         All people with acne should be advised:

o    To avoid over cleaning the skin (which may cause dryness and irritation) - acne is not caused by poor hygiene.

o    To use non-comedogenic make-up, cleansers and/or emollients with a pH close to the skin if needed.

o    To avoid picking and squeezing spots which may increase the risk of scarring.

o    That acne treatments are effective but take time to work - usually up to 8 weeks.

o    That acne treatments may irritate the skin, especially at the start of treatment - concentration or application frequency may need to be reduced if skin irritation occurs.

·         In mild acne where open and closed comedones (blackheads and whiteheads) predominate:

o    A single topical treatment such as a topical retinoid (for example adapalene, if not contraindicated) or benzoyl peroxide should be considered as first-line treatment.

o    If both topical retinoids and benzoyl peroxide are poorly tolerated, azelaic acid can be considered.

·         In moderate acne where inflammatory lesions (papules and pustules) predominate and response to topical preparations alone is inadequate:

o    Addition of an oral antibiotic such as lymecycline or doxycycline (for a maximum of 3 months) can be considered.

·         A topical retinoid (if not contraindicated) or benzoyl peroxide should always be co-prescribed with oral antibiotics to reduce the risk of antibiotic resistance.

·         Macrolide antibiotics (such as erythromycin) should generally be avoided due to high levels of P. acnes resistance but can be used if tetracyclines are contraindicated (for example in pregnancy).

·         Non-response to two different courses of antibiotics, or scarring are indications for referral to dermatology for consideration of treatment with isotretinoin.

o    Combined oral contraceptives (if not contraindicated) in combination with topical agents can be considered as an alternative to systemic antibiotics in women – prescription should be guided by the UK Medical Eligibility Criteria for Contraceptive Use.

·         Referral to dermatology should be arranged if:

o    A severe variant of acne such as acne conglobata or acne fulminans (immediate referral) is suspected.

o    Acne is severe, there is visible scarring or the person is at risk of scarring or significant hyperpigmentation.

o    Multiple treatments in primary care have failed.

o    Significant psychological distress is associated with acne, regardless of severity.

o    There is diagnostic uncertainty.

·         Follow-up should be arranged 8-12 weeks after initiation of each treatment step:

o    If there has been an adequate response, treatment should be continued for at least 12 weeks.

o    If acne has cleared or almost cleared, maintenance therapy with topical retinoids (if not contraindicated) or azelaic acid should be considered.

o    If there has not been an adequate response, adherence to treatment, adverse effects and use of comedongenic make up or face creams should be considered before swapping to an alternative product or the next treatment step.

Isotretinoin last line

 

From <https://mle.ncl.ac.uk/cases/page/13311/>

 

 

 

 

Eczema

Sunday, 27 December 2020

21:08

lllness affecting the skin is the fourth most frequent cause of all human disease. It affects some 1.9 billion people at any time, almost one-third of the world’s population.

 

In the UK 1 in 5 children have atopic eczema

 

 

 

Eczema, like most chronic conditions, can have a profound impact on patients’ quality of life and self-esteem and can contribute to mental illness.

 

Eczema is a complex, chronic, itchy, inflammatory disease that arises from a complex interaction of genetic and environmental factors.

 

 The typical appearance of eczema consists of flares, with red, inflamed patches which sometimes blister and weep. Between flares there can be normal skin or chronic skin changes of dry thickened patches – worsened by excoriations from scratching. 

 

There are varying patterns of distribution depending on age.

 

Eczema can be seen alongside hayfever and/or asthma as part of an ‘atopic triad’.

 

Eczema can be managed with emollients, steroid cream, Tacrolimus, Pimecrolimus, Alitretinoin and phototherapy.

 

 

Flexors usually

 

 

 

CML and AML chromo

Sunday, 3 January 2021

20:49

The 9:22 translocation (the Philadelphia chromosome) is typically found in chronic phase chronic myeloid leukaemia. The translocation encodes for a protein with tyrosine kinase activity which is responsible for the disease and its manifestations. Translocation 15:17 is typically seen in acute pro-myelocytic leukaemia. Translocation 8:21 and inverted 16 are all associated with good prognosis in acute myeloid leukaemia. Abnormalities of 5,7 and 8 are seen in acute myeloid leukaemia and are associated with a poor prognosis. They may be seen in patients with a preceding history of myelodysplasia which has transformed to acute myeloid leukaemia. 

 

 

 

Psoriasis

27 December 2020

21:36

 

Model answer "Psoriasis is a complex, chronic, multifactorial, inflammatory disease that involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate"

 

 

 

 

Key points:

 

Psoriasis is a complex, chronic, multifactorial, inflammatory disease that involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate

 

 

The classic appearance of psoriasis consists of well-dermarcated, red, plaques with silver scale

 

 

Chronic plaque psoriasis is the most common pattern and consists of plaques on extensor surfaces

 

 

Pitting, leukonychia, onycholysis, subungual hyperkeratosis, and oil drop are all nail signs of psoriasis – don’t forget to examine nails!

 

 

Psoriasis can be managed with topical steroids, phototherapy, systemic drugs and biologics depending on the patient and their disease severity

 

 

Psoriasis, like most chronic conditions, can have a profound impact on patients’ quality of life and self-esteem and can contribute to mental illness

 

 

Psoriasis is a systemic inflammatory condition and its affects aren’t limited to the skin i.e. psoriatic arthritis, cardiovascular risk

 

 

 

 

Medically unexplained physical symptoms

27 December 2020

22:16

 

Summary

 

Medically unexplained physical symptoms are common - they account for almost half of all GP consultations and an equivalent proportion in the hospital setting.

Ensure that you have completed a thorough history and examination to ensure that an underlying physical cause has been excluded.

Avoid using diagnostic labels where possible - offer the patient reassurance and the offer of an 'open door' to discuss their concerns.

Medically unexplained physical symptoms should be managed holistically. Management compromises a range of psychological and pharmaceutical therapies.

Remember that all actions are not necessarily harmless - arranging investigations and prescribing medications come with their own risks. This should be weighed against any potential benefits.

 

 

 

Asthma

27 December 2020

22:25

Under 17-

Clinical History

 

As with any diagnostic process, a key part is taking a thorough and structured history. Features to ask about include

Wheeze, cough or breathlessness

Specific triggers: common ones include cold temperatures, exercise or dust

Personal or family history of atopic disorders such as eczema or hayfever

While important, history alone is not sufficient to make a diagnosis an objective test should be used.

 

Physical Examination

Asthma is generally associated with expiratory polyphonic wheeze. A physical examination will also help identify other causes of respiratory symptoms and will help in building your differential diagnosis.

Remember that examination results can be normal in people with asthma as wheeze is not always present.

 

 

 

Under 5s or unable to tolerate objective tests

Treat based on symptoms and clinical judgement and arrange for regular review. If symptoms persist, arrange for objective tests at the age of 5 or as soon as they are able to reasonably tolerate the tests if they are unable to manage at 5.

 

Spirometery

Spirometery is an objective testing method which should be performed if asthma is suspected. A forced expiratory volume in 1 second/ forced vital capacity (FEV1/FVC) ratio of less then 70% is positive for obstructive airway disease and will be more suggestive of asthma

 

As part of the procedure, consider a   in those with obstrutive spirometery results. An improvement in FEV1 of 12% or more is a positive test.

 

FeNO test (fractional exhaled nitric oxide)

In the age range of 5-16, consider this test if there is diagnostic uncertainty after initial assessment. This implies either a normal spirometery test or an obstructive spirometery test with a negative bronchodilatory reversibility test.

A FeNO level of 35  or more is a postive test.

 

Other Tests:

Skin prick testing, serum IgE, and eosinophil counts should not be routinely offered as they are not diagnostic.

Consider offering the above after a formal diagnosis of asthma has been made to help identify triggers.

 

 

 

Over 17

 

Initial Assessment:

Initial investigation with clinical history and physical examination are much the same as with ages 5-16. Important to ask in both cases whether they smoke, though this will be more relevant in the older population

 

Fractional Exhaled Nitric Oxide Test

Regard a FeNO level of 40 or more as a positive test.

Be aware that a person's current smoking status can lower FeNO levels both acutely and cumulatively. However, a high level remains useful in supporting a diagnosis of asthma test to adults (aged 17 and over) if a diagnosis of asthma is being considered.

 

 

 

Spirometery

Similar to ages 5-16, a FEV1/FVC of less then 70% is a positive test and suggestive of obstructive airway disease.

Offer a BDR test to adults with obstructive spirometery. an improvement in FEV1 of 12% or more is a positive test

 

Peak Flow Variability

In cases where the diagnosis is unclear (normal spirometery or obstructive spirometery with positive BDR but FeNO levels of 39ppb or less) after initital assessment and FeNO test then monitor peak flow variability for 2-4 weeks.

Greater then 20% variability is a positive test.

 

Other Tests:

Skin prick testing, serum IgE, and eosinophil counts should not be routinely offered as they are not diagnostic.

Consider offering the above after a formal diagnosis of asthma has been made to help identify triggers.

 

 

Machine generated alternative text: Classification of asthma severity Mild intermittent asthma Mild persistent days 'week Moderate persistent Daily Symptoms (e.g., wheezing, cough) Ni httime symptoms (e.g., difficulty falling asleep because of symptoms, awakenings) 2 days/week Rare > 80% persistent Throughout the day Often times/month times/week (most > 80% 60-80% nights) < 60%

 

Short-acting Beta agonist (SABA) such as salbutamol 100microgram or terbutaline 250microgram. Usually prescribed when required (two puffs  as required)

Method of Action:

These acheive bronchodilation through activation of beta-2 receptors on the airway smooth muscle. Onset in most preperations will be within 5 minutes. Primary use if for relief of breathlessness and chest tightness associated with exacerbations

Side effects:

Fine tremor most noticible in hands and tachycardia. Also asoociated with hypokalaemia in large doses.

 

 

 

Long-acting Beta2 adrenoreceptor (LABA) such as salmeterol or formoterol. Inhaled once or twice daily and combined with inhaled corticosteroid as fixed-dose combinations (salmeterol/fluticasone and formoterol/budesonide) in the same inhaler.

Method of Actions:

Acheive bronchodilation via activation of beta-2 receptors on the airway smooth muscle.  Use is typically or maintenance of peristant asthma not controled with inhaled corticosteroids.

Also used as maintenance treatment for COPD patients with persitant breathlessness.

Side Effects:

Fine Tremor in hands, headache, muscle cramps and tachycardia.

 

Inhaled corticosteroids:

Patients who have regular persistent symptoms need inhaled corticosteroids. Beclometasone is the most used and available in doses of 50,100,200 and 250 micrograms per puff. Others are budesonide,fluticasone propionate,fluticasone furoate, mometasone furoate and triamcinolone.

Method of Action:

Anti-inflammatory effect on bronchial mucosa and reduces hyper-responsiveness of the bronchial tract to exogenic challenges. Used as prophylactic management of mild, moderate and severe persistant asthma.

Note that the onset of action can take up to 6 weeks to see full response! It is important to emphasise this to patients as some may give up on the ICS as they do not immediately feel the perceived benefits!

Commonly patients experience local side effectus such as oral thrush. Other more rare side effects include: subcapsular cataract (rare), osteoporosis (high dose, such as beclometasone >800mcg daily) and growth retardation (>400 mcg daily) in children. 

 

 

Oral corticosteroids and steroid sparing agents

Usually used for acute exacerbation or longer-term use when other drugs have not controlled symptoms successfully. A typical dose for an acute exacerbation of asthma would be 40mg of prednisolone for 5 days.

 

Leukotriene receptor antagonists-

Examples such as montelukast and zafirlukast are given orally and effective in aspirin-intolerant asthmatic patients, rhinitis associated asthma and viral wheeze. Should be started when the symptom is not controlled after SABA and low/medium dose ICS.

 

Antimuscarinic bronchodilators

Short acting antimuscarinic bronchodilators (ipratropium) is usually used in severe exacerbation of asthma. It is not been shown to be of any benefit in patient on standard therapy.

Long-acting antimuscarinics (tiotropium,aclidinium) can be tried in severe cases.

 

 

 

Anti-inflammatory drugs

Sodium cromoglicate and nedocromil sodium prevent activation of mast cells,eosinophils and epithelial cells. They are not commonly used.

 

 

Monoclonal antibodies-

Omalizumab is given subcutaneously every 2-4 weeks and very effective although expensive. It is a recombinant humanized monoclonal antibody directed against IgE and down regulates the activity of mast cell and basophils. Newer agents are mepolizumab,reslizumab and benralizumab.

 

 

Antibiotics-

Probably a bit of a trick entry this one. There is little evidence that antibiotics help in acute exacerbations and should not be used in the treatment of an exacerbation unless the underlying cuase is thought to be infective ( which is rare in asthma).

 

 

Please see NICE guidelines for the recommended treatment pathway. These are recommendations and where asthma is well controlled on current treatment there is no need to change to try and adhere to these guidelines

SABA

1. Start with SABA reliever therapy. For those with infrequent short lived wheeze and normal lung function, this alone may be sufficient.

 

SABA + ICS

2. In most cases, an additional low dose ICS is the first line maintenance therapy in adults. Start when symptoms at presentations clearly suggest uncontrolled asthma ( such as three exacerbations a week or nocturnal waking).

 

SABA + ICS + LRTA

3. If uncontrolled despite ICS and SABA therapy then offer a LTRA in addition to the ICS and review response over 4-8 weeks.

 

SABA + LABA + ICS +/- LRTA

4. If uncontrolled, offer a LABA and ICS inhaler and review the LRTA treatment. This involves a discussion with the patient to establish whether or not to continue the LRTA. Should be based on side effects vs what perceived benefit the patient has experienced.

 

MART +/-LRTA + ICS

5. If uncontrolled, offer to change the ICS and LABA to a combined ICS and LABA inhaler (MART). This inhaler also included a fast acting LABA and can be used for both maintenance and relief of sympoms. This is in addition to the low dose maintenance ICS

 

MART or LABA+ICS+SABA  with moderate dose increase of ICS  +/- LRTA

6. If uncontrolled consider increasing the ICS dose to moderate dose.

 

MART or LABA+ICS+SABA  with high dose increase of ICS  +/- LRTA. Options as below. Refer to specialist.

7. If Uncontrolled consider increasing ICS to high maintenance dose, trial an additional drug such as a long-acting muscarinic recptor agonist or theophylline or seek specialist advice.

 

From <https://mle.ncl.ac.uk/cases/page/14739/>

 

For exercise induces asthma, having a reliever inhaler prior to activity can often help manage symptoms.

 

Likewise, maintaining an asthma diary and an asthma action plan can help direct management

 

 

From <https://mle.ncl.ac.uk/cases/page/14745/>

 

·         Asthma is a lifelong chronic inflammatory disease of the respiratory system characterized by bronchial hyperresponsiveness, episodic exacerbations (asthma attacks), and reversible airflow obstruction.

·         Allergic (extrinsic) asthma usually develops in childhood and is triggered by allergens such as pollen, dust mites, and certain foods.

·         Nonallergic (environmental or intrinsic) asthma usually develops in patients over the age of forty and can have various triggers, such as cold air, medication (e.g., aspirin), exercise, and viral infection.

·         The cardinal symptoms of asthma are intermittent dyspnea, coughing, and high-pitched expiratory wheezing. Symptoms remit in response to antiasthmatic medication or resolve spontaneously upon removal of the trigger.

·         Confirmation of the diagnosis involves pulmonary function tests, allergy tests, and chest x-ray. First-line treatment consists of inhaled bronchodilators (e.g., short-acting beta-2 agonists) for acute exacerbations and inhaled corticosteroids (e.g., budesonide) for long-term asthma control.

·         Patients should be taught the correct usage of inhalers for self-medication and measurement of peak expiratory flow (PEF) to self-monitor disease progression and severity.

·         Severe asthma exacerbation can be life-threatening and may require emergency treatment and/or hospitalization.

·         As patients get older, the management of asthma changes as well. Regular review of the patient at least once a year is recommended. At the same time, changes in treatment may also be needed due to other comorbidities such as arthritis or cardiac disease.

 

 

From <https://mle.ncl.ac.uk/cases/page/13033/>

 

 

 

 

 

Hypertension

27 December 2020

22:59

 

NICE recommend assessing frailty in primary care settings when patients have multiple morbidities and/or who are at risk of adverse events (e.g. falls). NICE recommend assessing frailty using one or more of the following:

·         an informal assessment of gait speed (for example, time taken to answer the door, time taken to walk from the waiting room)

·         self-reported health status (that is, 'how would you rate your health status on a scale from 0 to 10?', with scores of 6 or less indicating frailty)

·         a formal assessment of gait speed, with more than 5 seconds to walk 4 metres indicating frailty

·         the PRISMA-7 questionnaire, with scores of 3 and above indicating frailty.

In hypertension, many of the medications we prescribe can cause postural hypotension as a side effect, which can cause dizziness and syncope. If someone is frail, and we give them a medication that could potentially make them dizzy and fall, we could significantly worsen their frailty and quality of life. 

 

 

From <https://mle.ncl.ac.uk/cases/page/9615/>

 

 

 

66% has comorbidity

 

 

 

Key Points

 

Most cases (95%) of hypertension are primary (essential), where there is no definitive, treatable cause of the raised blood pressure. Secondary hypertension (5%) causes include renal, obesity, pregnancy-induced, endocrine and drug-related. It is essential to screen for secondary causes when a patient presents with hypertension.

 

 

When history taking it is important to ask about all the modifiable lifestyle factors that increase blood pressure, such as smoking, increased alcohol intake, diet high in salt/saturated fat and low levels of physical activity.

 

 

Important clinical indicators that signal end organ damage are changes on fundoscopy (papilledema, AV nicking, haemorrhages, exudates) and proteinuria.

 

 

It is key to assess a patient’s cardiovascular risk using an appropriate tool (such as QRISK3)

 

 

Many patients often struggle to take anti-hypertensive medication regularly either due to lack of symptoms from hypertension, side effects of medication or medication fatigue.

 

 

66% of patients with hypertension have a co-morbid condition

 

 

It is important to assess the risks and benefits of starting someone on blood pressure medication, particularly in the elderly, due to their side effects.

 

 

 

 

Breast cancers

27 December 2020

23:04

Most breast lumps are benign and include fibroadenomas, papillomas, breast cysts, and breast abscesses. Malignant breast lumps may include DCIS but these are very rarely mass forming (asymptomatic) and usually present via screening.

 

 

From <https://mle.ncl.ac.uk/cases/page/9312/>

 

 

Triple assessment-

Clinical assessment +/- imaging +/- biopsy

 

From <https://mle.ncl.ac.uk/cases/page/9312/>

 

 

Breast cancer presentation-

 

Breast lump – either painful / painless

 

Nipple changes / eczema / blood stained discharge

 

Nipple or skin tethering and indrawn

 

Axillary lymphadenopathy

 

Screen detected abnormality

 

Incidental finding on other imaging (e.g. CT chest)

 

Inflammatory breast cancer

 

 

 

 

The two imaging modalities used in the breast one stop clinic are mammogram and ultrasound.

 

 Mammogram: This is a dual plane X-ray of the breast. All patients over 40 have a bilateral mammogram in the one stop clinic (assuming that they haven’t had a mammogram in the last year). Mammogram is rarely performed on patients under the age of 40 as their higher breast density makes it difficult to detect a dense abnormality (like cancer) leading to very poor test sensitivity.

 

 Ultrasound: All patients who have a breast abnormality on initial clinical assessment will undergo ultrasound of the abnormality (regardless of age). Note that it is an ultrasound of the abnormality in the breast as opposed to an ultrasound scan of the whole breast to “look for” an abnormality; although breast ultrasound is an excellent tool for assessing a lesion, it has a very low sensitivity as a breast screening tool to find an abnormality.

 

 

As the risk of breast cancer increases with age, breast screening in the UK is offered to all women at the age of 50 who are registered with a GP. They are invited for screening every three years until their 71st birthday. They can choose to continue with the programme after this time period at their own request. The procedure is a bilateral mammogram, taken in a horizontal and vertical plane.

 

From <https://mle.ncl.ac.uk/cases/page/10066/>

 

In all aspects of medicine, choosing a treatment requires a risk/benefit assessment. Breast cancer prognosis varies from excellent to very poor, and these very different prognoses will have very different risk/benefit balances. Because of this, treatment “package” needs to be individualised for the patient. Before discussing treatment options in this tutorial, it is therefore important to outline the multiple factors that contribute to the prognostic information in the diagnoses of breast cancer patients. 

The most basic prognostic factors are grade of tumour, size of tumour, and axilla lymph node status.

Grade: a measure of cellular differentiation, from grade 1 (well differentiated) to grade 3 (poorly differentiated). Essentially, a measure of how “aggressive” the individual cells are deemed to be.

Lymph nodes can be scored from 1-3, with 1 = 0 nodes affected and 3 = >3 nodes affected.

These basic prognostic factors can be combined to give a 5-year survival probability in the Nottingham Prognostic Index (NPI):

(0.2*size) + grade + lymph node score

A score below 2.5 has a 93% 5-year survival, and a score of 5.5+ has a 50% 5-year survival.

Other prognostic factors include histology and stage.

 

From <https://mle.ncl.ac.uk/cases/page/9311/>

 

 

·         Molecular subtyping involves testing ER status, HER2 status, and in some patients oncotype DX

·         ER status predicts response to hormone therapy

·         HER2 predicts response to trastuzumab and has a poor prognosis

·         HER2+ and triple negative cancers are given chemotherapy

·         TNM stage and sometimes oncotype DX determine whether chemotherapy is necessary in ER+ HER2- cases

 

 

From <https://mle.ncl.ac.uk/cases/page/10495/>

 

 

Risks of radiotherapy include:

Short term: rib fracture, sunburn, blistering, oesophagitis, pneumonitis, lymphoedema to breast and arm, fatigue

Long term: lung fibrosis, osteonecrosis, coronary artery disease, pericarditis, leathery skin, secondary malignancies (angiosarcoma, lung cancers)

Contraindications:

There are some absolute and relative contraindications that would prevent a patient from receiving radiotherapy. These include:

Absolute contraindications:

·         Connective tissue disorders with significant vasculitis

·         Prior radiotherapy in the same part of the body

·         Li-Fraumeni syndrome (TP53 mutation), due to risk of secondary malignancies

Relative contraindications:

·         Significant pre-existing lung disease

·         Pacemaker in the radiotherapy field

·         Pregnancy

 

From <https://mle.ncl.ac.uk/cases/page/10497/>

 

 

Key points:

·         Local treatments include surgery and radiotherapy

·         Surgery is split into the breast operation and axilla operation

·         The breast operation can be a mastectomy or breast conserving surgery with radiotherapy

·         The axilla operation can be clearance, sentinel node biopsy, or omitted

·         Radiotherapy reduces recurrence

·         Radiotherapy is contraindicated in a number of patients

·         Don’t take blood from an arm that has had axillary clearance – it can trigger lymphoedema

 

 

From <https://mle.ncl.ac.uk/cases/page/10497/>

 

 

Who gets it?

Anyone ER+ will usually receive hormone therapy.

What is it?

Hormone therapies aim to prevent the binding of oestrogen to oestrogen receptors by various modes of action, and therefore inhibit ER+ tumour cell proliferation.

In premenopausal women, the commonest drug used is tamoxifen. Tamoxifen is a SERM (selective oestrogen receptor modulator), which competitively binds the oestrogen receptors present in breast tissue.

In postmenopausal women, aromatase inhibitors (AIs) are usually used instead of tamoxifen. AIs include letrozole, anastrozole, and exemestane. They work by blocking non-ovarian sources of oestrogen, such as from fat cells. AIs show a lower rate of recurrence than tamoxifen, however as they only affect non-ovarian sources of oestrogen, they do not work in premenopausal women.

 

 

From <https://mle.ncl.ac.uk/cases/page/10498/>

 

Chemo-

Regime options include FEC (fluorouracil, epirubicin, and cyclophosphamide) and EC (epirubicin and cyclophosphamide). These regimes may have other medications added on top of them. Taxanes (e.g. docetaxel) may be added in patients with poor prognoses, for example node positive patients (a common example of a taxane containing regime is FEC-T). Taxanes comes with the risk of additional side effects, such as neuropathy, but reduce recurrence risk. Platinum-based medications (e.g. carboplatin) may be added if the cancer is triple negative.

 

From <https://mle.ncl.ac.uk/cases/page/10499/>

 

 

Side effects

Common side effects of chemotherapy include:

Nausea, appetite and weight loss, changes to taste, changes to skin and nails, severe fatigue, immunosuppression, easy bleeding and bruising, bowel disturbance, hair loss

Potentially serious complications include:

Deterioration in kidney function, thrombosis, changes in hearing

Severe complications include:

Cardiotoxicity, neutropenic sepsis (especially with taxanes), death

Possible late effects include:

peripheral neuropathy, early menopause, infertility, secondary malignancy (with certain chemotherapies)

It is important to discuss these risks with the patient prior to treatment.

 

From <https://mle.ncl.ac.uk/cases/page/10499/>

 

 

 

Key points:

·         Systemic treatments include hormone therapy, chemotherapy, HER2 therapy, and bisphosphonates

·         Hormone therapy is given in ER+ cancers

·         Tamoxifen is the hormone therapy drug used in premenopausal patients, and AIs are preferred in postmenopausal patients

·         Chemotherapy regimes include FEC and EC

·         Taxanes may be added if the cancer has poor prognosis

·         Platinum-based medications may be added in triple negative cancers

·         Chemotherapy has a high morbidity

·         Serious complications include cardiotoxicity, neutropenic sepsis, and death

·         There is a future risk of infertility and sometimes secondary malignancy

 

From <https://mle.ncl.ac.uk/cases/page/10499/>

 

 

 

 

 

 

Heart failure

28 December 2020

00:47

What is Heart Failure?

Heart failure is a complex and progressive (i.e. it will naturally deteriorate over time) clinical syndrome that you will encounter frequently in your clinical practice. In short, heart failure is the result of impaired ventricular filling or contractility, whether due to structural or functional causes.

This is not synonymous with "cardiomyopathy" or "left ventricular dysfunction" - these are themselves possible structural or functional causes for developing heart failure.

The major clinical manifestations of heart failure are: fluid retention, dyspnoea, and fatigue.

 

From <https://mle.ncl.ac.uk/cases/page/13016/>

 

 

 

 

 

 

 

 

 

From <https://mle.ncl.ac.uk/cases/page/14541/>

 

 

 

 

 

Arthroscopy

28 December 2020

01:34

 

A meniscal tear is the commonest soft tissue ailment of the knee joint and causes pain, swelling and mechanical symptoms. It can affect patients of all ages. Patients whose symptoms are refractory to first line conservative treatment and are medically fit to undergo an anaesthetic can benefit from arthroscopic knee surgery. A meniscectomy removes the pain stimulus emanating from the meniscal tear but in some patients, increases the risk of developing secondary OA. New arthroscopic techniques, including meniscal repair, have shown promising results but is a more technically demanding procedure with a stricter selection criteria that is dependent on the tear pattern and has a more entailed post-operative rehabilitation programme.

 

 

 

 

 

Joint Replacement 

28 December 2020

01:35

The prevalence of osteoarthritis is rising as the life expectancy of the general population continues to rise and patients live long enough to develop degenerative diseases. OA causes debilitating pain in the affected joints and has a major impact on quality of life. Patients whose symptoms are refractory to first line conservative treatment and are medically fit to undergo an anaesthetic can significantly benefit from major joint replacement surgery.    

 

 

From <https://mle.ncl.ac.uk/cases/page/10552/>

 

 

 

 

Breast conserving surgery

28 December 2020

01:36

 

The majority of women presenting with breast cancer undergo breast conserving surgery (and therefore breast radiotherapy) as opposed to a mastectomy. There are a number of forms of breast conserving surgery ranging from a simple wide local excision to breast reduction surgery or combined with volume replacement procedures.  

 

 

From <https://mle.ncl.ac.uk/cases/page/10548/>

 

 

 

Cataract surgery

28 December 2020

01:36

 

In a nutshell

Cataract is an opacification of the crystalline lens. It is managed surgically by removal of the cataract and insertion of a new clear lens.

Patients should be referred for cataract surgery only when they have significant visual loss and are fit enough for surgery. 

Cataract surgery is usually performed as a day case surgery under topical or local anaesthetic. The cataract is removed using a technique called phacoemulsification. Visual recovery is usually immediate depending on anaesthetic used. 

Post operatively patients have a short course of antibiotic eye drops and a reducing course of steroid eye drops for 4-6 weeks. 

The most important risk is that of ENDOPHTHALMITIS which is potentially sight threatening. Any patient with increasing pain, redness and loss of vision should attend their place of surgery ASAP. This is one of the very few true ocular emergencies. 

Posterior Capsular Opacity can occur subsequent to cataract surgery and can be treated by YAG capsulotomy. 

 

 

From <https://mle.ncl.ac.uk/cases/page/9931/>

 

 

 

Cholecystectomy 

28 December 2020

01:38

 

Laparoscopic cholecystectomy is a commonly performed general surgical operation usually for symptomatic gallstones. In the elective setting it is usually performed as a day case procedure with no routine follow-up.

Recovery is rapid, although patients should show some caution with regards to strenuous activity in the first few postoperative weeks.

 

 

From <https://mle.ncl.ac.uk/cases/page/8708/>

 

 

 

Colectomy

28 December 2020

01:38

 

Colectomy is a major surgical procedure which may be used to treat a variety of benign pathologies as well as malignancy. It may also be performed as an emergency procedure. This is most commonly due to benign problems such as ischaemia, or perforation, but patients may also present with bowel obstruction due to malignancy.

 

A stoma may be created in high risk patients where concerns about an anastomosis healing exist, or due to necessity in the case of sub-total and total colectomies.

 

Patients usually stay in hospital for approximately a week after surgery and can take several weeks or months to recover fully from the operation.

 

 

 

 

Colonosopy

28 December 2020

01:39

 

 

 

Cystoscopy

28 December 2020

01:39

Cystoscopy is a commonly performed diagnostic procedure that allows imaging of the inside of the bladder.  It is usually performed to identify a source of haematuria in patients who may have a bladder cancer, or to follow up patients how have had bladder cancer to detect recurrence.

It is performed under local anaesthetic as a day case or outpatient procedure.

Recovery is rapid, although sometimes complicated by infection or bleeding.

Treatment procedures can also be performed transurethrally.  These usually require general anaesthetic, take longer to recover from and usually require an overnight stay.

 

 

From <https://mle.ncl.ac.uk/cases/page/8689/>

 

 

 

 

Hernia repair

28 December 2020

01:40

Inguinal hernia repair is a commonly performed operation to treat symptomatic inguinal herniae. It may be performed as an open operation or a laparoscopic operation. NICE guidelines indicate that a laparoscopic approach should be considered for those with a bilateral hernia (allowing both to be easily fixed at the same time) and those with a recurrent inguinal hernia, where the initial approach was an open operation.

It is usually performed under a general anaesthetic but may be done under a spinal anaesthetic or local anaesthetic.

Recovery is rapid, although sometimes complicated by infection or bleeding and care must be taken by the patient not to over exert themselves in the first 6 weeks whilst wound heals and is strengthened by the mesh.

 

 

From <https://mle.ncl.ac.uk/cases/page/8713/>

 

 

 

 

Mastectomy

28 December 2020

01:41

Although most breast cancer is treated with breast conserving surgery, a mastectomy is still a common operation in breast cancer and patients considered high risk for developing breast cancer. Mastectomy can be performed with or without a simultaneous reconstruction procedure, of which there are many options. Physical recovery is fairly rapid but psychological recovery can take time and require professional support.

 

From <https://mle.ncl.ac.uk/cases/page/8724/>

 

 

 

 

Cystopathology

03 January 2021

16:53

The types of cytological sampling are:

·         Exfoliative cytology

·         Abrasive cytology

·         Interventional (aspiration) cytology

·         Imprint cytology

Each of these types, and the methods by which they are collected are described in more detail in the following sections.

 

From <https://mle.ncl.ac.uk/cases/page/14658/>

 

 

 

 

Exfoliative cytology involves the collection and microscopic examination of shed or desquamated epithelial cells.

The cells are collected from body fluids including sputum, urine, bile, cerebrospinal fluid, vaginal discharge, pleural fluid, ascitic fluid, and fluid from cysts often using a syringe or cotton swap.

The samples collected contain cells that have been shed from surrounding tissues. For example, sputum will contain cells derived from the buccal cavity, pharynx, larynx, trachea and lungs.

The sample collected should be processed as soon as possible to prevent deterioration of the cells by drying out or through enzymatic or bacterial activity.

 

From <https://mle.ncl.ac.uk/cases/page/14658/>

 

Abrasive cytology involves the removal and examination of of cells from mucosal linings and body surfaces.

The cells are collected by scraping, brushing or washing the surface of the tissue of interest. Unlike exfoliative cytopathology, this enables the sample to be enriched with cells obtained directly form the surface of the tissue of interest.

Samples can be taken form superficial or deep lesions in tissues such as skin (scraping of lesion), cervix (cervival Pap smear), gastrointestinal tract (endoscopy and gastric lavage) and the oral oral mucosa (buccal smear). 

The video below describes what is involved in a cervical smear test.

From <https://mle.ncl.ac.uk/cases/page/1465

Aspiration cytology involves the removal and examination of cells form a palpable solid lump or mass.

The cells are removed from lumps or masses, e.g. surface breast, lymph node or tumour masses, with or without suction by needle aspiration. This is commonly called fine needle aspiration (FNA) cytology. The needle can be inserted directly for palpable lumps, or under radiological (ultrasound or CT) guidance for non-palpable lumps. 

You may find this video showing how to collect a sample of cells by fine needle aspiration interesting.

 

From <https://mle.ncl.ac.uk/cases/page/14658/>

 

Imprint cytology involves the collection and examination of cells from the surface of tissues.

The cells are collecting my making in imprint of the tissue in question onto a glass slide, leaving cells on the slide when it is removed.

 

 

From <https://mle.ncl.ac.uk/cases/page/14658/>

 

Stains used in cytopathology include:

·         Papanicolaou (Pap) stain. Pap stain is actually comprised of 5 stains that provide a multicoloured cell sample allowing identification of different cell types and cellular features. Pap stain is very reliable and widely used, notably for cervical smears (Pap test or Pap smear).

·         Haematoxylin and eosin (H&E) stain. It is one of the main stains used in histopathology and cytopathology. Eosin stains the cytoplasm and extracellular matrix of cells pink, while haematoxylin stains nuclei blue and is often used for fluids and aspirates.

·         Other stains you many come across are Romanaowski, Leishman and Giemsa (May Grunwald Geimsa) stains, which may be used for fluids and aspirated samples.

 

From <https://mle.ncl.ac.uk/cases/page/14662/>

 

Indications for cytopathological investigations include:

·         To support diagnosis by differentiating between malignant and benign lesions

·         To support the diagnosis of malignancy and the identification of the neoplasic cells in the tumour

·         To support the diagnosis of pre-malignant disease

·         Identification of inflammation and some types of pathogens

·         To examine/monitor squamous cells in vaginal smears which are influenced by ovarian hormones

·         To monitor responses to chemotherapy and radiotherapy.

 

From <https://mle.ncl.ac.uk/cases/page/14664/>

 

 

 

 

Advantages of cytopathology

·         Good morphological detail can be obtained

·         Able to characterise the cellular components of various fluids

·         Relatively quick to obtain a sample and determine a diagnosis

·         Cost effective

·         Minimally invasive diagnostic procedures that do not require surgery or anaesthesia

 

Limitations of cytopathology

·         Tumors cannot be graded

·         Margins cannot be evaluated

·         Limited information can be achieved about the structural arrangement of the cells within a lesion

·         Less definitive diagnosis can be achieve as to specific tumour type or distribution of inflammatory infiltrate

·         Potential for negative test due to relatively small sample size and blind nature of many collection techniques meaning he sample may not be representative of the primary lesion

 

Cyctopathology can aid clinical diagnosis, but results must be considered in the context of the overall case. Negative results should not be treated as conclusive given the limitations.

 

From <https://mle.ncl.ac.uk/cases/page/14727/>

 

 

Tissue samples, or biopsies, can be taken from almost anywhere on or in your body, including the skin, organs and other structures. 

There are different types of biopsy which include: 

·         Excision – a sample of tissue is removed in a surgical procedure. 

·         Endoscopic – a sample of tissue is removed using an endoscope. 

·         Punch – a sample of skin is obtained by punching a small hole in the skin

·         Needle – a sample of tissue is removed from and organ or tissue under the skin using a needle, guided by ultrasound, X-ray, CT or MRI.

 

 

 

 

 

 

Histopathology

03 January 2021

17:01

 

 

Histopathology includes macroscopic examination of the tissue, as well as examination of very thin sections of the tissue under a microscope. 

In this section we will consider:

·         How samples are collected

·         How samples are processed

·         Indications for how histology can support the detection, or exclusion, of disease and its management

·         The advantages and limitations of histology

 

 

From <https://mle.ncl.ac.uk/cases/page/14666/>

 

 

Once collected, the sample is fixed to harden and preserve the tissue in a solution such as formaldehyde. The gross biopsy is then examined and described before sections are selected to be dissected for microscopic study.  The sample is then processed further as described in the next section.

 

From <https://mle.ncl.ac.uk

Surgical pathology is the study of tissues removed from living patients during surgery that help diagnosis, informs the ongoing surgical procedure, and helps determine a treatment plan. For example, when performing cancer surgery, pathological examination of the tissue removed can help the surgeon to determine whether or not to remove more surrounding tissues.

 

From <https://mle.ncl.ac.uk/cases/page/14657/>

 

ses/page/14667/>

 

 

 

 

The indications for histopathological investigation include:

·         To aid diagnosis, or exclusion of, disease

·         To support surgical procedures by determining resection margins

·         To help determine appropriate treatment options

·         To determine sentinel lymph node involvement

·         To support the determination of a prognosis by type, grade and stage of malignant disease

·         Monitoring response to treatment and clinical course of disease

 

 

From <https://mle.ncl.ac.uk/cases/page/14729/>

 

 

 

Advantages of histopathology

·         Enables evaluation of resection margins

·         Provides information about the structural arrangement of tissue within the lesion, e.g. vascular and lymphatic invasion

·         Provides more information than cytology providing a more definitive diagnosis as to the specific type of tumour

·         Provides information to inform staging, prognosis and treatment options

·         Can be used to monitor response to treatment and clinical course of disease, e.g. in coeliac disease, ulcerative colitis and cervical dysplasia

 

Limitations of histopathology

·         Sample collection can be invasive and traumatic

·         Processing and obtaining a diagnosis can take longer than the likes of cytopathology

·         More expensive than cytopathology

 

From <https://mle.ncl.ac.uk/cases/page/14730/>

 

 

 

 

 

Population-based management of conditions

03 January 2021

17:03

 

"The aim of medicine is to prevent disease and prolong life, the ideal of medicine is to eliminate the need of a physician." William Mayo (1861-1939)                                                                 

Population approaches may be defined as the science and art of promoting and protecting health and well-being, preventing ill-health and prolonging life through the organised efforts of society. 

The principles of population health are : (Faculty of Public Health 2020) 

1.  Health Protection. Measures to control communicable diseases and environmental hazards including public health emergencies 

2.  Health Promotion and Disease Prevention. Societal and individual  interventions to promote and protect health

3.  Health and Care Public Health. The organisation and delivery of safe and high quality services to prevention, treat and care for patients and improve their outcomes. 

These are underpinned by epidemiology and health improvement which tackles health inequalities. 

 

 

From <https://mle.ncl.ac.uk/cases/page/13225/>

 

 

Factors that Affect Health Smallest Impact Largest Impact Counseling & Education Clinical Interventions Long-lasting Protective Interventions Changing the Context to make individuals' default decisions healthy Socioeconomic Factors Examples Eat healthy, be physically active Rx for high blood pressure, high cholesterol, diabetes Immunizations, brief intervention, cessation treatment, colonoscop Fluoridation, Og trans fat, iodization, smoke- free laws, tobacco tax Poverty, education, housing, inequality CDC

 

 

 

Therapeutics

03 January 2021

18:28

The Drug Discovery & Development Process c5c5c5c5c5

 

Adverse drug reactions- Classification 1 • Type A (augmented') • Dose related • Predictable • Usually common but not severe(but some maybe life-threaten fig) • Type 8 (Bizarre') • Not dose related • Unpredictable • May be verysevere/fatal

 

Adverse drug reactions Classification (2) • Type C ('Chronic treatment effects') • e.g. osteoporosis with steroids • Type D ('Delayed effects') • e.g. drug-induced cancers • Type E ('End-of treatment effects') • Wthdrav.ral syndromes

 

Adverse drug reaction

 

Cost effectiveness Costeffectiveness ratio (CER) Incremental CER (ICER, bet'.veen 2 treatments) Costof intervention Health gains produced Cost difference Differences in health ga ins Health gains typically measuredas Quality Adjusted Life Years (QALY)

 

NHS prescribing, England

 

Prescribing in England top 20 drugs prescribed in primary care (2017)

 

NHS prescribing, 017/ Lg England 16 777

 

NHS prescribing, 017/ Lg England 16 777

 

Our responsibilities GMC: Good practice in prescribing and managing medicines and devices (2013) • In providing clinical careyou must: • prescribe drugs or treatment, including repeat prescriptions, only v.hen you have adequate knowledge of the patient's health and are satisfiedthatthe drugs or treatment serve the paflent's needs. • provide effective treatments based on the best available evidence • check that the care or treatment you provide for each patient is compatible wth any other treatments the patient IS receiving, including (where possible) self-prescribedover- the-cou nter medications

 

 

 

 

MOSLER

06 January 2021

23:33

Risk and benefits

What is going to happen if we don’t do anything-

Risk of rupture per year

1 year 9.4 % 5.5 to 5.9cm risk of rupture

1 in 10 4 year aftersurgery die open and endocasvular surgery

30 days after surgery 4/100 die open, 1/100 endovacular

 

https://www.nhs.uk/conditions/abdominal-aortic-aneurysm/

 

Risk of doing something-

Risk of surgery- risk of heart attack during surgery, having a major embolic clot , risk of bleeding, risk of losing a leg

Risk to life (MI) and risk  to limb (ischaemia)  (major risks), rupture of AAA,

Minor risks, risk of bleeding after surgery, risk of infections after surgery, problems with bowels, risk of another operation to put it correct, lung complication, kidney, non fatal stroke,COVID risk coming to hospital,

 

Higher risk of death if they have COVID during surgery

Anaesthetic risks but usually very low.

 

Benefits-

Prognostic- increase their life expectancy, no more symptoms

Stent option- endovascular options

Other options?

 

Medication wouldn’t solve this problem, can reduce risk- aspirin can help but if it ruptures they bleed more

 

 

3 options-

Treat conservatively doing nothing,

 

Do surgery, laparotomy, graft to replace

 

Do stenting, to avoid it rupturing. (higher chance another surgery) say less invasive endovacular done by interventiona radiologist usually covered by surgerons)

 

Vascular MDR to discuss this patient- recommend one of the following options( surgeron, radiologist, IR, gastro doctor, cardiologist, anaesthetic( fit for surgery))

 

Gold standard

 

 

Change lifestyle factors

Medical management with beta-blockers, cessation of smoking and management of risk factors, such as dyslipidemia and hypertension, may be helpful in patients with small- to medium-sized aneurysms that are not treated surgically.

 

Advice them for both surgery and conservative management-  secondary prevention for pt going to surgery, primary prevention for someone not going to surgery

From <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076160/>

 

 

 

They will do preoperative assessments to check his risks for surgery, ?diabetes

Cardiology assessment-

MDT!!!!

 

 

Ask about past medical history- hypertension, heart failure, previous myocardial infaraction, smoke? Family history?

Previous surgery? Stents? Abdominal surgery?(risky if redo surgery)

 

Size of patient? 5.5 cm AAA in small is different to large person

Body surface area, body mass index to measure

 

 

Ultrasound- simple way to identify Aneurysm, best would be CT , reconstruction, 3D picture, extent of AAA, position of AAA, relation to other vessels (coeliac, mesentary, renal arteries), bifurcation graft or simple one graft.

 

AAAs are mostly asymptomatic and found incidentally. The incidence of AAA is higher in Caucasian men, individuals older than 60 years of age and smokers. Diagnosis is usually reached using imaging modalities. Aneurysm rupture is a medical emergency and risk of aneurysm rupture increases with increasing diameter, rapid expansion, symptomatic aneurysm and history of smoking. Surgical intervention is recommended for all symptomatic aneurysms and asymptomatic aneurysms greater than 5.5 cm in diameter. Regular surveillance through imaging studies should be conducted in asymptomatic aneurysms 3 cm to 5.5 cm in size. Medical management with beta-blockers, cessation of smoking and management of risk factors, such as dyslipidemia and hypertension, may be helpful in patients with small- to medium-sized aneurysms that are not treated surgically.

 

From <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076160/>

 

 

 

 

 

Wriske 1

15 January 2021

00:22

Situation You are a Foundation Year 2 doctor working in General Practice. Patient detail Name                                                 Alan Black  Address                                             13 Singapore Street                                                             Hartley                                                             NE42 3PP Date of birth                                      13/06/1951  Patient number                                 4403 753 742 History Mr Black attended today with a 3 day history of burning pain passing urine and of urinary frequency.  You saw him 2 days ago with the same symptoms and submitted a mid-stream urine sample and some blood tests.  The results are now available. He has a history of atrial fibrillation and of chronic kidney disease. He is on long term treatment with Apixaban                                           5mg twice daily He has no known allergies. He would like treatment for his infection if appropriate, and an ongoing prescription for 4 weeks supply of his anticoagulants. Examination Temperature:                                    37.9 Centigrade Pulse:                                                100 beats per minute Blood pressure:                                113/57 mm HG Respiratory rate:                              20 breaths per minute Oxygen saturations:                         95% on air. Investigations Blood Haemoglobin                                     146 g/L (115-165) White cell count                                11.5 x 109/L (4-11) Neutrophils                                        8.2 x 109/L (1.5-7.0) Platelets                                              367 x 109/L (150–400) sodium                                                141 mmol/L (137–144) potassium                                           3.9 mmol/L (3.5–4.9) urea                                                     15.0 mmol/L (2.5–7.0) creatinine                                            220 µmol/L (60–110)


 

 

 

Wriske 2

15 January 2021

00:23

Situation

You are a Foundation year 2 doctor working in General Practice.

 

Patient details

Name:                                    David Bannister

Address:                                47 Hauxey Lane

                                               Newtown

                                               NE56  1EE

Date of birth:                        24/02/1932

Patient number:                    4956 545 223

 

History

David Bannister has come to the Practice for review. 

He has a known diagnosis of pancreatic cancer with widespread metastatic disease.

His regular medications are

Morphine sulphate modified release tablets        30 mg 12 hourly

Mr Bannister’s dose of morphine was increased 5 days ago to improve control of his pain.  The increased dose has been effective in pain control, but he has started to suffer from hallucinations.

 

Examination

Temperature:                                                36.8 centigrade

Pulse:                                                             90 beats per minute

Blood pressure:                                            118/87 mm Hg

Respiratory rate                                           14 breaths per minute

Oxygen saturations (on air)                         98%

His airway is patent.

He is alert and responsive.  He is orientated and does not appear confused.  The rest of his physical examination is normal.

 

Investigation

His blood glucose level is 5.3 mmol/L (usual fasting range 3.0 – 6.0).

Renal and liver function are normal

·         TASK

You think the hallucinations may be an adverse effect of the morphine. 

You decide to prescribe oxycodone in a twice daily preparation form in a dose equivalent to Mr Bannister’s current morphine dose in the hope that analgesia will remain effective but without this side effect.

Please prescribe this on the FP10 prescription provided in Question 2 Answer

 

From <https://mle.ncl.ac.uk/cases/page/19168/>

 

 

 

Wriske 3

15 January 2021

00:23

Situation

You are a Foundation doctor in medicine, working with your consultant Dr Brown, in outpatients at Compassion Hospital.

 

Patient details

Name:                         Khaled Aljboor

Date of birth:             24/01/1985

Patient number:        4385 375 473

 

History

This patient has been referred because he is suffering from increasing shortness of breath on exertion.  The shortness of breath has been present for about 5 years now, but has been getting gradually worse. 

There is marked variability in his symptoms.  Sometimes he is able to walk only 20 meters before stopping, and is unable to climb a flight of stairs.  However, he is still able to ride his bicycle as a hobby on weekends, and he thinks his breathing is much better when he is on holiday.

He has a past history of eczema affecting his hands.

He regularly uses an emollient cream and occasionally 1% hydrocortisone cream on his hands.  He is on no other medications.  He has no known allergies.

Mr Aljboor works Monday to Thursday in a car bodywork repair shop where his job is re-spraying paint on cars after they are repaired. He has never smoked.  He uses no recreational drugs.  He drinks around 18 units of alcohol per week.  He has no pets.

 

Examination

Temperature:                   37.1 °C

Pulse:                               90 beats per minute

Blood pressure:              140/64mm Hg

Respiratory rate:             28 breaths per minute

Oxygen saturations:       98% on air

 

Chest expansion is reduced bilaterally.

Percussion is normal.

There is expiratory wheeze throughout the lung fields.

·         Investigations - Spirometry

Click on the thumbnail below to open his spirometry recording

Machine generated alternative text: IMAGE AB (Question 3) Flow/Volume Graph 16 14 12 10 Volume (L) Volume/ Time Graph Time (s) 10 12 14 16

His FEV1 increases by one litre after nebulized bronchodilator, but his FVC is unchanged.

·         TASK

1. Write a report of the spirometry result in his medical notes on the paper provided in Question 3 Answer 

The structured report of the spirometry should include measurements of the following items:

·         Forced expiratory volume in one second

·         Forced vital capacity

·         FEV1/FVC ratio

2. Underneath your report in his medical notes write the likely differential diagnosis/cause of his symptoms considering the clinical and spirometry findings

 

From <https://mle.ncl.ac.uk/cases/page/19169/>

 

 

 

Wriske 4

15 January 2021

00:23

Situation

You are a Foundation Year 2 doctor working in General Practice.

 

Patient details

Name:                                    Alda Storey

Date of birth:                         22/01/1945

Address:                                 Apple Cottage, Hedgerow Lane, Corbridge. NE67 1EE

Patient number:                    444 565 7898

 

History

Mrs Storey has asked for a repeat prescription for her regular medications.  She has a history of myocardial infarction and of peripheral vascular disease.  Her medications were all started for secondary prevention of vascular disease.

Atorvastatin   80 mg             once a day

Bisoprolol      5 mg                once a day

Clopidogrel   75 mg              once a day

She came to the surgery last week for some blood tests to monitor her treatment, and the results are below.

 

Investigations

Haemoglobin                                    146 g/L (115-165)

White cell count                               8.5 x 109/L (4-11)

Neutrophils                                       6.0 x 109/L (1.5-7.0)

Platelets                                             367 x 109/L (150–400)      

 

Sodium                                              140 mmol/L (137–144)

Potassium                                          4.2 mmol/L (3.5–4.9)

Urea                                                   6.4 mmol/L (2.5–7.0)

Creatinine                                          88 µmol/L (60–110)

Glucose                                              5.2 mmol/L

 

 Albumin                                              40 g/L (37–49)

Globulins                                            26 g/L (24–27)

Total Bilirubin                                     20 µmol/L (1–22)

Alanine Aminotransferase                160 U/L (5–35)

Alkaline Phosphatase                       170U/L (45–105)

 

Prothrombin Time                            13s (11.5–15.5)

Activated Partial Thromboplastin Time     32s (30–40)

Fibrinogen                                        5.1g/L (1.8–5.4)

·         TASK

Please prescribe her medications on the FP10 prescribing sheet provided in the Question 4 Answer, making any alterations to the regular prescription which are necessary given the blood results 

 

From <https://mle.ncl.ac.uk/cases/page/19172/>

 

 

 

Cheat sheet

24 December 2020

21:00

 

 

 

 

 

24 December 2020

14:03

Myeloma: features

Multiple myeloma is a neoplasm of the bone marrow plasma cells. The peak incidence is patients aged 60-70 years.

 

Clinical features

·         bone disease: bone pain, osteoporosis + pathological fractures (typically vertebral), osteolytic lesions

·         lethargy

·         infection

·         hypercalcaemia (see below)

·         renal failure

·         other features: amyloidosis e.g. Macroglossia, carpal tunnel syndrome; neuropathy; hyperviscosity

Investigations

·         monoclonal proteins (usually IgG or IgA) in the serum and urine (Bence Jones proteins)

·         increased plasma cells in the bone marrow

·         historically a skeletal survey has been done to look for bone lesions. However, whole-body MRI is increasingly used and is now recommended in the 2016 NICE guidelines

·         X-rays: 'rain-drop skull' (likened to the pattern rain forms after hitting a surface and splashing, where it leaves a random pattern of dark spots). Note that a very similar, but subtly different finding is found in primary hyperparathyroidism - 'pepperpot skull'

The diagnostic criteria for multiple myeloma requires one major and one minor criteria or three minor criteria in an individual who has signs or symptoms of multiple myeloma.

 

Major criteria

·         Plasmacytoma (as demonstrated on evaluation of biopsy specimen)

·         30% plasma cells in a bone marrow sample

·         Elevated levels of M protein in the blood or urine

Minor criteria

·         10% to 30% plasma cells in a bone marrow sample.

·         Minor elevations in the level of M protein in the blood or urine.

·         Osteolytic lesions (as demonstrated on imaging studies).

·         Low levels of antibodies (not produced by the cancer cells) in the blood.

Hypercalcaemia in myeloma

·         primary factor: due primarily to increased osteoclastic bone resorption caused by local cytokines (e.g. IL-1, tumour necrosis factor) released by the myeloma cells

·         much less common contributing factors: impaired renal function, increased renal tubular calcium reabsorption and elevated PTH-rP levels

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:03

Direct oral anticoagulants

The table below summaries the three direct oral anticoagulants (DOACs): dabigatran, rivaroxaban and apixaban.

 

 

 

Dabigatran

Rivaroxaban

Apixaban

UK brand name

Pradaxa

Xarelto

Eliquis

Mechanism of action

Direct thrombin inhibitor

Direct factor Xa inhibitor

Direct factor Xa inhibitor

Route

Oral

Oral

Oral

Excretion

Majority renal

Majority liver

Majority faecal

NICE indications

Prevention of VTE following hip/knee surgery

 

Treatment of DVT and PE

 

Prevention of stroke in non-valvular AF*

Prevention of VTE following hip/knee surgery

 

Treatment of DVT and PE

 

Prevention of stroke in non-valvular AF*

Prevention of VTE following hip/knee surgery

 

Treatment of DVT and PE

 

Prevention of stroke in non-valvular AF*

Reversal

Idarucizumab

Andexanet alfa**

Andexanet alfa**

*NICE stipulate that certain other risk factors should be present. These are complicated and differ between the DOACs but generally require one of the following to be present:

·         prior stroke or transient ischaemic attack

·         age 75 years or older

·         hypertension

·         diabetes mellitus

·         heart failure

**Andexanet alfa is a recombinant form of human factor Xa protein

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:03

G6PD deficiency

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect. It is more common in people from the Mediterranean and Africa and is inherited in an X-linked recessive fashion. Many drugs can precipitate a crisis as well as infections and broad (fava) beans

 

Pathophysiology

·         G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone

o    this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH

o    i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH

·         NADPH is important for converting oxidizied glutathine back to it's reduced form

·         reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide

·         ↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

Features

·         neonatal jaundice is often seen

·         intravascular haemolysis

·         gallstones are common

·         splenomegaly may be present

·         Heinz bodies on blood films. Bite and blister cells may also be seen

Diagnosis is made by using a G6PD enzyme assay

·         levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results

Some drugs causing haemolysis

·         anti-malarials: primaquine

·         ciprofloxacin

·         sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas

Some drugs thought to be safe

·         penicillins

·         cephalosporins

·         macrolides

·         tetracyclines

·         trimethoprim

Comparing G6PD deficiency to hereditary spherocytosis:

 

 

 

 

Comparison of G6PD deficiency to hereditary spherocytosis

 

 

G6PD deficiency

Hereditary spherocytosis

Gender

Male (X-linked recessive)

Male + female (autosomal dominant)

Ethnicity

African + Mediterranean descent

Northern European descent

Typical history

• Neonatal jaundice

• Infection/drugs precipitate haemolysis

• Gallstones

• Neonatal jaundice

• Chronic symptoms although haemolytic crises may be precipitated by infection

• Gallstones

• Splenomegaly is common

Blood film

Heinz bodies

Spherocytes (round, lack of central pallor)

Diagnostic test

Measure enzyme activity of G6PD

Osmotic fragility test

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:03

Iron deficiency anaemia

Iron deficiency anaemia is the most common anaemia worldwide. Iron is needed to make the haemoglobin in red blood cells, therefore a deficiency of iron leads to a reduction in red blood cells/haemoglobin i.e. anaemia. Iron deficiency anaemia has the highest incidence amongst preschool-age children. The main causes are excessive blood loss, inadequate dietary intake, poor intestinal absorption and increased iron requirements.

 

Epidemiology

·         Globally, iron deficiency is the most common cause of anaemia

·         Preschool-age children have the highest prevalence of iron deficiency anaemia

Causes

·         Excessive blood loss: blood loss due to menorrhagia is the most common cause in pre-menopausal women, whereas gastrointestinal bleeding is the most common cause in men (always suspect colon cancer) and post-menopausal women.

·         Inadequate dietary intake: as meat is a good source of iron, vegans and vegetarians are more likely to develop iron deficiency anaemia due to a lack of meat in their diet. However dark green leafy vegetables are another good source of iron, therefore people who don’t eat meat can still receive enough iron through purely dietary sources.

·         Poor intestinal absorption: conditions which affect the small intestine, such as coeliac disease, can prevent sufficient iron being absorbed.

·         Increased iron requirements: children have increased iron demands during periods of rapid growth. Women also have increased demands during pregnancy as the baby will receive their iron supply from the mother. In addition, an increase in plasma volume during pregnancy causes iron deficiency anaemia through dilution i.e. the proportion of fluid in comparison to red blood cells increases.

Features

·         Fatigue

·         Shortness of breath on exertion

·         Palpitations

·         Pallor

·         Nail changes: this includes koilonychia (spoon-shaped nails)

·         Hair loss

·         Atrophic glossitis

·         Post-cricoid webs

·         Angular stomatitis

Investigations

·         Taking a history is the most important step in looking for potential causes of iron deficiency. It is useful to inquire about: changes in diet, medication history, menstrual history, weight loss, change in bowel habit

·         Full blood count (FBC) demonstrates hypochromic microcytic anaemia

·         Serum ferritin this will likely be low, as serum ferritin correlates with iron stores. However, it is important to recognise that ferritin can be raised during states of inflammation; so a raised ferritin does not necessarily rule out iron deficiency anaemia if the is co-occurring inflammation. For patients with co-occurring inflammatory disease, other iron studies can be performed.

·         Total iron-binding capacity (TIBC)/transferrin this will be high. A high TIBC reflects low iron stores. . Note that the transferrin saturation will however be low

·         Blood film anisopoikilocytosis (red blood cells of different sizes and shapes) , target cells, 'pencil' poikilocytes

·         Endoscopy to rule out malignancy, males and post-menopausal females who present with unexplained iron-deficiency anaemia should be considered for further gastrointestinal investigations. Post-menopausal women with a haemoglobin level ≤10 and men with a haemoglobin level ≤11 should be referred to a gastroenterologist within 2 weeks.

Management

·         The underlying cause of the iron-deficiency anaemia must be identified and managed. It is particularly important that malignancy has been excluded by taking an adequate history and appropriate investigations if warranted

·         Oral ferrous sulfate: patients should continue taking iron for 3 months after the iron deficiency has been corrected in order to replenish iron stores. Common side effects of iron supplementation include nausea, abdominal pain, constipation, diarrhoea

·         Iron-rich diet: this includes dark-green leafy vegetables, meat, iron-fortified bread

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:03

Sickle-cell crises

Sickle cell anaemia is characterised by periods of good health with intervening crises

 

A number of types of crises are recognised:

·         thrombotic, 'painful crises'

·         sequestration

·         acute chest syndrome

·         aplastic

·         haemolytic

Thrombotic crises

·         also known as painful crises or vaso-occlusive crises

·         precipitated by infection, dehydration, deoxygenation

·         painful vaso-occlusive crises should be diagnosed clinically - there isn't one test that can confirm them although tests may be done to exclude other complications

·         infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain

Sequestration crises

·         sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia

Acute chest syndrome

·         dyspnoea, chest pain, pulmonary infiltrates, low pO2

·         the most common cause of death after childhood

Aplastic crises

·         caused by infection with parvovirus

·         sudden fall in haemoglobin

Haemolytic crises

·         rare

·         fall in haemoglobin due an increased rate of haemolysis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

 

Acute chest crisis management:

·         Hydration

·         O2 therapy

·         Broad spectrum IV Abx

·         Pain relief

·         Incentive spirometry (if able)

·         Bronchodilators is element of bronchospasm

·         Transfusion

either top-up or exchange

Need to be aware of patients’ baseline

·         Early involvement of haematology and critical care

 

 

 

 

 

24 December 2020

14:03

Von Willebrand's disease

Von Willebrand's disease is the most common inherited bleeding disorder. The majority of cases are inherited in an autosomal dominant fashion* and characteristically behaves like a platelet disorder i.e. epistaxis and menorrhagia are common whilst haemoarthroses and muscle haematomas are rare

 

Role of von Willebrand factor

·         large glycoprotein which forms massive multimers up to 1,000,000 Da in size

·         promotes platelet adhesion to damaged endothelium

·         carrier molecule for factor VIII

Types

·         type 1: partial reduction in vWF (80% of patients)

·         type 2*: abnormal form of vWF

·         type 3**: total lack of vWF (autosomal recessive)

Investigation

·         prolonged bleeding time

·         APTT may be prolonged

·         factor VIII levels may be moderately reduced

·         defective platelet aggregation with ristocetin

Management

·         tranexamic acid for mild bleeding

·         desmopressin (DDAVP): raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells

·         factor VIII concentrate

*type 2A VWD is caused by defective platelet adhesion due to decreased high molecular weight VWF multimers (i.e. the VWF protein is too small). Type 2B is characterised by a pathological increase of VWF-platelet interaction. Type 2M is caused by a decrease in VWF-platelet interaction (not related to loss of high molecular weight multimers). Type 2N is caused by abnormal binding of the VWF to Factor VIII. There is no clear correlation between symptomatic presentation and type of VWD however common themes amongst patients include excessive mucocutaneous bleeding, bruising in the absence of trauma and menorrhagia in females.

 

**type 3 von Willebrand's disease (most severe form) is inherited as an autosomal recessive trait. Around 80% of patients have type 1 disease

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:03

Blood products: CMV negative and irradiated blood

Cytomegalovirus (CMV) is transmitted in leucocytes. As most blood products (except granulocyte transfusions) are now leucocyte depleted CMV negative products are rarely required.

 

Irradiated blood products are depleted of T-lymphocytes and used to avoid transfusion-associated graft versus host disease (TA-GVHD) caused by engraftment of viable donor T lymphocytes.

 

The table below shows the indications for CMV and irradiated blood:

 

 

Situation

CMV negative

Irradiated

Granulocyte transfusions

✓

✓

Intra-uterine transfusions

✓

✓

Neonates up to 28 days post expected date of delivery

✓

✓

Pregnancy: Elective transfusions during pregnancy (not during labour or delivery)

✓

 

Bone marrow / stem cell transplants

 

✓

Immunocompromised (e.g. chemotherapy or congenital)

 

✓

Patients with/previous Hodgkins Disease

 

✓

HIV

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Chronic myeloid leukaemia

The Philadelphia chromosome is present in more than 95% of patients with chronic myeloid leukaemia (CML). It is due to a translocation between the long arm of chromosome 9 and 22 - t(9:22)(q34; q11). This results in part of the ABL proto-oncogene from chromosome 9 being fused with the BCR gene from chromosome 22. The resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal

 

Presentation (60-70 years)

·         anaemia: lethargy

·         weight loss and sweating are common

·         splenomegaly may be marked → abdo discomfort

·         an increase in granulocytes at different stages of maturation +/- thrombocytosis

·         decreased leukocyte alkaline phosphatase

·         may undergo blast transformation (AML in 80%, ALL in 20%)

Management

·         imatinib is now considered first-line treatment

·         hydroxyurea

·         interferon-alpha

·         allogenic bone marrow transplant

Imatinib

·         inhibitor of the tyrosine kinase associated with the BCR-ABL defect

·         very high response rate in chronic phase CML

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Hereditary spherocytosis

Basics

·         most common hereditary haemolytic anaemia in people of northern European descent

·         autosomal dominant defect of red blood cell cytoskeleton

·         the normal biconcave disc shape is replaced by a sphere-shaped red blood cell

·         red blood cell survival reduced as destroyed by the spleen

Presentation

·         failure to thrive

·         jaundice, gallstones

·         splenomegaly

·         aplastic crisis precipitated by parvovirus infection

·         degree of haemolysis variable

·         MCHC elevated

Diagnosis

·         the osmotic fragility test was previously the recommend investigation of choice. However, it is now deemed unreliable and is no longer recommended

·         the British Journal of Haematology (BJH) guidelines state that 'patients with a family history of HS, typical clinical features and laboratory investigations (spherocytes, raised mean corpuscular haemoglobin concentration[MCHC], increase in reticulocytes) do not require any additional tests

·         if the diagnosis is equivocal the BJH recommend the cryohaemolysis test and EMA binding

·         for atypical presentations electrophoresis analysis of erythrocyte membranes is the method of choice

Management

·         acute haemolytic crisis:

o    treatment is generally supportive

o    transfusion if necessary

·         longer term treatment:

o    folate replacement

o    splenectomy

Comparing G6PD deficiency to hereditary spherocytosis:

 

 

 

 

Comparison of G6PD deficiency to hereditary spherocytosis

 

 

G6PD deficiency

Hereditary spherocytosis

Gender

Male (X-linked recessive)

Male + female (autosomal dominant)

Ethnicity

African + Mediterranean descent

Northern European descent

Typical history

• Neonatal jaundice

• Infection/drugs precipitate haemolysis

• Gallstones

• Neonatal jaundice

• Chronic symptoms although haemolytic crises may be precipitated by infection

• Gallstones

• Splenomegaly is common

Blood film

Heinz bodies

Spherocytes (round, lack of central pallor)

Diagnostic test

Measure enzyme activity of G6PD

EMA binding test

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Platelet transfusion: active bleeding

Active bleeding

 

Offer platelet transfusions to patients with a platelet count of <30 x 10 9 with clinically significant bleeding (World Health organisation bleeding grade 2- e.g. haematemesis, melaena, prolonged epistaxis)

 

Platelet thresholds for transfusion are higher (maximum < 100 x 10 9) for patients with severe bleeding (World Health organisation bleeding grades 3&4), or bleeding at critical sites, such as the CNS.

 

It should be noted that platelet transfusions have the highest risk of bacterial contamination compared to other types of blood product.

 

Pre-invasive procedure (prophylactic)

 

Platelet transfusion for thrombocytopenia before surgery/ an invasive procedure. Aim for plt levels of:

·         > 50×109/L for most patients

·         50-75×109/L if high risk of bleeding

·         >100×109/L if surgery at critical site

If no active bleeding or planned invasive procedure

 

A threshold of 10 x 109 except where platelet transfusion is contradindicated or there are alternative treatments for their condition

 

For example, do not perform platelet transfusion for any of the following conditions:

·         Chronic bone marrow failure

·         Autoimmune thrombocytopenia

·         Heparin-induced thrombocytopenia, or

·         Thrombotic thrombocytopenic purpura.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Sickle-cell anaemia

Sickle-cell anaemia is an autosomal recessive condition that results for synthesis of an abnormal haemoglobin chain termed HbS. It is more common in people of African descent as the heterozygous condition offers some protection against malaria. Around 10% of UK Afro-Caribbean's are carriers of HbS (i.e. heterozygous). Such people are only symptomatic if severely hypoxic.

 

Symptoms in homozygotes don't tend to develop until 4-6 months when the abnormal HbSS molecules take over from fetal haemoglobin.

 

Pathophysiology

·         polar amino acid glutamate is substituted by non-polar valine in each of the two beta chains (codon 6). This decreases the water solubility of deoxy-Hb

·         in the deoxygenated state the HbS molecules polymerise and cause RBCs to sickle

·         HbAS patients sickle at p02 2.5 - 4 kPa, HbSS patients at p02 5 - 6 kPa

·         sickle cells are fragile and haemolyse; they block small blood vessels and cause infarction

Investigations

·         definitive diagnosis of sickle cell disease is by haemoglobin electrophoresis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

 

 

 

 

 

 

24 December 2020

14:04

Venous thromboembolism: risk factors

Common predisposing factors include malignancy, pregnancy and the period following an operation. The comprehensive list below is partly based on the 2010 SIGN venous thromboembolism (VTE) guidelines:

 

General

·         increased risk with advancing age

·         obesity

·         family history of VTE

·         pregnancy (especially puerperium)

·         immobility

·         hospitalisation

·         anaesthesia

·         central venous catheter: femoral >> subclavian

Underlying conditions

·         malignancy

·         thrombophilia: e.g. Activated protein C resistance, protein C and S deficiency

·         heart failure

·         antiphospholipid syndrome

·         Behcet's

·         polycythaemia

·         nephrotic syndrome

·         sickle cell disease

·         paroxysmal nocturnal haemoglobinuria

·         hyperviscosity syndrome

·         homocystinuria

Medication

·         combined oral contraceptive pill: 3rd generation more than 2nd generation

·         hormone replacement therapy: the risk of VTE is higher in women taking oestrogen + progestogen preparations compared to those taking oestrogen-only preparations

·         raloxifene and tamoxifen

·         antipsychotics (especially olanzapine) have recently been shown to be a risk factor

It should be remembered however that around 40% of patients diagnosed with a PE have no major risk factors.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

·         Congenital thrombophilias (i.e antithrombin deficiency, protein Cor S deficiency, prothrombin gene mutaions)

·         Acquired: Antiphospholipid syndrome, Myeloproliferative conditions

·         Inflammatory states: malignancy, surgery

·         Poor mobility

·         Compression

 

 

 

 

 

24 December 2020

14:04

Vitamin B12 deficiency

Vitamin B12 is mainly used in the body for red blood cell development and also maintenance of the nervous system. It is absorbed after binding to intrinsic factor (secreted from parietal cells in the stomach) and is actively absorbed in the terminal ileum. A small amount of vitamin B12 is passively absorbed without being bound to intrinsic factor.

 

Causes of vitamin B12 deficiency

·         pernicious anaemia: most common cause

·         post gastrectomy

·         vegan diet or a poor diet

·         disorders/surgery of terminal ileum (site of absorption)

o    Crohn's: either diease activity or following ileocaecal resection

·         metformin (rare)

Features of vitamin B12 deficiency

·         macrocytic anaemia

·         sore tongue and mouth

·         neurological symptoms

o    the dorsal column is usually affected first (joint position, vibration) prior to distal paraesthesia

·         neuropsychiatric symptoms: e.g. mood disturbances

Management

·         if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months

·         if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Blood products: red bloods cells

NICE published guidelines on the use of blood products in 2015.

 

They recommended the following thresholds for transfusion:

 

 

 

Patients without ACS

Patients with ACS

Transfusion threshold

70 g/L

80 g/L

Target after transfusion

70-90 g/L

80-100 g/L

(ACS = acute coronary syndrome)

 

Please note that these thresholds should not be used in patients with ongoing major haemorrhage or patients who require regular blood transfusions for chronic anaemia.

 

Practical points

·         red blood cells should be stored at 4°C prior to infusion

·         in a non-urgent scenario, a unit of RBC is usually transfused over 90-120 minutes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Chronic lymphocytic leukaemia: features and investigation

Chronic lymphocytic leukaemia (CLL) is caused by a monoclonal proliferation of well-differentiated lymphocytes which are almost always B-cells (99%). It is the most common form of leukaemia seen in adults.

 

Features

·         often none: may be picked up by an incidental finding of lymphocytosis

·         constitutional: anorexia, weight loss

·         bleeding, infections

·         lymphadenopathy more marked than chronic myeloid leukaemia

Investigations

·         full blood count:

o    lymphocytosis

o    anaemia

·         blood film: smudge cells (also known as smear cells)

·         immunophenotyping is the key investigation

 

 

Image sourced from Wikipedia

Peripheral blood film showing smudge B cells

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Hodgkin's lymphoma

Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades

 

Features

·         lymphadenopathy (75%) - painless, non-tender, asymmetrical

·         systemic (25%): weight loss, pruritus, night sweats, fever (Pel-Ebstein)

·         alcohol pain in HL

·         normocytic anaemia, eosinophilia

·         LDH raised

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:04

Polycythaemia vera: features

Polycythaemia vera (previously called polycythaemia rubra vera) is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets. It has recently been established that a mutation in JAK2 is present in approximately 95% of patients with polycythaemia vera and this has resulted in significant changes to the diagnostic criteria. The incidence of polycythaemia vera peaks in the sixth decade.

 

Features

·         hyperviscosity

·         pruritus, typically after a hot bath

·         splenomegaly

·         haemorrhage (secondary to abnormal platelet function)

·         plethoric appearance

·         hypertension in a third of patients

·         low ESR

Following history and examination, the British Committee for Standards in Haematology (BCSH) recommend the following tests are performed

·         full blood count/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients)

·         JAK2 mutation

·         serum ferritin

·         renal and liver function tests

If the JAK2 mutation is negative and there is no obvious secondary causes the BCSH suggest the following tests:

·         red cell mass

·         arterial oxygen saturation

·         abdominal ultrasound

·         serum erythropoietin level

·         bone marrow aspirate and trephine

·         cytogenetic analysis

·         erythroid burst-forming unit (BFU-E) culture

Other features that may be seen in PRV include a low ESR and a raised leukocyte alkaline phosphatase

 

The diagnostic criteria for polycythaemia vera have recently been updated by the BCSH. This replaces the previous polycythaemia vera Study Group criteria.

 

JAK2-positive polycythaemia vera - diagnosis requires both criteria to be present

 

 

Criteria

Notes

A1

High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)

A2

Mutation in JAK2

JAK2-negative PRV - diagnosis requires A1 + A2 + A3 + either another A or two B criteria

 

 

Criteria

Notes

A1

Raised red cell mass (>25% above predicted) OR haematocrit >0.60 in men, >0.56 in women

A2

Absence of mutation in JAK2

A3

No cause of secondary erythrocytosis

A4

Palpable splenomegaly

A5

Presence of an acquired genetic abnormality (excluding BCR-ABL) in the haematopoietic cells

B1

Thrombocytosis (platelet count >450 * 109/l)

B2

Neutrophil leucocytosis (neutrophil count > 10 * 109/l in non-smokers; > 12.5*109/l in smokers)

B3

Radiological evidence of splenomegaly

B4

Endogenous erythroid colonies or low serum erythropoietin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Post-thrombotic syndrome

It is increasingly recognised that patients may develop complications following a DVT. Venous outflow obstruction and venous insufficiency result in chronic venous hypertension. The resulting clinical syndrome is known as post-thrombotic syndrome. The following features maybe seen:

·         painful, heavy calves

·         pruritus

·         swelling

·         varicose veins

·         venous ulceration

Compression stockings have in the past been offered to patients with deep vein thrombosis to help reduce the risk of post-thrombotic syndrome.

 

However, Clinical Knowledge Summaries now state the following:

 

 

Do not offer elastic graduated compression stockings to prevent post-thrombotic syndrome or VTE recurrence after a proximal DVT. This recommendation does not cover the use of elastic stockings for the management of leg symptoms after DVT.

 

However, once post-thrombotic syndrome has developed compression stockings are a recommended treatment. Other recommendations including keeping the leg elevated.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Thrombophilia: causes

Inherited

 

Gain of function polymorphisms

·         factor V Leiden (activated protein C resistance): most common cause of thrombophilia

·         prothrombin gene mutation: second most common cause

Deficiencies of naturally occurring anticoagulants

·         antithrombin III deficiency

·         protein C deficiency

·         protein S deficiency

The table below shows the prevalence and relative risk of venous thromboembolism (VTE) of the different inherited thrombophilias:

 

 

Condition

Prevalence

Relative risk of VTE

Factor V Leiden (heterozygous)

5%

4

Factor V Leiden (homozygous)

0.05%

10

Prothrombin gene mutation (heterozygous)

1.5%

3

Protein C deficiency

0.3%

10

Protein S deficiency

0.1%

5-10

Antithrombin III deficiency

0.02%

10-20

Acquired

Antiphospholipid syndrome

 

Drugs

·         the combined oral contraceptive pill

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:04

Tumour lysis syndrome

Tumour lysis syndrome (TLS) is a potentially deadly condition related to the treatment of high-grade lymphomas and leukaemias. It can occur in the absence of chemotherapy but is usually triggered by the introduction of combination chemotherapy. On occasion, it can occur with steroid treatment alone. Awareness of the condition is critical as prophylactic medication can be given to prevent the potentially deadly effects of tumour cell lysis.

 

Patients at high risk of TLS should be given IV allopurinol or IV rasburicase immediately prior to and during the first days of chemotherapy. Rasburicase is a recombinant version of urate oxidase, an enzyme that metabolizes uric acid to allantoin. Allantoin is much more water-soluble than uric acid and is, therefore, more easily excreted by the kidneys. Patients in lower-risk groups should be given oral allopurinol during chemotherapy cycles in an attempt to avoid the condition. Rasburicase and allopurinol should not be given together in the management of tumour lysis syndrome as this reduces the effect of rasburicase.

 

TLS occurs from the breakdown of the tumour cells and the subsequent release of chemicals from the cell. It leads to a high potassium and high phosphate level in the presence of a low calcium. It should be suspected in any patient presenting with an acute kidney injury in the presence of a high phosphate and high uric acid level.

 

From 2004 TLS has been graded using the Cairo-Bishop scoring system -

Laboratory tumor lysis syndrome: abnormality in two or more of the following, occurring within three days before or seven days after chemotherapy.

·         uric acid > 475umol/l or 25% increase

·         potassium > 6 mmol/l or 25% increase

·         phosphate > 1.125mmol/l or 25% increase

·         calcium < 1.75mmol/l or 25% decrease

Clinical tumor lysis syndrome: laboratory tumour lysis syndrome plus one or more of the following:

·         increased serum creatinine (1.5 times upper limit of normal)

·         cardiac arrhythmia or sudden death

·         seizure

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Abnormal coagulation

Cause

Factors affected

Heparin

Prevents activation factors 2,9,10,11

Warfarin

Affects synthesis of factors 2,7,9,10

DIC

Factors 1,2,5,8,11

Liver disease

Factors 1,2,5,7,9,10,11

Interpretation blood clotting test results

 

Disorder

APTT

PT

Bleeding time

Haemophilia

Increased

Normal

Normal

von Willebrand's disease

Increased

Normal

Increased

Vitamin K deficiency

Increased

Increased

Normal

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Antiphospholipid syndrome: pregnancy

Antiphospholipid syndrome is an acquired disorder characterised by a predisposition to both venous and arterial thromboses, recurrent fetal loss and thrombocytopenia. It may occur as a primary disorder or secondary to other conditions, most commonly systemic lupus erythematosus (SLE)

 

In pregnancy the following complications may occur:

·         recurrent miscarriage

·         IUGR

·         pre-eclampsia

·         placental abruption

·         pre-term delivery

·         venous thromboembolism

Management

·         low-dose aspirin should be commenced once the pregnancy is confirmed on urine testing

·         low molecular weight heparin once a fetal heart is seen on ultrasound. This is usually discontinued at 34 weeks gestation

·         these interventions increase the live birth rate seven-fold

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Beta-thalassaemia trait

The thalassaemias are a group of genetic disorders characterised by a reduced production rate of either alpha or beta chains. Beta-thalassaemia trait is an autosomal recessive condition characterised by a mild hypochromic, microcytic anaemia. It is usually asymptomatic

 

Features

·         mild hypochromic, microcytic anaemia - microcytosis is characteristically disproportionate to the anaemia

·         HbA2 raised (> 3.5%)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:05

Blood products

Whole blood fractions

 

 

Fraction

Key points

Packed red cells

Used for transfusion in chronic anaemia and cases where infusion of large volumes of fluid may result in cardiovascular compromise. Product obtained by centrifugation of whole blood.

Platelet rich plasma

Usually administered to patients who are thrombocytopaenic and are bleeding or require surgery. It is obtained by low speed centrifugation.

Platelet concentrate

Prepared by high speed centrifugation and administered to patients with thrombocytopaenia.

Fresh frozen plasma

·         Prepared from single units of blood.

·         Contains clotting factors, albumin and immunoglobulin.

·         Unit is usually 200 to 250ml.

·         Usually used in correcting clotting deficiencies in patients with hepatic synthetic failure who are due to undergo surgery.

·         Usual dose is 12-15ml/Kg-1.

·         It should not be used as first line therapy for hypovolaemia.

Cryoprecipitate

·         Formed from supernatant of FFP.

·         Rich source of Factor VIII and fibrinogen.

·         Allows large concentration of factor VIII to be administered in small volume.

SAG-Mannitol Blood

Removal of all plasma from a blood unit and substitution with:

·         Sodium chloride

·         Adenine

·         Anhydrous glucose

·         Mannitol

Up to 4 units of SAG M Blood may be administered. Thereafter whole blood is preferred. After 8 units, clotting factors and platelets should be considered.

Cell saver devices

These collect patients own blood lost during surgery and then re-infuse it. There are two main types:

·         Those which wash the blood cells prior to re-infusion. These are more expensive to purchase and more complicated to operate. However, they reduce the risk of re-infusing contaminated blood back into the patient.

·         Those which do not wash the blood prior to re-infusion.

Their main advantage is that they avoid the use of infusion of blood from donors into patients and this may reduce risk of blood borne infection. It may be acceptable to Jehovah's witnesses. It is contraindicated in malignant disease for risk of facilitating disease dissemination.

 

Blood products used in warfarin reversal

In some surgical patients the use of warfarin can pose specific problems and may require the use of specialised blood products

 

Immediate or urgent surgery in patients taking warfarin(1) (2):

 

1. Stop warfarin

 

2. Vitamin K (reversal within 4-24 hours)

-IV takes 4-6h to work (at least 5mg)

-Oral can take 24 hours to be clinically effective

 

3. Fresh frozen plasma

Used less commonly now as 1st line warfarin reversal

-30ml/kg-1

-Need to give at least 1L fluid in 70kg person (therefore not appropriate in fluid overload)

-Need blood group

-Only use if human prothrombin complex is not available

 

4. Human Prothrombin Complex (reversal within 1 hour)

-Bereplex 50 u/kg

-Rapid action but factor 6 short half life, therefore give with vitamin K

 

References

1. Dentali, F., C. Marchesi, et al. (2011). 'Safety of prothrombin complex concentrates for rapid anticoagulation reversal of vitamin K antagonists. A meta-analysis.' Thromb Haemost 106(3): 429-438.

 

2. http://www.transfusionguidelines.org/docs/pdfs/bbt-03warfarin-reversal-flowchart-2006.pdf

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Burkitt's lymphoma

Burkitt's lymphoma is a high-grade B-cell neoplasm. There are two major forms:

·         endemic (African) form: typically involves maxilla or mandible

·         sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV

Burkitt's lymphoma is associated with the c-myc gene translocation, usually t(8:14). The Epstein-Barr virus (EBV) is strongly implicated in the development of the African form of Burkitt's lymphoma and to a lesser extent the sporadic form.

 

Microscopy findings

·         'starry sky' appearance: lymphocyte sheets interspersed with macrophages containing dead apoptotic tumour cells

Management is with chemotherapy. This tends to produce a rapid response which may cause 'tumour lysis syndrome'. Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*) is often given before the chemotherapy to reduce the risk of this occurring. Complications of tumour lysis syndrome include:

·         hyperkalaemia

·         hyperphosphataemia

·         hypocalcaemia

·         hyperuricaemia

·         acute renal failure

*allantoin is 5-10 times more soluble than uric acid, so renal excretion is more effective

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Cryoprecipitate

·         Blood product made from plasma

·         Usually transfused as 6 unit pool

·         Indications include massive haemorrhage and uncontrolled bleeding due to haemophilia

Composition

 

Agent

Quantity

Factor VIII

100IU

Fibrinogen

250mg

von Willebrand factor

Variable

Factor XIII

Variable

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Disseminated intravascular coagulation - diagnosis

Under homeostatic conditions, coagulation and fibrinolysis are coupled. The activation of the coagulation cascade yields thrombin that converts fibrinogen to fibrin; the stable fibrin clot being the final product of hemostasis. The fibrinolytic system breaks down fibrinogen and fibrin. Activation of the fibrinolytic system generates plasmin (in the presence of thrombin), which is responsible for the lysis of fibrin clots. The breakdown of fibrinogen and fibrin results in polypeptides (fibrin degradation products). In a state of homeostasis, the presence of plasmin is critical, as it is the central proteolytic enzyme of coagulation and is also necessary for fibrinolysis.

 

In DIC, the processes of coagulation and fibrinolysis are dysregulated, and the result is widespread clotting with resultant bleeding. Regardless of the triggering event of DIC, once initiated, the pathophysiology of DIC is similar in all conditions. One critical mediator of DIC is the release of a transmembrane glycoprotein (tissue factor =TF). TF is present on the surface of many cell types (including endothelial cells, macrophages, and monocytes) and is not normally in contact with the general circulation, but is exposed to the circulation after vascular damage. For example, TF is released in response to exposure to cytokines (particularly interleukin 1), tumour necrosis factor, and endotoxin. This plays a major role in the development of DIC in septic conditions. TF is also abundant in tissues of the lungs, brain, and placenta. This helps to explain why DIC readily develops in patients with extensive trauma. Upon activation, TF binds with coagulation factors that then triggers the extrinsic pathway (via Factor VII) which subsequently triggers the intrinsic pathway (XII to XI to IX) of coagulation.

 

Causes of DIC

·         sepsis

·         trauma

·         obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome)

·         malignancy

 

Diagnosis

 

A typical blood picture includes:

·         low platelets

·         prolonged APTT, prothrombin and bleeding time

·         fibrin degradation products are often raised

·         schistocytes due to microangiopathic haemolytic anaemia

 

Disorder

Prothrombin time

APTT

Bleeding time

Platelet count

Warfarin administration

Prolonged

Normal

Normal

Normal

Aspirin administration

Normal

Normal

Prolonged

Normal

Heparin

Often normal (may be prolonged)

Prolonged

Normal

Normal

DIC

Prolonged

Prolonged

Prolonged

Low

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Factor V Leiden

Factor V Leiden (activated protein C resistance) is the most common inherited thrombophilia, being present in around 5% of the UK population.

 

It is due to a gain of function mutation in the Factor V Leiden protein. The result of the mis-sense mutation is that activated factor V (a clotting factor) is inactivated 10 times more slowly by activated protein C than normal. This explains the alternative name for factor V Leiden of activated protein C resistance,

 

Heterozygotes have a 4-5 fold risk of venous thrombosis. Homozygotes have a 10 fold risk of venous thrombosis but the prevalence is much lower at 0.05%.

 

Screening for factor V Leiden is not recommended, even after a venous thromboembolism. The logic behind this is that a previous thromboembolism itself is a risk factor for further events and this should dictate specific management in the future, rather than the particular thrombophilia identified.

 

The table below shows the prevalence and relative risk of venous thromboembolism (VTE) of the different inherited thrombophilias:

 

 

Condition

Prevalence

Relative risk of VTE

Factor V Leiden (heterozygous)

5%

4

Factor V Leiden (homozygous)

0.05%

10

Prothrombin gene mutation (heterozygous)

1.5%

3

Protein C deficiency

0.3%

10

Protein S deficiency

0.1%

5-10

Antithrombin III deficiency

0.02

10-20

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Haemophilia

Haemophilia is a X-linked recessive disorder of coagulation. Up to 30% of patients have no family history of the condition. Haemophilia A is due to a deficiency of factor VIII whilst in haemophilia B (Christmas disease) there is a lack of factor IX

 

Features

·         haemoarthroses, haematomas

·         prolonged bleeding after surgery or trauma

Blood tests

·         prolonged APTT

·         bleeding time, thrombin time, prothrombin time normal

Up to 10-15% of patients with haemophilia A develop antibodies to factor VIII treatment.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Immune thrombocytopenia (ITP) in adults

Immune (or idiopathic) thrombocytopenic purpura (ITP) is an immune-mediated reduction in the platelet count. Antibodies are directed against the glycoprotein IIb/IIIa or Ib-V-IX complex.

 

Children with ITP usually have an acute thrombocytopenia that may follow infection or vaccination. In contract, adults tend to have a more chronic condition.

 

ITP in adults

 

Epidemiology

·         more common in older females

Presentation

·         may be detected incidentally following routine bloods

·         symptomatic patients may present with

o    petichae, purpura

o    bleeding (e.g. epistaxis)

o    catastrophic bleeding (e.g. intracranial) is not a common presentation

Management

·         first-line treatment for ITP is oral prednisolone

·         pooled normal human immunoglobulin (IVIG) may also be used

·         splenectomy is now less commonly used

Evan's syndrome

·         ITP in association with autoimmune haemolytic anaemia (AIHA)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Macrocytic anaemia

Macrocytic anaemia can be divided into causes associated with a megaloblastic bone marrow and those with a normoblastic bone marrow

 

 

Megaloblastic causes

Normoblastic causes

·         vitamin B12 deficiency

·         folate deficiency

·         alcohol

·         liver disease

·         hypothyroidism

·         pregnancy

·         reticulocytosis

·         myelodysplasia

·         drugs: cytotoxics

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:05

Management of suspected haematological malignancy in young people

Any of the following features in a person aged 0-24 years should prompt a very urgent full blood count (within 48 hours) to investigate for leukaemia:

·         Pallor

·         Persistent fatigue

·         Unexplained fever

·         Unexplained persistent infections

·         Generalised lymphadenopathy

·         Persistent or unexplained bone pain

·         Unexplained bruising

·         Unexplained bleeding

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Myelofibrosis

Overview

·         a myeloproliferative disorder

·         thought to be caused by hyperplasia of abnormal megakaryocytes

·         the resultant release of platelet derived growth factor is thought to stimulate fibroblasts

·         haematopoiesis develops in the liver and spleen

Features

·         e.g. elderly person with symptoms of anaemia e.g. fatigue (the most common presenting symptom)

·         massive splenomegaly

·         hypermetabolic symptoms: weight loss, night sweats etc

Laboratory findings

·         anaemia

·         high WBC and platelet count early in the disease

·         'tear-drop' poikilocytes on blood film

·         unobtainable bone marrow biopsy - 'dry tap' therefore trephine biopsy needed

·         high urate and LDH (reflect increased cell turnover)

 

 

 

Blood film showing the typical 'tear-drop' poikilocytes of myelofibrosis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Neutropenic sepsis

Neutropenic sepsis is a relatively common complication of cancer therapy, usually as a consequence of chemotherapy. It most commonly occurs 7-14 days after chemotherapy. It may be defined as a neutrophil count of < 0.5 * 109 in a patient who is having anticancer treatment and has one of the following:

·         a temperature higher than 38ºC or

·         other signs or symptoms consistent with clinically significant sepsis

Prophylaxis

·         if it is anticipated that patients are likely to have a neutrophil count of < 0.5 * 109 as a consequence of their treatment they should be offered a fluoroquinolone

Management

·         antibiotics must be started immediately, do not wait for the WBC

·         NICE recommends starting empirical antibiotic therapy with piperacillin with tazobactam (Tazocin) immediately

·         many units add vancomycin if the patient has central venous access but NICE do not support this approach

·         following this initial treatment patients are usually assessed by a specialist and risk-stratified to see if they may be able to have outpatient treatment

·         if patients are still febrile and unwell after 48 hours an alternative antibiotic such as meropenem is often prescribed +/- vancomycin

·         if patients are not responding after 4-6 days the Christie guidelines suggest ordering investigations for fungal infections (e.g. HRCT), rather than just starting therapy antifungal therapy blindly

·         there may be a role for G-CSF in selected patients

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Polycythaemia

Polycythaemia may be relative, primary (polycythaemia rubra vera) or secondary

 

Relative causes

·         dehydration

·         stress: Gaisbock syndrome

Primary

·         polycythaemia rubra vera

Secondary causes

·         COPD

·         altitude

·         obstructive sleep apnoea

·         excessive erythropoietin: cerebellar haemangioma, hypernephroma, hepatoma, uterine fibroids*

To differentiate between true (primary or secondary) polycythaemia and relative polycythaemia red cell mass studies are sometimes used. In true polycythaemia the total red cell mass in males > 35 ml/kg and in women > 32 ml/kg

 

*uterine fibroids may cause menorrhagia which in turn leads to blood loss - polycythaemia is rarely a clinical problem

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

Whole blood viscosity is dependent upon Hct, red cell deformability and plasma viscosity.

pt should be venesected on a weekly basis initially to a Hct of around 0.45.

 

An elevated Hct is associated particularly with an increased risk of cerebro vascular accident and myocardial infarction.

The degree of elevation of his platelet count and his history of TIA’s make anti-platelet therapy with Aspirin and treatment to reduce his platelet count (cyto-reductive therapy e.g. interferon or hydroxycarbamide) into the normal range appropriate.

 

Anti-coagulant therapy is not indicated as he doesn’t have atrial fibrillation to suggest this as a cause of his transient ischaemic attacks.

 Anti-coagulation therapy has no role in the routine management of primary polycythaemia

 

The risk/benefit balance of Aspirin in this situation outweighs that of Warfarin because of the risks of bleeding associated with anti-coagulant therapy.

 

From <https://mle.ncl.ac.uk/cases/page/15729/>

 

 

 

 

 

 

24 December 2020

14:06

Thrombocytosis

Thrombocytosis is an abnormally high platelet count, usually > 400 * 109/l.

 

Causes of thrombocytosis

·         reactive: platelets are an acute phase reactant - platelet count can increase in response to stress such as a severe infection, surgery. Iron deficiency anaemia can also cause a reactive thrombocytosis

·         malignancy

·         essential thrombocytosis (see below), or as part of another myeloproliferative disorder such as chronic myeloid leukaemia or polycythaemia rubra vera

·         hyposplenism

Essential thrombocytosis

 

Essential thrombocytosis is one of the myeloproliferative disorders which overlaps with chronic myeloid leukaemia, polycythaemia rubra vera and myelofibrosis. Megakaryocyte proliferation results in an overproduction of platelets.

 

Features

·         platelet count > 600 * 109/l

·         both thrombosis (venous or arterial) and haemorrhage can be seen

·         a characteristic symptom is a burning sensation in the hands

·         a JAK2 mutation is found in around 50% of patients

Management

·         hydroxyurea (hydroxycarbamide) is widely used to reduce the platelet count

·         interferon-α is also used in younger patients

·         low-dose aspirin may be used to reduce the thrombotic risk

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Aplastic anaemia

Characterised by pancytopenia and a hypoplastic bone marrow

 

Peak incidence of acquired = 30 years old

 

Features

·         normochromic, normocytic anaemia

·         leukopenia, with lymphocytes relatively spared

·         thrombocytopenia

·         may be the presenting feature acute lymphoblastic or myeloid leukaemia

·         a minority of patients later develop paroxysmal nocturnal haemoglobinuria or myelodysplasia

Causes

·         idiopathic

·         congenital: Fanconi anaemia, dyskeratosis congenita

·         drugs: cytotoxics, chloramphenicol, sulphonamides, phenytoin, gold

·         toxins: benzene

·         infections: parvovirus, hepatitis

·         radiation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Autoimmune haemolytic anaemia

Autoimmune haemolytic anaemia (AIHA) may be divided in to 'warm' and 'cold' types, according to at what temperature the antibodies best cause haemolysis. It is most commonly idiopathic but may be secondary to a lymphoproliferative disorder, infection or drugs. AIHA is characterised by a positive direct antiglobulin test (Coombs' test)

 

Warm AIHA

 

In warm AIHA the antibody (usually IgG) causes haemolysis best at body temperature and haemolysis tends to occur in extravascular sites, for example the spleen. Management options include steroids, immunosuppression and splenectomy

 

Causes of warm AIHA

·         autoimmune disease: e.g. systemic lupus erythematosus*

·         neoplasia: e.g. lymphoma, CLL

·         drugs: e.g. methyldopa

Cold AIHA

 

The antibody in cold AIHA is usually IgM and causes haemolysis best at 4 deg C. Haemolysis is mediated by complement and is more commonly intravascular. Features may include symptoms of Raynaud's and acrocynaosis. Patients respond less well to steroids

 

Causes of cold AIHA

·         neoplasia: e.g. lymphoma

·         infections: e.g. mycoplasma, EBV

*systemic lupus erythematosus can rarely be associated with a mixed-type autoimmune haemolytic anaemia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Beta-thalassaemia major

Overview

·         absence of beta chains

·         chromosome 11

Features

·         presents in first year of life with failure to thrive and hepatosplenomegaly

·         microcytic anaemia

·         HbA2 & HbF raised

·         HbA absent

Management

·         repeated transfusion → iron overload

·         s/c infusion of desferrioxamine

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Blood films: pathological cell forms

Pathological red cell forms

 

 

Abnormality

Associated condition(s)

Appearance

Target cells

Sickle-cell/thalassaemia

Iron-deficiency anaemia

Hyposplenism

Liver disease

 

 

 

 

'Tear-drop' poikilocytes

Myelofibrosis

 

 

 

 

Spherocytes

Hereditary spherocytosis

Autoimmune hemolytic anaemia

 

 

 

 

Basophilic stippling

Lead poisoning

Thalassaemia

Sideroblastic anaemia

Myelodysplasia

 

 

 

 

Howell-Jolly bodies

Hyposplenism

 

 

 

 

Heinz bodies

G6PD deficiency

Alpha-thalassaemia

 

 

 

 

Schistocytes ('helmet cells')

Intravascular haemolysis

Mechanical heart valve

Disseminated intravascular coagulation

 

 

 

 

'Pencil' poikilocytes

Iron deficency anaemia

 

 

 

 

Burr cells (echinocytes)

Uraemia

Pyruvate kinase deficiency

 

 

 

 

Acanthocytes

Abetalipoproteinemia

 

 

 

 

Other blood film abnormalities:

·         hypersegmented neutrophils: megaloblastic anaemia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Graft versus host disease

Graft versus host disease (GVHD) is a multi-system complication of allogeneic bone marrow transplantation. Less frequently, it may also occur following solid organ transplantation or transfusion in immunocompromised patients. The disease occurs when T cells in the donor tissue (the graft) mount an immune response toward recipient (host) cells. It is not to be confused with transplant rejection (in which recipient immune cells activate an immune response toward the donor tissue). Prognosis is generally poor.

 

Three conditions required for diagnosis of GVHD, known as the Billingham criteria 1:

·         The transplanted tissue contains immunologically functioning cells

·         The recipient and donor are immunologically different

·         The recipient is immunocompromised

Estimates of incidence vary from 9-50% post allogeneic bone marrow transplant despite prophylaxis with calcineurin inhibitors. The following principal risk factors have been identified 2:

·         Poorly matched donor and recipient (particularly HLA)

·         Type of conditioning used prior to transplantation

·         Gender disparity between donor and recipient

·         Graft source (bone marrow or peripheral blood source associated with higher risk than umbilical cord blood)

Acute and chronic GVHD are considered separate syndromes:

 

Acute GVHD

·         Is classically defined as onset is classically within 100 days of transplantation*

·         Usually affects the skin (>80%), liver (50%), and gastrointestinal tract (50%)

·         Multi-organ involvement carries a worse prognosis**

Chronic GVHD

·         May occur following acute disease, or can arise de novo

·         Classically occurs after 100 days following transplantation

·         Has a more varied clinical picture: often lung and eye involvement in addition to skin and GI, although any organ system may be involved

Signs and symptoms - note that diagnosis is largely clinical and based on the exclusion of other pathology:

 

Acute GVHD

·         Painful maculopapular rash (often neck, palms and soles), which may progress to erythroderma or a toxic epidermal necrolysis-like syndrome

·         Jaundice

·         Watery or bloody diarrhoea

·         Persistent nausea and vomiting

·         Can also present as a culture-negative fever

Chronic GVHD

·         Skin: Many manifestations including poikiloderma, scleroderma, vitiligo, lichen planus

·         Eye: Often keratoconjunctivitis sicca, also corneal ulcers, scleritis

·         GI: Dysphagia, odynophagia, oral ulceration, ileus. Oral lichenous changes are a characteristic early sign (2)

·         Lung: my present as obstructive or restrictive pattern lung disease

Investigations (largely dependent on which organs are involved):

·         LFTs may demonstrate cholestatic jaundice. Hepatitis screen/ultrasound may be useful to exclude other causes

·         Abdominal imaging may reveal air-fluid levels and small bowel thickening ('ribbon sign')

·         Lung function testing

·         Biopsy of affected tissue may aid in diagnosis if there is uncertainty

Management consists of immunosuppression and supportive measures. Intravenous steroids are the mainstay of immunosuppressive treatment in severe cases of acute GVHD. Extended courses of steroid therapy are often needed in chronic GVHD and dose tapering is vital. Second-line therapies include anti-TNF, mTOR inhibitors and extracorporeal photopheresis. Excessive immunosuppression may predispose patients to infection, and also limit the beneficial graft-versus-tumour effect of the transplant.

 

Topical steroid therapy may be sufficient in mild disease with limited cutaneous involvement.

 

*Please note that there is some contention as to whether timeframe or clinical features should be used to define acute vs chronic GVHD. Persistent, recurrent or late-onset acute GVHD may occur, while chronic GVHD may manifest before the 100 day cutoff. As such, diagnosis is often based on clinical manifestation as well as timeframe.

 

**A prognostic staging system for acute GVHD exists based on serum bilirubin, abdominal imaging findings and level of cutaneous involvement, but is beyond the scope of these notes.

 

References

1. Ferrara, J., Levine, J., Reddy, P. & Holler, E. Graft-versus-host disease. The Lancet 373, 1550-1561 (2009).

2. Lazaryan, A. et al. Risk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors. Biology of Blood and Marrow Transplantation 22, 134-140 (2016).

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Granulocyte-colony stimulating factors

Recombinant human granulocyte-colony stimulating factors are used to increase neutrophil counts in patients who are neutropenic secondary to chemotherapy or other factors.

 

Examples include:

·         filgrastim

·         perfilgrastim

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Haematological malignancies: genetics

Below is a brief summary of the common translocations associated with haematological malignancies

 

t(9;22) - Philadelphia chromosome

·         present in > 95% of patients with CML

·         this results in part of the Abelson proto-oncogene being moved to the BCR gene on chromosome 22

·         the resulting BCR-ABL gene codes for a fusion protein which has tyrosine kinase activity in excess of normal

·         poor prognostic indicator in ALL

t(15;17)

·         seen in acute promyelocytic leukaemia (M3)

·         fusion of PML and RAR-alpha genes

t(8;14)

·         seen in Burkitt's lymphoma

·         MYC oncogene is translocated to an immunoglobulin gene

t(11;14)

·         Mantle cell lymphoma

·         deregulation of the cyclin D1 (BCL-1) gene

t(14;18)

·         follicular lymphoma

·         increased BCL-2 transcription

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Haematological malignancies: infections

Viruses

·         EBV: Hodgkin's and Burkitt's lymphoma, nasopharyngeal carcinoma

·         HTLV-1: Adult T-cell leukaemia/lymphoma

·         HIV-1: High-grade B-cell lymphoma

Bacteria

·         Helicobacter pylori: gastric lymphoma (MALT)

Protozoa

·         malaria: Burkitt's lymphoma

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Haemolytic anaemias: by cause

Hereditary haemolytic anaemias can be subdivided into membrane, metabolism or haemoglobin defects

 

Hereditary causes

·         membrane: hereditary spherocytosis/elliptocytosis

·         metabolism: G6PD deficiency

·         haemoglobinopathies: sickle cell, thalassaemia

 

Acquired haemolytic anaemias can be subdivided into immune and non-immune causes

 

Acquired: immune causes

·         autoimmune: warm/cold antibody type

·         alloimmune: transfusion reaction, haemolytic disease newborn

·         drug: methyldopa, penicillin

Acquired: non-immune causes

·         microangiopathic haemolytic anaemia (MAHA): TTP/HUS, DIC, malignancy, pre-eclampsia

·         prosthetic cardiac valves

·         paroxysmal nocturnal haemoglobinuria

·         infections: malaria

·         drug: dapsone

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Hyposplenism

Causes

·         splenectomy

·         sickle-cell

·         coeliac disease, dermatitis herpetiformis

·         Graves' disease

·         systemic lupus erythematosus

·         amyloid

Features

·         Howell-Jolly bodies

·         siderocytes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Iron deficiency anaemia vs. AOCD

 

Iron deficiency anaemia

Anaemia of chronic disease

Serum iron

Low < 8

Low < 15

TIBC

High

Low

Transferrin saturation

Low

Low

Ferritin

Low

High

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Laboratory findings in haematological disease

The table below shows some very selective laboratory findings that are commonly tested in the exam:

 

 

Test

Interpretation

Haptoglobin

 

(Remember haptoglobin binds to free haemoglobin)

Decrease

·         intravascular haemolysis

MCHC

Increased

·         hereditary spherocytosis

·         autoimmune haemolytic anemia*

Decreased

·         microcytic anaemia (e.g. iron deficiency)

*associated with spherocytosis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Lead poisoning

Along with acute intermittent porphyria, lead poisoning should be considered in questions giving a combination of abdominal pain and neurological signs. Lead poisoning results in defective ferrochelatase and ALA dehydratase function.

 

Features

·         abdominal pain

·         peripheral neuropathy (mainly motor)

·         fatigue

·         constipation

·         blue lines on gum margin (only 20% of adult patients, very rare in children)

Investigations

·         the blood lead level is usually used for diagnosis. Levels greater than 10 mcg/dl are considered significant

·         full blood count: microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology

·         raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria

·         urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased)

·         in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

Management - various chelating agents are currently used:

·         dimercaptosuccinic acid (DMSA)

·         D-penicillamine

·         EDTA

·         dimercaprol

 

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Lymphadenopathy

There are many causes of generalised lymphadenopathy

 

Infective

·         infectious mononucleosis

·         HIV, including seroconversion illness

·         eczema with secondary infection

·         rubella

·         toxoplasmosis

·         CMV

·         tuberculosis

·         roseola infantum

Neoplastic

·         leukaemia

·         lymphoma

Others

·         autoimmune conditions: SLE, rheumatoid arthritis

·         graft versus host disease

·         sarcoidosis

·         drugs: phenytoin and to a lesser extent allopurinol, isoniazid

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Microcytic anaemia

Causes

·         iron-deficiency anaemia

·         thalassaemia*

·         congenital sideroblastic anaemia

·         anaemia of chronic disease (more commonly a normocytic, normochromic picture)

·         lead poisoning

A question sometimes seen in exams gives a history of a normal haemoglobin level associated with a microcytosis. In patients not at risk of thalassaemia, this should raise the possibility of polycythaemia rubra vera which may cause an iron-deficiency secondary to bleeding.

 

New onset microcytic anaemia in elderly patients should be urgently investigated to exclude underlying malignancy.

 

*in beta-thalassaemia minor the microcytosis is often disproportionate to the anaemia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Myelodysplastic syndrome

Overview

·         also known as myelodysplasia

·         acquired neoplastic disorder of hematopoietic stem cells

·         pre-leukaemia, may progress to AML

Features

·         more common with age

·         presents with bone marrow failure (anaemia, neutropaenia, thrombocytopenia)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:06

Myeloma

 

 

Myeloma classically causes hypercalcaemia, pancytopenia and an AKI.

 

Multiple myeloma (MM) is a haematological malignancy characterised by plasma cell proliferation. It arises due to genetic mutations which occur as B-lymphocytes differentiate into mature plasma cells. MM is the second most common haematological malignancy.

 

Presentation:

 

The median age at presentation is 70-years-old.

 

Use the mnemonicCRABBI:

·         Calcium

o    Hypercalcaemia occurs as a result of increased osteoclast activity within the bones

o    This leads to constipation, nausea, anorexia and confusion

·         Renal

o    Monoclonal production of immunoglobulins results in light chain deposition within the renal tubules

o    This causes renal damage which presents as dehydration and increasing thirst

o    Other causes of renal impairment in myeloma include amyloidosis, nephrocalcinosis, nephrolithiasis

·         Anaemia

o    Bone marrow crowding suppresses erythropoiesis leading to anaemia

o    This causes fatigue and pallor

·         Bleeding

o    bone marrow crowding also results in thrombocytopenia which puts patients at increased risk of bleeding and bruising

·         Bones

o    Bone marrow infiltration by plasma cells and cytokine-mediated osteoclast overactivity creates lytic bone lesions

o    This may present as pain (especially in the back) and increases the risk of fragility fractures

·         Infection

o    a reduction in the production of normal immunoglobulins results in increased susceptibility to infection

 

Investigations

·         Bloods will show anaemia (FBC) and thrombocytopenia (FBC); raised urea and creatinine (U&E) and raised calcium

·         Peripheral blood film: rouleaux formation

·         Serum or urine protein electrophoresis: raised concentrations of monoclonal IgA/IgG proteins will be present in the serum. In the urine, they are known as Bence Jones proteins

·         Bone marrow aspiration and trephine biopsy: confirms the diagnosis if the number of plasma cells is significantly raised

·         Whole-body MRI (or CT if MRI is not suitable) is used to survey the skeleton for bone lesions

A common X-ray finding is a 'rain-drop' skull. This is numerous randomly placed dark spots seen on X-ray which occur due to bone lysis.

 

Diagnosis

 

It is important to accurately diagnose multiple myeloma, as unlike its pre-malignant counterparts (Monoclonal gammopathy of undetermined significance and Smoldering myeloma), treatment must begin immediately due to the risk of complications occurring as a result on end-organ damage.

Symptomatic multiple myeloma is defined at diagnosis by the presence of the following three factors:

·         Monoclonal plasma cells in the bone marrow >10%

·         Monoclonal protein within the serum or the urine (as determined by electrophoresis)

·         Evidence of end-organ damage e.g. hypercalcaemia, elevated creatinine, anaemia or lytic bone lesions/fractures

Management

 

Myeloma is a chronic relapsing and remitting malignancy which is currently deemed incurable. Management aims to control symptoms, reduce complications and prolong survival.

 

For those who have just been diagnosed with symptomatic multiple myeloma, treatment begins with induction therapy:

·         For patients who are suitable for autologous stem cell transplantation* induction therapy consists of Bortezomib + Dexamethasone

·         For patients who are unsuitable for autologous stem cell transplantation*, induction therapy consists of Thalidomide + an Alkylating agent + Dexamethasone

Typically it is younger, healthier patients who are suitable for stem cell transplantation and rigorous chemotherapy regimes.

 

After completion of treatment, patients are monitored every 3 months with blood tests and electrophoresis. Many will achieve remission and will not need further therapy for some time.

 

Many patients do relapse after initial therapy. If this occurs the 1st line recommended treatment is Bortezomib monotherapy. Some patients may also be suitable for a repeat autologous stem cell transplant*, but this is decided on a case-by-case basis.

 

Complications

 

A large part of multiple myeloma treatment involves managing complications:

·         Pain: treat with analgesia (using the WHO analgesic ladder)

·         Pathological fracture: Zoledronic acid is given to prevent and manage osteoporosis and fragility fractures as these are a large cause of morbidity and mortality, particularly in the elderly.

·         Infection: patients receive annual influenza vaccinations. They may also receive Immunoglobulin replacement therapy.

·         VTE prophylaxis

·         Fatigue: treat all possible underlying causes. If symptoms persist consider an erythropoietin analogue.

*An autologous stem cell transplant is used after high dose chemotherapy administration which targets stem cells. It involves the removal of a patient's own stem cells prior to chemotherapy, which are then replaced after chemotherapy. This is different from Allogenic stem cell transplantation where stem cells are sourced from HLA matching donors. Allogenic stem cell transplantation is currently only used as part of clinical trials when treating multiple myeloma.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:06

Neutropaenia

Neutropaenia refers to a low neutrophil counts, < 1.5 * 109. A normal neutophil count is 2.0 - 7.5 * 109.

 

It is important to recognise as it predisposes to severe infection.

 

Neutropaenia may be further subdivided as follows:

 

 

Severity

Neutrophil count

Mild

1.0 - 1.5 * 109

Moderate

0.5 - 1.0 * 109

Severe

< 0.5 * 109

Causes

·         viral

o    HIV

o    Epstein-Barr virus

o    hepatitis

·         drugs

o    cytotoxics

o    carbimazole

o    clozapine

·         benign ethnic neutropaenia

o    common in people of black African and Afro-Caribbean ethnicity

o    requires no treatment

·         haematological malignancy

o    myelodysplastic malignancies

o    aplastic anemia

·         rheumatological conditions

·         systemic lupus erythematosus: mechanisms include circulating antineutrophil antibodies

·         rheumatoid arthritis: e.g. hypersplenism as in Felty's syndrome

·         severe sepsis

·         haemodialysis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

 

 

 

24 December 2020

14:07

Non-Hodgkin's lymphoma

Lymphoma is the malignant proliferation of lymphocytes which accumulate in lymph nodes or other organs. Lymphoma may be classified as either Hodgkin's lymphoma (a specific type of lymphoma characterized by the presence of Reed-Sternberg cells) or non-Hodgkin's lymphoma (every other type of lymphoma that is not Hodgkin's lymphoma). Non-Hodgkin's lymphoma is the 6th most common cause of cancer in the UK. Non-Hodgkin's lymphoma may affect either B or T-cells and can be further classified as high grade or low grade.

 

Epidemiology

·         Non-Hodgkin's lymphoma is much more common than Hodgkin's lymphoma

·         While different subtypes can affect different ages, it typically affects the elderly with one-third of cases occurring in those over 75 years of age

·         The incidence rate is 28 for men and 20 for females per 100,000 of the population

Risk factors

·         Elderly

·         Caucasians

·         History of viral infection (specifically Epstein-Barr virus)

·         Family history

·         Certain chemical agents (pesticides, solvents)

·         History of chemotherapy or radiotherapy

·         Immunodeficiency (transplant, HIV, diabetes mellitus)

·         Autoimmune disease (SLE, Sjogren's, coeliac disease)

Symptoms

·         Painless lymphadenopathy (non-tender, rubbery, asymmetrical)

·         Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)

·         Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)

While differentiating Hodgkin's lymphoma from non-Hodgkin's lymphoma is done by biopsy certain elements of the clinical presentation can help point towards one rather than the other.

·         Lymphadenopathy in Hodgkin's lymphoma can experience alcohol-induced pain in the node

·         'B' symptoms typically occur earlier in Hodgkin's lymphoma and later in non-Hodgkin's lymphoma

·         Extra-nodal disease is much more common in non-Hodgkin's lymphoma than in Hodgkin's lymphoma

Signs

·         Signs of weight loss

·         Lymphadenopathy (typically in the cervical, axillary or inguinal region)

·         Palpable abdominal mass - hepatomegaly, splenomegaly, lymph nodes

·         Testicular mass

·         Fever

Investigations

·         Excisional node biopsy is the diagnostic investigation of choice (certain subtypes will have a classical appearance on biopsy such as Burkitt's lymphoma having a 'starry sky' appearance)

·         CT chest, abdomen and pelvis (to assess staging)

·         HIV test (often performed as this is a risk factor for non-Hodgkin's lymphoma)

·         FBC and blood film (patient may have a normocytic anaemia and can help rule out other haematological malignancy such as leukaemia)

·         ESR (useful as a prognostic indicator)

·         LDH (a marker of cell turnover, useful as a prognostic indicator)

·         Other investigations can be ordered as the clinical picture indicates (LFT's if liver metastasis suspected, PET CT or bone marrow biopsy to look for bone involvement, LP if neurological symptoms)

Staging

- The most common staging system used for non-Hodgkin's lymphoma is the Ann Arbor system.

·         → Stage 1 - One node affected

·         → Stage 2 - More than one node affected on the same side of the diaphragm

·         → Stage 3 - One node affected on either side of the diaphragm

·         → Stage 4 - Extra-nodal involvement e.g. Spleen, bone marrow or CNS

·         The stage is combined with the letter A or B to indicate the presence of 'B' symptoms. With the letter A indicating no B symptoms present and B indicating any of the beta symptoms present. For example, a patient with a single node affected and no 'B' symptoms would be stage 1A.

Management

·         Management is dependent on the specific sub-type of non-Hodgkin's lymphoma and will typically take the form of watchful waiting, chemotherapy or radiotherapy.

·         All patients will receive flu/pneumococcal vaccines

·         Patients with neutropenia may require antibiotic prophylaxis

Complications

·         Bone marrow infiltration causing anaemia, neutropenia or thrombocytopenia

·         Superior vena cava obstruction

·         Metastasis

·         Spinal cord compression

·         Complications related to treatment e.g. Side effects of chemotherapy

Prognosis

·         Low-grade non-Hodgkin's lymphoma has a better prognosis

·         High-grade non-Hodgkin's lymphoma has a worse prognosis but a higher cure rate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Normocytic anaemia

Causes of normocytic anaemia include

·         anaemia of chronic disease

·         chronic kidney disease

·         aplastic anaemia

·         haemolytic anaemia

·         acute blood loss

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Pregnancy: DVT/PE

Overview

·         pregnancy is a hypercoagulable state

·         majority occur in last trimester

Pathophysiology

·         increase in factors VII, VIII, X and fibrinogen

·         decrease in protein S

·         uterus presses on IVC causing venous stasis in legs

Management

·         warfarin contraindicated

·         S/C low-molecular weight heparin preferred to IV heparin (less bleeding and thrombocytopenia)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Primary immunodeficiency

Primary immunodeficiency disorders may be classified according to which component of the immune system they affect.

 

Neutrophil disorders

 

 

Disorder

Underlying defect

Notes

Chronic granulomatous disease

Lack of NADPH oxidase reduces ability of phagocytes to produce reactive oxygen species

Causes recurrent pneumonias and abscesses, particularly due to catalase-positive bacteria (e.g. Staphylococcus aureus and fungi (e.g. Aspergillus)

Negative nitroblue-tetrazolium test

Abnormal dihydrorhodamine flow cytometry test

 

Chediak-Higashi syndrome

Microtubule polymerization defect which leads to a decrease in phagocytosis

Affected children have 'partial albinism' and peripheral neuropathy. Recurrent bacterial infections are seen

Giant granules in neutrophils and platelets

Leukocyte adhesion deficiency

Defect of LFA-1 integrin (CD18) protein on neutrophils

Recurrent bacterial infections.

Delay in umbilical cord sloughing may be seen

Absence of neutrophils/pus at sites of infection

B-cell disorders

 

 

Disorder

Underlying defect

Notes

Common variable immunodeficiency

Many varying causes

Hypogammaglobulinemia is seen. May predispose to autoimmune disorders and lymphona

Bruton's (x-linked) congenital agammaglobulinaemia

Defect in Bruton's tyrosine kinase (BTK) gene that leads to a severe block in B cell development

X-linked recessive. Recurrent bacterial infections are seen

Absence of B-cells with reduced immunoglogulins of all classes

Selective immunoglobulin A deficiency

Maturation defect in B cells

Most common primary antibody deficiency. Recurrent sinus and respiratory infections

 

Associated with coeliac disease and may cause false negative coeliac antibody screen

 

Severe reactions to blood transfusions may occur (anti-IgA antibodies → analphylaxis)

T-cell disorders

 

 

Disorder

Underlying defect

Notes

DiGeorge syndrome

22q11.2 deletion, failure to develop 3rd and 4th pharyngeal pouches

Common features include congenital heart disease (e.g. tetralogy of Fallot), learning difficulties, hypocalcaemia, recurrent viral/fungal diseases, cleft palate

Combined B- and T-cell disorders

 

 

Disorder

Underlying defect

Notes

Severe combined immunodeficiency

Many varying causes. Most common (X-linked) due to defect in the common gamma chain, a protein used in the receptors for IL-2 and other interleukins. Other causes include adenosine deaminase deficiency

Recurrent infections due to viruses, bacteria and fungi.

Reduced T-cell receptor excision circles

Stem cell transplantation may be successful

Ataxic telangiectasia

Defect in DNA repair enzymes

Autosomal recessive. Features include cerebellar ataxia, telangiectasia (spider angiomas), recurrent chest infections and 10% risk of developing malignancy, lymphoma or leukaemia

Wiskott-Aldrich syndrome

Defect in WASP gene

X-linked recessive. Features include recurrent bacterial infections, eczema, thrombocytopaenia.

Low IgM levels

Increased risk of autoimmune disorders and malignancy

Hyper IgM Syndromes

Mutations in the CD40 gene

Infection/Pneumocystis pneumonia, hepatitis, diarrhoea

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Sickle-cell anaemia: management

Crisis management

·         analgesia e.g. opiates

·         rehydrate

·         oxygen

·         consider antibiotics if evidence of infection

·         blood transfusion

·         exchange transfusion: e.g. if neurological complications

Longer-term management

·         Hydroxyurea (Hydroxycarbamide)

o    increases the HbF levels and is used in the prophylactic management of sickle cell anaemia to prevent painful episodes

·         NICE CKS suggest that sickle cell patients should receive the pneumococcal polysaccharide vaccine every 5 years

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Sickle-cell crises: management

General management

·         analgesia e.g. opiates

·         rehydrate

·         oxygen

·         consider antibiotics if evidence of infection

·         blood transfusion

·         exchange transfusion: e.g. if neurological complications

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Thrombocytopenia

Causes of severe thrombocytopenia

·         ITP

·         DIC

·         TTP

·         haematological malignancy

Causes of moderate thrombocytopenia

·         heparin induced thrombocytopenia (HIT)

·         drug-induced (e.g. quinine, diuretics, sulphonamides, aspirin, thiazides)

·         alcohol

·         liver disease

·         hypersplenism

·         viral infection (EBV, HIV, hepatitis)

·         pregnancy

·         SLE/antiphospholipid syndrome

·         vitamin B12 deficiency

Pseudothrombocytopenia has been reported in association with the use of EDTA as an anticoagulant

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Thrombotic thrombocytopenic purpura

Pathogenesis of thrombotic thrombocytopenic purpura (TTP)

·         abnormally large and sticky multimers of von Willebrand's factor cause platelets to clump within vessels

·         in TTP there is a deficiency of ADAMTS13 (a metalloprotease enzyme) which breakdowns ('cleaves') large multimers of von Willebrand's factor

·         overlaps with haemolytic uraemic syndrome (HUS)

Features

·         rare, typically adult females

·         fever

·         fluctuating neuro signs (microemboli)

·         microangiopathic haemolytic anaemia

·         thrombocytopenia

·         renal failure

Causes

·         post-infection e.g. urinary, gastrointestinal

·         pregnancy

·         drugs: ciclosporin, oral contraceptive pill, penicillin, clopidogrel, aciclovir

·         tumours

·         SLE

·         HIV

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Thymoma

Thymomas are the most common tumour of the anterior mediastinum and is usually detected between the sixth and seventh decades of life.

 

Associated with

·         myasthenia gravis (30-40% of patients with thymoma)

·         red cell aplasia

·         dermatomyositis

·         also : SLE, SIADH

Causes of death

·         compression of airway

·         cardiac tamponade

 

 

© Image used on license from Radiopaedia

Chest x-ray and accompanying CT scan of a patient with a thymoma. In the chest x-ray there is a partially delineated mediastinal mass (anterior mediastinum) with regular borders, bulging the left upper mediastinal contour.

 

 

© Image used on license from Radiopaedia

CT slice at the bifurcation of the main bronchus showing an invasive thymoma presenting as an anterior mediastinal mass

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:07

Tranexamic acid

Tranexamic acid is a synthetic derivative of lysine. Its primary mode of action is as an antifibrinolytic that reversibly binds to lysine receptor sites on plasminogen or plasmin. This prevents plasmin from binding to and degrading fibrin.

 

Tranexamic acid is most commonly prescribed to help treat menorrhagia.

 

The role of tranexamic acid in trauma was investigated in the CRASH 2 trial and has been shown to be of benefit in bleeding trauma when administered in the first 3 hours. Tranexamic acid is given as an IV bolus followed by an infusion in cases of major haemorrhage.

 

There is also ongoing research looking at the role of tranexamic acid in traumatic brain injury.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:08

Waldenstrom's macroglobulinaemia

Waldenstrom's macroglobulinaemia is an uncommon condition seen in older men. It is a lymphoplasmacytoid malignancy characterised by the secretion of a monoclonal IgM paraprotein

 

Features

·         monoclonal IgM paraproteinaemia

·         systemic upset: weight loss, lethargy

·         hyperviscosity syndrome e.g. visual disturbance

o    the pentameric configuration of IgM increases serum viscosity

·         hepatosplenomegaly

·         lymphadenopathy

·         cryoglobulinaemia e.g. Raynaud's

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:49

Blood product transfusion complications

Blood product transfusion complications may be broadly classified into the following:

·         immunological: acute haemolytic, non-haemolytic febrile, allergic/anaphylaxis

·         infective

·         transfusion-related acute lung injury (TRALI)

·         transfusion-associated circulatory overload (TACO)

·         other: hyperkalaemia, iron overload, clotting

The table below summaries some of the key features:

 

 

Reaction

Features

Management

Non-haemolytic febrile reaction

 

Thought to be caused by antibodies reacting with white cell fragments in the blood product and cytokines that have leaked from the blood cell during storage

Fever, chills

 

Red cell transfusion (1-2%)

Platelet transfusion (10-30%)

Slow or stop the transfusion

 

Paracetamol

 

Monitor

Minor allergic reaction

 

Thought to be caused by foreign plasma proteins

Pruritus, urticaria

Temporarily stop the transfusion

 

Antihistamine

 

Monitor

Anaphylaxis

 

Can be caused by patients with IgA deficiency who have anti-IgA antibodies

Hypotension, dyspnoea, wheezing, angioedema.

Stop the transfusion

 

IM adrenaline

 

ABC support

·         oxygen

·         fluids

Acute haemolytic reaction

 

ABO-incompatible blood e.g. secondary to human error

Fever, abdominal pain, hypotension

Stop transfusion

 

Confirm diagnosis

·         check the identity of patient/name on blood product

·         send blood for direct Coombs test, repeat typing and cross-matching

Supportive care

·         fluid resuscitation

Transfusion-associated circulatory overload (TACO)

 

Excessive rate of transfusion, pre-existing heart failure

Pulmonary oedema, hypertension

Slow or stop transfusion

 

Consider intravenous loop diuretic (e.g. furosemide) and oxygen

Transfusion-related acute lung injury (TRALI)

 

Non-cardiogenic pulmonary oedema thought to be secondary to increased vascular permeability caused by host neutrophils that become activated by substances in donated blood

Hypoxia, pulmonary infiltrates on chest x-ray, fever, hypotension

Stop the transfusion

 

Oxygen and supportive care

Further information is provided below:

 

Acute haemolytic transfusion reaction

 

Acute haemolytic transfusion reaction results from a mismatch of blood group (ABO) which causes massive intravascular haemolysis. This is usually the result of red blood cell destruction by IgM-type antibodies.

 

Symptoms begin minutes after the transfusion is started and include a fever, abdominal and chest pain, agitation and hypotension.

 

Treatment should include immediate transfusion termination, generous fluid resuscitation with saline solution and informing the lab

 

Complications include disseminated intravascular coagulation, and renal failure

 

 

Non-haemolytic febrile reaction

 

Febrile reactions

·         due to white blood cell HLA antibodies

·         often the result of sensitization by previous pregnancies or transfusions

·         paracetamol may be given

 

Allergic/anaphylaxis reaction

 

Allergic reactions to blood transfusions are caused by hypersensitivity reactions to components within the transfusion. Symptoms typically arise within minutes of starting the transfusion and severity can range from urticaria to anaphylaxis with hypotension, dyspnoea, wheezing, and stridor, or angioedema.

 

Simple urticaria should be treated by discontinuing the transfusion and with an antihistamine. Once the symptoms resolve, the transfusion may be continued with no need for further workup.

 

More severe allergic reaction or anaphylaxis should be treated urgently. The transfusion should be permanently discontinued, intramuscular adrenaline should be administered and supportive care. Antihistamine, corticosteroids and bronchodilators should also be considered for these patients.

 

 

Transfusion-related acute lung injury (TRALI)

 

A rare but potentially fatal complication of blood transfusion. Characterised by the development of hypoxaemia / acute respiratory distress syndrome within 6 hours of transfusion. Features include:

·         hypoxia

·         pulmonary infiltrates on chest x-ray

·         fever

·         hypotension

 

Transfusion-associated circulatory overload (TACO)

 

A relatively common reaction due to fluid overload resulting in pulmonary oedema. As well as features of pulmonary oedema the patient may also by hypertensive, a key difference from patients with TRALI.

 

 

Infective

 

Transmission of vCJD

·         although the absolute risk is very small, vCJD may be transmitted via blood transfusion

·         a number of steps have been taken to minimise this risk, including:

o    from late 1999 onward, all donations have undergone removal of white cells (leucodepletion) in order to reduce any vCJD infectivity present

o    from 1999, plasma derivatives have been fractionated from imported plasma rather than being sourced from UK donors. Fresh Frozen Plasma (FFP) used for children and certain groups of adults needing frequent transfusions is also imported

o    from 2004 onward, recipients of blood components have been excluded from donating blood

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

Mnemonic for transfusion reactions:

 

Got a bad unit

 

G raft vs. Host disease

O verload

T hrombocytopaenia

 

A lloimmunization

 

B lood pressure unstable

A cute haemolytic reaction

D elayed haemolytic reaction

 

U rticaria

N eutrophilia

I nfection

T ransfusion associated lung injury

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

 

 

21 December 2020

21:50

Deep vein thrombosis: diagnosis and management

NICE updated their guidelines on the investigation and management of venous thromboembolism (VTE) in 2020. Some of the key changes include recommending the following:

·         the use of direct oral anticoagulants (DOACs) as first-line treatment for most people with VTE, including as interim anticoagulants before a definite diagnosis is made

·         the use of DOACs in patients with active cancer, as opposed to low-molecular weight heparin as was the previous recommendation

·         routine cancer screening is no longer recommended following a VTE diagnosis

If a patient is suspected of having a DVT a two-level DVT Wells score should be performed:

 

Two-level DVT Wells score

 

 

Clinical feature

Points

Active cancer (treatment ongoing, within 6 months, or palliative)

1

Paralysis, paresis or recent plaster immobilisation of the lower extremities

1

Recently bedridden for 3 days or more or major surgery within 12 weeks requiring general or regional anaesthesia

1

Localised tenderness along the distribution of the deep venous system

1

Entire leg swollen

1

Calf swelling at least 3 cm larger than asymptomatic side

1

Pitting oedema confined to the symptomatic leg

1

Collateral superficial veins (non-varicose)

1

Previously documented DVT

1

An alternative diagnosis is at least as likely as DVT

-2

Clinical probability simplified score

·         DVT likely: 2 points or more

·         DVT unlikely: 1 point or less

If a DVT is 'likely' (2 points or more)

·         a proximal leg vein ultrasound scan should be carried out within 4 hours

o    if the result is positive then a diagnosis of DVT is made and anticoagulant treatment should start

o    if the result is negative a D-dimer test should be arranged. A negative scan and negative D-dimer makes the diagnosis unlikely and alternative diagnoses should be considered

·         if a proximal leg vein ultrasound scan cannot be carried out within 4 hours a D-dimer test should be performed and interim therapeutic anticoagulation administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours)

o    interim therapeutic anticoagulation used to mean giving low-molecular weight heparin

o    NICE updated their guidance in 2020. They now recommend using an anticoagulant that can be continued if the result is positive.

o    this means normally a direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban

·         if the scan is negative but the D-dimer is positive:

o    stop interim therapeutic anticoagulation

o    offer a repeat proximal leg vein ultrasound scan 6 to 8 days later

If a DVT is 'unlikely' (1 point or less)

·         perform a D-dimer test

o    this should be done within 4 hours. If not, interim therapeutic anticoagulation should be given until the result is available

o    if the result is negative then DVT is unlikely and alternative diagnoses should be considered

o    if the result is positive then a proximal leg vein ultrasound scan should be carried out within 4 hours

o    if a proximal leg vein ultrasound scan cannot be carried out within 4 hours interim therapeutic anticoagulation should be administered whilst waiting for the proximal leg vein ultrasound scan (which should be performed within 24 hours)

D-dimer tests

·         NICE recommend either a point-of-care (finger prick) or laboratory-based test

·         age-adjusted cut-offs should be used for patients > 50 years old

 

 

Management

 

The cornerstone of VTE management is anticoagulant therapy. This was historically done with warfarin, often preceded by heparin until the INR was stable. However, the development of DOACs, and an evidence base supporting their efficacy, has changed modern management.

 

Choice of anticoagulant

·         the big change in the 2020 guidelines was the increased use of DOACs

·         apixaban or rivaroxaban (both DOACs) should be offered first-line following the diagnosis of a DVT

o    instead of using low-molecular weight heparin (LMWH) until the diagnosis is confirmed, NICE now advocate using a DOAC once a diagnosis is suspected, with this continued if the diagnosis is confirmed

o    if neither apixaban or rivaroxaban are suitable then either LMWH followed by dabigatran or edoxaban OR LMWH followed by a vitamin K antagonist (VKA, i.e. warfarin)

·         if the patient has active cancer

o    previously LMWH was recommended

o    the new guidelines now recommend using a DOAC, unless this is contraindicated

·         if renal impairment is severe (e.g. < 15/min) then LMWH, unfractionated heparin or LMWH followed by a VKA

·         if the patient has antiphospholipid syndrome (specifically 'triple positive' in the guidance) then LMWH followed by a VKA should be used

Length of anticoagulation

·         all patients should have anticoagulation for at least 3 months

·         continuing anticoagulation after this period is partly determined by whether the VTE was provoked or unprovoked

o    a provoked VTE is due to an obvious precipitating event e.g. immobilisation following major surgery. The implication is that this event was transient and the patient is no longer at increased risk

o    an unprovoked VTE occurs in the absence of an obvious precipitating event, i.e. there is a possibility that there are unknown factors (e.g. mild thrombophilia) making the patient more at risk from further clots

·         if the VTE was provoked the treatment is typically stopped after the initial 3 months (3 to 6 months for people with active cancer)

·         if the VTE was unprovoked then treatment is typically continued for up to 3 further months (i.e. 6 months in total)

o    NICE recommend that whether a patient has a total of 3-6 months anticoagulant is based upon balancing a person's risk of VTE recurrence and their risk of bleeding

o    the HAS-BLED score can be used to help assess the risk of bleeding

o    NICE state: 'Explain to people with unprovoked DVT or PE and a low bleeding risk that the benefits of continuing anticoagulation treatment are likely to outweigh the risks. '. The implication of this is that in the absence of a bleeding risk factors, patients are generally better off continuing anticoagulation for a total of 6 months

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

21 December 2020

21:40

Chronic lymphocytic leukaemia: complications

Complications

·         anaemia

·         hypogammaglobulinaemia leading to recurrent infections

·         warm autoimmune haemolytic anaemia in 10-15% of patients

·         transformation to high-grade lymphoma (Richter's transformation)

Richter's transformation

 

Ritcher's transformation occurs when leukaemia cells enter the lymph node and change into a high-grade, fast-growing non-Hodgkin's lymphoma. Patients often become unwell very suddenly.

 

Ritcher's transformation is indicated by one of the following symptoms:

·         lymph node swelling

·         fever without infection

·         weight loss

·         night sweats

·         nausea

·         abdominal pain

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From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

22 December 2020

20:42

Hodgkin's lymphoma: histological classification and prognosis

Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades

 

Histological classification

 

 

Type

Frequency

Prognosis

Notes

Nodular sclerosing

Most common (around 70%)

Good prognosis

More common in women. Associated with lacunar cells

Mixed cellularity

Around 20%

Good prognosis

Associated with a large number of Reed-Sternberg cells

Lymphocyte predominant

A*round 5%

Best prognosis

 

Lymphocyte depleted

Rare

Worst prognosis

 

'B' symptoms also imply a poor prognosis

·         weight loss > 10% in last 6 months

·         fever > 38ºC

·         night sweats

Other factors associated with a poor prognosis identified in a 1998 NEJM paper included:

·         age > 45 years

·         stage IV disease

·         haemoglobin < 10.5 g/dl

·         lymphocyte count < 600/µl or < 8%

·         male

·         albumin < 40 g/l

·         white blood count > 15,000/µl

*Reed-Sternberg cells with nuclei surrounded by a clear space

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

21 December 2020

21:49

Blood films: typical pictures

Hyposplenism e.g. post-splenectomy, coeliac disease (occurs in around 30% of coeliac patients)

·         target cells

·         Howell-Jolly bodies

·         Pappenheimer bodies

·         siderotic granules

·         acanthocytes

Iron-deficiency anaemia

·         target cells

·         'pencil' poikilocytes

·         if combined with B12/folate deficiency a 'dimorphic' film occurs with mixed microcytic and macrocytic cells

Myelofibrosis

·         'tear-drop' poikilocytes

Intravascular haemolysis

·         schistocytes

Megaloblastic anaemia

·         hypersegmented neutrophils

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:49

Blood products: FFP, cryoprecipitate and prothrombin complex

NICE published guidelines on the use of blood products in 2015.

 

Fresh frozen plasma (FFP)

·         most suited for 'clinically significant' but without 'major haemorrhage' in patients with a prothrombin time (PT) ratio or activated partial thromboplastin time (APTT) ratio > 1.5

·         typically 150-220 mL

·         can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding

·         In contrast to red cells, the universal donor of FFP is AB blood because it lacks any anti-A or anti-B antibodies

Cryoprecipitate

·         contains concentrated Factor VIII:C, von Willebrand factor, fibrinogen, Factor XIII and fibronectin, produced by further processing of Fresh Frozen Plasma (FFP). Clinically it is most commonly used to replace fibrinogen

·         much smaller volume than FFP, typically 15-20mL

·         most suited for patients for 'clinically significant' but without 'major haemorrhage' who have a fibrinogen concentration < 1.5 g/L

·         example use cases include disseminated intravascular coagulation, liver failure and hypofibrinogenaemia secondary to massive transfusion. It may also be used in an emergency situation for haemophiliacs (when specific factors not available) and in von Willebrand disease

·         can be used prophylactically in patients undergoing invasive surgery where there is a risk of significant bleeding where the fibrinogen concentration < 1.0 g/L

Prothrombin complex concentrate

·         used for the emergency reversal of anticoagulation in patients with either severe bleeding or a head injury with suspected intracerebral haemorrhage

·         can be used prophylactically in patients undergoing emergency surgery depending on the particular circumstance

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

20:14

Hodgkin's lymphoma: staging

Hodgkin's lymphoma is a malignant proliferation of lymphocytes characterised by the presence of the Reed-Sternberg cell. It has a bimodal age distributions being most common in the third and seventh decades

 

Ann-Arbor staging of Hodgkin's lymphoma

·         I: single lymph node

·         II: 2 or more lymph nodes/regions on same side of diaphragm

·         III: nodes on both sides of diaphragm

·         IV: spread beyond lymph nodes

Each stage may be subdivided into A or B

·         A = no systemic symptoms other than pruritus

·         B = weight loss > 10% in last 6 months, fever > 38c, night sweats (poor prognosis)

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

Lymphocyte-depleted Hodgkin lymphoma is the rarest form of Hodgkin's lymphoma as well as the most aggressive . It is typically seen in young adults aged 30-37 years of age. Risk factors include a family history and being immunocompromised. Treatment of Lymphocyte-depleted Hodgkin lymphoma is typically adjusted for prognostic factors and the cancer stage (Stage IV being associated with the worst prognosis).

 

Negative prognostic factors include:

·         The presence of B symptoms (night sweats, weight loss and fever)

·         Male gender

·         Being aged >45 years old at diagnosis

·         High WCC, low Hb, high ESR or low blood albumin

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

Acute promyelocytic leukemia

29 December 2020

15:14

The most common symptoms and their causes are:

·         Anaemia – breathlessness, fatigue

·         Low white cells – frequent, persistent infections

·         Low platelets – bruising and/or bleeding

·         DIC – bruising/bleeding which may be very severe

 

From <https://www.leukaemiacare.org.uk/support-and-information/information-about-blood-cancer/blood-cancer-information/leukaemia/acute-promyelocytic-leukaemia/>

 

 

 

t(15;17)

·         seen in acute promyelocytic leukaemia (M3)

·         fusion of PML and RAR-alpha genes

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

APL is diagnosed by tests which may include:

·         Blood tests

·         Bone marrow samples

Other tests may be done

Occasionally, it is not clear from the blood film whether the abnormal cells are promyelocytes. By examining the proteins found on the outside of the cell, called cell markers, it is possible to identify the cells with certainty.

Another test looks for an abnormality called PML-RARA. This is an abnormal “fusion gene” – PML and RARA are two genes which are normally found on different chromosomes. In APL the two chromosomes swap over part of their DNA, which joins the PML and RARA genes together. This test is important because the main drugs used to treat APL work directly on the PML-RARA gene; in the very rare cases of APL without PML-RARA, other treatments can be used.

These tests may be repeated from time to time during your treatment. This is to find out how the APL is responding to treatm

 

 

From <https://www.leukaemiacare.org.uk/support-and-information/information-about-blood-cancer/blood-cancer-information/leukaemia/acute-promyelocytic-leukaemia/>

 

Treatment of patients who are suspected of having APL should be treated immediately, even before the diagnosis is made, because they can quickly develop potentially life-threatening bleeding or blood clotting symptoms. A firm diagnosis of APL using genetic testing can be performed later, and treatment can be discontinued if APL is not confirmed.

Patients with APL are generally subdivided into the following two groups according to their white blood count as treatment recommendations can differ for each group:

 

·         Low- to intermediate-risk: patients with a white blood cell count of 10,000 cells per microlitre of blood or less.

·         High-risk: patients with a white blood cell count of more than 10,000 cells per microlitre of blood.

 

 

From <https://www.leukaemiacare.org.uk/support-and-information/information-about-blood-cancer/blood-cancer-information/leukaemia/acute-promyelocytic-leukaemia/>

 

 

Treatment of patients who are suspected of having APL should be treated immediately, even before the diagnosis is made, because they can quickly develop potentially life-threatening bleeding or blood clotting symptoms. A firm diagnosis of APL using genetic testing can be performed later, and treatment can be discontinued if APL is not confirmed.

Patients with APL are generally subdivided into the following two groups according to their white blood count as treatment recommendations can differ for each group:

 

·         Low- to intermediate-risk: patients with a white blood cell count of 10,000 cells per microlitre of blood or less.

·         High-risk: patients with a white blood cell count of more than 10,000 cells per microlitre of blood.

 

 

From <https://www.leukaemiacare.org.uk/support-and-information/information-about-blood-cancer/blood-cancer-information/leukaemia/acute-promyelocytic-leukaemia/>

 

 

First-line treatment

First-line treatment for APL includes all-trans retinoic acid (ATRA), which is an active by- product of vitamin A. ATRA blocks the effect of the PML-RARA gene that prevents the promyelocyte cells maturing into normal white blood cells (differentiation). 

ATRA is not a chemotherapeutic drug and is called a differentiating agent. It is given in combination with another drug in patients with APL to prevent any drug resistance.

ATRA can sometimes be given with chemotherapy drugs called anthracyclines. Anthracyclines, such as daunorubicin and idarubicin, interfere with the DNA and reproduction of white blood cells, including the leukaemia cells. ATRA is given as a capsule, while anthracyclines are given intravenously.

In 2018, NICE approved a drug called arsenic trioxide (ATO) for the first-line treatment of APL in previously untreated patients, with low- to intermediate-risk disease and patients whose APL has returned (relapsed) or did not respond to chemotherapy (refractory). ATO is also a differentiating agent and acts in a similar way to ATRA.

Because differentiating agents have less side effects to chemotherapy drugs, especially anthracyclines, the combination of ATRA and ATO alone is a preferred first-line therapy, particularly as studies found it to be at least as effective as the combination of ATRA and anthracyclines, if not more so, with a reduced risk of disease relapse.

Induction treatment

To achieve remission (induction therapy), the 2019 guidelines from the European Leukaemia Network (European LeukemiaNet) recommend the following regimens:

·         Low-to-intermediate risk patients: ATRA and ATO

·         High-risk patients: Both of the following regimens achieve similar results; however, ATO is not approved for high-risk patients by NICE as yet.

o    ATRA and ATO plus a cytoreductive chemotherapy such as cytarabine. Cytoreductive means that the chemotherapy reduces the number of cells.

o    ATRA plus anthracyclines. The most frequently used regimen being called AIDA.

The treatment for APL that has developed as a consequence of prior chemotherapy is normally similar to APL associated with the PML-RARA gene, although your doctor may choose to use a different drug in this situation.

In addition to induction treatment, patients with APL require supportive care in the form of blood product transfusions to maintain the platelet count and the blood clotting indicators as normal as possible and to prevent the risk of bleeding. Blood chemical levels (particularly potassium and magnesium which are important for electrical conduction in the heart) will be monitored closely. Sometimes it is necessary to also give potassium and/or magnesium supplements.

Consolidation treatment

To consolidate remission in patients who have not received chemotherapy-based treatment, four courses of ATO and seven courses of ATRA are recommended. This can usually be given as an outpatient.

For patients who received ATRA and chemotherapy regimens, two to three courses of anthracycline- based chemotherapy should be given for consolidation therapy. This is usually given as an inpatient.

Maintenance treatment

For low- to intermediate-risk patients, maintenance treatment after consolidation with ATO and ATRA is not recommended, but for high-risk patients on ATRA and chemotherapy who are showing clinical benefit, maintenance may be initiated with tablets for two years.

Second-line treatment

First-line treatment is generally successful in most patients with APL. However, for patients who haven’t gone into first remission or who have relapsed, second-line treatment options are available.

Relapse or being refractory to first-line treatment can occur in any patient with APL, regardless of whether they have been treated with ATRA with ATO or ATRA with chemotherapy. However, these events are uncommon in low- to intermediate-risk patients.

The second-line treatment you have for relapsed or refractory APL will depend mainly on which first- line treatment you were given. If you have had ATRA with ATO as first-line treatment, then you will receive ATRA with chemotherapy, and vice-versa (you will be given ATRA with ATO if you had ATRA with chemotherapy as first-line treatment).

In young, fit patients, an autologous stem cell transplant can be performed. With an autologous stem cell transplant, you are given intensive chemotherapy to destroy all the leukaemia cells. However, as the chemotherapy will also kill your own bone marrow cells, you are given a transplant of your own healthy stem cells which were collected before the intensive chemotherapy. However, in patients who were responding well to ATO and then relapsed, a transplant is not always necessary.

 

 

From <https://www.leukaemiacare.org.uk/support-and-information/information-about-blood-cancer/blood-cancer-information/leukaemia/acute-promyelocytic-leukaemia/>

 

 

 

 

 

 

24 December 2020

13:54

Primary hyperaldosteronism

Primary hyperaldosteronism was previously thought to be most commonly caused by an adrenal adenoma, termed Conn's syndrome. However, recent studies have shown that bilateral idiopathic adrenal hyperplasia is the cause in up to 70% of cases. Differentiating between the two is important as this determines treatment. Adrenal carcinoma is an extremely rare cause of primary hyperaldosteronism.

 

Features

·         hypertension

·         hypokalaemia

o    e.g. muscle weakness

o    this is a classical feature in exams but studies suggest this is seen in only 10-40% of patients

·         alkalosis

Investigations

·         the 2016 Endocrine Society recommend that a plasma aldosterone/renin ratio is the first-line investigation in suspected primary hyperaldosteronism

o    should show high aldosterone levels alongside low renin levels (negative feedback due to sodium retention from aldosterone)

·         following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess

·         Adrenal Venous Sampling (AVS) can be done to identify the gland secreting excess hormone in primary hyperaldosteronism

Management

·         adrenal adenoma: surgery

·         bilateral adrenocortical hyperplasia: aldosterone antagonist e.g. spironolactone

 

 

© Image used on license from Radiopaedia

CT abdomen showing a right-sided adrenal adenoma in a patient who presented with hypertension and hypokalaemia. The adenoma can be seen 'next to' or 'below' the liver.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

13:54

SGLT-2 inhibitors

SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

 

Examples include canagliflozin, dapagliflozin and empagliflozin.

 

Important adverse effects include

·         urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported

·         normoglycaemic ketoacidosis

·         increased risk of lower-limb amputation: feet should be closely monitored

Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:54

Graves' disease: features

Graves' disease is the most common cause of thyrotoxicosis. It is typically seen in women aged 30-50 years.

 

Features

·         typical features of thyrotoxicosis

·         specific signs limited to Grave's (see below)

Features seen in Graves' but not in other causes of thyrotoxicosis

·         eye signs (30% of patients)

o    exophthalmos

o    ophthalmoplegia

·         pretibial myxoedema

·         thyroid acropachy, a triad of:

o    digital clubbing

o    soft tissue swelling of the hands and feet

o    periosteal new bone formation

Autoantibodies

·         TSH receptor stimulating antibodies (90%)

·         anti-thyroid peroxidase antibodies (75%)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

Corneal involvement in Grave's disease indicates severe eye pathology

Important for meLess important

The severity of Grave's eye disease can be graded using the mnemonic NOSPECS

·         No signs / symptoms

·         Only signs (e.g: upper lid retraction)

·         Signs & symptoms (including soft-tissue involvement)

·         Proptosis

·         Extra-ocular muscle involvement

·         Corneal involvement

·         Sight loss due to optic nerve involvement

Therefore the correct answer is corneal involvement.

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

 

24 December 2020

13:55

Primary hyperparathyroidism

In exams, primary hyperparathyroidism is stereotypically seen in elderly females with an unquenchable thirst and an inappropriately normal or raised parathyroid hormone level. It is most commonly due to a solitary adenoma

 

Causes of primary hyperparathyroidism

·         80%: solitary adenoma

·         15%: hyperplasia

·         4%: multiple adenoma

·         1%: carcinoma

Features - 'bones, stones, abdominal groans and psychic moans'

·         polydipsia, polyuria

·         peptic ulceration/constipation/pancreatitis

·         bone pain/fracture

·         renal stones

·         depression

·         hypertension

Associations

·         hypertension

·         multiple endocrine neoplasia: MEN I and II

Investigations

·         raised calcium, low phosphate

·         PTH may be raised or (inappropriately, given the raised calcium) normal

·         technetium-MIBI subtraction scan

·         pepperpot skull is a characteristic X-ray finding of hyperparathyroidism

Treatment

·         the definitive management is total parathyroidectomy

·         conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage

·         calcimimetic agents such as cinacalcet are sometimes used in patients who are unsuitable for surgery

 

 

© Image used on license from Radiopaedia

Bilateral hand radiographs in a middle-aged woman demonstrating generalised osteopenia, erosion of the terminal phalangeal tufts (acro-osteolysis) and subperiosteal resorption of bone particularly the radial aspects of the 2nd and 3rd middle phalanges. These changes are consistent with a diagnosis of hyperparathyroidism.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:55

 

 

Addison's disease

Autoimmune destruction of the adrenal glands is the commonest cause of primary hypoadrenalism in the UK, accounting for 80% of cases. This is termed Addison's disease and results in reduced cortisol and aldosterone being produced.

 

Features

·         lethargy, weakness, anorexia, nausea & vomiting, weight loss, 'salt-craving'

·         hyperpigmentation (especially palmar creases)*, vitiligo, loss of pubic hair in women, hypotension, hypoglycaemia

·         hyponatraemia and hyperkalaemia may be seen

·         crisis: collapse, shock, pyrexia

Other causes of hypoadrenalism

 

Primary causes

·         tuberculosis

·         metastases (e.g. bronchial carcinoma)

·         meningococcal septicaemia (Waterhouse-Friderichsen syndrome)

·         HIV

·         antiphospholipid syndrome

Secondary causes

·         pituitary disorders (e.g. tumours, irradiation, infiltration)

Exogenous glucocorticoid therapy

 

*Primary Addison's is associated with hyperpigmentation whereas secondary adrenal insufficiency is not

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 hyperpigmentation could be caused by the stimulant effect of excess ACTH on the melanocytes to produce melanin

 

 

Investigation

ACTH stimulation test (Short synacthen (tetracosactide) test)

How it is done:

Baseline cortisol and ACTH levels are performed. Synthetic ACTH 0.25mg is given IM or IV. 30 and 60 minutes after the injection, blood samples are drawn for cortisol levels.

 

Cortisol usually increase >600 after 30 minutes

Management:

Glucocorticoid replacement with hydrocortisone and fludrocortisone to replace mineralocorticoid

Patient may present with adrenal crisis if undiagnosed with appreciable mortality. An acute adrenal crisis can manifest with vomiting, abdominal pain, and hypovolaemic shock

 

 

 

 

 

 

 

 

 

24 December 2020

13:55

Cushing's syndrome: investigations

Investigations are divided into confirming Cushing's syndrome and then localising the lesion. A hypokalaemic metabolic alkalosis may be seen, along with impaired glucose tolerance. Ectopic ACTH secretion (e.g. secondary to small cell lung cancer) is characteristically associated with very low potassium levels. An insulin stress test is used to differentiate between true Cushing's and pseudo-Cushing's

 

Tests to confirm Cushing's syndrome

 

The two most commonly used tests are:

·         overnight dexamethasone suppression test (most sensitive)

·         24 hr urinary free cortisol

Localisation tests

 

The first-line localisation is 9am and midnight plasma ACTH (and cortisol) levels. If ACTH is suppressed then a non-ACTH dependent cause is likely such as an adrenal adenoma

 

Both low- and high-dose dexamethasone suppression tests may be used to localise the pathology resulting in Cushing's syndrome. These tests may be interpreted as follows:

 

 

Cortisol following

low-dose dexamethasone

Cortisol following

high-dose dexamethasone

ACTH

Interpretation

↓

↓

↔

Normal

↔

↔

↓

Cushing's syndrome due to other causes (e.g. adrenal adenomas)

↔

↓

↑

Cushing's disease (i.e. pituitary adenoma → ACTH secretion)

↔

↔

↑

Ectopic ACTH syndrome likely

CRH stimulation

·         if pituitary source then cortisol rises

·         if ectopic/adrenal then no change in cortisol

Petrosal sinus sampling of ACTH may be needed to differentiate between pituitary and ectopic ACTH secretion

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

Suppression after high dose dexamethasone indicates pituitary source

 High ACTH excludes adrenal source

 

 

Needs pituitary imaging, preferably MRI Corticotrophin releasing hormone test can be used to confirm pituitary source in difficult cases if imaging inconclusive. Should see an exaggerated ACTH and cortisol response at 30 mins post injection. Inferior petrosal sinus sampling will help confirm pituitary source

 

If pituitary adenoma identified then transsphenoidal surgery ± radiotherapy first choice

 

 

 

 

24 December 2020

13:55

Diabetes mellitus: sick day rules

The following are key messages that should be given to all patients with diabetes if they become unwell:

·         Increase frequency of blood glucose monitoring to four hourly or more frequently

·         Encourage fluid intake aiming for at least 3 litres in 24hrs

·         If unable to take struggling to eat may need sugary drinks to maintain carbohydrate intake

·         It is useful to educate patients so that they have a box of 'sick day supplies' that they can access if they become unwell

·         Access to a mobile phone has been shown to reduce progression of ketosis to diabetic ketoacidosis

If a patient is taking oral hypoglycaemic medication, they should be advised to continue taking their medication even if they are not eating much. Remember that the stress response to illness increases cortisol levels pushing blood sugars high even without much oral intake. The possible exception is with metformin, which should be stopped if a patient is becoming dehydrated because of the potential impact upon renal function.

 

If a patient is on insulin, they must not stop it due to the risk of diabetic ketoacidosis. They should continue their normal insulin regime but ensure that they are checking their blood sugars frequently. Patients should be able to check their ketone levels and if these are raised and blood sugars are also raised they may need to give corrective doses of insulin. The corrective dose to be given varies by patient, but a rule of thumb would be total daily insulin dose divided by 6 (maximum 15 units). NHS Scotland have produced a useful flowsheet for patients to follow:

 

http://www.diabetesinscotland.org.uk/ketocard/ketosheet.pdf

 

Possible indications that a patient might require admission to hospital would include:

·         Suspicion of underlying illness requiring hospital treatment eg myocardial infarction

·         Inability to keep fluids down - admit if persisting more than a few hours

·         Persistent diarrhoea

·         Significant ketosis in an insulin dependent diabetic despite additional insulin

·         Blood glucose persistently >20mmol/l despite additional insulin

·         Patient unable to manage adjustments to usual diabetes management

·         Lack of support at home e.g. a patient who lives alone and is at risk of becoming unconscious

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:55

Hypercalcaemia: causes

Two conditions account for 90% of cases of hypercalcaemia:

·         1. Primary hyperparathyroidism: commonest cause in non-hospitalised patients

·         2. Malignancy: the commonest cause in hospitalised patients. This may be due to number of processes, including; bone metastases, myeloma, PTHrP from squamous cell lung cancer

Other causes include

·         sarcoidosis*

·         vitamin D intoxication

·         acromegaly

·         thyrotoxicosis

·         Milk-alkali syndrome

·         drugs: thiazides, calcium containing antacids

·         dehydration

·         Addison's disease

·         Paget's disease of the bone**

*other causes of granulomas may lead to hypercalcaemia e.g. Tuberculosis and histoplasmosis

 

**usually normal in this condition but hypercalcaemia may occur with prolonged immobilisation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Thyroid function tests

The interpretation of thyroid function tests is usually straightforward:

 

 

Diagnosis

TSH

Free T4

Notes

Thyrotoxicosis (e.g. Graves' disease)

Low

High

In T3 thyrotoxicosis the free T4 will be normal

Primary hypothyroidism (primary atrophic hypothyroidism)

High

Low

 

Secondary hypothyroidism

Low

Low

Replacement steroid therapy is required prior to thyroxine

Sick euthyroid syndrome*

Low**

Low

Common in hospital inpatients

T3 is particularly low in these patients

Subclinical hypothyroidism

High

Normal

 

Poor compliance with thyroxine

High

Normal

 

Steroid therapy

Low

Normal

 

 

 

 

Venn diagram showing how different causes of thyroid dysfunction may manifest. Note how many causes of hypothyroidism may have an initial thyrotoxic phase.

*now referred to as non-thyroidal illness

**TSH may be normal in some cases

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Diabetes mellitus: a very basic introduction

Diabetes mellitus is one of the most common conditions encountered in clinical practice and represents a significant burden on the health systems of the developed world. It is now estimated that 8% of the total NHS budget is now spent on managing patients with diabetes mellitus.

 

What is diabetes mellitus?

 

Diabetes mellitus may be defined as a chronic condition characterised by abnormally raised levels of blood glucose.

 

 

Why is the management of diabetes mellitus so important?

 

Before the advent of insulin therapy untreated type 1 diabetes would usually result in death. Poorly treated type 1 diabetes mellitus can still result in significant morbidity and mortality (as a result of diabetic ketoacidosis). However, the main focus of diabetes management now is reducing the incidence of macrovascular (ischaemic heart disease, stroke) and microvascular (eye, nerve and kidney damage) complications.

 

 

 

Type

Notes

Type 1 diabetes mellitus (T1DM)

Autoimmune disorder where the insulin-producing beta cells of the islets of Langerhans in the pancreas are destroyed by the immune system

This results in an absolute deficiency of insulin resulting in raised glucose levels

Patients tend to develop T1DM in childhood/early adult life and typically present unwell, possibly in diabetic ketoacidosis

Type 2 diabetes mellitus (T2DM)

This is the most common cause of diabetes in the developed world. It is caused by a relative deficiency of insulin due to an excess of adipose tissue. In simple terms there isn't enough insulin to 'go around' all the excess fatty tissue, leading to blood glucose creeping up.

Prediabetes

This term is used for patients who don't yet meet the criteria for a formal diagnosis of T2DM to be made but are likely to develop the condition over the next few years. They, therefore, require closer monitoring and lifestyle interventions such as weight loss

Gestational diabetes

Some pregnant develop raised glucose levels during pregnancy. This is important to detect as untreated it may lead to adverse outcomes for the mother and baby

Maturity onset diabetes of the young (MODY)

A group of inherited genetic disorders affecting the production of insulin. Results in younger patients developing symptoms similar to those with T2DM, i.e. asymptomatic hyperglycaemia with progression to more severe complications such as diabetic ketoacidosis

Latent autoimmune diabetes of adults (LADA)

The majority of patients with autoimmune-related diabetes present younger in life. There are however a small group of patients who develop such problems later in life. These patients are often misdiagnosed as having T2DM

Other types

Any pathological process which damages the insulin-producing cells of the pancreas may cause diabetes to develop. Examples include chronic pancreatitis and haemochromatosis.

 

Drugs may also cause raised glucose levels. A common example is glucocorticoids which commonly result in raised blood glucose levels

 

Symptoms and signs

 

The presentation of diabetes mellitus depends very much on the type:

 

 

Type 1 DM

Type 2 DM

Weight loss

Polydipsia

Polyuria

 

May present with diabetic ketoacidosis

·         abdominal pain

·         vomiting

·         reduced consciousness level

Often picked up incidentally on routine blood tests

Polydipsia

Polyuria

Remember that the polyuria and polydipsia are due to water being 'dragged' out of the body due to the osmotic effects of excess blood glucose being excreted in the urine (glycosuria).

 

 

Investigations

 

There are 4 main ways to check blood glucose:

·         a finger-prick bedside glucose monitor

·         a one-off blood glucose. This may either be fasting or non-fasting

·         a HbA1c. This measures the amount of glycosylated haemoglobin and represents the average blood glucose over the past 2-3 months

·         a glucose tolerance test. In this test, a fasting blood glucose is taken after which a 75g glucose load is taken. After 2 hours a second blood glucose reading is then taken

The diagnostic criteria are determined by WHO.

 

If the patient is symptomatic:

·         fasting glucose greater than or equal to 7.0 mmol/l

·         random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)

If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

 

In 2011 WHO released supplementary guidance on the use of HbA1c for the diagnosis of diabetes:

·         a HbA1c of greater than or equal to 6.5% (48 mmol/mol) is diagnostic of diabetes mellitus

·         a HbAlc value of less than 6.5% does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)

·         in patients without symptoms, the test must be repeated to confirm the diagnosis

·         it should be remembered that misleading HbA1c results can be caused by increased red cell turnover

 

 

 

 

Diagram showing the spectrum of diabetes diagnosis

 

 

Management

 

The principle of managing diabetes mellitus are as follows:

·         drug therapy to normalise blood glucose levels

·         monitoring for and treating any complications related to diabetes

·         modifying any other risk factors for other conditions such as cardiovascular disease

Type 1 diabetes

·         patients always require insulin to control the blood sugar levels. This is because there is an absolute deficiency of insulin with no pancreatic tissue left to stimulate with drugs

·         different types of insulin are available according to their duration of action

Type 2 diabetes

·         the majority of patients with type 2 diabetes are controlled using oral medication

·         the first-line drug for the vast majority of patients is metformin

·         second-line drugs include sulfonylureas, gliptins and pioglitazone. Please see the table below for further information

·         if oral medication is not controlling the blood glucose to a sufficient degree then insulin is used

The table below shows some of the main drugs used in the management of diabetes mellitus:

 

 

Drug class

Mechanism of action

Route

Main side-effects

Notes

Insulin

Direct replacement for endogenous insulin

Subcutaneous

Hypoglycaemia

Weight gain

Lipodystrophy

Used in all patients with T1DM and some patients with poorly controlled T2DM

 

Can be classified according to source (analogue, human sequence and porcine) and duration of action (short, immediate, long-acting)

Metformin

Increases insulin sensitivity

Decreases hepatic gluconeogenesis

Oral

Gastrointestinal upset

Lactic acidosis*

First-line medication in the management of T2DM

 

Cannot be used in patients with an eGFR of < 30 ml/min

Sulfonylureas

Stimulate pancreatic beta cells to secrete insulin

Oral

Hypoglycaemia

Weight gain

Hyponatraemia

Examples include gliclazide and glimepiride

Thiazolidinediones

Activate PPAR-gamma receptor in adipocytes to promote adipogenesis and fatty acid uptake

Oral

Weight gain

Fluid retention

Only currently available thiazolidinedione is pioglitazone

DPP-4 inhibitors (-gliptins)

Increases incretin levels which inhibit glucagon secretion

Oral

Generally well tolerated but increased risk of pancreatitis

 

SGLT-2 inhibitors (-gliflozins)

Inhibits reabsorption of glucose in the kidney

Oral

Urinary tract infection

Typically result in weight loss

GLP-1 agonists (-tides)

Incretin mimetic which inhibits glucagon secretion

Subcutaneous

Nausea and vomiting

Pancreatitis

Typically result in weight loss

NICE provide guidelines on how drug therapy should be used in T2DM:

 

 

 

 

 

*common in exams, much less common in clinical practice

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Diabetic neuropathy

Diabetes typically leads to sensory loss and not motor loss in peripheral neuropathy. Painful diabetic neuropathy is a common problem in clinical practice.

 

NICE updated it's guidance on the management of neuropathic pain in 2013. Diabetic neuropathy is now managed in the same way as other forms of neuropathic pain:

·         first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin

·         if the first-line drug treatment does not work try one of the other 3 drugs

·         tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain

·         topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)

·         pain management clinics may be useful in patients with resistant problems

Gastrointestinal autonomic neuropathy

 

Gastroparesis

·         symptoms include erratic blood glucose control, bloating and vomiting

·         management options include metoclopramide, domperidone or erythromycin (prokinetic agents)

Chronic diarrhoea

·         often occurs at night

Gastro-oesophageal reflux disease

·         caused by decreased lower esophageal sphincter (LES) pressure

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Parathyroid glands and disorders of calcium metabolism

Hyperparathyroidism

 

Disease type

Hormone profile

Clinical features

Cause

Primary hyperparathyroidism

·         PTH (Elevated)

·         Ca2+ (Elevated)

·         Phosphate (Low)

·         Urine calcium : creatinine clearance ratio > 0.01

·         May be asymptomatic if mild

·         Recurrent abdominal pain (pancreatitis, renal colic)

·         Changes to emotional or cognitive state

Most cases due to solitary adenoma (80%), multifocal disease occurs in 10-15% and parathyroid carcinoma in 1% or less

Secondary hyperparathyroidism

·         PTH (Elevated)

·         Ca2+ (Low or normal)

·         Phosphate (Elevated)

·         Vitamin D levels (Low)

·         May have few symptoms

·         Eventually may develop bone disease, osteitis fibrosa cystica and soft tissue calcifications

Parathyroid gland hyperplasia occurs as a result of low calcium, almost always in a setting of chronic renal failure

Tertiary hyperparathyroidism

·         Ca2+ (Normal or high)

·         PTH (Elevated)

·         Phosphate levels (Decreased or Normal)

·         Vitamin D (Normal or decreased)

·         Alkaline phosphatase (Elevated)

·         Metastatic calcification

·         Bone pain and / or fracture

·         Nephrolithiasis

·         Pancreatitis

Occurs as a result of ongoing hyperplasia of the parathyroid glands after correction of underlying renal disorder, hyperplasia of all 4 glands is usually the cause

Differential diagnoses

It is important to consider the rare but relatively benign condition of benign familial hypocalciuric hypercalcaemia, caused by an autosomal dominant genetic disorder. Diagnosis is usually made by genetic testing and concordant biochemistry (urine calcium : creatinine clearance ratio <0.01-distinguished from primary hyperparathyroidism).

 

Treatment

 

Primary hyperparathyroidism

Indications for surgery

·         Elevated serum Calcium > 1mg/dL above normal

·         Hypercalciuria > 400mg/day

·         Creatinine clearance < 30% compared with normal

·         Episode of life threatening hypercalcaemia

·         Nephrolithiasis

·         Age < 50 years

·         Neuromuscular symptoms

·         Reduction in bone mineral density of the femoral neck, lumbar spine, or distal radius of more than 2.5 standard deviations below peak bone mass (T score lower than -2.5)

Secondary hyperparathyroidism

Usually managed with medical therapy.

 

Indications for surgery in secondary (renal) hyperparathyroidism:

·         Bone pain

·         Persistent pruritus

·         Soft tissue calcifications

Tertiary hyperparathyroidism

Allow 12 months to elapse following transplant as many cases will resolve

The presence of an autonomously functioning parathyroid gland may require surgery. If the culprit gland can be identified then it should be excised. Otherwise total parathyroidectomy and re-implantation of part of the gland may be required.

 

References

1. Pitt S et al. Secondary and Tertiary Hyperparathyroidism, State of the Art Surgical Management. Surg Clin North Am 2009 Oct;89(5):1227-39.

 

2. MacKenzie-Feder J et al. Primary Hyperparathyroidism: An Overview. Int J Endocrinol 2011; 2011: 251410.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Pregnancy: thyroid problems

In pregnancy, there is an increase in the levels of thyroxine-binding globulin (TBG). This causes an increase in the levels of total thyroxine but does not affect the free thyroxine level.

 

Thyrotoxicosis

 

Untreated thyrotoxicosis increases the risk of fetal loss, maternal heart failure and premature labour

 

Graves' disease is the most common cause of thyrotoxicosis in pregnancy. It is also recognised that activation of the TSH receptor by HCG may also occur - often termed transient gestational hyperthyroidism. HCG levels will fall in the second and third trimester

 

Management

·         propylthiouracil has traditionally been the antithyroid drug of choice

·         however, propylthiouracil is associated with an increased risk of severe hepatic injury

·         therefore NICE Clinical Knowledge Summaries advocate the following: 'Propylthiouracil is used in the first trimester of pregnancy in place of carbimazole, as the latter drug may be associated with an increased risk of congenital abnormalities. At the beginning of the second trimester, the woman should be switched back to carbimazole'

·         maternal free thyroxine levels should be kept in the upper third of the normal reference range to avoid fetal hypothyroidism

·         thyrotrophin receptor stimulating antibodies should be checked at 30-36 weeks gestation - helps to determine the risk of neonatal thyroid problems

·         block-and-replace regimes should not be used in pregnancy

·         radioiodine therapy is contraindicated

Hypothyroidism

 

Key points

·         thyroxine is safe during pregnancy

·         serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum

·         women require an increased dose of thyroxine during pregnancy

o    by up to 50% as early as 4-6 weeks of pregnancy

·         breastfeeding is safe whilst on thyroxine

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Addison's disease: management

Patients who have Addison's disease are usually given both glucocorticoid and mineralocorticoid replacement therapy.

 

This usually means that patients take a combination of:

·         hydrocortisone: usually given in 2 or 3 divided doses. Patients typically require 20-30 mg per day, with the majority given in the morning dose

·         fludrocortisone

Patient education is important:

·         emphasise the importance of not missing glucocorticoid doses

·         consider MedicAlert bracelets and steroid cards

·         discuss how to adjust the glucocorticoid dose during an intercurrent illness (see below)

Management of intercurrent illness

·         in simple terms the glucocorticoid dose should be doubled

·         the Addison's Clinical Advisory Panel have produced guidelines detailing particular scenarios - please see the CKS link for more details

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:58

Subacute (De Quervain's) thyroiditis

Subacute thyroiditis (also known as De Quervain's thyroiditis and subacute granulomatous thyroiditis) is thought to occur following viral infection and typically presents with hyperthyroidism.

 

There are typically 4 phases;

·         phase 1 (lasts 3-6 weeks): hyperthyroidism, painful goitre, raised ESR

·         phase 2 (1-3 weeks): euthyroid

·         phase 3 (weeks - months): hypothyroidism

·         phase 4: thyroid structure and function goes back to normal

Investigations

·         thyroid scintigraphy: globally reduced uptake of iodine-131

Management

·         usually self-limiting - most patients do not require treatment

·         thyroid pain may respond to aspirin or other NSAIDs

·         in more severe cases steroids are used, particularly if hypothyroidism develops

 

 

 

Venn diagram showing how different causes of thyroid dysfunction may manifest. Note how many causes of hypothyroidism may have an initial thyrotoxic phase.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Hyperosmolar hyperglycaemic state

Hyperosmolar hyperglycaemic state (HHS) is a medical emergency which is extremely difficult to manage and has a significant associated mortality. Hyperglycaemia results in osmotic diuresis, severe dehydration, and electrolyte deficiencies. HHS typically presents in the elderly with type 2 diabetes mellitus (T2DM), however the incidence in younger adults is increasing. It can be the initial presentation of T2DM.

 

It is extremely important to differentiate HHS from diabetic ketoacidosis (DKA) as the management is different, and treatment of HHS with insulin (e.g. as part of a DKA protocol) can result in adverse outcomes. The first 24 hours of treatment is very labour intensive so these patients are best managed in either a medical high dependency unit.

 

HHS has a higher mortality than DKA and may be complicated by vascular complications such as myocardial infarction, stroke or peripheral arterial thrombosis. Seizures, cerebral oedema and central pontine myelinolysis (CPM) are uncommon but documented complications of HHS. Whilst DKA presents within hours of onset, HHS comes on over many days, and consequently the dehydration and metabolic disturbances are more extreme.

 

Pathophysiology

·         Hyperglycaemia results in osmotic diuresis with associated loss of sodium and potassium

·         Severe volume depletion results in a significant raised serum osmolarity (typically > than 320 mosmol/kg), resulting in hyperviscosity of blood.

·         Despite these severe electrolyte losses and total body volume depletion, the typical patient with HHS, may not look as dehydrated as they are, because hypertonicity leads to preservation of intravascular volume.

Clinical features

·         General: fatigue, lethargy, nausea and vomiting

·         Neurological: altered level of consciousness, headaches, papilloedema, weakness

·         Haematological: hyperviscosity (may result in myocardial infarctions, stroke and peripheral arterial thrombosis)

·         Cardiovascular: dehydration, hypotension, tachycardia

Diagnosis

·         1. Hypovolaemia

·         2. Marked Hyperglycaemia (>30 mmol/L) without significant ketonaemia or acidosis

·         3. Significantly raised serum osmolarity (> 320 mosmol/kg)

·         Note: A precise definition of HHS does not exist, however the above 3 criteria are helpful in distinguishing between HHS and DKA. It is also important to remember that a mixed HHS / DKA picture can occur.

Management

 

The goals of management of HHS can be summarised as follows:

·         1. Normalise the osmolality (gradually)

·         2. Replace fluid and electrolyte losses

·         3. Normalise blood glucose (gradually)

Fluid replacement

·         Fluid losses in HHS are estimated to be between 100 - 220 ml/kg (e.g. 10-22 litres in an individual weighing 100 kg).

·         The rate of rehydration will be determined by assessing the combination of initial severity and any pre-existing co-morbidities (e.g. heart failure and chronic kidney disease). Caution is needed, particularly in the elderly, where too rapid rehydration may precipitate heart failure but insufficient may fail to reverse an acute kidney injury.

·         Intravenous (IV) 0.9% sodium chloride solution is the first line fluid for restoring total body fluid.

·         It is important to remember that isotonic 0.9% sodium chloride solution is already relatively hypotonic compared to the serum in someone with HHS. Therefore in most cases it is very effective at restoring normal serum osmolarity.

·         If the serum osmolarity is not declining despite positive balance with 0.9% sodium chloride, then the fluid should be switched to 0.45% sodium chloride solution which is more hypotonic relative to the HHS patients serum osmolarity

·         IV fluid replacement should aim to achieve a positive balance of 3-6 litres by 12 hours and the remaining replacement of estimated fluid losses within the next 12 hours.

·         Existing guidelines encourage vigorous initial fluid replacement and this alone (without insulin) will result in a gradual decline in plasma glucose and serum osmolarity. A rapid decline is potentially harmful (see below) therefore insulin should NOT be used in the first instance unless there is significant ketonaemia or acidosis

·         The aim of treatment should be to replace approximately 50% of estimated fluid loss within the first 12 hours and the remainder in the following 12 hours. However this is just a guide, and clinical judgement should be applied, particularly in patient with co-morbidities such as heart failure and chronic kidney disease (which may limit the speed of correction).

Monitoring response to treatment

·         The key parameter in managing HHS is the osmolality to which glucose and sodium are the main contributors. Rapid changes of serum osmolarity are dangerous and can result in cardiovascular collapse and central pontine myelinolysis (CPM).

·         Guidelines suggest that serum osmolarity, sodium and glucose levels should be plotted on a graph to permit appreciation of the rate of change. They should be plotted hourly initially.

·         Not all laboratories have readily available access to serum osmolarity measurements. If not available then a calculated osmolarity can be estimated with 2Na + glucose + urea

·         Fluid replacement alone (without insulin) will gradually lower blood glucose which will reduce osmolality

·         A reduction of serum osmolarity will cause a shift of water into the intracellular space. This inevitably results in a rise in serum sodium (a fall in blood glucose of 5.5 mmol/L will result in a 2.4 mmol/L rise in sodium). This is not necessarily an indication to give hypotonic solutions. If the inevitable rise in serum Na+ is much greater than 2.4 mmol/L for each 5.5 mmol/L fall in blood glucose this would suggest insufficient fluid replacement. Rising sodium is only a concern if the osmolality is NOT declining concurrently.

·         Rapid changes must be avoided. A safe rate of fall of plasma glucose of between 4 and 6 mmol/hr is recommended. The rate of fall of plasma sodium should not exceed 10 mmol/L in 24 hours.

·         A target blood glucose of between 10 and 15 mmol/L is a reasonable goal.

·         Complete normalisation of electrolytes and osmolality may take up to 72 hours.

Insulin

·         Fluid replacement alone with 0.9% sodium chloride solution will result in a gradual decline of blood glucose and osmolarity

·         Because most patients with HHS are insulin sensitive (e.g. it usually occurs in T2DM), administration of insulin can result in a rapid decline of serum glucose and thus osmolarity.

·         Insulin treatment prior to adequate fluid replacement may result in cardiovascular collapse as the water moves out of the intravascular space, with a resulting decline in intravascular volume.

·         A steep decline in serum osmolarity may also precipitate CPM.

·         Measurement of ketones is essential for determining if insulin is required.

·         If significant ketonaemia is present (3β-hydroxy butyrate is more than 1 mmol/L) this indicates relative hypoinsulinaemia and insulin should be started at time zero (e.g. mixed DKA / HHS picture). The recommended insulin dose is a fixed rate intravenous insulin infusion given at 0.05 units per kg per hour.

·         If significant ketonaemia is not present (3β-hydroxy butyrate is less than 1 mmol/L) then do NOT start insulin.

Potassium

·         Patients with HHS are potassium deplete but less acidotic than those with DKA so potassium shifts are less pronounced

·         Hyperkalaemia can be present with acute kidney injury

·         Patients on diuretics may be profoundly hypokalaemic

·         Potassium should be replaced or omitted as required

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Hypoglycaemia

Causes

·         insulinoma - increased ratio of proinsulin to insulin

·         self-administration of insulin/sulphonylureas

·         liver failure

·         Addison's disease

·         alcohol

Other possible causes in children

·         nesidioblastosis - beta cell hyperplasia

Physiological response to hypoglycaemia

·         hormonal response: the first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later

·         sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

Causes of hypoglycaemia can be remembered by the mnemonic EXPLAIN

·         Exogenous drugs (typically sulfonylureas or insulin)

·         Pituitary insufficiency

·         Liver failure

·         Addison's disease

·         Islet cell tumours (insulinomas)

·         Non-pancreatic neoplasms

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

EXPLAIN:

·         Exogenous drugs such alcohol, aspirin poisoning, pentamidine, quinine sulfate, ACE-inhibitor

·         Pituitary insufficiency

·         Liver failure

·         Addison's disease

·         Islet cell tumours eg insulinoma

·         Non-pancreatic neoplasms

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

24 December 2020

13:59

MODY

 

 

 

·         MODY is a rare form of diabetes often termed monogenic with an autosomal dominant inheritance.

The key features of MODY are:

·         Being diagnosed with diabetes under the age of 25.

·         Absence of ketoacidosis

·         Having a parent with diabetes, with diabetes in two or more generations.

·         Not necessarily requiring insulin.  

MODY is very rare compared with type 1 and type 2 diabetes – experts estimate that only 1–2% of people with diabetes (20-40,000 people) in the UK have it. But because MODY is so rare, doctors may not be aware of it, so it’s estimated that about 90% of people with it are mistakenly diagnosed with type 1 or type 2 diabetes at first.

There are many genes identified with MODY. Some of the known genes are

HNF 1 Alpha, HNF 4 Alpha, HNF 1 Beta and Glucokinase

 

 

Maturity-onset diabetes of the young (MODY) is characterised by the development of type 2 diabetes mellitus in patients < 25 years old. It is typically inherited as an autosomal dominant condition. Over six different genetic mutations have so far been identified as leading to MODY.

 

It is thought that around 1-2% of patients with diabetes mellitus have MODY, and around 90% are misclassified as having either type 1 or type 2 diabetes mellitus.

 

 

MODY 3

·         60% of cases

·         due to a defect in the HNF-1 alpha gene

·         is associated with an increased risk of HCC

MODY 2

·         20% of cases

·         due to a defect in the glucokinase gene

MODY 5

·         rare

·         due to a defect in the HNF-1 beta gene

·         liver and renal cysts

Features of MODY

·         typically develops in patients < 25 years

·         a family history of early onset diabetes is often present

·         ketosis is not a feature at presentation

·         patients with the most common form are very sensitive to sulfonylureas, insulin is not usually necessary

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Myxoedema coma

Myxoedema coma typically presents with confusion and hypothermia.

 

Myxoedema coma is a medical emergency requiring treatment with

·         IV thyroid replacement

·         IV fluid

·         IV corticosteroids (until the possibility of coexisting adrenal insufficiency has been excluded)

·         electrolyte imbalance correction

·         sometimes rewarming

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Pituitary adenoma

A pituitary adenoma is a benign tumour of the pituitary gland. They are common (10% of all people1) but in most cases will never be found (asymptomatic) or are found as an incidental finding. They account for around 10% of adult brain tumours2.

 

 

It is recommended that all patients with a pituitary incidentaloma, including those without symptoms, undergo clinical and laboratory evaluations for hormone hypersecretion and hypopituitarism.

 

 

 

Pituitary adenomas can be classified according to:

·         size (a microadenoma is <1cm and a macroadenoma is >1cm)

·         hormonal status (a secretory/functioning adenoma produces and excess of a particular hormone and a non-secretory/functioning adenoma does not produce a hormone to excess)

Prolactinomas are the most common type and they produce an excess of prolactin. After prolactinomas, non-secreting adenomas are the next most common, then GH secreting and then ACTH secreting adenomas.

 

Pituitary adenomas typically cause symptoms by:

·         excess of a hormone (e.g. Cushing’s disease due to excess ACTH, acromegaly due to excess GH or amenorrhea and galactorrhea due to excess prolactin)

·         depletion of a hormone(s) (due to compression of the normal functioning pituitary gland)

o    non-functioning tumours, therefore, present with generalised hypopituitarism

·         stretching of the dura within/around pituitary fossa (causing headaches)

·         compression of the optic chiasm (causing a bitemporal hemianopia due to crossing nasal fibers)

Alternatively, pituitary adenomas, particularly microadenomas, can be an incidental finding on neuroimaging and therefore called a ‘pituitary incidentaloma’.

 

Investigation requires:

·         a pituitary blood profile (including: GH, prolactin, ACTH, FH, LSH and TFTs)

·         formal visual field testing

·         MRI brain with contrast

Differential diagnoses include:

·         pituitary hyperplasia

·         craniopharyngioma

·         meningioma

·         brain metastases

·         lymphoma

·         hypophysitis

·         vascular malformation (e.g. aneurysm)

Treatment may include a combination of:

·         hormonal therapy (e.g. bromocriptine is the first line treatment for prolactinomas)

·         surgery (e.g. transsphenoidal transnasal hypophysectomy)

o    e.g. if progression in size

·         radiotherapy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

criteria for surgical removal of a pituitary mass:

·         A visual field deficit due to the lesion.

·         Other visual abnormalities, such as ophthalmoplegia or neurological compromise due to compression by the lesion.

·         Lesion abutting or compressing the optic nerves or chiasm on MRI.

·         Pituitary apoplexy with visual disturbance.

·         Hypersecreting tumours other than prolactinomas

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

24 December 2020

13:59

Prolactin and galactorrhoea

Prolactin is secreted by the anterior pituitary gland with release being controlled by a wide variety of physiological factors. Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia

 

Features of excess prolactin

·         men: impotence, loss of libido, galactorrhoea

·         women: amenorrhoea, galactorrhoea

Causes of raised prolactin

·         prolactinoma

·         pregnancy

·         oestrogens

·         physiological: stress, exercise, sleep

·         acromegaly: 1/3 of patients

·         polycystic ovarian syndrome

·         primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)

Drug causes of raised prolactin

·         metoclopramide, domperidone

·         phenothiazines

·         haloperidol

·         very rare: SSRIs, opioids

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Sick euthyroid syndrome

In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).

 

Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Thyroid disorders: a very basic introduction

Disorders of thyroid function are very commonly encountered in clinical practice. Around 2% of the UK population has hypothyroidism (an under active thyroid gland) whilst around 1% have thyrotoxicosis (an over active gland). Both hypothyroidism and hyperthyrodism (also known as thyrotoxicosis) are around 10 times more common in women than men.

 

 

Structure and function

 

The thyroid gland is one of the largest endocrine organs in the body. It is a bi-lobed structure which is found in the anterior neck. As with many endocrine organs, it is part of a hypothalamus-pituitary-end organ system with negative feedback cycles to maintain normal circulating levels of the hormone, in this case thyroxine and triiodothyronine.

 

On a simple level the hypothalamus secretes thyrotropin-releasing hormone (TRH) which stimulates the anterior pituitary to secrete thyroid-stimulating hormone (TSH). This then acts on the thyroid gland increasing the production of thyroxine (T4) and triiodothyronine (T3), the two main thyroid hormones. These then act on a wide variety of tissues, helping to regulate the use of energy sources, protein synthesis, and controls the body's sensitivity to other hormones.

 

 

How are thyroid problems classified?

 

Hypothyroidism may be classified as follows:

·         primary hypothyroidism: there is a problem with the thyroid gland itself, for example an autoimmune disorder affecting thyroid tissue (see below)

·         secondary hypothyroidism: usually due to a disorder with the pituitary gland (e.g.pituitary apoplexy) or a lesion compressing the pituitary gland

·         congenital hypothyroidism: due to a problem with thyroid dysgenesis or thyroid dyshormonogenesis

Whilst there are a number of causes thyrotoxicosis the vast majority are primary in nature. Congenital thyrotoxicosis is not seen and secondary hyperthyroidism is rare, account for less than 1% of cases.

 

 

What causes thyroid problems?

 

The majority of thyroid problems seen in the developed world are a consequence of autoimmunity.

 

The table below shows the different autoimmune problems which cause thyroid dysfunction:

 

 

 

Hypothyroidism

Thyrotoxicosis

Most common cause

Hashimoto's thyroiditis

·         most common cause in the developed world

·         autoimmune disease, associated with type 1 diabetes mellitus, Addison's or pernicious anaemia

·         may cause transient thyrotoxicosis in the acute phase

·         5-10 times more common in women

Graves' disease

·         most common cause of thyrotoxicosis

·         as well as typically features of thyrotoxicosis other features may be seen including thyroid eye disease

Other causes

Subacute thyroiditis (de Quervain's)

·         associated with a painful goitre and raised ESR

Riedel thyroiditis

·         fibrous tissue replacing the normal thyroid parenchyma

·         causes a painless goitre

Postpartum thyroiditis

 

Drugs

·         lithium

·         amiodarone

Iodine deficiency

·         the most common cause of hypothyroidism in the developing world

Toxic multinodular goitre

·         autonomously functioning thyroid nodules that secrete excess thyroid hormones

Drugs

·         amiodarone

It should be remembered that a lot of the conditions mentioned above don't always cause either hypothyroidism or hyperthyroidism, there is sometimes some overlap, as shown below:

 

 

 

 

Venn diagram showing how different causes of thyroid dysfunction may manifest. Note how many causes of hypothyroidism may have an initial thyrotoxic phase.

 

Symptoms and signs

 

Thyroid disorders can present in a large variety of ways. Often (but not always) the symptoms present are the opposite depending on whether the thyroid gland is under or over active, for example hypothyroidism may result in weight gain whilst thyrotoxicosis normally leads to weight loss

 

 

Feature

Hypothyroidism

Thyrotoxicosis

General

Weight gain

 

Lethargy

 

Cold intolerance

Weight loss

 

'Manic', restlessness

 

Heat intolerance

Cardiac

-

Palpitations, may even provoke arrhythmias e.g. atrial fibrillation

Skin

Dry (anhydrosis), cold, yellowish skin

 

Non-pitting oedema (e.g. hands, face)

 

Dry, coarse scalp hair, loss of lateral aspect of eyebrows

Increased sweating

 

Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli

 

Thyroid acropachy: clubbing

Gastrointestinal

Constipation

Diarrhoea

Gynaecological

Menorrhagia

Oligomenorrhea

Neurological

Decreased deep tendon reflexes

 

Carpal tunnel syndrome

Anxiety

 

Tremor

 

Investigations and diagnosis

 

The principle investigation is 'thyroid function tests', or TFTs for short:

·         these primarily look at serum TSH and T4 levels

·         T3 can be measured but is only useful clinically in a small number of cases

·         remember that TSH and T4 levels will often be 'opposite' in cases of primary hypo- or hyperthyroidism. For example in hypothyroidism the T4 level is low (i.e. not enough thyroxine) but the TSH level is high, because the hypothalamus/pituitary has detected low levels of T4 and is trying to get the thyroid gland to produce more

·         TSH levels are more sensitive than T4 levels for monitoring patients with existing thyroid problems and are often used to guide treatment

The table below shows how thyroid function tests are interpreted:

 

 

Diagnosis

TSH

Free T4

Notes

Thyrotoxicosis (e.g. Graves' disease)

Low

High

 

Primary hypothyroidism (e.g. Hashimoto's thyroiditis)

High

Low

 

Secondary hypothyroidism

Low

Low

 

Sick euthyroid syndrome

Low

Low

Common in hospital inpatients. Changes are reversible upon recovery from the systemic illness and no treatment is usually needed

Subclinical hypothyroidism

High

Normal

This is a common finding and represents patients who are 'on the way' to developing hypothyroidism but still have normal thyroxine levels. Note how the TSH levels, as mentioned above, are a more sensitive and early marker of thyroid problems

Poor compliance with thyroxine

High

Normal

Patients who are poorly compliant may only take their thyroxine in the days before a routine blood test. The thyroxine levels are hence normal but the TSH 'lags' and reflects longer term low thyroxine levels

A number of thyroid autoantibodies can be tested for (remember the majority of thyroid disorders are autoimmune). The 3 main types are:

·         Anti-thyroid peroxidase (anti-TPO) antibodies

·         TSH receptor antibodies

·         Thyroglobulin antibodies

There is significant overlap between the type of antibodies present and particular diseases, but generally speaking TSH receptor antibodies are present in around 90-100% of patients with Graves' disease and anti-TPO antibodies are seen in around 90% of patients with Hashimoto's thyroiditis.

 

Other tests include:

·         nuclear scintigraphy; toxic multinodular goitre reveals patchy uptake

 

Treatment

 

This clearly depends on the cause. For patients with hypothyrodism thyroxine is given in the form of levothyroxine to replace the underlying deficiency.

 

Patients with thyrotoxicosis may be treated with:

·         propranolol: this is often used at the time of diagnosis to control thyrotoxic symptoms such as tremor

·         carbimazole: blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production. Agranulocytosis is an important adverse effect to be aware of

·         radioiodine treatment

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Acromegaly: management

Trans-sphenoidal surgery is the first-line treatment for acromegaly in the majority of patients.

 

If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:

·         somatostatin analogue

o    directly inhibits the release of growth hormone

o    for example octreotide

o    effective in 50-70% of patients

·         pegvisomant

o    GH receptor antagonist - prevents dimerization of the GH receptor

o    once daily s/c administration

o    very effective - decreases IGF-1 levels in 90% of patients to normal

o    doesn't reduce tumour volume therefore surgery still needed if mass effect

·         dopamine agonists

o    for example bromocriptine

o    the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues

o    effective only in a minority of patients

External irradiation is sometimes used for older patients or following failed surgical/medical treatment

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Addison's disease: investigations

In a patient with suspected Addison's disease the definite investigation is an ACTH stimulation test (short Synacthen test). Plasma cortisol is measured before and 30 minutes after giving Synacthen 250ug IM. Adrenal autoantibodies such as anti-21-hydroxylase may also be demonstrated.

 

If an ACTH stimulation test is not readily available (e.g. in primary care) then sending a 9 am serum cortisol can be useful:

·         > 500 nmol/l makes Addison's very unlikely

·         < 100 nmol/l is definitely abnormal

·         100-500 nmol/l should prompt a ACTH stimulation test to be performed

Associated electrolyte abnormalities are seen in around one-third of undiagnosed patients:

·         hyperkalaemia

·         hyponatraemia

·         hypoglycaemia

·         metabolic acidosis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:59

Carbimazole

Carbimazole is used in the management of thyrotoxicosis. It is typically given in high doses for 6 weeks until the patient becomes euthyroid before being reduced.

 

Mechanism of action

·         blocks thyroid peroxidase from coupling and iodinating the tyrosine residues on thyroglobulin → reducing thyroid hormone production

·         in contrast propylthiouracil as well as this central mechanism of action also has a peripheral action by inhibiting 5'-deiodinase which reduces peripheral conversion of T4 to T3

Adverse effects

·         agranulocytosis

·         crosses the placenta, but may be used in low doses during pregnancy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Cushing's syndrome: causes

It should be noted that exogenous causes of Cushing's syndrome (e.g. glucocorticoid therapy) are far more common than endogenous ones.

 

ACTH dependent causes

·         Cushing's disease (80%): pituitary tumour secreting ACTH producing adrenal hyperplasia

·         ectopic ACTH production (5-10%): e.g. small cell lung cancer is the most common causes

ACTH independent causes

·         iatrogenic: steroids

·         adrenal adenoma (5-10%)

·         adrenal carcinoma (rare)

·         Carney complex: syndrome including cardiac myxoma

·         micronodular adrenal dysplasia (very rare)

Pseudo-Cushing's

·         mimics Cushing's

·         often due to alcohol excess or severe depression

·         causes false positive dexamethasone suppression test or 24 hr urinary free cortisol

·         insulin stress test may be used to differentiate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

DVLA: diabetes mellitus

Until recently people with diabetes who used insulin could not hold a HGV licence. The DVLA changed the rules in October 2011. The following standards need to be met (and also apply to patients using other hypoglycaemic inducing drugs such as sulfonylureas):

·         there has not been any severe hypoglycaemic event in the previous 12 months

·         the driver has full hypoglycaemic awareness

·         the driver must show adequate control of the condition by regular blood glucose monitoring*, at least twice daily and at times relevant to driving

·         the driver must demonstrate an understanding of the risks of hypoglycaemia

·         here are no other debarring complications of diabetes

From a practical point of view patients on insulin who want to apply for a Group 2 (HGV) licence need to complete a VDIAB1I form.

 

Other specific points for group 1 drivers:

·         if on insulin then patient can drive a car as long as they have hypoglycaemic awareness, not more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months and no relevant visual impairment. Drivers are normally contacted by DVLA

·         if on tablets or exenatide no need to notify DVLA. If tablets may induce hypoglycaemia (e.g. sulfonylureas) then there must not have been more than one episode of hypoglycaemia requiring the assistance of another person within the preceding 12 months

·         if diet controlled alone then no requirement to inform DVLA

*to demonstrate adequate control, the Secretary of State's Honorary Medical Advisory Panel on Diabetes Mellitus has recommended that applicants will need to have used blood glucose meters with a memory function to measure and record blood glucose levels for at least 3 months prior to submitting their application

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Hypothyroidism: features

General

·         Weight gain

·         Lethargy

·         Cold intolerance

Skin

·         Dry (anhydrosis), cold, yellowish skin

·         Non-pitting oedema (e.g. hands, face)

·         Dry, coarse scalp hair, loss of lateral aspect of eyebrows

Gastrointestinal

·         Constipation

Gynaecological

·         Menorrhagia

Neurological

·         Decreased deep tendon reflexes

·         Carpal tunnel syndrome

A hoarse voice is also occasionally noted.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Kallmann's syndrome

Kallmann's syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann's syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.

 

The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.

 

Features

·         'delayed puberty'

·         hypogonadism, cryptorchidism

·         anosmia

·         sex hormone levels are low

·         LH, FSH levels are inappropriately low/normal

·         patients are typically of normal or above average height

Cleft lip/palate and visual/hearing defects are also seen in some patients

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Klinefelter's syndrome

Klinefelter's syndrome is associated with karyotype 47, XXY.

 

Features

·         often taller than average

·         lack of secondary sexual characteristics

·         small, firm testes

·         infertile

·         gynaecomastia - increased incidence of breast cancer

·         elevated gonadotrophin levels but low testosterone

Diagnosis is by karyotype (chromosomal analysis).

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Obesity: therapeutic options

The management of obesity consists of a step-wise approach:

·         conservative: diet, exercise

·         medical

·         surgical

Orlistat is a pancreatic lipase inhibitor used in the management of obesity. Adverse effects include faecal urgency/incontinence and flatulence. A lower dose version is now available without prescription ('Alli'). NICE have defined criteria for the use of orlistat. It should only be prescribed as part of an overall plan for managing obesity in adults who have:

·         BMI of 28 kg/m^2 or more with associated risk factors, or

·         BMI of 30 kg/m^2 or more

·         continued weight loss e.g. 5% at 3 months

·         orlistat is normally used for < 1 year

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Prediabetes and impaired glucose regulation

Prediabetes is a term which is increasingly used where there is impaired glucose levels which are above the normal range but not high enough for a diagnosis of diabetes mellitus. The term includes patients who have been labelled as having either impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Diabetes UK estimate that around 1 in 7 adults in the UK have prediabetes. Many individuals with prediabetes will progress on to developing type 2 diabetes mellitus (T2DM) and they are therefore at greater risk of microvascular and macrovascular complications.

 

Terminology

·         Diabetes UK currently recommend using the term prediabetes when talking to patients and impaired glucose regulation when talking to other healthcare professionals

·         research has shown that the term 'prediabetes' has the most impact and is most easily understood

Identification of patients with prediabetes

·         NICE recommend using a validated computer based risk assessment tool for all adults aged 40 and over, people of South Asian and Chinese descent aged 25-39, and adults with conditions that increase the risk of type 2 diabetes

·         patients identified at high risk should have a blood sample taken

·         a fasting plasma glucose of 6.1-6.9 mmol/l or an HbA1c level of 42-47 mmol/mol (6.0-6.4%) indicates high risk

 

 

 

Diagram showing the spectrum of diabetes diagnosis

 

Management

·         lifestyle modification: weight loss, increased exercise, change in diet

·         at least yearly follow-up with blood tests is recommended

·         NICE recommend metformin for adults at high risk 'whose blood glucose measure (fasting plasma glucose or HbA1c) shows they are still progressing towards type 2 diabetes, despite their participation in an intensive lifestyle-change programme'

Impaired fasting glucose and impaired glucose tolerance

 

There are two main types of IGR:

·         impaired fasting glucose (IFG) - due to hepatic insulin resistance

·         impaired glucose tolerance (IGT) - due to muscle insulin resistance

·         patients with IGT are more likely to develop T2DM and cardiovascular disease than patients with IFG

Definitions

·         a fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)

·         impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l

·         people with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Subclinical hypothyroidism

Basics

·         TSH raised but T3, T4 normal

·         no obvious symptoms

Significance

·         risk of progressing to overt hypothyroidism is 2-5% per year (higher in men)

·         risk increased by the presence of thyroid autoantibodies

Management

 

Not all patients require treatment. NICE Clinical Knowledge Summaries (CKS) have produced guidelines. Note that not all patients will fall within the age boundaries given and hence these are guidelines in the broader sense.

 

TSH is between 4 - 10mU/L and the free thyroxine level is within the normal range

·         if < 65 years with symptoms suggestive of hypothyroidism, give a trial of levothyroxine. If there is no improvement in symptoms, stop levothyroxine

·         'in older people (especially those aged over 80 years) follow a 'watch and wait' strategy, generally avoiding hormonal treatment'

·         if asymptomatic people, observe and repeat thyroid function in 6 months

TSH is > 10mU/L and the free thyroxine level is within the normal range

·         start treatment (even if asymptomatic) with levothyroxine if <= 70 years

·         'in older people (especially those aged over 80 years) follow a 'watch and wait' strategy, generally avoiding hormonal treatment'

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Sulfonylureas

Sulfonylureas are oral hypoglycaemic drugs used in the management of type 2 diabetes mellitus. They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.

 

Common adverse effects

·         hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)

·         weight gain

Rarer adverse effects

·         hyponatraemia secondary to syndrome of inappropriate ADH secretion

·         bone marrow suppression

·         hepatotoxicity (typically cholestatic)

·         peripheral neuropathy

Sulfonylureas should be avoided in breastfeeding and pregnancy.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Thyroid eye disease

Thyroid eye disease affects between 25-50% of patients with Graves' disease.

 

Pathophysiology

·         it is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation

·         the inflammation results in glycosaminoglycan and collagen deposition in the muscles

Prevention

·         smoking is the most important modifiable risk factor for the development of thyroid eye disease

·         radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease. In a recent study of patients with Graves' disease around 15% developed, or had worsening of, eye disease. Prednisolone may help reduce the risk

Features

·         the patient may be eu-, hypo- or hyperthyroid at the time of presentation

·         exophthalmos

·         conjunctival oedema

·         optic disc swelling

·         ophthalmoplegia

·         inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy

Management

·         topical lubricants may be needed to help prevent corneal inflammation caused by exposure

·         steroids

·         radiotherapy

·         surgery

Monitoring patients with established thyroid eye disease

 

For patients with established thyroid eye disease the following symptoms/signs should indicate the need for urgent review by an ophthalmologist (see EUGOGO guidelines):

·         unexplained deterioration in vision

·         awareness of change in intensity or quality of colour vision in one or both eyes

·         history of eye suddenly 'popping out' (globe subluxation)

·         obvious corneal opacity

·         cornea still visible when the eyelids are closed

·         disc swelling

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Toxic multinodular goitre

Toxic multinodular goitre describes a thyroid gland that contains a number of autonomously functioning thyroid nodules resulting in hyperthyroidism.

 

Nuclear scintigraphy reveals patchy uptake.

 

The treatment of choice is radioiodine therapy.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:00

Acromegaly: investigations

Growth hormone (GH) levels vary during the day and are therefore not diagnostic.

 

Serum IGF-1 levels have now overtaken the oral glucose tolerance test (OGTT) with serial GH measurements as the first-line test. The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.

 

The Endocrine Society guidelines suggest the following:

 

 

1.1 We recommend measurement of IGF-1 levels in patients with typical clinical manifestations of acromegaly, especially those with acral and facial features.

...

1.5 In patients with elevated or equivocal serum IGF-1 levels, we recommend confirmation of the diagnosis by finding lack of suppression of GH to < 1 μg/L following documented hyperglycemia during an oral glucose load.

 

Serum IGF-1 may also be used to monitor disease

 

Oral glucose tolerance test

·         in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia

·         in acromegaly there is no suppression of GH

·         may also demonstrate impaired glucose tolerance which is associated with acromegaly

A pituitary MRI may demonstrate a pituitary tumour.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Combined deficiency of magnesium and calcium

Magnesium is required for both PTH secretion and its action on target tissues. Hypomagnesaemia may both cause hypocalcaemia and render patients unresponsive to treatment with calcium and vitamin D supplementation.

 

Magnesium is the fourth most abundant cation in the body. The body contains 1000mmol, with half contained in bone and the remainder in muscle, soft tissues and extracellular fluid. There is no one specific hormonal control of magnesium and various hormones including PTH and aldosterone affect the renal handling of magnesium.

 

Magnesium and calcium interact at a cellular level also and as a result decreased magnesium will tend to affect the permeability of cellular membranes to calcium, resulting in hyperexcitability.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Congenital adrenal hyperplasia

Overview

·         group of autosomal recessive disorders

·         affect adrenal steroid biosynthesis

·         in response to resultant low cortisol levels the anterior pituitary secretes high levels of ACTH

·         ACTH stimulates the production of adrenal androgens that may virilize a female infant

Cause

·         21-hydroxylase deficiency (90%)

·         11-beta hydroxylase deficiency (5%)

·         17-hydroxylase deficiency (very rare)

 

 

Image sourced from Wikipedia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Diabetes mellitus: Ramadan

We know that type 2 diabetes mellitus is more common in people of Asian ethnicity and a significant proportion of those patients in the UK will be Muslim. The BMJ published an excellent and comprehensive review of this issue in 20101.

 

It is important that we can give appropriate advice to Muslim patients to allow them safely observe their fast. This is particularly important from 2014 as Ramadan is due to fall in the long days of the summer months for several years henceforth.

 

Clearly it is a personal decision whether a patient decides to fast. It may however be worthwhile exploring the fact that people with chronic conditions are exempt from fasting or may be able to delay fasting to the shorter days of the winter months. It is however known that many Muslim patients with diabetes do not class themselves as having a chronic/serious condition which should exempt them from fasting. Around 79% of Muslim patients with type 2 diabetes mellitus fast Ramadan2.There is an excellent patient information leaflet from Diabetes UK and the Muslim Council of Britain which explores these options in more detail.

 

If a patient with type 2 diabetes mellitus does decide to fast:

·         they should try and and eat a meal containing long-acting carbohydrates prior to sunrise (Suhoor)

·         patients should be given a blood glucose monitor to allow them to check their glucose levels, particularly if they feel unwell

·         for patients taking metformin the expert consensus is that the dose should be split one-third before sunrise (Suhoor) and two-thirds after sunset (Iftar)

·         expert consensus also recommends switching once-daily sulfonylureas to after sunset. For patients taking twice-daily preparations such as gliclazide it is recommended that a larger proportion of the dose is taken after after sunset

·         no adjustment is needed for patients taking pioglitazone

1. Management of people with diabetes wanting to fast during Ramadan BMJ 2010;340:c3053

2. Salti I et al. Results of the Epidemiology of Diabetes and Ramadan (EPIDIAR) study. Diabetes Care 2004;27:2306-11.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Graves' disease: management

Despite many trials there is no clear guidance on the optimal management of Graves' disease. Treatment options include titration of anti-thyroid drugs (ATDs, for example carbimazole), block-and-replace regimes, radioiodine treatment and surgery. Propranolol is often given initially to block adrenergic effects

 

ATD titration

·         carbimazole is started at 40mg and reduced gradually to maintain euthyroidism

·         typically continued for 12-18 months

·         patients following an ATD titration regime have been shown to suffer fewer side-effects than those on a block-and-replace regime

Block-and-replace

·         carbimazole is started at 40mg

·         thyroxine is added when the patient is euthyroid

·         treatment typically lasts for 6-9 months

The major complication of carbimazole therapy is agranulocytosis

 

Radioiodine treatment

·         contraindications include pregnancy (should be avoided for 4-6 months following treatment) and age < 16 years. Thyroid eye disease is a relative contraindication, as it may worsen the condition

·         the proportion of patients who become hypothyroid depends on the dose given, but as a rule the majority of patient will require thyroxine supplementation after 5 years

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Growth hormone therapy

NICE guidance recommended growth hormone therapy for the following indications

·         proven growth hormone deficiency

·         Turner's syndrome

·         Prader-Willi syndrome

·         chronic renal insufficiency before puberty

Key points

·         given by subcutaneous injection

·         treatment should be discontinued if there is a poor response in the first year of therapy

Adverse effects

·         headache

·         benign intracranial hypertension

·         fluid retention

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Hypoparathyroidism

Primary hypoparathyroidism

·         decrease PTH secretion

·         e.g. secondary to thyroid surgery*

·         low calcium, high phosphate

·         treated with alfacalcidol

The main symptoms of hypoparathyroidism are secondary to hypocalcaemia:

·         tetany: muscle twitching, cramping and spasm

·         perioral paraesthesia

·         Trousseau's sign: carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic

·         Chvostek's sign: tapping over parotid causes facial muscles to twitch

·         if chronic: depression, cataracts

·         ECG: prolonged QT interval

Pseudohypoparathyroidism

·         target cells being insensitive to PTH

·         due to abnormality in a G protein

·         associated with low IQ, short stature, shortened 4th and 5th metacarpals

·         low calcium, high phosphate, high PTH

·         diagnosis is made by measuring urinary cAMP and phosphate levels following an infusion of PTH. In hypoparathyroidism this will cause an increase in both cAMP and phosphate levels. In pseudohypoparathyroidism type I neither cAMP nor phosphate levels are increased whilst in pseudohypoparathyroidism type II only cAMP rises.

Pseudopseudohypoparathyroidism

·         similar phenotype to pseudohypoparathyroidism but normal biochemistry

*this may seem an oxymoron, but most medical textbooks classify hypoparathyroidism which is secondary to surgery as being 'primary hypoparathyroidism'

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Hypothyroidism: causes

Hypothyroidism affects around 1-2% of women in the UK and is around 5-10 times more common in females than males.

 

Primary hypothyroidism

 

Hashimoto's thyroiditis

·         most common cause

·         autoimmune disease, associated with IDDM, Addison's or pernicious anaemia

·         may cause transient thyrotoxicosis in the acute phase

·         5-10 times more common in women

Subacute thyroiditis (de Quervain's)

 

Riedel thyroiditis

 

After thyroidectomy or radioiodine treatment

 

Drug therapy (e.g. lithium, amiodarone or anti-thyroid drugs such as carbimazole)

 

Dietary iodine deficiency

 

 

 

 

Venn diagram showing how different causes of thyroid dysfunction may manifest. Note how many causes of hypothyroidism may have an initial thyrotoxic phase.

Secondary hypothyroidism (rare)

 

From pituitary failure

 

Other associated conditions

·         Down's syndrome

·         Turner's syndrome

·         coeliac disease

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Insulin

Insulin is a peptide hormone, produced by beta cells of the pancreas, and is central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, skeletal muscles, and fat tissue to absorb glucose from the blood. In the liver and skeletal muscles, glucose is stored as glycogen, and in fat cells (adipocytes) it is stored as triglycerides.

 

Structure

 

The human insulin protein is composed of 51 amino acids, and has a molecular weight of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds.

 

Synthesis

 

Pro-insulin is formed by the rough endoplasmic reticulum in pancreatic beta cells. Then pro-insulin is cleaved to form insulin and C-peptide. Insulin is stored in secretory granules and released in response to Ca2+.

 

Function

 

Basics

·         Secreted in response to hyperglycaemia

·         Glucose utilisation and glycogen synthesis

·         Inhibits lipolysis

·         Reduces muscle protein loss

·         Increases cellular uptake of potassium (via stimulation of Na+/K+ ATPase pump)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Insulin stress test

Basics

·         used in investigation of hypopituitarism

·         IV insulin given, GH and cortisol levels measured

·         with normal pituitary function GH and cortisol should rise

Contraindications

·         epilepsy

·         ischaemic heart disease

·         adrenal insufficiency

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Insulin therapy

Insulin therapy revolutionised the management of diabetes mellitus when it was developed in the 1920's. It is still the only available treatment for type 1 diabetes mellitus (T1DM) and is widely used in type 2 diabetes mellitus (T2DM) where oral hypoglycaemic agents fail to gain adequate control.

 

It can sometimes seem daunting to understand the various types of insulin but it is important you have a basic grasp to avoid potential harm to patients.

 

Classification of insulin

 

By manufacturing process

·         porcine: extracted and purified from pig pancreas

·         human sequence insulin: either produced by enzyme modification of porcine insulin (emp) or biosynthetically by recombinant DNA using bacteria (crb, prb) or yeast (pyr)

·         analogues

By duration of action

 

 

 

Onset

Peak

Duration

Rapid-acting insulin analogues

5 mins

1 hour

3-5 hours

Short-acting insulin

30 mins

3 hours

6-8 hours

Intermediate-acting insulin

2 hours

5-8 hours

12-18 hours

Long-acting insulin analogues

1-2 hours

Flat profile

Up to 24 hours

Premixed preparations

-

-

-

Patients often require a mixture of preparations (e.g. both short and long acting) to ensure stable glycaemic control throughout the day.

 

Rapid-acting insulin analogues

·         the rapid-acting human insulin analogues act faster and have a shorter duration of action than soluble insulin (see below)

·         may be used as the bolus dose in 'basal-bolus' regimes (rapid/short-acting 'bolus' insulin before meals with intermediate/long-acting 'basal' insulin once or twice daily)

·         insulin aspart: NovoRapid

·         insulin lispro: Humalog

Short-acting insulins

·         soluble insulin examples: Actrapid (human, pyr), Humulin S (human, prb)

·         may be used as the bolus dose in 'basal-bolus' regimes

Intermidate-acting insulins

·         isophane insulin

·         many patients use isophane insulin in a premixed formulation with

Long-acting insulins

·         insulin determir (Levemir): given once or twice daily

·         insulin glargine (Lantus): given once daily

Premixed preparations

·         combine intermediate acting insulin with either a rapid-acting insulin analogue or soluble insulin

·         Novomix 30: 30% insulin aspart (rapid-acting), 70% insulin aspart protamine (intermediate-acting)

·         Humalog Mix25: 25% insulin lispro (rapid-acting), 75% insulin lispro protamine (intermediate-acting); Humalog Mix50: 50% insulin lispro, 50% insulin lispro protamine

·         Humulin M3: biphasic isophane insulin (human, prb) - 30% soluble (short-acting), 70% isophane (intermediate-acting)

·         Insuman Comb 15: biphasic isophane insulin 9human, prb) - 30% soluble (short-acting), 70% isophane (intermediate-acting)

Administration of insulin

 

The vast majority of patients administer insulin subcutaneously. It is important to rotate injection sites to prevent lipodystrophy. Insulin pumps are available ('continuous subcutaneous insulin infusions') which delivers a continuous basal infusion and a patient-activated bolus dose at meal times.

 

Intravenous insulin is used for patients who are acutely unwell, for example with diabetic ketoacidosis. Inhaled insulin is available but not widely used and oral insulin analogues are in development but have considerable technical hurdles to clear.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Insulinoma

An insulinoma is a neuroendocrine tumour deriving mainly from pancreatic Islets of Langerhans cells

 

Basics

·         most common pancreatic endocrine tumour

·         10% malignant, 10% multiple

·         of patients with multiple tumours, 50% have MEN-1

Features

·         of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc

·         rapid weight gain may be seen

·         high insulin, raised proinsulin:insulin ratio

·         high C-peptide

Diagnosis

·         supervised, prolonged fasting (up to 72 hours)

·         CT pancreas

Management

·         surgery

·         diazoxide and somatostatin if patients are not candidates for surgery

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

Prolactinoma

Prolactinomas are a type of pituitary adenoma, a benign tumour of the pituitary gland.

 

Pituitary adenomas can be classified according to:

·         size (a microadenoma is <1cm and a macroadenoma is >1cm)

·         hormonal status (a secretory/functioning adenoma produces and excess of a particular hormone and a non-secretory/functioning adenoma does not produce a hormone to excess)

Prolactinomas are the most common type and they produce an excess of prolactin.

 

Features of excess prolactin

·         men: impotence, loss of libido, galactorrhoea

·         women: amenorrhoea, infertility, galactorrhoea, osteoporosis

Diagnosis

·         MRI

Management

·         in the majority of cases, symptomatic patients are treated medically with dopamine agonists (e.g. cabergoline, bromocriptine) which inhibit the release of prolactin from the pituitary gland

·         surgery is performed for patients who cannot tolerate or fail to respond to medical therapy. A trans-sphenoidal approach is generally preferred unless there is a significant extra-pituitary extension

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:01

PTH

A hormone is a chemical messenger which is secreted by an endocrine gland and designed to generate a specific response by binding to a cellular receptor. This receptor may be intracellular (commonly steroid hormone receptors) or on the cell surface membrane.

 

Parathyroid hormone (PTH) is a polypeptide hormone secreted from the parathyroid gland. It has an important role in calcium homeostasis. It acts on cell-surface receptors to generate a coordinated response throughout the body and maintain blood calcium within a narrow range.

 

It is vital that calcium does not rise too high or fall too low, as hyper- and hypo- calcaemia can have serious consequences. Calcium enters the body through the intestines and leaves through urine and faeces. The main reservoir of calcium in the body is the bone, containing about 1 kg of complexed calcium and phosphate. In the blood, calcium exists in three main forms:

·         free calcium

·         bound to albumin

·         complexed with anions

It is free calcium which is physiologically active and can travel into cells to exert a function.

 

Structure and function

 

PTH, a single-chain polypeptide containing 84 amino acids, is secreted from the Chief cells of the parathyroid glands, located on the posterior aspect of the thyroid. It is generated in response to low levels of calcium in the blood, where it travels to effector organs to increase levels of the electrolyte back to normal concentrations.

 

Effector organs associated with PTH include the bone and kidney:

·         At the bone PTH acts to increase the activity of osteoclastic cells, which are responsible for bone resorption. In this way, the bone releases some of its calcium, and phosphate, stores into the bloodstream.

·         At the kidney PTH as two actions. One is to increase the hydroxylation and activation of vitamin D in the proximal convoluted tubules. Another in to increase calcium reabsorption from the distal convoluted tubules and increase phosphate excretion.

Active vitamin D has a similar action to PTH, however, it is a steroid hormone. One of its unique actions is to increase dietary calcium absorption from the intestine by increasing expression of calcium-binding hormone.

 

Regulation

 

While PTH is very important in maintaining adequate levels of calcium in the bloodstream, it is equally as important that its actions don't cause hypercalcaemia. Regulation is therefore vital. This is achieved through a negative feedback loop:

·         calcium levels in the blood fall, which is detected by the parathyroid gland

·         chief cells secrete PTH into the blood

·         calcium is released from bone and reabsorbed from the renal tubules, causing its level to rise

·         increased calcium levels are detected by the parathyroid gland, which decreases PTH secretion

Clinical relevance

 

Primary hyperparathyroidism is a condition in which the parathyroid gland is overactive. This is often due to hyperplasia, an adenoma or malignancy. Symptoms of hypercalcaemia develop, which includes renal calculi, constipation, polyuria, abdominal pain and low mood. One treatment is surgical removal of the glands.

 

PTHrp is a polypeptide which has a similar structure to PTH, hence its name 'related peptide'. It can be secreted from cancer cells, notably squamous cell bronchial carcinoma, to cause hypercalcaemia. PTHrp has all the same effects as PTH, however it cannot activate vitamin D.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:02

Stress response: Endocrine and metabolic changes

·         Surgery precipitates hormonal and metabolic changes causing the stress response.

·         Stress response is associated with: substrate mobilization, muscle protein loss, sodium and water retention, suppression of anabolic hormone secretion, activation of the sympathetic nervous system, immunological and haematological changes.

·         The hypothalamic-pituitary axis and the sympathetic nervous systems are activated and there is a failure of the normal feedback mechanisms of control of hormone secretion.

 

A summary of the hormonal changes associated with the stress response:

 

 

Increased

Decreased

No Change

Growth hormone

Insulin

Thyroid stimulating hormone

Cortisol

Testosterone

Luteinizing hormone

Renin

Oestrogen

Follicle stimulating hormone

Adrenocorticotrophic hormone (ACTH)

 

 

Aldosterone

 

 

Prolactin

 

 

Antidiuretic hormone

 

 

Glucagon

 

 

 

 

Sympathetic nervous system

·         Stimulates catecholamine release

·         Causes tachycardia and hypertension

Pituitary gland

·         ACTH and growth hormone (GH) is stimulated by hypothalamic releasing factors, corticotrophin releasing factor (CRF) and somatotrophin (or growth hormone releasing factor)

·         Perioperative increased prolactin secretion occurs by release of inhibitory control

·         Secretion of thyroid stimulating hormone (TSH), luteinizing hormone (LH) and follicle stimulating hormone (FSH) does not change significantly

·         ACTH stimulates cortisol production within a few minutes of the start of surgery. More ACTH is produced than needed to produce a maximum adrenocortical response.

Cortisol

·         Significant increases within 4-6 hours of surgery (>1000 nmol litre-1).

·         The usual negative feedback mechanism fails and concentrations of ACTH and cortisol remain persistently increased.

·         The magnitude and duration of the increase correlate with the severity of stress and the response is not abolished by the administration of corticosteroids.

·         The metabolic effects of cortisol are enhanced:

Skeletal muscle protein breakdown to provide gluconeogenic precursors and amino acids for protein synthesis in the liver

Stimulation of lipolysis

'Anti-insulin effect'

Mineralocorticoid effects

Anti-inflammatory effects

 

 

Growth hormone

·         Increased secretion after surgery has a minor role

·         Most important for preventing muscle protein breakdown and promote tissue repair by insulin growth factors

Alpha Endorphin

·         Increased

Antidiuretic hormone

·         An important vasopressor and enhances haemostasis

·         Renin is released causing the conversion of angiotensinogen to angiotensin I

·         Angiotensin II formed by ACE on angiotensin 1, which causes the secretion of aldosterone from the adrenal cortex. This increases sodium reabsorption at the distal convoluted tubule

Insulin

·         Release inhibited by stress

·         Occurs via the inhibition of the beta cells in the pancreas by the α2-adrenergic inhibitory effects of catecholamines

·         Insulin resistance by target cells occurs later

·         The perioperative period is characterized by a state of functional insulin deficiency

Thyroxine (T4) and tri-iodothyronine (T3)

·         Circulating concentrations are inversely correlated with sympathetic activity and after surgery there is a reduction in thyroid hormone production, which normalises over a few days.

Metabolic effect of endocrine response

 

Carbohydrate metabolism

·         Hyperglycaemia is a main feature of the metabolic response to surgery

·         Due to increase in glucose production and a reduction in glucose utilization

·         Catecholamines and cortisol promote glycogenolysis and gluconeogenesis

·         Initial failure of insulin secretion followed by insulin resistance affects the normal responses

·         The proportion of the hyperglycaemic response reflects the severity of surgery

·         Hyperglycaemia impairs wound healing and increase infection rates

Protein metabolism

·         Initially there is inhibition of protein anabolism, followed later, if the stress response is severe, by enhanced catabolism

·         The amount of protein degradation is influenced by the type of surgery and also by the nutritional status of the patient

·         Mainly skeletal muscle protein is affected

·         The amino acids released form acute phase proteins (fibrinogen, C reactive protein, complement proteins, a2-macroglobulin, amyloid A and ceruloplasmin) and are used for gluconeogenesis

·         Nutritional support has little effect on preventing catabolism

Lipid metabolism

Increased catecholamine, cortisol and glucagon secretion, and insulin deficiency, promotes lipolysis and ketone body production.

 

Salt and water metabolism

·         ADH causes water retention, concentrated urine, and potassium loss and may continue for 3 to 5 days after surgery

·         Renin causes sodium and water retention

Cytokines

·         Glycoproteins

·         Interleukins (IL) 1 to 17, interferons, and tumour necrosis factor

·         Synthesized by activated macrophages, fibroblasts, endothelial and glial cells in response to tissue injury from surgery or trauma

·         IL-6 main cytokine associated with surgery. Peak 12 to 24 h after surgery and increase by the degree of tissue damage Other effects of cytokines include fever, granulocytosis, haemostasis, tissue damage limitation and promotion of healing.

 

Modifying the response

·         Opioids suppress hypothalamic and pituitary hormone secretion

·         At high doses the hormonal response to pelvic and abdominal surgery is abolished. However, such doses prolong recovery and increase the need for postoperative ventilatory support

·         Spinal anaesthesia can reduce the glucose, ACTH, cortisol, GH and epinephrine changes, although cytokine responses are unaltered

·         Cytokine release is reduced in less invasive surgery

·         Nutrition prevents the adverse effects of the stress response. Enteral feeding improves recovery

·         Growth hormone and anabolic steroids may improve outcome

·         Normothermia decreases the metabolic response

References

Deborah Burton, Grainne Nicholson, and George Hall

Endocrine and metabolic response to surgery .

 

Contin Educ Anaesth Crit Care Pain (2004) 4(5): 144-147 doi:10.1093/bjaceaccp/mkh040

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:02

Subclinical hyperthyroidism

Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as:

·         normal serum free thyroxine and triiodothyronine levels

·         with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)

Causes

·         multinodular goitre, particularly in elderly females

·         excessive thyroxine may give a similar biochemical picture

The importance in recognising subclinical hyperthyroidism lies in the potential effect on the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and increase the likelihood of dementia

 

Management

·         TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention

·         a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:02

Sulfonylureas: side-effects

Common adverse effects

·         hypoglycaemic episodes (more common with long acting preparations such as chlorpropamide)

·         weight gain

Rarer adverse effects

·         syndrome of inappropriate ADH secretion

·         bone marrow suppression

·         liver damage (cholestatic)

·         peripheral neuropathy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:02

Thyrotoxicosis: causes and investigation

Graves' disease accounts for around 50-60% of cases of thyrotoxicosis.

 

Causes

·         Graves' disease

·         toxic nodular goitre

·         acute phase of subacute (de Quervain's) thyroiditis

·         acute phase of post-partum thyroiditis

·         acute phase of Hashimoto's thyroiditis (later results in hypothyroidism)

·         amiodarone therapy

Investigation

·         TSH down, T4 and T3 up

·         thyroid autoantibodies

·         other investigations are not routinely done but includes isotope scanning

 

 

 

Venn diagram showing how different causes of thyroid dysfunction may manifest. Note how many causes of hypothyroidism may have an initial thyrotoxic phase.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:02

Thyrotoxicosis: features

General

·         Weight loss

·         'Manic', restlessness

·         Heat intolerance

Cardiac

·         palpitations, tachycardia

·         high-output cardiac failure may occur in elderly patients, a reversible cardiomyopathy can rarely develop

Skin

·         Increased sweating

·         Pretibial myxoedema: erythematous, oedematous lesions above the lateral malleoli

·         Thyroid acropachy: clubbing

Gastrointestinal

·         Diarrhoea

Gynaecological

·         Oligomenorrhea

Neurological

·         Anxiety

·         Tremor

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

20:56

 

Diabetes mellitus: management of type 2

NICE updated its guidance on the management of type 2 diabetes mellitus (T2DM) in 2015. Key points are listed below:

·         HbA1c targets have changed. They are now dependent on what antidiabetic drugs a patient is receiving and other factors such as frailty

·         there is more flexibility in the second stage of treating patients (i.e. after metformin has been started) - you now have a choice of 4 oral antidiabetic agents

 

It's worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)

 

 

Dietary advice

·         encourage high fibre, low glycaemic index sources of carbohydrates

·         include low-fat dairy products and oily fish

·         control the intake of foods containing saturated fats and trans fatty acids

·         limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake

·         discourage use of foods marketed specifically at people with diabetes

·         initial target weight loss in an overweight person is 5-10%

 

HbA1c targets

 

This is area which has changed in 2015

·         individual targets should be agreed with patients to encourage motivation

·         HbA1c should be checked every 3-6 months until stable, then 6 monthly

·         NICE encourage us to consider relaxing targets on 'a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes'

·         in 2015 the guidelines changed so HbA1c targets are now dependent on treatment:

Lifestyle or single drug treatment

 

 

Management of T2DM

HbA1c target

Lifestyle

48 mmol/mol (6.5%)

Lifestyle + metformin

48 mmol/mol (6.5%)

Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea)

53 mmol/mol (7.0%)

Practical examples

·         a patient is newly diagnosed with HbA1c and wants to try lifestyle treatment first. You agree a target of 48 mmol/mol (6.5%)

·         you review a patient 6 months after starting metformin. His HbA1c is 51 mmol/mol (6.8%). You increase his metformin from 500mg bd to 500mg tds and reinforce lifestyle factors

Patient already on treatment

 

 

Management of T2DM

HbA1c target

Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%)

53 mmol/mol (7.0%)

 

Drug treatment

 

The 2015 NICE guidelines introduced some changes into the management of type 2 diabetes. There are essentially two pathways, one for patients who can tolerate metformin, and one for those who can't:

 

 

 

 

Tolerates metformin:

·         metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions

·         if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list:

o    sulfonylurea

o    gliptin

o    pioglitazone

o    SGLT-2 inhibitor

·         if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:

o    metformin + gliptin + sulfonylurea

o    metformin + pioglitazone + sulfonylurea

o    metformin + sulfonylurea + SGLT-2 inhibitor

o    metformin + pioglitazone + SGLT-2 inhibitor

o    OR insulin therapy should be considered

Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)

·         if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if:

o    BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or

o    BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or

weight loss would benefit other significant obesity related comorbidities

·         only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months

Practical examples

·         you review an established type 2 diabetic on maximum dose metformin. Her HbA1c is 55 mmol/mol (7.2%). You do not add another drug as she has not reached the threshold of 58 mmol/mol (7.5%)

·         a type 2 diabetic is found to have a HbA1c of 62 mmol/mol (7.8%) at annual review. They are currently on maximum dose metformin. You elect to add a sulfonylurea

Cannot tolerate metformin or contraindicated

·         if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions, consider one of the following:

o    sulfonylurea

o    gliptin

o    pioglitazone

·         if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:

o    gliptin + pioglitazone

o    gliptin + sulfonylurea

o    pioglitazone + sulfonylurea

·         if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy

Starting insulin

·         metformin should be continued. In terms of other drugs NICE advice: 'Review the continued need for other blood glucose lowering therapies'

·         NICE recommend starting with human NPH insulin (isophane, intermediate acting) taken at bed-time or twice daily according to need

 

Risk factor modification

 

Hypertension

·         blood pressure targets are the same as for patients without type 2 diabetes (see table below)

·         ACE inhibitors are first-line

 

 

Clinic BP

ABPM / HBPM

Age < 80 years

140/90 mmHg

135/85 mmHg

Age > 80 years

150/90 mmHg

145/85 mmHg

Antiplatelets

·         should not be offered unless a patient has existing cardiovascular disease

Lipids

·         following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on

 

 

 

Graphic showing choice of statin.

*this is a bit confusing because isn't the diagnostic criteria for T2DM HbA1c 48 mmol/mol (6.5%)? So shouldn't all patients be offered metformin at diagnosis? Our interpretation of this is that some patients upon diagnosis will elect to try lifestyle measures, which may reduce their HbA1c below this level. If it then rises to the diagnostic threshold again metformin should be offered

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

21 December 2020

21:48

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) may be a complication existing type 1 diabetes mellitus or be the first presentation, accounting for around 6% of cases. Rarely, under conditions of extreme stress, patients with type 2 diabetes mellitus may also develop DKA.

 

Whilst DKA remains a serious condition mortality rates have decreased from 8% to under 1% in the past 20 years.

 

Pathophysiology

·         DKA is caused by uncontrolled lipolysis (not proteolysis) which results in an excess of free fatty acids that are ultimately converted to ketone bodies

The most common precipitating factors of DKA are infection, missed insulin doses and myocardial infarction.

 

Features

·         abdominal pain

·         polyuria, polydipsia, dehydration

·         Kussmaul respiration (deep hyperventilation)

·         Acetone-smelling breath ('pear drops' smell)

Diagnostic criteria

 

 

American Diabetes Association (2009)

Joint British Diabetes Societies (2013)

Key points

·         glucose > 13.8 mmol/l

·         pH < 7.30

·         serum bicarbonate <18 mmol/l

·         anion gap > 10

·         ketonaemia

Key points

·         glucose > 11 mmol/l or known diabetes mellitus

·         pH < 7.3

·         bicarbonate < 15 mmol/l

·         ketones > 3 mmol/l or urine ketones ++ on dipstick

Management

·         fluid replacement: most patients with DKA are deplete around 5-8 litres. Isotonic saline is used initially. Please see an example fluid regime below.

·         insulin: an intravenous infusion should be started at 0.1 unit/kg/hour. Once blood glucose is < 15 mmol/l an infusion of 5% dextrose should be started

·         correction of hypokalaemia

·         long-acting insulin should be continued, short-acting insulin should be stopped

JBDS example of fluid replacement regime for patient with a systolic BP on admission 90mmHg and over

 

 

Fluid

Volume

0.9% sodium chloride 1L

1000ml over 1st hour

0.9% sodium chloride 1L with potassium chloride

1000ml over next 2 hours

0.9% sodium chloride 1L with potassium chloride

1000ml over next 2 hours

0.9% sodium chloride 1L with potassium chloride

1000ml over next 4 hours

0.9% sodium chloride 1L with potassium chloride

1000ml over next 4 hours

0.9% sodium chloride 1L with potassium chloride

1000ml over next 6 hours

Please note that slower infusion may be indicated in young adults (aged 18-25 years) as they are at greater risk of cerebral oedema.

 

JBDS potassium guidelines

 

 

Potassium level in first 24 hours (mmol/L)

Potassium replacement in mmol/L of infusion solution

Over 5.5

Nil

3.5-5.5

40

Below 3.5

Senior review as additional potassium needs to be given

Complications of DKA and its treatment

·         gastric stasis

·         thromboembolism

·         arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia

·         iatrogenic due to incorrect fluid therapy: cerebral oedema*, hypokalaemia, hypoglycaemia

·         acute respiratory distress syndrome

·         acute kidney injury

* children/young adults are particularly vulnerable to cerebral oedema following fluid resuscitation in DKA and often need 1:1 nursing to monitor neuro-observations, headache, irritability, visual disturbance, focal neurology etc. It usually occurs 4-12 hours following commencement of treatment but can present at any time. If there is any suspicion a CT head and senior review should be sought

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

16:16

Diabetes mellitus (type 2): diagnosis

The diagnosis of type 2 diabetes mellitus can be made by either a plasma glucose or a HbA1c sample. Diagnostic criteria vary according to whether the patient is symptomatic (polyuria, polydipsia etc) or not.

 

If the patient is symptomatic:

·         fasting glucose greater than or equal to 7.0 mmol/l

·         random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)

If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.

 

 

 

 

 

Diagram showing the spectrum of diabetes diagnosis

 

 

In 2011 WHO released supplementary guidance on the use of HbA1c on the diagnosis of diabetes:

·         a HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus

·         a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)

·         in patients without symptoms, the test must be repeated to confirm the diagnosis

·         it should be remembered that misleading HbA1c results can be caused by increased red cell turnover (see below)

Conditions where HbA1c may not be used for diagnosis:

·         haemoglobinopathies

·         haemolytic anaemia

·         untreated iron deficiency anaemia

·         suspected gestational diabetes

·         children

·         HIV

·         chronic kidney disease

·         people taking medication that may cause hyperglycaemia (for example corticosteroids)

Impaired fasting glucose and impaired glucose tolerance

 

A fasting glucose greater than or equal to 6.1 but less than 7.0 mmol/l implies impaired fasting glucose (IFG)

 

Impaired glucose tolerance (IGT) is defined as fasting plasma glucose less than 7.0 mmol/l and OGTT 2-hour value greater than or equal to 7.8 mmol/l but less than 11.1 mmol/l

 

Diabetes UK suggests:

·         'People with IFG should then be offered an oral glucose tolerance test to rule out a diagnosis of diabetes. A result below 11.1 mmol/l but above 7.8 mmol/l indicates that the person doesn't have diabetes but does have IGT.'

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:48

Addisonian crisis

Causes

·         sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison's, Hypopituitarism)

·         adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)

·         steroid withdrawal

Management

·         hydrocortisone 100 mg im or iv

·         1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic

·         continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action

·         oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

Features of an addisonian crisis:

·         Hyponatraemia

·         Hyperkalaemia

·         Hypoglycaemia

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

22 December 2020

19:10

Corticosteroids

Corticosteroids are amongst the most commonly prescribed therapies in clinical practice. They are used both systemically (oral or intravenous) or locally (skin creams, inhalers, eye drops, intra-articular). They augment and in some cases replace the natural glucocorticoid and mineralocorticoid activity of endogenous steroids.

 

The relative glucocorticoid and mineralocorticoid activity of commonly used steroids is shown below:

 

 

Minimal glucocorticoid activity, very high mineralocorticoid activity,

Glucocorticoid activity, high mineralocorticoid activity,

Predominant glucocorticoid activity, low mineralocorticoid activity

Very high glucocorticoid activity, minimal mineralocorticoid activity

Fludrocortisone

Hydrocortisone

Prednisolone

Dexamethasone

Betmethasone

Side-effects

 

The side-effects of corticosteroids are numerous and represent the single greatest limitation on their usage. Side-effects are more common with systemic and prolonged therapy.

 

Glucocorticoid side-effects

·         endocrine: impaired glucose regulation, increased appetite/weight gain, hirsutism, hyperlipidaemia

·         Cushing's syndrome: moon face, buffalo hump, striae

·         musculoskeletal: osteoporosis, proximal myopathy, avascular necrosis of the femoral head

·         immunosuppression: increased susceptibility to severe infection, reactivation of tuberculosis

·         psychiatric: insomnia, mania, depression, psychosis

·         gastrointestinal: peptic ulceration, acute pancreatitis

·         ophthalmic: glaucoma, cataracts

·         suppression of growth in children

·         intracranial hypertension

·         neutrophilia

Mineralocorticoid side-effects

·         fluid retention

·         hypertension

Selected points on the use of corticosteroids:

·         patients on long-term steroids should have their doses doubled during intercurrent illness

·         the BNF suggests gradual withdrawal of systemic corticosteroids if patients have: received more than 40mg prednisolone daily for more than one week, received more than 3 weeks treatment or recently received repeated courses

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

20:51

Phaeochromocytoma

Pheochromocytoma

Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome

 

Basics

·         bilateral in 10%

·         malignant in 10%

·         extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)

Features are typically episodic

·         hypertension (around 90% of cases, may be sustained)

·         headaches

·         palpitations

·         sweating

·         anxiety

Tests

·         24 hr urinary collection of metanephrines (sensitivity 97%*)

·         this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)

Surgery is the definitive management. The patient must first however be stabilized with medical management:

·         alpha-blocker (e.g. phenoxybenzamine), given before a

·         beta-blocker (e.g. propranolol)

*BMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e1042 (Published 20 February 2012

 

Labetalol has both alpha and beta action

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

 

 

22 December 2020

18:01

Thyroid cancer

Features of hyperthyroidism or hypothyroidism are not commonly seen in patients with thyroid malignancies as they rarely secrete thyroid hormones

 

Main points

 

 

Type

Percentage

 

Papillary

70%

Often young females - excellent prognosis

Follicular

20%

 

Medullary

5%

Cancer of parafollicular (C) cells, secrete calcitonin, part of MEN-2

Anaplastic

1%

Not responsive to treatment, can cause pressure symptoms

Lymphoma

Rare

Associated with Hashimoto's thyroiditis

Management of papillary and follicular cancer

·         total thyroidectomy

·         followed by radioiodine (I-131) to kill residual cells

·         yearly thyroglobulin levels to detect early recurrent disease

Further information

 

 

Type

Notes

Papillary carcinoma

·         Usually contain a mixture of papillary and colloidal filled follicles

·         Histologically tumour has papillary projections and pale empty nuclei

·         Seldom encapsulated

·         Lymph node metastasis predominate

·         Haematogenous metastasis rare

Follicular adenoma

·         Usually present as a solitary thyroid nodule

·         Malignancy can only be excluded on formal histological assessment

Follicular carcinoma

·         May appear macroscopically encapsulated, microscopically capsular invasion is seen. Without this finding the lesion is a follicular adenoma.

·         Vascular invasion predominates

·         Multifocal disease raree

Medullary carcinoma

·         C cells derived from neural crest and not thyroid tissue

·         Serum calcitonin levels often raised

·         Familial genetic disease accounts for up to 20% cases

·         Both lymphatic and haematogenous metastasis are recognised, nodal disease is associated with a very poor prognosis.

Anaplastic carcinoma

·         Most common in elderly females

·         Local invasion is a common feature

·         Treatment is by resection where possible, palliation may be achieved through isthmusectomy and radiotherapy. Chemotherapy is ineffective.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:48

Diabetes mellitus: management of type 1

The long-term management of type 1 diabetics is an important and complex process requiring the input of many different clinical specialties and members of the healthcare team. A diagnosis of type 1 diabetes can still reduce the life expectancy of patients by 13 years and the micro and macrovascular complications are well documented.

 

NICE released guidelines on the diagnosis and management of type 1 diabetes in 2015. We've only highlighted a very select amount of the guidance here which will be useful for any clinician looking after a patient with type 1 diabetes.

 

HbA1c

·         should be monitored every 3-6 months

·         adults should have a target of HbA1c level of 48 mmol/mol (6.5%) or lower. NICE do however recommend taking into account factors such as the person's daily activities, aspirations, likelihood of complications, comorbidities, occupation and history of hypoglycaemia

Self-monitoring of blood glucose

·         recommend testing at least 4 times a day, including before each meal and before bed

·         more frequent monitoring is recommended if frequency of hypoglycaemic episodes increases; during periods of illness; before, during and after sport; when planning pregnancy, during pregnancy and while breastfeeding

Blood glucose targets

·         5-7 mmol/l on waking and

·         4-7 mmol/l before meals at other times of the day

Type of insulin

·         offer multiple daily injection basal–bolus insulin regimens, rather than twice‑daily mixed insulin regimens, as the insulin injection regimen of choice for all adults

·         twice‑daily insulin detemir is the regime of choice. Once-daily insulin glargine or insulin detemir is an alternative

·         offer rapid‑acting insulin analogues injected before meals, rather than rapid‑acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes

Metformin

·         NICE recommend considering adding metformin if the BMI >= 25 kg/m²

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

19:45

Diabetes mellitus: GLP-1 drugs

A number of drugs to treat diabetes mellitus have become available in recent years. Much research has focused around the role of glucagon-like peptide-1 (GLP-1), a hormone released by the small intestine in response to an oral glucose load

 

Whilst it is well known that insulin resistance and insufficient B-cell compensation occur other effects are also seen in type 2 diabetes mellitus (T2DM). In normal physiology an oral glucose load results in a greater release of insulin than if the same load is given intravenously - this known as the incretin effect. This effect is largely mediated by GLP-1 and is known to be decreased in T2DM.

 

Increasing GLP-1 levels, either by the administration of an analogue (glucagon-like peptide-1, GLP-1 mimetics, e.g. exenatide) or inhibiting its breakdown (dipeptidyl peptidase-4 ,DPP-4 inhibitors - the gliptins), is therefore the target of two recent classes of drug.

 

 

Glucagon-like peptide-1 (GLP-1) mimetics (e.g. exenatide)

 

Exenatide is an example of a glucagon-like peptide-1 (GLP-1) mimetic. These drugs increase insulin secretion and inhibit glucagon secretion. One of the major advances of GLP-1 mimetics is that they typically result in weight loss, in contrast to many medications such as insulin, sulfonylureas and thiazolidinediones. They are sometimes used in combination with insulin in T2DM to minimise weight gain.

 

Exenatide must be given by subcutaneous injection within 60 minutes before the morning and evening meals. It should not be given after a meal.

 

Liraglutide is the other GLP-1 mimetic currently available. One the main advantages of liraglutide over exenatide is that it only needs to be given once a day.

 

Both exenatide and liraglutide may be combined with metformin and a sulfonylurea. Standard release exenatide is also licensed to be used with basal insulin alone or with metformin. Please see the BNF for a more complete list of licensed indications.

 

NICE state the following:

 

 

Consider adding exenatide to metformin and a sulfonylurea if:

·         BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight, or

·         BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.

NICE like patients to have achieved a > 11 mmol/mol (1%) reduction in HbA1c and 3% weight loss after 6 months to justify the ongoing prescription of GLP-1 mimetics.

 

The major adverse effect of GLP-1 mimetics is nausea and vomiting. The Medicines and Healthcare products Regulatory Agency has issued specific warnings on the use of exenatide, reporting that is has been linked to severe pancreatitis in some patients.

 

 

Dipeptidyl peptidase-4 (DPP-4) inhibitors (e.g. Vildagliptin, sitagliptin)

 

Key points

·         DPP-4 inhibitors increase levels of incretins (GLP-1 and GIP)

·         oral preparation

·         trials to date show that the drugs are relatively well tolerated with no increased incidence of hypoglycaemia

·         do not cause weight gain

NICE guidelines on DPP-4 inhibitors

·         NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if further weight gain would cause significant problems, a thiazolidinedione is contraindicated or the person has had a poor response to a thiazolidinedione

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

22 December 2020

19:14

Glycosylated haemoglobin

Glycosylated haemoglobin (HbA1c) is the most widely used measure of long-term glycaemic control in diabetes mellitus. HbA1c is produced by the glycosylation of haemoglobin at a rate proportional to the glucose concentration. The level of HbA1c therefore is dependant on

·         red blood cell lifespan

·         average blood glucose concentration

A number of conditions can interfere with accurate HbA1c interpretation:

 

 

Lower-than-expected levels of HbA1c (due to reduced red blood cell lifespan)

Higher-than-expected levels of HbA1c (due to increased red blood cell lifespan)

Sickle-cell anaemia

GP6D deficiency

Hereditary spherocytosis

Vitamin B12/folic acid deficiency

Iron-deficiency anaemia

Splenectomy

HbA1c is generally thought to reflect the blood glucose over the previous '3 months' although there is some evidence it is weighed more strongly to glucose levels of the past 2-4 weeks. NICE recommend 'HbA1c should be checked every 3-6 months until stable, then 6 monthly'.

 

The relationship between HbA1c and average blood glucose is complex but has been studied by the Diabetes Control and Complications Trial (DCCT). A new internationally standardised method for reporting HbA1c has been developed by the International Federation of Clinical Chemistry (IFCC). This will report HbA1c in mmol per mol of haemoglobin without glucose attached.

 

 

HBA1c

(%)

Average plasma glucose

(mmol/l)

IFCC-HbA1c (mmol/mol)

5

5.5

 

6

7.5

42

7

9.5

53

8

11.5

64

9

13.5

75

10

15.5

 

11

17.5

 

12

19.5

 

From the above we can see that average plasma glucose = (2 * HbA1c) - 4.5

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21 December 2020

21:48

Gynaecomastia

Gynaecomastia describes an abnormal amount of breast tissue in males and is usually caused by an increased oestrogen:androgen ratio. It is important to differentiate the causes of galactorrhoea (due to the actions of prolactin on breast tissue) from those of gynaecomastia

 

Causes of gynaecomastia

·         physiological: normal in puberty

·         syndromes with androgen deficiency: Kallman's, Klinefelter's

·         testicular failure: e.g. mumps

·         liver disease

·         testicular cancer e.g. seminoma secreting hCG

·         ectopic tumour secretion

·         hyperthyroidism

·         haemodialysis

·         drugs: see below

Drug causes of gynaecomastia

·         spironolactone (most common drug cause)

·         cimetidine

·         digoxin

·         cannabis

·         finasteride

·         GnRH agonists e.g. goserelin, buserelin

·         oestrogens, anabolic steroids

Very rare drug causes of gynaecomastia

·         tricyclics

·         isoniazid

·         calcium channel blockers

·         heroin

·         busulfan

·         methyldopa

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

20:23

Hypothyroidism: management

Key points

·         initial starting dose of levothyroxine should be lower in elderly patients and those with ischaemic heart disease. The BNF recommends that for patients with cardiac disease, severe hypothyroidism or patients over 50 years the initial starting dose should be 25mcg od with dose slowly titrated. Other patients should be started on a dose of 50-100mcg od

·         following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks

·         the therapeutic goal is 'normalisation' of the thyroid stimulating hormone (TSH) level. As the majority of unaffected people have a TSH value 0.5-2.5 mU/l it is now thought preferable to aim for a TSH in this range

·         women with established hypothyroidism who become pregnant should have their dose increased 'by at least 25-50 micrograms levothyroxine'* due to the increased demands of pregnancy. The TSH should be monitored carefully, aiming for a low-normal value

·         there is no evidence to support combination therapy with levothyroxine and liothyronine

Side-effects of thyroxine therapy

·         hyperthyroidism: due to over treatment

·         reduced bone mineral density

·         worsening of angina

·         atrial fibrillation

Interactions

·         iron, calcium carbonate

o    absorption of levothyroxine reduced, give at least 4 hours apart

*source: NICE Clinical Knowledge Summaries

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

22 December 2020

19:12

 

Multiple endocrine neoplasia

The table below summarises the three main types of multiple endocrine neoplasia (MEN). MEN is inherited as an autosomal dominant disorder.

 

Men-2 Men-1

 

MEN type I

MEN type IIa

MEN type IIb

3 P's

Parathyroid (95%): hyperparathyroidism due to parathyroid hyperplasia

Pituitary (70%)

Pancreas (50%): e.g. insulinoma, gastrinoma (leading to recurrent peptic ulceration)

 

Also: adrenal and thyroid

Medullary thyroid cancer (70%)

 

2 P's

Parathyroid (60%)

Phaeochromocytoma

 

Medullary thyroid cancer

 

1 P

Phaeochromocytoma

 

Marfanoid body habitus

Neuromas

MEN1 gene

 

Most common presentation = hypercalcaemia

RET oncogene

RET oncogene

 

 

 

Venn diagram showing the different types of MEN and their associated features

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:48

Thiazolidinediones

Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance. Rosiglitazone was withdrawn in 2010 following concerns about the cardiovascular side-effect profile.

 

The PPAR-gamma receptor is an intracellular nuclear receptor. It's natural ligands are free fatty acids and it is thought to control adipocyte differentiation and function.

 

Adverse effects

·         weight gain

·         liver impairment: monitor LFTs

·         fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin

·         recent studies have indicated an increased risk of fractures

·         bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

19:53

 

 

 

 

Tuesday, 22 December 2020

23:33

Hashimoto's thyroiditis

Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is an autoimmune disorder of the thyroid gland. It is typically associated with hypothyroidism although there may be a transient thyrotoxicosis in the acute phase. It is 10 times more common in women

 

Features

·         features of hypothyroidism

·         goitre: firm, non-tender

·         anti-thyroid peroxidase (TPO) and also anti-thyroglobulin (Tg) antibodies

Associations

·         other autoimmune conditions e.g. coeliac disease, type 1 diabetes mellitus, vitiligo

·         Hashimoto's thyroiditis is associated with the development of MALT lymphoma

 

 

 

Venn diagram showing how different causes of thyroid dysfunction may manifest. Note how many causes of hypothyroidism may have an initial thyrotoxic phase.

 

 

 

 

21 December 2020

21:48

Thyroid storm

Thyroid storm is a rare but life-threatening complication of thyrotoxicosis. It is typically seen in patients with established thyrotoxicosis and is rarely seen as the presenting feature. Iatrogenic thyroxine excess does not usually result in thyroid storm.

 

Precipitating events:

·         thyroid or non-thyroidal surgery

·         trauma

·         infection

·         acute iodine load e.g. CT contrast media

Clinical features include:

·         fever > 38.5ºC

·         tachycardia

·         confusion and agitation

·         nausea and vomiting

·         hypertension

·         heart failure

·         abnormal liver function test - jaundice may be seen clinically

Management:

·         symptomatic treatment e.g. paracetamol

·         treatment of underlying precipitating event

·         beta-blockers: typically IV propranolol

·         anti-thyroid drugs: e.g. methimazole or propylthiouracil

·         Lugol's iodine

·         dexamethasone - e.g. 4mg IV qds - blocks the conversion of T4 to T3

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

20:52

Insulin therapy: side-effects

Hypoglycaemia

·         patients should be taught the signs of hypoglycaemia: sweating, anxiety, blurred vision, confusion, aggression

·         conscious patients should take 10-20g of a short-acting carbohydrate (e.g. a glass of Lucozade or non-diet drink, three or more glucose tablets, glucose gel)

·         every person treated with insulin should have a glucagon kit for emergencies where the patient is not able to orally ingest a short-acting carbohydrate

·         patients who have frequent hypoglycaemic episodes may develop reduced awareness. If this develops then allowing glycaemic control to slip for a period of time may restore their awareness

·         beta-blockers reduce hypoglycaemic awareness

Lipodystrophy

·         typically presents as atrophy/lumps of subcutaneous fat

·         can be prevented by rotating the injection site

·         may cause erractic insulin absorption

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

22 December 2020

17:06

Graves' disease: features

Graves' disease is the most common cause of thyrotoxicosis. It is typically seen in women aged 30-50 years.

 

Features

·         typical features of thyrotoxicosis

·         specific signs limited to Grave's (see below)

Features seen in Graves' but not in other causes of thyrotoxicosis

·         eye signs (30% of patients)

o    exophthalmos

o    ophthalmoplegia

·         pretibial myxoedema

·         thyroid acropachy, a triad of:

o    digital clubbing

o    soft tissue swelling of the hands and feet

o    periosteal new bone formation

Autoantibodies

·         TSH receptor stimulating antibodies (90%)

·         anti-thyroid peroxidase antibodies (75%)

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

17:08

 

SGLT-2 inhibitors

SGLT-2 inhibitors reversibly inhibit sodium-glucose co-transporter 2 (SGLT-2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.

 

Examples include canagliflozin, dapagliflozin and empagliflozin.

 

Important adverse effects include

·         urinary and genital infection (secondary to glycosuria). Fournier’s gangrene has also been reported

·         normoglycaemic ketoacidosis

·         increased risk of lower-limb amputation: feet should be closely monitored

Patients taking SGLT-2 drugs often lose weight, which can be beneficial in type 2 diabetes mellitus.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

Wednesday, 23 December 2020

00:27

Myxoedema coma

Myxoedema coma typically presents with confusion and hypothermia.

 

Myxoedema coma is a medical emergency requiring treatment with 

·         IV thyroid replacement

·         IV fluid

·         IV corticosteroids (until the possibility of coexisting adrenal insufficiency has been excluded)

·         electrolyte imbalance correction

·         sometimes rewarming

 

 

 

 

22 December 2020

19:28

Diabetes mellitus: management of type 1

The long-term management of type 1 diabetics is an important and complex process requiring the input of many different clinical specialties and members of the healthcare team. A diagnosis of type 1 diabetes can still reduce the life expectancy of patients by 13 years and the micro and macrovascular complications are well documented.

 

NICE released guidelines on the diagnosis and management of type 1 diabetes in 2015. We've only highlighted a very select amount of the guidance here which will be useful for any clinician looking after a patient with type 1 diabetes.

 

HbA1c

·         should be monitored every 3-6 months

·         adults should have a target of HbA1c level of 48 mmol/mol (6.5%) or lower. NICE do however recommend taking into account factors such as the person's daily activities, aspirations, likelihood of complications, comorbidities, occupation and history of hypoglycaemia

Self-monitoring of blood glucose

·         recommend testing at least 4 times a day, including before each meal and before bed

·         more frequent monitoring is recommended if frequency of hypoglycaemic episodes increases; during periods of illness; before, during and after sport; when planning pregnancy, during pregnancy and while breastfeeding

Blood glucose targets

·         5-7 mmol/l on waking and

·         4-7 mmol/l before meals at other times of the day

Type of insulin

·         offer multiple daily injection basal–bolus insulin regimens, rather than twice‑daily mixed insulin regimens, as the insulin injection regimen of choice for all adults

·         twice‑daily insulin detemir is the regime of choice. Once-daily insulin glargine or insulin detemir is an alternative

·         offer rapid‑acting insulin analogues injected before meals, rather than rapid‑acting soluble human or animal insulins, for mealtime insulin replacement for adults with type 1 diabetes

Metformin

·         NICE recommend considering adding metformin if the BMI >= 25 kg/m²

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

31 December 2020

19:58

 

 

 

Levothyroxine not associated with diabetes

31 December 2020

20:05

Levothyroxine is not associated with inducing diabetes. In patients with diabetes starting thyroxine, doses of antidiabetic drugs including insulin may need to be increased.

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

24 December 2020

14:25

Haematuria

The management of patients with haematuria is often difficult due to the absence of widely followed guidelines. It is sometimes unclear whether patients are best managed in primary care, by urologists or by nephrologists.

 

The terminology surrounding haematuria is changing. Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population.

 

Causes of transient or spurious non-visible haematuria

·         urinary tract infection

·         menstruation

·         vigorous exercise (this normally settles after around 3 days)

·         sexual intercourse

Causes of persistent non-visible haematuria

·         cancer (bladder, renal, prostate)

·         stones

·         benign prostatic hyperplasia

·         prostatitis

·         urethritis e.g. Chlamydia

·         renal causes: IgA nephropathy, thin basement membrane disease

Spurious causes - red/orange urine, where blood is not present on dipstick

·         foods: beetroot, rhubarb

·         drugs: rifampicin, doxorubicin

Management

 

Current evidence does not support screening for haematuria. The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population hence these patients should also be investigated.

 

Testing

·         urine dipstick is the test of choice for detecting haematuria

·         persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart

·         renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked

·         urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected

NICE urgent cancer referral guidelines were updated in 2015.

 

Urgent referral (i.e. within 2 weeks)

 

Aged >= 45 years AND:

·         unexplained visible haematuria without urinary tract infection, or

·         visible haematuria that persists or recurs after successful treatment of urinary tract infection

Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test

 

Non-urgent referral

 

Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection

 

Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note:

·         patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Hyperkalaemia: management

Untreated hyperkalaemia may cause life-threatening arrhythmias. Precipitating factors should be addressed (e.g. acute renal failure) and aggravating drugs stopped (e.g. ACE inhibitors). Management may be categorised by the aims of treatment

 

Stabilisation of the cardiac membrane

·         intravenous calcium gluconate

o    does NOT lower serum potassium levels

Short-term shift in potassium from extracellular to intracellular fluid compartment

·         combined insulin/dextrose infusion

·         nebulised salbutamol

Removal of potassium from the body

·         calcium resonium (orally or enema)

o    enemas are more effective than oral as potassium is secreted by the rectum

·         loop diuretics

·         dialysis

o    haemofiltration/haemodialysis should be considered for patients with AKI with persistent hyperkalaemia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Diabetes insipidus

Diabetes insipidus (DI) is a condition characterised by either a deficiency of antidiuretic hormone, ADH, (cranial DI) or an insensitivity to antidiuretic hormone (nephrogenic DI).

 

Causes of cranial DI

·         idiopathic

·         post head injury

·         pituitary surgery

·         craniopharyngiomas

·         histiocytosis X

·         DIDMOAD is the association of cranial Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy and Deafness (also known as Wolfram's syndrome)

·         haemochromatosis

Causes of nephrogenic DI

·         genetic: the more common form affects the vasopression (ADH) receptor, the less common form results from a mutation in the gene that encodes the aquaporin 2 channel

·         electrolytes: hypercalcaemia, hypokalaemia

·         drugs: demeclocycline, lithium

·         tubulo-interstitial disease: obstruction, sickle-cell, pyelonephritis

Features

·         polyuria

·         polydipsia

Investigation

·         high plasma osmolality, low urine osmolality

·         a urine osmolality of >700 mOsm/kg excludes diabetes insipidus

·         water deprivation test

Management

·         nephrogenic diabetes insipidus: thiazides, low salt/protein diet

- central diabetes insipidus can be treated with desmopressin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Haemolytic uraemic syndrome

Haemolytic uraemic syndrome is generally seen in young children and produces a triad of:

·         acute kidney injury

·         microangiopathic haemolytic anaemia

·         thrombocytopenia

Most cases are secondary (termed 'typical HUS'):

·         classically Shiga toxin-producing Escherichia coli (STEC) 0157:H7 ('verotoxigenic', 'enterohaemorrhagic'). This is the most common cause in children, accounting for over 90% of cases

·         pneumococcal infection

·         HIV

·         rare: systemic lupus erythematosus, drugs, cancer

Primary HUS ('atypical') is due to complement dysregulation.

 

Investigations

·         full blood count: anaemia, thrombocytopaenia, fragmented blood film

·         U&E: acute kidney injury

·         stool culture

o    looking for evidence of STEC infection

o    PCR for Shiga toxins

Management

·         treatment is supportive e.g. Fluids, blood transfusion and dialysis if required

·         there is no role for antibiotics, despite the preceding diarrhoeal illness in many patients

·         the indications for plasma exchange in HUS are complicated. As a general rule plasma exchange is reserved for severe cases of HUS not associated with diarrhoea

·         eculizumab (a C5 inhibitor monoclonal antibody) has evidence of greater efficiency than plasma exchange alone in the treatment of adult atypical HUS

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Minimal change disease

Minimal change disease nearly always presents as nephrotic syndrome, accounting for 75% of cases in children and 25% in adults.

 

The majority of cases are idiopathic, but in around 10-20% a cause is found:

·         drugs: NSAIDs, rifampicin

·         Hodgkin's lymphoma, thymoma

·         infectious mononucleosis

Pathophysiology

·         T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss

·         the resultant reduction of electrostatic charge → increased glomerular permeability to serum albumin

Features

·         nephrotic syndrome

·         normotension - hypertension is rare

·         highly selective proteinuria

o    only intermediate-sized proteins such as albumin and transferrin leak through the glomerulus

·         renal biopsy

o    normal glomeruli on light microscopy

o    electron microscopy shows fusion of podocytes and effacement of foot processes

Management

·         majority of cases (80%) are steroid-responsive

·         cyclophosphamide is the next step for steroid-resistant cases

Prognosis is overall good, although relapse is common. Roughly:

·         1/3 have just one episode

·         1/3 have infrequent relapses

·         1/3 have frequent relapses which stop before adulthood

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Renal transplant: HLA typing and graft failure

The human leucocyte antigen (HLA) system is the name given to the major histocompatibility complex (MHC) in humans. It is coded for on chromosome 6.

 

Some basic points on the HLA system

·         class 1 antigens include A, B and C. Class 2 antigens include DP,DQ and DR

·         when HLA matching for a renal transplant the relative importance of the HLA antigens are as follows DR > B > A

Graft survival

·         1 year = 90%, 10 years = 60% for cadaveric transplants

·         1 year = 95%, 10 years = 70% for living-donor transplants

Post-op problems

·         ATN of graft

·         vascular thrombosis

·         urine leakage

·         UTI

Hyperacute rejection (minutes to hours)

·         due to pre-existing antibodies against ABO or HLA antigens

·         an example of a type II hypersensitivity reaction

·         leads to widespread thrombosis of graft vessels → ischaemia and necrosis of the transplanted organ

·         no treatment is possible and the graft must be removed

Acute graft failure (< 6 months)

·         usually due to mismatched HLA. Cell-mediated (cytotoxic T cells)

·         other causes include cytomegalovirus infection

·         may be reversible with steroids and immunosuppressants

Causes of chronic graft failure (> 6 months)

·         both antibody and cell mediated mechanisms cause fibrosis to the transplanted kidney (chronic allograft nephropathy)

·         recurrence of original renal disease (MCGN > IgA > FSGS)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Acute interstitial nephritis

Acute interstitial nephritis accounts for 25% of drug-induced acute kidney injury.

 

Causes

·         drugs: the most common cause, particularly antibiotics

o    penicillin

o    rifampicin

o    NSAIDs

o    allopurinol

o    furosemide

·         systemic disease: SLE, sarcoidosis, and Sjögren's syndrome

·         infection: Hanta virus , staphylococci

Pathophysiology

·         histology: marked interstitial oedema and interstitial infiltrate in the connective tissue between renal tubules

Features

·         fever, rash, arthralgia

·         eosinophilia

·         mild renal impairment

·         hypertension

Investigations

·         sterile pyuria

·         white cell casts

 

Tubulointerstitial nephritis with uveitis

 

Tubulointerstitial nephritis with uveitis (TINU) usually occurs in young females. Symptoms include fever, weight loss and painful, red eyes. Urinalysis is positive for leukocytes and protein.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Acute kidney injury: acute tubular necrosis vs. prerenal uraemia

 

Pre-renal uraemia ('azotemia')

Acute tubular necrosis

Urine sodium

< 20 mmol/L

> 40 mmol/L

Urine osmolality

> 500 mOsm/kg

< 350 mOsm/kg

Fractional sodium excretion*

< 1%

> 1%

Response to fluid challenge

Good

Poor

Serum urea:creatinine ratio

Raised

Normal

Fractional urea excretion**

< 35%

>35%

Urine:plasma osmolality

> 1.5

< 1.1

Urine:plasma urea

> 10:1

< 8:1

Specific gravity

> 1020

< 1010

Urine

Normal/ 'bland' sediment

Brown granular casts

Prerenal uraemia - kidneys hold on to sodium to preserve volume

 

 

*fractional sodium excretion = (urine sodium/plasma sodium) / (urine creatinine/plasma creatinine) x 100

 

**fractional urea excretion = (urine urea /blood urea ) / (urine creatinine/plasma creatinine) x 100

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

ADPKD: features

Features

·         hypertension

·         recurrent UTIs

·         abdominal pain

·         renal stones

·         haematuria

·         chronic kidney disease

Extra-renal manifestations

·         liver cysts (70% - the commonest extra-renal manifestation): may cause hepatomegaly

·         berry aneurysms (8%): rupture can cause subarachnoid haemorrhage

·         cardiovascular system: mitral valve prolapse, mitral/tricuspid incompetence, aortic root dilation, aortic dissection

·         cysts in other organs: pancreas, spleen; very rarely: thyroid, oesophagus, ovary

 

 

© Image used on license from PathoPic

Extensive cysts are seen in an enlarged kidney

 

 

© Image used on license from Radiopaedia

CT of the abdomen demonstrates both kidneys to be markedly enlarged by innumerable cysts ranging in size from a few millimeters to multiple centimeters with cysts also present in the liver

 

 

© Image used on license from Radiopaedia

CT showing multiple cysts of varying sizes in the liver, and bilateral kidneys with little remaining normal renal parenchyma.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:25

Chronic kidney disease: mineral bone disease management

Pathophysiology

 

Basic problems in chronic kidney disease (CKD):

·         1-alpha hydroxylation normally occurs in the kidneys → CKD leads to low vitamin D

·         the kidneys normally excrete phosphate → CKD leads to high phosphate

This, in turn, causes other problems:

·         the high phosphate level 'drags' calcium from the bones, resulting in osteomalacia

·         low calcium: due to lack of vitamin D, high phosphate

·         secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D

 

Management

 

The aim is to reduce phosphate and parathyroid hormone levels.

 

Overview

·         reduced dietary intake of phosphate is the first-line management

·         phosphate binders

·         vitamin D: alfacalcidol, calcitriol

·         parathyroidectomy may be needed in some cases

Phosphate binders

·         aluminium-based binders are less commonly used now

·         calcium-based binders

o    problems include hypercalcemia and vascular calcification

·         sevelamer

o    a non-calcium based binder that is now increasingly used

o    binds to dietary phosphate and prevents its absorption

o    also appears to have other beneficial effects including reducing uric acid levels and improving the lipid profiles of patients with chronic kidney disease

 

 

© Image used on license from Radiopaedia

X-ray of a Brown tumour caused by secondary hyperparathyroidism in a young female with chronic kidney disease

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Erythropoietin

Erythropoietin is a haematopoietic growth factor that stimulates the production of erythrocytes. Erythropoietin is secreted by the kidney in response to cellular hypoxia. The main uses of erythropoietin are to treat the anaemia associated with chronic kidney disease and that associated with cytotoxic therapy.

 

Side-effects of erythropoietin

·         accelerated hypertension potentially leading to encephalopathy and seizures (blood pressure increases in 25% of patients)

·         bone aches

·         flu-like symptoms

·         skin rashes, urticaria

·         pure red cell aplasia* (due to antibodies against erythropoietin)

·         raised PCV increases risk of thrombosis (e.g. Fistula)

·         iron deficiency 2nd to increased erythropoiesis

There are a number of reasons why patients may fail to respond to erythropoietin therapy:

·         iron deficiency

·         inadequate dose

·         concurrent infection/inflammation

·         hyperparathyroid bone disease

·         aluminium toxicity

*the risk is greatly reduced with darbepoetin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Acid - base disorders

Metabolic acidosis

 

Metabolic acidosis is commonly classified according to the anion gap.

 

Normal anion gap ( = hyperchloraemic metabolic acidosis)

·         gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula

·         renal tubular acidosis

·         drugs: e.g. acetazolamide

·         ammonium chloride injection

·         Addison's disease

Raised anion gap

·         lactate: shock, hypoxia

·         ketones: diabetic ketoacidosis, alcohol

·         urate: renal failure

·         acid poisoning: salicylates, methanol

Metabolic alkalosis

 

Metabolic alkalosis may be caused by a loss of hydrogen ions or a gain of bicarbonate. It is due mainly to problems of the kidney or gastrointestinal tract

 

Causes

·         vomiting / aspiration (e.g. peptic ulcer leading to pyloric stenos, nasogastric suction)

·         diuretics

·         liquorice, carbenoxolone

·         hypokalaemia

·         primary hyperaldosteronism

·         Cushing's syndrome

·         Bartter's syndrome

·         congenital adrenal hyperplasia

Respiratory acidosis

 

Respiratory acidosis may be caused by a number of conditions

·         COPD

·         decompensation in other respiratory conditions e.g. life-threatening asthma / pulmonary oedema

·         sedative drugs: benzodiazepines, opiate overdose

Respiratory alkalosis

 

Common causes

·         anxiety leading to hyperventilation

·         pulmonary embolism

·         salicylate poisoning

·         CNS disorders: stroke, subarachnoid haemorrhage, encephalitis

·         altitude

·         pregnancy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Acute vs. chronic renal failure

Best way to differentiate is renal ultrasound - most patients with CRF have bilateral small kidneys

 

Exceptions

·         autosomal dominant polycystic kidney disease

·         diabetic nephropathy

·         amyloidosis

·         HIV-associated nephropathy

Other features suggesting CRF rather than ARF

·         hypocalcaemia (due to lack of vitamin D)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Chronic kidney disease: proteinuria

Proteinuria is an important marker of chronic kidney disease, especially for diabetic nephropathy. NICE recommend using the albumin:creatinine ratio (ACR) in preference to the protein:creatinine ratio (PCR) when identifying patients with proteinuria as it has greater sensitivity. For quantification and monitoring of proteinuria, PCR can be used as an alternative, although ACR is recommended in diabetics. Urine reagent strips are not recommended unless they express the result as an ACR

 

Approximate equivalent values

 

 

ACR (mg/mmol)

PCR (mg/mmol)

Urinary protein excretion (g/24 h)

30

50

0.5

70

100

1

Collecting an ACR sample

·         by collecting a 'spot' sample it avoids the need to collect urine over a 24 hour period in order to detect or quantify proteinuria

·         should be a first-pass morning urine specimen

·         if the initial ACR is between 3 mg/mmol and 70 mg/mmol, this should be confirmed by a subsequent early morning sample. If the initial ACR is 70 mg/mmol or more, a repeat sample need not be tested.

Interpreting the ACR results

·         the NICE guidelines state 'regard a confirmed ACR of 3 mg/mmol or more as clinically important proteinuria'

NICE recommendations for referral to a nephrologist:

·         a urinary albumin:creatinine ratio (ACR) of 70 mg/mmol or more, unless known to be caused by diabetes and already appropriately treated

·         a urinary ACR of 30 mg/mmol or more, together with persistent haematuria (two out of three dipstick tests show 1+ or more of blood) after exclusion of a urinary tract infection

·         consider referral to a nephrologist for people with an ACR between 3-29 mg/mmol who have persistent haematuria and other risk factors such as a declining eGFR, or cardiovascular disease

Frequency of monitoring eGFR (number of times per year by eGFR and ACR categories) for people with or at risk of CKD

 

 

eGFR categories (mL/min/1.73 m2)

ACR categories (mg/mmol)

 

 

 

A1 (< 3) Normal to mildly increased

A2 (3-30) Moderately increased

A3 (> 30) Severely increased

G1 >=90 Normal and high

=< 1

1

>= 1

G2 60-89 Mild reduction related to normal range for a young adult

=< 1

1

>= 1

G3a 45-59 Mild to moderate reduction

1

1

2

G3b 30-44 Moderate to severe reduction

=< 2

2

>= 2

G4 15-29 Severe reduction

2

2

3

G5 <15 Kidney failure

4

>=4

>=4

Management

·         ACE inhibitors (or angiotensin II receptor blockers) are key in the management of proteinuria

o    they should be used first-line in patients with coexistent hypertension and CKD

o    if the ACR > 70 mg/mmol they are indicated regardless of the patient's blood pressure

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Membranous glomerulonephritis

Membranous glomerulonephritis is the commonest type of glomerulonephritis in adults and is the third most common cause of end-stage renal failure (ESRF). It usually presents with nephrotic syndrome or proteinuria.

 

Renal biopsy demonstrates:

·         electron microscopy: the basement membrane is thickened with subepithelial electron dense deposits. This creates a 'spike and dome' appearance

Causes

·         idiopathic: due to anti-phospholipase A2 antibodies

·         infections: hepatitis B, malaria, syphilis

·         malignancy (in 5-20%): prostate, lung, lymphoma, leukaemia

·         drugs: gold, penicillamine, NSAIDs

·         autoimmune diseases: systemic lupus erythematosus (class V disease), thyroiditis, rheumatoid

Management

·         all patients should receive an ACE inhibitor or an angiotensin II receptor blocker (ARB):

o    these have been shown to reduce proteinuria and improve prognosis

·         immunosuppression

o    as many patients spontaneously improve only patient with severe or progressive disease require immunosuppression

o    corticosteroids alone have not been shown to be effective. A combination of corticosteroid + another agent such as cyclophosphamide is often used

·         consider anticoagulation for high-risk patients

Prognosis - rule of thirds

·         one-third: spontaneous remission

·         one-third: remain proteinuric

·         one-third: develop ESRF

Good prognostic features include female sex, young age at presentation and asymptomatic proteinuria of a modest degree at the time of presentation.

 

 

 

© Image used on license from PathoPic

Silver-stained section showing thickened basement membrane, subepithelial spikes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Nephrotic syndrome

Triad of:

·         1. Proteinuria (> 3g/24hr) causing

·         2. Hypoalbuminaemia (< 30g/L) and

·         3. Oedema

Loss of antithrombin-III, proteins C and S and an associated rise in fibrinogen levels predispose to thrombosis. Loss of thyroxine-binding globulin lowers the total, but not free, thyroxine levels.

 

 

 

 

Diagram showing the glomerulonephritides and how they typically present

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Peritoneal dialysis

Peritoneal dialysis (PD) is a form of renal replacement therapy. It is sometimes used as a stop-gap to haemodialysis or for younger patients who do not want to have to visit hospital three times a week.

 

The majority of patients do Continuous Ambulatory Peritoneal Dialysis (CAPD), which involves four 2-litre exchanges/day.

 

Complications

·         peritonitis: coagulase-negative staphylococci such as Staphylococcus epidermidis is the most common cause. Staphylococcus aureus is another common cause

·         sclerosing peritonitis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Acute kidney injury: pathophysiology

Basic steps

·         Final pathway is tubular cell death.

·         renal medulla is a relatively hypoxic environment making it susceptible to renal tubular hypoxia.

·         Renovascular autoregulation maintains renal blood flow across a range of arterial pressures.

·         Estimates of GFR are the best indices of renal function. Useful clinical estimates can be obtained by considering serum creatinine, age, race, gender and body size. eGFR calculations such as the Cockcroft and Gault equation are less reliable in populations with high GFRs.

·         Nephrotoxic stimuli such as aminoglycosides and radiological contrast media induce apoptosis. Myoglobinuria and haemolysis result in necrosis. Overlap exists and proinflammatory cytokines play and important role in potentiating ongoing damage.

·         Post-operative renal failure is more likely to occur in patients who are elderly, have peripheral vascular disease, high BMI, have COPD, receive vasopressors, are on nephrotoxic medication or undergo emergency surgery.

·         Avoiding hypotension will reduce the risk of renal tubular damage.

·         There is no evidence that administration of ACE inhibitors or dopamine reduces the incidence of post-operative renal failure.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:26

Alport's syndrome

Alport's syndrome is usually inherited in an X-linked dominant pattern*. It is due to a defect in the gene which codes for type IV collagen resulting in an abnormal glomerular-basement membrane (GBM). The disease is more severe in males with females rarely developing renal failure.

 

A favourite question is an Alport's patient with a failing renal transplant. This may be caused by the presence of anti-GBM antibodies leading to a Goodpasture's syndrome like picture.

 

Alport's syndrome usually presents in childhood. The following features may be seen:

·         microscopic haematuria

·         progressive renal failure

·         bilateral sensorineural deafness

·         lenticonus: protrusion of the lens surface into the anterior chamber

·         retinitis pigmentosa

·         renal biopsy: splitting of lamina densa seen on electron microscopy

Diagnosis

·         molecular genetic testing

·         renal biopsy

o    electron microscopy: characteristic finding is of the longitudinal splitting of the lamina densa of the glomerular basement membrane, resulting in a 'basket-weave' appearance

*in around 85% of cases - 10-15% of cases are inherited in an autosomal recessive fashion with rare autosomal dominant variants existing

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Anti-glomerular basement membrane (GBM) disease (Goodpasture's syndrome)

Anti-glomerular basement membrane (GBM) disease (previously known as Goodpasture's syndrome) is a rare type of small-vessel vasculitis associated with both pulmonary haemorrhage and rapidly progressive glomerulonephritis. It is caused by anti-glomerular basement membrane (anti-GBM) antibodies against type IV collagen. Goodpasture's syndrome is more common in men (sex ratio 2:1) and has a bimodal age distribution (peaks in 20-30 and 60-70 age bracket). It is associated with HLA DR2.

 

Features

·         pulmonary haemorrhage

·         rapidly progressive glomerulonephritis

o    this typically results in a rapid onset acute kidney injury

o    nephritis → proteinuria + haematuria

Investigations

·         renal biopsy: linear IgG deposits along the basement membrane

·         raised transfer factor secondary to pulmonary haemorrhages

Management

·         plasma exchange (plasmapheresis)

·         steroids

·         cyclophosphamide

One of the main complications is pulmonary haemorrhage. Factors which increase the likelihood of this include:

·         smoking

·         lower respiratory tract infection

·         pulmonary oedema

·         inhalation of hydrocarbons

·         young males

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Arteriovenous fistulas

Arteriovenous fistulas are direct connections between arteries and veins. They may occur pathologically but are generally formed surgically to allow access for haemodialysis.

 

They are now regarded as the preferred method of access for haemodialysis due to the lower rates of complications.

 

The time taken for an arteriovenous fistula to develop is 6 to 8 weeks.

 

Potential complications include:

·         infection

·         thrombosis

o    may be detected by the absence of a bruit

·         stenosis

o    may present with acute limb pain

·         steal syndrome

 

 

Image sourced from Wikipedia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Chronic kidney disease: bone disease

Basic problems in chronic kidney disease

·         low vitamin D (1-alpha hydroxylation normally occurs in the kidneys)

·         high phosphate

·         low calcium: due to lack of vitamin D, high phosphate

·         secondary hyperparathyroidism: due to low calcium, high phosphate and low vitamin D

Several clinical manifestations may result:

 

Osteitis fibrosa cystica

·         aka hyperparathyroid bone disease

Adynamic

·         reduction in cellular activity (both osteoblasts and osteoclasts) in bone

·         may be due to over treatment with vitamin D

Osteomalacia

·         due to low vitamin D

Osteosclerosis

 

Osteoporosis

 

 

 

© Image used on license from Radiopaedia

X-ray of a Brown tumour caused by secondary hyperparathyroidism in a young female with chronic kidney disease

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Diabetic nephropathy: management

Screening

·         all patients should be screened annually using urinary albumin:creatinine ratio (ACR)

·         should be an early morning specimen

·         ACR > 2.5 = microalbuminuria

Management

·         dietary protein restriction

·         tight glycaemic control

·         BP control: aim for < 130/80 mmHg

·         benefits independent of blood pressure control have been demonstrated for ACE inhibitors (ACE-i) and angiotensin II receptor blockers (A2RB). Combinations of ACE-i and A2RB are not commonly used anymore following the ON-TARGET trial which showed worse outcomes for patients on dual blockade

·         control dyslipidaemia e.g. Statins

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

IgA nephropathy

IgA nephropathy (also known as Berger's disease) is the commonest cause of glomerulonephritis worldwide. It classically presents as macroscopic haematuria in young people following an upper respiratory tract infection.

 

Associated conditions

·         alcoholic cirrhosis

·         coeliac disease/dermatitis herpetiformis

·         Henoch-Schonlein purpura

Pathophysiology

·         thought to be caused by mesangial deposition of IgA immune complexes

·         there is considerable pathological overlap with Henoch-Schonlein purpura (HSP)

·         histology: mesangial hypercellularity, positive immunofluorescence for IgA & C3

Presentations

·         young male, recurrent episodes of macroscopic haematuria

·         typically associated with a recent respiratory tract infection

·         nephrotic range proteinuria is rare

·         renal failure is unusual and seen in a minority of patients

Differentiating between IgA nephropathy and post-streptococcal glomerulonephritis

·         post-streptococcal glomerulonephritis is associated with low complement levels

·         main symptom in post-streptococcal glomerulonephritis is proteinuria (although haematuria can occur)

·         there is typically an interval between URTI and the onset of renal problems in post-streptococcal glomerulonephritis

 

 

 

Management

·         steroids/immunosuppressants not be shown to be useful

Prognosis

·         25% of patients develop ESRF

·         markers of good prognosis: frank haematuria

·         markers of poor prognosis: male gender, proteinuria (especially > 2 g/day), hypertension, smoking, hyperlipidaemia, ACE genotype DD

 

 

© Image used on license from PathoPic

Proliferation and hypercellularity of the mesangium is seen in the glomerulus

 

 

© Image used on license from PathoPic

Immunostaining for IgA in a patient with HSP

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Nephrotic syndrome: complications

Complications

·         increased risk of thromboembolism related to loss of antithrombin III and plasminogen in the urine

o    deep vein thrombosis, pulmonary embolism

o    renal vein thrombosis, resulting in a sudden deterioration in renal function

·         hyperlipidaemia

o    increasing risk of acute coronary syndrome, stroke etc

·         chronic kidney disease

·         increased risk of infection due to urinary immunoglobulin loss

·         hypocalcaemia (vitamin D and binding protein lost in urine)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Nephrotoxicity due to contrast media

Contrast media nephrotoxicity may be defined as a 25% increase in creatinine occurring within 3 days of the intravascular administration of contrast media.

 

Risk factors include

·         known renal impairment (especially diabetic nephropathy)

·         age > 70 years

·         dehydration

·         cardiac failure

·         the use of nephrotoxic drugs such as NSAIDs

Contrast-induced nephropathy occurs 2 -5 days after administration.

 

Prevention

·         the evidence base currently supports the use of intravenous 0.9% sodium chloride at a rate of 1 mL/kg/hour for 12 hours pre- and post- procedure. There is also evidence to support the use of isotonic sodium bicarbonate

·         N-acetylcysteine has been given in the past but recent evidence suggests it is not effective*

* Outcomes after Angiography with Sodium Bicarbonate and Acetylcysteine. N Engl J Med. 2018;378(7):603

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Post-streptococcal glomerulonephritis

Post-streptococcal glomerulonephritis typically occurs 7-14 days following a group A beta-haemolytic Streptococcus infection (usually Streptococcus pyogenes). It is caused by immune complex (IgG, IgM and C3) deposition in the glomeruli. Young children are most commonly affected.

 

Features

·         general

o    headache

o    malaise

·         visible haematuria

·         proteinuria

o    this may result in oedema

·         hypertension

·         oliguria

·         bloods:

o    low C3

o    raised ASO titre

 

vi

 

 

IgA nephropathy and post-streptococcal glomerulonephritis are often confused as they both can cause renal disease following an URTI

Renal biopsy features

·         post-streptococcal glomerulonephritis causes acute, diffuse proliferative glomerulonephritis

·         endothelial proliferation with neutrophils

·         electron microscopy: subepithelial 'humps' caused by lumpy immune complex deposits

·         immunofluorescence: granular or 'starry sky' appearance

Carries a good prognosis

 

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:27

Renal replacement therapy

Chronic kidney disease (CKD) is a relatively common condition, affecting 1 in 8 people in the UK. Around 10% of those with CKD will go on to develop renal failure, which is defined as a glomerular filtration rate of less than 15ml/min. For patients with renal failure, the management options are renal replacement therapy (RRT), to take over the physiology of the kidneys, or conservative management, which will be palliative.

 

There are several types of renal replacement therapy available to patients:

·         haemodialysis

·         peritoneal dialysis

·         renal transplant

The decision about which RRT option to pick should be made jointly by the patient and their healthcare team, taking into account the following:

·         predicted quality of life

·         predicted life expectancy

·         patient preference

·         co-existing medical conditions

Haemodialysis is the most common form of renal replacement therapy. This involves regular filtration of the blood through a dialysis machine in hospital. Most patients need dialysis 3 times per week, with each session lasting 3-5 hours. At least 8 weeks before the commencement of treatment, the patient must undergo surgery to create an arteriovenous fistula, which provides the site for haemodialysis. Most commonly this is created in the lower arm. Some patients may be trained to perform home haemodialysis so that they do not have to regularly attend hospital.

 

Peritoneal dialysis is another form of renal replacement therapy where the filtration occurs within the patient's abdomen. Dialysis solution is injected into the abdominal cavity through a permanent catheter. The high dextrose concentration of the solution draws waste products from the blood into the abdominal cavity across the peritoneum. After several hours of dwell time, the dialysis solution is then drained, removing the waste products from the body, and exchanged for new dialysis solution. There are two types of peritoneal dialysis:

·         Continuous ambulatory peritoneal dialysis (CAPD) - as described above, with each exchange lasting 30-40 minutes and each dwell time lasting 4-8 hours. The patient may go about their normal activities with the dialysis solution inside their abdomen

·         Automated peritoneal dialysis (APD) - a dialysis machine fills and drains the abdomen while the patient is sleeping, performing 3-5 exchanges over 8-10 hours each night

Renal transplantation involves the receipt of a kidney from either a live or deceased donor. The average wait for a kidney in the UK is 3 years, though patients may also receive kidneys donated by cross-matched friends or family. The donor kidney is transplanted into the groin, with the renal vessels connected to the external iliac vessels. The failing kidneys are not removed. Following transplantation, the patient must take life-long immunosuppressants to prevent rejection of the new kidney. The average lifespan of a donor kidney is 10-12 years from deceased donors and 12-15 years from living donors.

 

Complications of renal replacement therapy

 

 

Haemodialysis

Peritoneal dialysis

Renal transplantation

Site infection

Peritonitis

DVT / PE

Endocarditis

Sclerosing peritonitis

Opportunistic infection

Stenosis at site

Catheter infection

Malignancies (particularly lymphoma and skin cancer)

Hypotension

Catheter blockage

Bone marrow suppression

Cardiac arrhythmia

Constipation

Recurrence of original disease

Air embolus

Fluid retention

Urinary tract obstruction

Anaphylactic reaction to sterilising agents

Hyperglycaemia

Cardiovascular disease

Disequilibration syndrome

Hernias

Graft rejection

 

Back pain

 

 

Malnutrition

 

The average life expectancy of a patient with renal failure that does not receive renal replacement therapy is 6 months. The symptoms of renal failure that is not being adequately managed with RRT are:

·         breathlessness

·         fatigue

·         insomnia

·         pruritus

·         poor appetite

·         swelling

·         weakness

·         weight gain/loss

·         abdominal cramps

·         nausea

·         muscle cramps

·         headaches

·         cognitive impairment

·         anxiety

·         depression

·         sexual dysfunction

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Renal transplant: immunosuppression

Example regime

·         initial: ciclosporin/tacrolimus with a monoclonal antibody

·         maintenance: ciclosporin/tacrolimus with MMF or sirolimus

·         add steroids if more than one steroid responsive acute rejection episode

Ciclosporin

·         inhibits calcineurin, a phosphotase involved in T cell activation

Tacrolimus

·         lower incidence of acute rejection compared to ciclosporin

·         also less hypertension and hyperlipidaemia

·         however, high incidence of impaired glucose tolerance and diabetes

Mycophenolate mofetil (MMF)

·         blocks purine synthesis by inhibition of IMPDH

·         therefore inhibits proliferation of B and T cells

·         side-effects: GI and marrow suppression

Sirolimus (rapamycin)

·         blocks T cell proliferation by blocking the IL-2 receptor

·         can cause hyperlipidaemia

Monoclonal antibodies

·         selective inhibitors of IL-2 receptor

·         daclizumab

·         basilximab

 

Monitoring

 

Patients on long-term immunosuppression for organ transplantation require regular monitoring for complications such as:

 

Cardiovascular disease - tacrolimus and ciclosporin can cause hypertension and hyperglycaemia. Tacrolimus can also cause hyperlipidaemia. Patients must be monitored for accelerated cardiovascular disease.

 

Renal failure - due to nephrotoxic effects of tacrolimus and ciclosporin/graft rejection/recurrence of original disease in transplanted kidney

 

Malignancy - patients should be educated about minimising sun exposure to reduce the risk of squamous cell carcinomas and basal cell carcinomas

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Spironolactone

Spironolactone is an aldosterone antagonist which acts in the cortical collecting duct.

 

Indications

·         ascites: patients with cirrhosis develop a secondary hyperaldosteronism. Relatively large doses such as 100 or 200mg are often used

·         hypertension: used in some patients as a NICE 'step 4' treatment

·         heart failure (see RALES study below)

·         nephrotic syndrome

·         Conn's syndrome

Adverse effects

·         hyperkalaemia

·         gynaecomastia: less common with eplerenone

RALES

·         NYHA III + IV, patients already taking ACE inhibitor

·         low dose spironolactone reduces all cause mortality

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Urine

Hyaline casts

·         consist of Tamm-Horsfall protein (secreted by distal convoluted tubule)

·         seen in normal urine, after exercise, during fever or with loop diuretics

Acute tubular necrosis

·         brown granular casts in urine

Prerenal uraemia

·         'bland' urinary sediment

Red cell casts

·         nephritic syndrome

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Acute kidney injury: NICE guidelines

This guideline tells what increases the risk of AKI:

·         1. Emergency surgery, ie, risk of sepsis or hypovolaemia

·         2. Intraperitoneal surgery

·         3. CKD, ie if eGFR < 60

·         4. Diabetes

·         5. Heart failure

·         6. Age >65 years

·         7. Liver disease

·         8. Use of nephrotoxic drugs

It also defines the criteria for diagnosing AKI

·         1. Rise in creatinine of 26 micromol/L or more in 48 hours OR

·         2. >= 50% rise in creatinine over 7 days OR

·         3. Fall in urine output to less than 0.5ml/kg/hour for more than 6 hours in adults (8 hours in children) OR

·         4. >= 25% fall in eGFR in children / young adults in 7 days.

Refer to a nephrologist if any of the following apply:

·         1. Renal tranplant

·         2. ITU patient with unknown cause of AKI

·         3. Vasculitis/ glomerulonephritis/ tubulointerstitial nephritis/ myeloma

·         4. AKI with no known cause

·         5. Inadequate response to treatment

·         6. Complications of AKI

·         7. Stage 3 AKI (see guideline for details)

·         8. CKD stage 4 or 5

·         9. Qualify for renal replacement hyperkalaemia / metabolic acidosis/ complications of uraemia/ fluid overload (pulmonary oedema)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Chronic kidney disease: hypertension

The majority of patients with chronic kidney disease (CKD) will require more than two drugs to treat hypertension. ACE inhibitors are first line and are particularly helpful in proteinuric renal disease (e.g. diabetic nephropathy). As these drugs tend to reduce filtration pressure a small fall in glomerular filtration pressure (GFR) and rise in creatinine can be expected. NICE suggest that a decrease in eGFR of up to 25% or a rise in creatinine of up to 30% is acceptable, although any rise should prompt careful monitoring and exclusion of other causes (e.g. NSAIDs). A rise greater than this may indicate underlying renovascular disease.

 

Furosemide is useful as a anti-hypertensive in patients with CKD, particularly when the GFR falls to below 45 ml/min*. It has the added benefit of lowering serum potassium. High doses are usually required. If the patient becomes at risk of dehydration (e.g. Gastroenteritis) then consideration should be given to temporarily stopping the drug

 

*the NKF K/DOQI guidelines suggest a lower cut-off of less than 30 ml/min

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Fibromuscular dysplasia

Renal artery stenosis secondary to atherosclerosis accounts for around 90% of renal vascular disease, with fibromuscular dysplasia being the most common cause of the remaining 10%.

 

Epidemiology

·         90% of patients are female

Features

·         hypertension

·         chronic kidney disease or more acute renal failure e.g. secondary to ACE-inhibitor initiation

·         'flash' pulmonary oedema

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Fluid compartment physiology

Body fluid compartments comprise intracellular and extracellular compartments. The latter includes interstitial fluid, plasma and transcellular fluid.

Typical figures are based on the 70 Kg male.

 

Body fluid volumes

 

Compartment

Volume in litres

Percentage of total volume

Intracellular

28 L

60-65%

Extracellular

14 L

35-40%

Plasma

3 L

5%

Interstitial

10 L

24%

Transcellular

1 L

3%

Figures are approximate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic syndrome and chronic kidney disease. It generally presents in young adults.

 

Causes

·         idiopathic

·         secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy

·         HIV

·         heroin

·         Alport's syndrome

·         sickle-cell

Focal segmental glomerulosclerosis is noted for having a high recurrence rate in renal transplants.

 

Investigations

·         renal biopsy

o    focal and segmental sclerosis and hyalinosis on light microscopy

o    effacement of foot processes on electron microscopy

Management

·         steroids +/- immunosuppressants

Prognosis

·         untreated FSGS has a < 10% chance of spontaneous remission

 

 

© Image used on license from PathoPic

Sclerosis of the glomerulus is seen next to Bowman's capsule

 

 

© Image used on license from PathoPic

Sclerosis is seen in the perihilar region of the glomerulus

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Hypokalaemia: features

Features

·         muscle weakness, hypotonia

·         hypokalaemia predisposes patients to digoxin toxicity - care should be taken if patients are also on diuretics

ECG features

·         U waves

·         small or absent T waves

·         prolonged PR interval

·         ST depression

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Polyuria

A recent review in the BMJ categorised the causes of polyuria by how common they were. This does not of course tally with how common they are in exams!

 

Common (>1 in 10)

·         diuretics, caffeine & alcohol

·         diabetes mellitus

·         lithium

·         heart failure

Infrequent (1 in 100)

·         hypercalcaemia

·         hyperthyroidism

Rare (1 in 1000)

·         chronic renal failure

·         primary polydipsia

·         hypokalaemia

Very rare (<1 in 10 000)

·         diabetes insipidus

 

Jakes A, Bhandari S. Investigating polyuria. BMJ 2013;347:f6772.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Reflux nephropathy

Overview

·         term used to chronic pyelonephritis secondary to vesico-uretic reflux

·         commonest cause of chronic pyelonephritis

·         scarring usually occurs in first 5 years

·         strong genetic disposition

·         renal scar may produce increased quantities of renin causing hypertension

Diagnosis

·         micturating cystography

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:28

Renal artery stenosis (secondary to atherosclerosis)

Renal artery stenosis secondary to atherosclerosis accounts for around 90% of renal vascular disease, with fibromuscular dysplasia being the most common cause of the remaining 10%.

 

Features

·         hypertension

·         chronic kidney disease

·         'flash pulmonary oedema'

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

Primary and secondary aldosteronism can be differentiated by looking at the renin levels. If renin is high then a secondary cause is more likely, i.e renal artery stenosis.

Renal artery stenosis - the patient has a high renin level and therefore a secondary aldosteronism is more likely. The reduced perfusion results in decreased stimulation of the baroreceptors (or stretch receptors) in the wall of the afferent arteriole. The renin–angiotensin–aldosterone system is activated and with the increased aldosterone the potassium may be low, and the sodium high.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

24 December 2020

14:28

Sterile pyuria

Causes

·         partially treated UTI

·         urethritis e.g. Chlamydia

·         renal tuberculosis

·         renal stones

·         appendicitis

·         bladder/renal cell cancer

·         adult polycystic kidney disease

·         analgesic nephropathy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:29

Systemic lupus erythematosus: renal complications

Lupus nephritis is a severe manifestation of systemic lupus erythematosus (SLE) that can result in end-stage renal disease. SLE patients should be monitored by performing urinalysis at regular check-up appointments to rule out proteinuria.

 

WHO classification

·         class I: normal kidney

·         class II: mesangial glomerulonephritis

·         class III: focal (and segmental) proliferative glomerulonephritis

·         class IV: diffuse proliferative glomerulonephritis

·         class V: diffuse membranous glomerulonephritis

·         class VI: sclerosing glomerulonephritis

Class IV (diffuse proliferative glomerulonephritis) is the most common and severe form. Renal biopsy characteristically shows the following findings:

·         glomeruli shows endothelial and mesangial proliferation, 'wire-loop' appearance

·         if severe, the capillary wall may be thickened secondary to immune complex deposition

·         electron microscopy shows subendothelial immune complex deposits

·         granular appearance on immunofluorescence

 

 

© Image used on license from PathoPic

Diffuse proliferative SLE. Proliferation of endothelial and mesangial cells. The thickening of the capillary wall results in a 'wire-loop' appearance. Some crescents are present.

Management

·         treat hypertension

·         corticosteroids if clinical evidence of disease

·         immunosuppressants e.g. azathioprine/cyclophosphamide

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

17:16

Acute kidney injury: a very basic introduction

Acute kidney injury (AKI), previously termed acute renal failure, describes a reduction in renal function following an insult to the kidneys. In years gone by the kidneys were very much a neglected organ in acute medicine - the recognition of decreasing renal function was often slow and action limited. Around 15% of patients admitted to hospital develop AKI.

 

Whilst most patients with AKI recover their renal function there are many patients who will have long term impaired kidney function due to AKI. As well as long-term morbidity, AKI may also result in acute complications including death. Whilst exact figures are difficult to calculate NICE estimate that inpatient mortality of AKI in the UK might typically be 25-30% or more.

 

Pre-renal:

·         Caused by inadequate renal perfusion e.g. dehydration, haemorrhage, heart failure, sepsis

·         Kidneys act to concentrate urine and retain sodium - urine osmolality high, urine sodium low

Renal:

·         Most common = acute tubular necrosis

·         Damage to tubular cells due to prolonged ischaemia or toxins

·         Kidneys can no longer concentrate urine or retain sodium - urine osmolality low, urine sodium high

·         Rarer causes = acute glomerulonephritis, acute interstitial nephritis

Post-renal:

·         Obstruction of urinary tract

·         Usually identified with hydronephrosis on renal ultrasound

 

 

 

 

 

© Image used on license from PathoPic

Specimen from a patient who had an acute kidney injury. Note the marked pallor of the cortex in certain areas, contrasting to the darker areas of surviving medullary tissue.

 

 

What causes AKI?

 

Causes of AKI are traditionally divided into prerenal, intrinsic and postrenal causes

 

Prerenal

 

Think of what causes big problems in other major organs. In the heart, a lack of blood flow (ischaemia) to the myocardium causes a myocardial infarction. In a similar fashion, 85% of strokes are caused by ischaemia to the brain. The same goes for the kidneys. One of the major causes of AKI is ischaemia, or lack of blood flowing to the kidneys.

 

Examples

·         hypovolaemia secondary to diarrhoea/vomiting

·         renal artery stenosis

Intrinsic

 

The second group of causes relate to intrinsic damage to the glomeruli, renal tubules or interstitium of the kidneys themselves. This may be due to toxins (drugs, contrast etc) or immune-mediated glomuleronephritis.

 

Examples

·         glomerulonephritis

·         acute tubular necrosis (ATN)

·         acute interstitial nephritis (AIN), respectively

·         rhabdomyolysis

·         tumour lysis syndrome

Postrenal

 

The third group relates to problems after the kidneys. This is where there is an obstruction to the urine coming from the kidneys resulting in things 'backing-up' and affecting the normal renal function. An example could be a unilateral ureteric stone or bilateral hydroneprosis secondary to acute urinary retention caused by benign prostatic hyperplasia.

 

Examples

·         kidney stone in ureter or bladder

·         benign prostatic hyperplasia

·         external compression of the ureter

 

 

© Image used on license from PathoPic

This patient had an invasive papillary tumour of the distal left ureter, indicated by the arrow. This resulted in the ureter becoming blocked, resulting in a left hydroureter and hydronephrosis. Note the thinning of the renal cortex of the left kidney compared to the right.

 

 

Who is at an increased risk of AKI?

 

One of the keys to reducing the incidence of AKI is identifying patient who are at increased risk. NICE support this approach and have published guidelines suggesting which patients are at greater risk.

 

Risk factors for AKI include:

·         chronic kidney disease

·         other organ failure/chronic disease e.g. heart failure, liver disease, diabetes mellitus

·         history of acute kidney injury

·         use of drugs with nephrotoxic potential (e.g. NSAIDs, aminoglycosides, ACE inhibitors, angiotensin II receptor antagonists [ARBs] and diuretics) within the past week

·         use of iodinated contrast agents within the past week

·         age 65 years or over

oliguria (urine output less than 0.5 ml/kg/hour)

·         neurological or cognitive impairment or disability, which may mean limited access to fluids because of reliance on a carer

 

Preventing AKI

 

By identifying patients at increased risk of AKI (see above) it may be possible to take steps to reduce the risk. For example, patients who are at risk of AKI and who are undergoing an investigation requiring contrast are usually given IV fluids to reduce the risk. Certain drugs such as ACE inhibitors and ARBs may also be temporarily stopped.

 

 

What happens when kidneys stop working?

 

It's best to work backwards and think about what kidneys actually do. The kidneys are primarily responsible for fluid balance and maintaining homeostasis. Therefore two of the key ways AKI may be detected are:

·         a reduced urine output. This is termed oliguria and is defined as a urine output of less than 0.5 ml/kg/hour

·         fluid overload

·         a rise in molecules that the kidney normal excretes/maintains a careful balance of. Examples include potassium, urea and creatinine

 

Symptoms and signs

 

Many patients with early AKI may experience no symptoms. However, as renal failure progresses the following may be seen:

·         reduced urine output

·         pulmonary and peripheral oedema

·         arrhythmias (secondary to changes in potassium and acid-base balance)

·         features of uraemia (for example, pericarditis or encephalopathy)

 

Detection

 

One of the most common blood tests performed on the wards is 'urea and electrolytes' or 'U&Es'. This returns a number of markers, including

·         sodium

·         potassium

·         urea

·         creatinine

NICE recommend that we can use a variety of different criteria to make an official diagnosis of AKI. They state:

 

 

Detect acute kidney injury, in line with the (p)RIFLE, AKIN or KDIGO definitions, by using any of the following criteria:

·         a rise in serum creatinine of 26 micromol/litre or greater within 48 hours

·         a 50% or greater rise in serum creatinine known or presumed to have occurred within the past 7 days

·         a fall in urine output to less than 0.5 ml/kg/hour for more than 6 hours in adults and more than

Urinalysis

·         all patients with suspected AKI should have urinalysis

Imaging

·         if patients have no identifiable cause for the deterioration or are at risk of urinary tract obstruction they should have a renal ultrasound within 24 hours of assessment.

 

Management

 

The management of AKI is largely supportive. This means patients require careful fluid balance to ensure that the kidneys are properly perfused but not excessively to avoid fluid overload. It is also important to review a patient's medication list to see what treatments may either be exacerbating their renal dysfunction or may be dangerous as a consequence of renal dysfunction. The table below gives some examples of common drugs:

 

 

Usually safe to continue in AKI

Should be stopped in AKI as may worsen renal function

May have to be stopped in AKI as increased risk of toxicity (but doesn't usually worsen AKI itself)

• Paracetamol

• Warfarin

• Statins

• Aspirin (at a cardioprotective dose of 75mg od)

• Clopidogrel

• Beta-blockers

• NSAIDs (except if aspirin at cardiac dose e.g. 75mg od)

• Aminoglycosides

• ACE inhibitors

• Angiotensin II receptor antagonists

• Diuretics

• Metformin

• Lithium

• Digoxin

Treatments which are not recommend include the routine use of loop diuretics (to artificially boost urine output) and low-dose dopamine (in an attempt to increase renal perfusion). There is however a role for loop diuretics in patients who experience significant fluid overload.

 

Hyperkalaemia also needs prompt treatment to avoid arrhythmias which may potentially be life-threatening. The table below categorises the different treatments for hyperkalaemia:

 

 

Stabilisation of the cardiac membrane

• Short-term shift in potassium from extracellular to intracellular fluid compartment

• Removal of potassium from the body

• Intravenous calcium gluconate

• Combined insulin/dextrose infusion

• Nebulised salbutamol

• Calcium resonium (orally or enema)

• Loop diuretics

• Dialysis

Specialist input from a nephrologist is required for cases where the cause is not known or where the AKI is severe.

 

All patients with suspected AKI secondary to urinary obstruction require prompt review by a urologist.

 

Renal replacement therapy (e.g. haemodialysis) is used when a patient is not responding to medical treatment of complications, for example hyperkalaemia, pulmonary oedema, acidosis or uraemia.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:51

Metabolic acidosis

Metabolic acidosis is commonly classified according to the anion gap. This can be calculated by: (Na+ + K+) - (Cl- + HCO-3). If a question supplies the chloride level then this is often a clue that the anion gap should be calculated. The normal range = 10-18 mmol/L

 

Normal anion gap ( = hyperchloraemic metabolic acidosis)

·         gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula

·         renal tubular acidosis

·         drugs: e.g. acetazolamide

·         ammonium chloride injection

·         Addison's disease

Raised anion gap

·         lactate: shock, sepsis, hypoxia

·         ketones: diabetic ketoacidosis, alcohol

·         urate: renal failure

·         acid poisoning: salicylates, methanol

Metabolic acidosis secondary to high lactate levels may be subdivided into two types:

·         lactic acidosis type A: sepsis, shock, hypoxia, burns

·         lactic acidosis type B: metformin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

Tuesday, 22 December 2020

18:25

Chronic kidney disease: anaemia

Patients with chronic kidney disease (CKD) may develop anaemia due to a variety of factors, the most significant of which is reduced erythropoietin levels. This is usually a normochromic normocytic anaemia and becomes apparent when the GFR is less than 35 ml/min (other causes of anaemia should be considered if the GFR is > 60 ml/min). Anaemia in CKD predisposes to the development of left ventricular hypertrophy - associated with a three fold increase in mortality in renal patients

 

Causes of anaemia in renal failure

·         reduced erythropoietin levels - the most significant factor

·         reduced erythropoiesis due to toxic effects of uraemia on bone marrow

·         reduced absorption of iron

·         anorexia/nausea due to uraemia

·         reduced red cell survival (especially in haemodialysis)

·         blood loss due to capillary fragility and poor platelet function

·         stress ulceration leading to chronic blood loss

Management

·         the 2011 NICE guidelines suggest a target haemoglobin of 10 - 12 g/dl

·         determination and optimisation of iron status should be carried out prior to the administration of erythropoiesis-stimulating agents (ESA). Many patients, especially those on haemodialysis, will require IV iron

·         ESAs such as erythropoietin and darbepoetin should be used in those 'who are likely to benefit in terms of quality of life and physical function'

 

 

 

 

21 December 2020

21:51

Rhabdomyolysis

Rhabdomyolysis will typically feature in the exam as a patient who has had a fall or prolonged epileptic seizure and is found to have an acute kidney injury on admission.

 

Features

·         acute kidney injury with disproportionately raised creatinine

·         elevated creatine kinase (CK)

·         myoglobinuria

·         hypocalcaemia (myoglobin binds calcium)

·         elevated phosphate (released from myocytes)

·         hyperkalaemia (may develop before renal failure)

·         metabolic acidosis

Causes

·         seizure

·         collapse/coma (e.g. elderly patients collapses at home, found 8 hours later)

·         ecstasy

·         crush injury

·         McArdle's syndrome

·         drugs: statins (especially if co-prescribed with clarithromycin)

Management

·         IV fluids to maintain good urine output

·         urinary alkalinization is sometimes used

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

Tuesday, 22 December 2020

18:20

Chronic kidney disease: eGFR and classification

Serum creatinine may not provide an accurate estimate of renal function due to differences in muscle. For this reason, formulas were developed to help estimate the glomerular filtration rate (estimated GFR or eGFR). The most commonly used formula is the Modification of Diet in Renal Disease (MDRD) equation, which uses the following variables:

·         serum creatinine

·         age

·         gender

·         ethnicity

Factors which may affect the result

·         pregnancy

·         muscle mass (e.g. amputees, body-builders)

·         eating red meat 12 hours prior to the sample being taken

CKD may be classified according to GFR:

 

 

CKD stage

GFR range

1

Greater than 90 ml/min, with some sign of kidney damage on other tests (if all the kidney tests* are normal, there is no CKD)

2

60-90 ml/min with some sign of kidney damage (if kidney tests* are normal, there is no CKD)

3a

45-59 ml/min, a moderate reduction in kidney function

3b

30-44 ml/min, a moderate reduction in kidney function

4

15-29 ml/min, a severe reduction in kidney function

5

Less than 15 ml/min, established kidney failure - dialysis or a kidney transplant may be needed

*i.e. normal U&Es and no proteinuria

eGFR variables - CAGE - Creatinine, Age, Gender, Ethnicity

 

 

A

 

Albuminuria categories in CKD

 

 

Category

ACR (mg/g)

Terms

A1

<30 or <3 mg/mmol

Normal to mildly increased

A2

30-300 or 3-29 mg/mmol

Moderately increased*

A3

>300 >30mg mmol

Severely increased**

Abbreviations: ACR, albumin-to-creatinine ratio; CKD, chronic kidney disease.

*Relative to young adult level.

**Including nephrotic syndrome (albumin excretion ACR >2220 mg/g)

 

 

**Collectively referred to as “CGA Staging”

 

From <https://www.kidney.org/professionals/explore-your-knowledge/how-to-classify-ckd>

 

 

 

 

Quick Reference Guide on Kidney Disease Screening | National Kidney Foundation

 

 

 

 

21 December 2020

21:50

Henoch-Schonlein purpura

Henoch-Schonlein purpura (HSP) is an IgA mediated small vessel vasculitis. There is a degree of overlap with IgA nephropathy (Berger's disease). HSP is usually seen in children following an infection.

 

Features

·         palpable purpuric rash (with localized oedema) over buttocks and extensor surfaces of arms and legs

·         abdominal pain

·         polyarthritis

·         features of IgA nephropathy may occur e.g. haematuria, renal failure

 

© Image used on license from DermNet NZ

Treatment

·         analgesia for arthralgia

·         treatment of nephropathy is generally supportive. There is inconsistent evidence for the use of steroids and immunosuppressants

Prognosis

·         usually excellent, HSP is a self-limiting condition, especially in children without renal involvement

·         around 1/3rd of patients have a relapse

 

© Image used on license from DermNet NZ

 

© Image used on license from DermNet NZ

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

23:00

Anion gap

The anion gap is calculated by:

 

(sodium + potassium) - (bicarbonate + chloride)

 

A normal anion gap is 8-14 mmol/L

 

It is useful to consider in patients with a metabolic acidosis:

 

Causes of a normal anion gap or hyperchloraemic metabolic acidosis

·         gastrointestinal bicarbonate loss: diarrhoea, ureterosigmoidostomy, fistula

·         renal tubular acidosis

·         drugs: e.g. acetazolamide

·         ammonium chloride injection

·         Addison's disease

Causes of a raised anion gap metabolic acidosis

·         lactate: shock, hypoxia

·         ketones: diabetic ketoacidosis, alcohol

·         urate: renal failure

·         acid poisoning: salicylates, methanol

·         5-oxoproline: chronic paracetamol use

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

22 December 2020

20:18

ADPKD

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney disease, affecting 1 in 1,000 Caucasians. Two disease loci have been identified, PKD1 and PKD2, which code for polycystin-1 and polycystin-2 respectively

 

 

ADPKD type 1

ADPKD type 2

85% of cases

15% of cases

Chromosome 16

Chromosome 4

Presents with renal failure earlier

 

The screening investigation for relatives is abdominal ultrasound:

 

Ultrasound diagnostic criteria (in patients with positive family history)

·         two cysts, unilateral or bilateral, if aged < 30 years

·         two cysts in both kidneys if aged 30-59 years

·         four cysts in both kidneys if aged > 60 years

Management

 

For select patients, tolvaptan (vasopressin receptor 2 antagonist) may be an option. NICE recommended it as an option for treating ADPKD in adults to slow the progression of cyst development and renal insufficiency only if:

·         they have chronic kidney disease stage 2 or 3 at the start of treatment

·         there is evidence of rapidly progressing disease and

·         the company provides it with the discount agreed in the patient access scheme.

 

 

© Image used on license from PathoPic

Extensive cysts are seen in an enlarged kidney

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

21 December 2020

23:10

Amyloidosis

Overview

·         amyloidosis is a term which describes the extracellular deposition of an insoluble fibrillar protein termed amyloid

·         amyloid is derived from many different precursor proteins

·         in addition to the fibrillar component, amyloid also contains a non-fibrillary protein called amyloid-P component, derived from the acute phase protein serum amyloid P

·         other non-fibrillary components include apolipoprotein E and heparan sulphate proteoglycans

·         the accumulation of amyloid fibrils leads to tissue/organ dysfunction

Classification

·         systemic or localized

·         further characterised by precursor protein (e.g. AL in myeloma - A for Amyloid, L for immunoglobulin Light chain fragments)

Diagnosis

·         Congo red staining: apple-green birefringence

·         serum amyloid precursor (SAP) scan

·         biopsy of rectal tissue

 

 

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

18:10

 

Chronic kidney disease: causes

Common causes of chronic kidney disease

·         diabetic nephropathy

·         chronic glomerulonephritis

·         chronic pyelonephritis

·         hypertension

·         adult polycystic kidney disease

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:35

 

Rapidly progressive glomerulonephritis

Rapidly progressive glomerulonephritis is a term used to describe a rapid loss of renal function associated with the formation of epithelial crescents in the majority of glomeruli.

 

Causes

·         Goodpasture's syndrome

·         Wegener's granulomatosis (c ANCA)

·         others: SLE, microscopic polyarteritis

Features

·         nephritic syndrome: haematuria with red cell casts, proteinuria, hypertension, oliguria

·         features specific to underlying cause (e.g. haemoptysis with Goodpasture's, vasculitic rash or sinusitis with Wegener's)

 

 

© Image used on license from PathoPic

Glomeruli are full of crescents.

 

 

© Image used on license from PathoPic

Another image showing the glomeruli full of crescents

 

cANCA - c = Crescenteric glomerulonephritis!

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

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21 December 2020

21:50

Fluid therapy

The prescription of intravenous fluids is one of the most common tasks that junior doctors need to do.

 

In the 2013 guidelines NICE recommend the following requirements for maintenance fluids:

·         25-30 ml/kg/day of water and

·         approximately 1 mmol/kg/day of potassium, sodium and chloride and

·         approximately 50-100 g/day of glucose to limit starvation ketosis

So, for a 80kg patient, for a 24 hour period, this would translate to:

·         2 litres of water

·         80mmol potassium

For the first 24 hours NICE recommend the following::

 

When prescribing for routine maintenance alone, consider using 25-30 ml/kg/day sodium chloride 0.18% in 4% glucose with 27 mmol/l potassium on day 1 (there are other regimens to achieve this).

 

The amount of fluid patients require obviously varies according to their recent and past medical history. For example a patient who is post-op and is having significant losses from drains will require more fluid whereas a patient with heart failure should be given less fluid to avoid precipitating pulmonary oedema.

 

The table below shows the electrolyte concentrations (in millimoles/litre) of plasma and the most commonly used fluids:

 

 

 

Na+

Cl-

K+

HCO3-

Glucose

Plasma

135-145

98-105

3.5-5

22-28

-

0.9% saline

154

154

-

-

-

5% glucose

-

-

-

-

50g

0.18% saline with 4% glucose

30

30

-

-

40g

Hartmann's solution

131

111

5

29

-

 

Specific points

 

0.9% saline

·         if large volumes are used there is an increased risk of hyperchloraemic metabolic acidosis

Hartmann's

·         contains potassium and therefore should not be used in patients with hyperkalaemia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

Wednesday, 23 December 2020

01:01

Haematuria

The management of patients with haematuria is often difficult due to the absence of widely followed guidelines. It is sometimes unclear whether patients are best managed in primary care, by urologists or by nephrologists.

 

The terminology surrounding haematuria is changing. Microscopic or dipstick positive haematuria is increasingly termed non-visible haematuria whilst macroscopic haematuria is termed visible haematuria. Non-visible haematuria is found in around 2.5% of the population.

 

Causes of transient or spurious non-visible haematuria

·         urinary tract infection

·         menstruation

·         vigorous exercise (this normally settles after around 3 days)

·         sexual intercourse

Causes of persistent non-visible haematuria

·         cancer (bladder, renal, prostate)

·         stones

·         benign prostatic hyperplasia

·         prostatitis

·         urethritis e.g. Chlamydia

·         renal causes: IgA nephropathy, thin basement membrane disease

Spurious causes - red/orange urine, where blood is not present on dipstick

·         foods: beetroot, rhubarb

·         drugs: rifampicin, doxorubicin

Management

 

Current evidence does not support screening for haematuria. The incidence of non-visible haematuria is similar in patients taking aspirin/warfarin to the general population hence these patients should also be investigated.

 

Testing

·         urine dipstick is the test of choice for detecting haematuria

·         persistent non-visible haematuria is often defined as blood being present in 2 out of 3 samples tested 2-3 weeks apart

·         renal function, albumin:creatinine (ACR) or protein:creatinine ratio (PCR) and blood pressure should also be checked

·         urine microscopy may be used but time to analysis significantly affects the number of red blood cells detected

NICE urgent cancer referral guidelines were updated in 2015.

 

Urgent referral (i.e. within 2 weeks)

 

Aged >= 45 years AND:

·         unexplained visible haematuria without urinary tract infection, or

·         visible haematuria that persists or recurs after successful treatment of urinary tract infection

Aged >= 60 years AND have unexplained nonvisible haematuria and either dysuria or a raised white cell count on a blood test

 

Non-urgent referral

 

Aged 60 >= 60 years with recurrent or persistent unexplained urinary tract infection

 

Since the investigation (or not) of non-visible haematuria is such as a common dilemma a number of guidelines have been published. They generally agree with NICE guidance, of note:

·         patients under the age of 40 years with normal renal function, no proteinuria and who are normotensive do not need to be referred and may be managed in primary care

 

 

 

 

22 December 2020

19:48

 

Hypokalaemia: features

Features

·         muscle weakness, hypotonia

·         hypokalaemia predisposes patients to digoxin toxicity - care should be taken if patients are also on diuretics

ECG features

·         U waves

·         small or absent T waves

·         prolonged PR interval

·         ST depression

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

This gentleman has severe hypokalaemia, defined as a serum potassium < 2.5mmol/l. Mild to moderate hypokalaemia can be asymptomatic but the more severe the electrolyte derangement the more likely that symptoms will develop. Symptoms include weakness, leg cramps, palpitations secondary to cardiac arrhythmias and ascending paralysis.

 

Causes can be secondary to:

 

1.) Increased potassium loss:

·         Drugs: thiazides, loop diuretics, laxatives, glucocorticoids, antibiotics

·         GI losses: diarrhoea, vomiting, ileostomy

·         Renal causes: dialysis

·         Endocrine disorders: hyperaldosteronism, Cushing's syndrome

2.) Trans-cellular shift

·         Insulin/glucose therapy

·         Salbutamol

·         Theophylline

·         Metabolic alkalosis

3.) Decreased potassium intake

 

4.) Magnesium depletion (associated with increased potassium loss)

 

ECG changes seen in hypokalaemia include:

·         U waves

·         T wave flattening

·         ST segment changes

Treatment of hypokalaemia depends on severity. Any causative agents should be removed. Gradual replacement of potassium via the oral route is preferred if possible.

 

Mild to moderate hypokalaemia 2.5 - 3.4 mmol/l can be treated with oral potassium provided the patient is not symptomatic and there are no ECG changes.

 

Severe hypokalaemia (<2.5mmol/l) or symptomatic hypokalaemia should be managed with IV replacement. The patient should be managed in an area where cardiac monitoring can take place. If there are no contraindications to fluid therapy (e.g. volume overload, heart failure) potassium should be diluted to low concentrations as higher concentrations can be phlebitic. The infusion rate should not exceed 20mmol/hr. In this case, 3 bags of 0.9% Saline with 40mmol KCL is the correct answer.

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

 

 

Intrinsic AKI differences

01 January 2021

16:24

Membranous glomerulonephritis histology:

basement membrane thickening on light microscopy

subepithelial spikes on sliver stain

positive immunohistochemistry for PLA2

classically causes nephrotic syndrome (protein +hypoalbuminaemia)

Membranous glomerulonephritis also causes a hypercoagulable state,

 

 

Minimal change disease would typically affect children, who would be normotensive, with no haematuria and no findings on light microscopy.

 

Goodpasture's disease would cause nephritic syndrome (never nephrotic), lung symptoms and more systemic upset. It also would not cause these histology findings.

 

Focal segmental glomerulosclerosis would cause similar symptoms, urine dip and blood test findings to membranous glomeulonephritis but would not cause these histology findings.

 

IgA nephropathy is the commonest cause of glomerulonephritis in adults worldwide, particularly affecting young males. It can cause nephrotic or nephritic syndrome or isolated haematuria. It would not cause these histology findings.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

nephrotic syndrome and nephritic syndrome are on a continuous spectrum

 

 

 

Causes of bladder outlet obstruction

04 January 2021

22:11

potential causes of bladder outlet obstruction:

·         Genitalia: Meatal stenosis, phimosis, paraphimosis, atrophic vaginitis

·         Urethra: Stones, strictures, diverticulum, posterior urethral valves, carcinoma, surgery

·         Prostate: Benign prostatic hyperplasia, calculi, abscess, prostate carcinoma

·         Gynaecologic: Prolapse, cystocele, pregnancy, ovarian mass, uterine tumour, cervical tumour

·         Bladder: Calculi, blood clot, tumour, bladder neck dysfunction

·         Bowel: Faecal impaction

·         Neurogenic: Multiple sclerosis, diabetes, spinal cord trauma, Parkinson disease, cerebrovascular accident

 

From <https://mle.ncl.ac.uk/cases/page/17216/>

 

 

 

 

Pulmonary renal syndrome

04 January 2021

22:21

 

Pulmonary-renal syndrome is almost always a manifestation of an underlying autoimmune disorder.

Goodpasture syndrome is the prototype cause, but PRS can also be caused by SLE, granulomatosis with polyangiitis, microscopic polyangiitis, and, less commonly, by other vasculitides, connective tissue disorders, and drug-induced vasculitides.

 

From <https://mle.ncl.ac.uk/cases/page/16998/>

 

 

Pulmonary-renal syndrome (PRS) is diffuse alveolar haemorrhage plus glomerulonephritis, often occurring simultaneously. Cause is almost always an autoimmune disorder. Diagnosis is by serologic tests and sometimes lung and renal biopsy. Treatment typically includes immunosuppression with corticosteroids and cytotoxic drugs.

 

Pulmonary-renal syndrome (PRS) is not a specific entity but is a syndrome that suggests a differential diagnosis and a specific sequence of testing.

 

 

Systemic Symptoms: night sweats, abdominal pain, bloody diarrhoea

Signs of Sepsis: Fever, lymphadenopathy

Signs of Autoimmune Conditions: Joint pains, myalgia, rash, sicca, epistaxis, deafness, ulcers

Other Significant PMH: DVT/ PE thrombotic disorders, SLE, Autoimmune conditions

 

Disorder Con nectlve tissu a disorder Goodpastures Syndrome ( Anti GdM disease) Renal Disorders Systemic vasculitis Other Examples Dermatomyostis Polymyositis Progressive systemic sclerosis SLE Idiopathic immune complex glomerulon aph ritis gA nephropathy Rapidly progressve GN plus heart failure aehcets disease Cryoglobulnaemia Granulomatosls with polyangiitis (GPA previou sly called Wegen er's) Microscopc polyangiitis (MPA), Eosinophilic granulomatosls wth polyangiitis (EGPA previously called Churg-Strauss) IqA associated vascultis Drugs ( propydthiouracil) Heart failure

There are many potential reasons for coughing up blood. Causes for haemoptysis include:

 

Bronchitis (acute or chronic), the most common cause of coughing up blood. Haemoptysis due to bronchitis is rarely life-threatening.

Bronchiectasis

Lung cancer or non-malignant lung tumours

Use of anticoagulation

Pneumonia

Pulmonary embolism

Congestive heart failure, especially due to mitral stenosis

Tuberculosis

Inflammatory or autoimmune conditions (lupus, Granulomatosis with polyangiitis (GPA previously called Wegener’s), Microscopic polyangiitis (MPA), or Eosinophilic granulomatosis with polyangiitis (EGPA, previously called Churg-Strauss) and many others)

Pulmonary arteriovenous malformations (AVMs)

Crack cocaine

Trauma, such as a gunshot wound or motor vehicle accident

 

 

 

Dialysis indications

04 January 2021

22:58

AKI and dialysis indications (AEIOU)

Acidosis

·         intractable metabolic acidosis

·         Bic 14, PH <7.2

Electrolytes

·         severe persistent hyperkalemia

·         >6 – esp if anuric

Intoxication

·         methanol, ethylene glycol, lithium, aspirin

Overload :hypervolemia

·         Diuretics not effective

·         Pulmonary oedema

Uraemia

·         uremic pericarditis

·         encephalopathy

 

From <https://mle.ncl.ac.uk/cases/page/17236/>

 

 

 

 

Lifestyle and health

23 December 2020

13:02

Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity. WHO and Health

 

 

What is classed as life style

Diet

Physical activity

Smoking

Alcohol

 

Non communicable diseases modified by life style modification

Obesity

Type 2 Diabetes

Lipid Disorders

Atherosclerotic cardiovascular diseases

Hypertension

Cancer

 

Best portions

·         33% Starchy carbohydrates Bulk of meals

·         33% Fruit & Vegetables 5+ a Day

·         15% Milk & Dairy 3 portions daily

·         12% Meat, Fish, Eggs, Beans Oily fish once a week

·         <8% High fat/sugary foods Avoid saturated fats

 

 

Exercise

Frequency: 3-5 days per week

Aerobic exercise: a minimum if 3 days a week are necessary to reach most exercise goals and minimize health benefits

Strength training: a minimum of 2 days per week

Flexibility training: a minimum of 3-5 days per week

Duration

Aerobic: 20-60 minutes of continuous aerobic activity

Strength: 1-3 sets of 8-12 repetitions

Stretching: Stretch all muscle groups and hold positions for 10-30 seconds

 

 

Benefits of exercise

Associated with lower all-cause mortality rates

Increases life span

Prevention of  cardiovascular disease, cancer (colon, breast), type 2 diabetes, hypertension, obesity

Mitigates negative effects of aging

Reduces dementia risk

Enhances executive function and attention, processing speed, memory

Decreases symptoms of depression, anxiety

Improves psychological well-being

Promotes brain cell growth

 

 

Alcohol

To keep health risks from alcohol to a low level it is safest not to drink more than 14 units a week on a regular basis

 

If you regularly drink as much as 14 units per week, it's best to spread your drinking evenly over three or more days. If you have one or two heavy drinking episodes a week, you increase your risk of long term illness and injury

 

 

 

 

 

Non-communicable diseases (NCD)

23 December 2020

13:26

Non-communicable diseases (NCDs) are also known as chronic diseases

Tend to be of long duration

Are mainly a result of lifestyle behaviour habits

May also be caused by non-modifiable risk factors such individual characteristics (age, sex, and genetic factors)

 

Deaths due to noncornmunicable diseases: age-standardized death rate (per 100 000 population) Both sexes, 2015 (p« 100 000 population) 401-500 501-600 601-700 701-800 801-900 not Not

 

Life expectancy, 1543 to 2015 80 years 70 years 60 years 50 years 40 years 30 years 1543 1600 1700 1800 1900 our World in Data United Kingdom World 2015

 

Life expectancy, 2019 Our World in Data <20 years No data 30 years 40 years 50 years 60 years 70 years 80 years 45 years 55 years 65 years 75 years >85 years Source: Riley (2005), Clio Infra (2015), and UN Population Division (2019) OurWorIdlnData.org/life-expectancy • CC BY Note: Shown is period life expectancy at birth, the average number of years a newborn would live if the pattern of mortality in the given year were to stay the same throughout its life.

 

NCD kill 41 million people annually – that’s 71% of all global deaths

Each year, 15 million people die prematurely from a NCD between the ages of 30 and 69 years

85% of these "premature" deaths occur in low- and middle-income countries

 

 

In England, over 15 million people live with NCDs

NCDs account for approximately 70% of the NHS annual budget

50% of all GP appointments

64% of outpatient appointments

70% of all inpatient bed days

 

Disproportionately affect people in deprived areas more  

 

 

 

Why increasing life expectancy

Vaccinations and antimicrobials medication are now widespread

– reduced burden from infectious (communicable) diseases

 

Living standards have improved and lifestyles have changed dramatically

Economic prosperity & globalisation

Urbanisation

Sedentary lifestyles 

 

 

Modifiable risk factors Unhealthy diets Physical inactivity Tobacco use (and Metabolic risk factors Hypertension Overweight / obesity second hand smoking) Hyperlipidaemia Alcohol misuse Hyperglycaemia Major public health concerns Major chronic diseases Cardiovascular diseases Diabetes Cancers Chronic respiratory diseases Preventable Morbidity Premature Mortality

 

Dementia and mental illness may be classified as NCDs.

 Often patients have two or more chronic diseases.

 

Cardiovascular disease

These account for most NCD deaths worldwide – killing 18 million people annually

In the UK, coronary heart disease and stroke are the biggest causes of disability and death

Men are at greater risk than women

 

Smoking, hypertension, harmful alcohol consumption, physical inactivity, obesity and diet can all cause CVDs.

 

Cancers

Cancers are the second biggest causes of morbidity and death and cause 9 million deaths annually worldwide

In the UK, 300,000 people are diagnosed with cancer with 130,000 deaths

There are more than 200 types of cancers: lung, colorectal and breast cancer are the top 3 causes of premature morbidity

Cancer incidence increases with age

Greatly affected by individual lifestyle behaviours

Tobacco smoking alone is estimated to cause more than a 25%  of all deaths from cancer

 

Note: although the number of cancer survivors is rising, survivors often have worse overall health than the rest of the population

 

Chronic respiratory diseases

COPD causes 3.9 million deaths annually

Around 835,000 people in the UK have been diagnosed with COPD

additional 2 million people living with the disease who have not been diagnosed.

Causes many years of disability before death

Smoking is the most important risk factor. Air pollution can also be a contributory cause

 

Public health smoking campaigns have achieved success and smoking rates are decreasing in the UK. However, there is a higher prevalence of smoking in more deprived areas.

 

Diabetes

Diabetes is a major non-communicable disease causing 1.6 million deaths annually

Around 3 million people in the UK have diabetes. This figure is expected to rise to 4 million people by 2025.

Diabetes has micro - and macro- vascular complications resulting in poor quality of life and premature mortality.

Almost 90% of new and existing cases of diabetes are type 2.

Type 2 diabetes has a strong association with obesity and diet

Changing lifestyle behaviours by tackling obesity and hyperlipidaemia can have a major impact on the burden on the disease

 

Preventing and managing NCDS

Prevent the Identifying the disease by diseases in their tackling the risk early stages factors Treating the complications adequately Primary and secondary care Government policies Public Health Campaigns Social prescribing in the community Individual lifestyle behaviour changes (WHO, 2018)

 

 

How do we reduce risk factors on an individual level?

Monitoring blood pressure in the community 

Checking lipid profiles for at risk patients  - offering statins

Offering weight reduction services for overweight and obese individuals

Referring smokers to smoking cessation services

 

 

Encouraging an overall healthy and active lifestyle

Set of 9 voluntary global NCD targets for 2025 Harmful use of alcohol 10% reduction Physical 10% reduction sodium intake 30% reduction Tobacco use 30% reduction kyld Health Organizatim mortality from NCDs 25% reduction Raised blood pressure 25% reduction Essential NCO medicines and technologies coverage Drug therapy and counseling 50% coverage Diabetes/ obesity 0% increase National

 

 

 

Epidemiology of Obesity

23 December 2020

13:34

 

 

Since the 1970s, obesity has nearly tripled worldwide

The WHO estimated that by 2016 more than 1.9 billion adults worldwide were overweight

That’s 39% of the world population.

Of those, 650 million were obese

That’s 13% of the world population. 

 

Share of adults that are obese, 1975 to 2016 Our World in Data Obesity is defined as having a body-mass index (BMI) equal to or greater than 30. BMI is a person's weight in kilograms divided by his or her height in metres squared. .org/obesity • CC BY 25% 20% 15% 10% 5% 0% 1975 1980 1985 Source: WHO, Global Health Observatory 1990 1995 2000 2005 2010 Americas Europe Eastern Mediterranean Africa South-East Asia 2016 OurWorldlnData

 

Share of adults that are overweight or obese, 1975 Being overweight is defined as having a body-mass index (BMI) greater than or equal to 25. Obesity is defined by a BMI greater than or equal to 30. BMI is a person's weight in kilograms divided by his or her height in metres Our World in Data squared. No data 0% Source: WHO, Global Health Observatory 30% 40% 50% 70% OurWorldlnData.org/obesity • CC BY

 

Share of adults that are overweight or obese, 1995 Our World in Data Being overweight is defined as having a body-mass index (BMI) greater than or equal to 25. Obesity is defined by a BMI greater than or equal to 30. BMI is a person's weight in kilograms divided by his or her height in metres squared. No data 0% 10% 20% 30% 50% 60% Source: WHO, Global Health Observatory 70% OurWorldlnData.org/obesity • CC BY

 

Share of adults that are overweight or obese, 2016 Our World in Data Being overweight is defined as having a body-mass index (BMI) greater than or equal to 25. Obesity is defined by a BMI greater than or equal to 30. BMI is a person's weight in kilograms divided by his or her height in metres squared. No data 0% 10% 20% 30% 60% Source: WHO, Global Health Observatory OurWorldlnData.org/obesity • CC BY

 

Adult obesity

Obesity is no longer just a high-income country problem.

It is on the rise in low- and middle-income countries, especially in urban settings.

 

Worldwide, obesity is more prevalence that underweight in every region except in parts of sub-Saharan Africa and Asia.

 

UK:

66%  of population are either overweight or obese

1 in every 4 adults are obese

 

The prevalence of obesity is similar among genders

67% of men and 60% of women

Scotland has the highest proportion of obesity (27.7%)

 

 

London south East East Midlands England North West South West Yorkshire & the Humber West Midlands North East 20 40 60 80 Percent

 

Prevalence of obesity if higher in the most deprived areas than the least deprived areas.

 

WHO estimated that by 2019:

38 million children under the age of 5 were overweight or obese

Over 340 million children and adolescents aged 5-19 were overweight or obese

 

The prevalence of overweight and obesity among children and adolescents has risen from 4% in 1975 to over 18% in 2016. 

This rise has been similar among both boys and girls

 

UK:

·         For children aged  4 & 5 years – 13% are overweight and 9% are obese

·         For children aged 10 & 11 year olds – 14% are overweight while 20% are obese

·         Younger generations are becoming obese earlier and staying obese into adulthood

·         Children living in deprived areas are more likely to be obese

 

Obesity and Social Deprivation

The Marmot review was published on February 2010 and looked at health inequalities in England

 

Addressed the social determinants of health, the conditions in which people are born, live, work and age and which can lead to health inequalities.

 

The review highlighted that there is a strong relationship between obesity and health inequalities

 

Obesity is attributed to the increased consumption of ready meals and high calorie drinks.  These foods have higher levels of saturated fats, sugar, and salt, and lower levels of micronutrients.

 

Ready meals are:

Often cheap

Readily available at all times of the day

 

More than 27% of adults and 20% of children eat food from fast food outlets at least once a week.

 

 

Public Health England England value Obesity and the environment Density of fast food outlets 31/12/2017 Fast food outlets by local authority Rate 100.000 population 939."27 "28-2578 Rate per 100.000 population 96.5

 

On average, there are more fast food chains in deprived areas than in more affluent areas.

 

Public Health England estimated that there were over 50,000 fast food takeaway, delivery services and fish and chip shops in England.

 

 

Those in deprived areas are:

More likely to eat healthy foods

Become obese from a younger age

Develop non-communicable diseases early on

NCDs further reduce their quality of life

And increases deprivation 

 

Projection trends suggest that by 2050, half of the entire adult population worldwide will be obese.
 

Obesity causes

more than 30,000 deaths each year.

Over 11, 000 hospital admissions

It also reduces life expectancy by up to 8 years (especially in severely obese individuals)

 

Individuals with obesity are:

·         2.5 times more likely to develop high blood pressure

·         3 times more likely to develop colon cancer

·         5 times more likely to develop type 2 diabetes

During the COVID-19 pandemic, evidence suggests that obese or overweight patients who developed the illness had poorer outcomes.

 

The annual cost of obesity Cost to wider economy E27bn Obesity medication E13.3bn Cost to NHS E5.1bn attributed days sickness 16m Social care E352m

The NHS projects that the annual cost to the NHS will to reach £9.7 billion and the cost to the wider economy will reach £49.9 billion by 2050

 

 

Obesity is preventable:

…so chronic conditions that are caused by obesity are also preventable.

 

If we stop the obesity trend and reverse it then  we can

Improve our patients’ quality of life

Prevent unnecessary death

Ultimately help our healthcare system 

 

 

 

 

 

 

 

 

 

 

 

Obesity Classification, investigations and management

23 December 2020

13:40

Definition:

·         Abnormal or excessive fat accumulation that presents a risk to health

·         Body Mass Index: Commonly used

·         Waist circumference in BMI <35

 

Obesity classification- NICE

 

Machine generated alternative text: Classification Healthy weight Overweight Obesity I Obesity Il Obesity Ill BMI (kg/m 18 5-24.9 25-29 9 30-34.9 35-39 9 40 or more Consider ethnicity: Example - South Asians Risks at lower BMI Caution: Muscular build

Ethnicity- South Asian- 23 BMI obesity

Primary cause- lifestyle

Secondary cause:

Endocrine-

Cushing’s syndrome

Hypothyroid

Pseudohypoparathyroid

Hypothalamic disorders

 

Genetic-

Prader Willi

Laurence Moon

Bardet Biedel

Cohen’s

Alstrom’s

 

Medications-

Steroids

Tricyclic antidepressants

Phenothiazines

Sodium valproate

Sulphonyl ureas, Insulin

 

Psychiatric-

Eating disorders: Bulimia nervosa

 

Conditions associated with Obesity-

Osteoarthritis              

Hypertension              

Type 2 Diabetes                     

Obstructive sleep apnoea                    

Reflux   Oesophagitis                     

Depression / Mental health problems                

Asthma                       

Heart failure

 

Prostate (235) Non.Hodgkin•s WmphOma (e35) All cancers (240) All other cancers (z30) Kidney (235) Multiple rnyeloma (235) • Gallbladder (230) Colon and rectum (z35) : Esophagus Stomach (235) Pancreas (235) : Liver (235) : Men 1.34 1.49 1.52 1,680 1.71 1.76 1.84 .94 2.61* Relaåve Risk of Death (95% Interval) 6

 

Multiple myeloma (235) Colon and rectum (240) mry (235) : Liver (235) . All ancers (240) (235) 1.44 Breast (240) Gallbladder (230) An other cancers (240) Esophagus (230) Pancreas (240) Cervix (235) • Kidnø (z 40) Uterus (240) , 1.46 1.51 1.68 1.88* 1.9S 2.12 2.13 2.51* 2.64 2.76 3.20 4.75 6.25 3 4 6 8 Relative Risk (95% Interval) 9 10

 

 

 

Assessment:

 

BMI: Not enough

EOSS

4M

Edmonton Obesity Staging System (EOSS) co-motidty moderate moderate Obesity SharmaAM & Kushner RF, Int J ores

 

EOSS: EDMONTON OBESITY STAGING SYSTEM - Staging Tool STAGE O • NO Sign Of obesit•rrelated factors • NO physical syrr,pto.ms • NO psychological symptoms • NO functional limitations Case with a BMI 32 no iSS•m I Kmutions. O Obesity STAGE 2 • Patient has an ESTABLISHED Obesity-related comorbidities requiring medical intervention • OR • • MODERATE obesity. related symptoms • MODERATE functional limitations in daily activities Case Exee•. pear male with a of •6 kg,'m' who has primary hypertension Skep apnea. Star Alberta Health Services STAGE 1 • Patient has Obesity-related SUBCLINiCAL risk factors • MILD physical symptoms - patient current* not requiring medical treatment for comorbidities • MILD Obesitvrelated psychological symptoms mild impairment Of well-being Case Exampw: 38 old BMI of S' 2 kz,'rr,•. hypertension. mild lower and pain Pat*nt does requre meek* imerventbn. • Patient has significant obesit•prelated end-organ • SIGNIFICANT obesity-realted psychological symptoms • SIGNIFICANT functional limitations • SIGNIFICANT impairment of well-being Case 49 old female with a BMI of 67 kg/ m' diagnosed with sleep CV and suffered stroke _ Patient's mobility is to ard Goss Stoøe 3 '*Ho WEIGHT surus •1m' I _ .34.9 O 1 Obesity Patient does not meet clinical criteria for admission at this time. Please refer to primary care for further preventati« treatment options. • SEVERE (potential end stage) from obesity related comorbådities - OR - • SEVERELY disabling • OR - • SEVERE functional limitations Example: 45 with a BMI Of 54 is a chair *cause of arthritis, severe disorder. StO* Sharma AM & Kushner RE, Int Obes 2X»9

 

Medical management:

 

Life style modification

Behavioural modification

Psychology support- Motivational consultation

Dietician support

Specialised weight management service

Assessment, investigations, Treatment of co-morbidities

 

NHS 4 tier weight management:

e 0 E Accessed via Tier 3 specialist centres in line with NHS England policy Referral to Tier 3 following suboptimal weight loss maintenance with Tiers via GPI Primary Care Primary care to advise and support lifestyle management: Diet physical activity Behavioural changes Tier 4 Bar iatric Tier 3 Specialist weight Tier 2 Lifestyle management Tier 1 Universal servtces Preoperative assessment : for specialised complex obesity services (induding bariatric surgery) Low-energy liquid diets, AOMs, assessment for bariatric surgery and/or : referral for endocrine . investigation primary care with community interventions (including referral : to commercial weight loss programmes) Primary care and community : advice to identify and reinforce healthy eating and physical activity messages

 

 

 

 

Obesity – A Public Health Perspective

23 December 2020

13:48

Overweight and obesity are defined as excessive fat accumulation that pose a risk to health.

The body mass index (BMI) is a crude population measure of obesity

 

BMI is calculated as a person’s weight (in kilograms) divided by the square of his or her height (in metres).

 

Between 18.5 to 24.9 Between 25 to 29.9 Between 30 to 39.9 40 and above • Healthy weight • Overweight • Obese • Severely obese

 

7 Key cause-

 

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– to put it simply …

Obesity and overweight are fundamentally a result of an energy imbalance between the number of calories consumed and calories expended

While there is an element of individual choice in food consumption, we must remember that we live in an obesogenic world.

 

7 main causes of obesity -

Increased consumption of energy-dense foods

Food is often processed and high in saturated fat and sugars

Ready meals are convenient and readily available

Fast-food chains are widespread with late opening hours

Marketing campaigns play a major influential role

 

Increased food production for commercial profit 

Food producers are pressured to turn a profit for stakeholders and make processed food in large volumes

This processed food is often sold affordably to encourage consumption

 

An increase in physical inactivity and sedentary lifestyle.

Changing work patterns (sitting at desks rather than manual labour)

Technology advances including changes to transportation ( more people are using cars, buses  or trains rather than walking, biking etc…)

 

Poor physical activity environment

There is reduced availability of safe green spaces for outdoor activity, especially in urban settings.

 

Individual biological physiology

Genes can impact how fat is metabolised as well as individual perception of fullness

 

Individual psychology

Stress and low self-esteem can impede a person’s ability to consciously control his or her food intake

Food can also be used as a psychological reward

 

Social psychology

Collective societal beliefs about food and body shape can play a role in determining how much people eat

These beliefs vary around the world 

 

Obesity and overweight are major risk factors for non-communicable diseases including:

Cardiovascular diseases

Diabetes mellitus

Hypertension

Stroke

Musculoskeletal disorders (especially osteoarthritis)

Cancers (including endometrial, breast, ovarian, prostate, liver, gallbladder, kidney, and colon)

Dyslipidaemia

 

The risk of developing a non-communicable disease increases as a person’s BMI increases.

Poor mental health

Poor quality sleep (sleep apnoea)

Increased stigmatization and discrimination

 

Change *the level doptn g health'/ living So Wing the 0b esity •epidemic' Inwrcwing the physic* Political action Economic qrægi•S / Reducing nequalities

 

 

 

At the individual level, people can: Limit consumption of proc foods wih •nouns of rats sat and sue.s Incrase conmmptin of fruit and veget*IeS, Engæe regula dai* ptwsal This is the basis of reventative and life le medicine

 

What is Public Health England doing about obesity?

The Eatwell Guide shows how much of what we eat overall should come from each food group to achieve a healthy, balanced diet.

 

Better Health Campaign

Launched on the 27th of July 2020 by Public Health England.

Response to national interest in obesity during the COVID pandemic

It is an opportunity for a “national reset moment”.

Gives individuals access to a range of mobile apps and online tools to help them stay in shape and make healthier food choices

It will also support people to live healthier lives in general with smoking cessation and mental health advise.

 

 

Reversing the obesity trend will improve quality of life and reduce morbidity and mortality from NCDs

 

 

 

 

Dietetic Management of Obesity

23 December 2020

14:17

Healthy eating will vary according to a person’s health and lifestyle.

 

In general, healthy eating will involve a variety of all food groups in proportions that are relevant to your patient.

 

The food groups are:

Vegetables & fruit

Starchy carbohydrates

Protein foods

Dairy foods & alternatives

Fats & oils.

 

Calories (kcal)

Calories or kilocalories (kcal) are a measurement of the amount of energy in our food and drinks.

The energy balance equation states that if we take in more energy than we use, we will store this energy in our body tissues, and gain weight.

Therefore, kcals and kcal reduction have become a useful tools in weight management.

 

There are many different equations that can be used to estimate someone’s energy expenditure.

In practice, I have not found these easy to use.

A patient’s weight, and the trend of their weight is a good indicator of their kcal requirements.

 

Practical kcal Reduction

Kcal counting apps  (accurate portions are key)

Looking at the kcal content of foods such as on food labelling

Meal replacement products

Portion control

Plate models.

 

Partial Meal Replacement Diets:

Uses meal replacement products to replace 1-2 meals per day to create a calorie deficit.

Meal replacement products: shakes, bar, soups and smoothies.

Each meal replacement typically contains between 200-230 kcal/serving, 15g protein and vitamins and minerals.

These can be used safely outside of Specialist Weight Management Services.

 

Meal Replacement Products

I.e. slimfast

 

Very Low Calorie Diets (VLCDs)

VLCDs are:

Any diet providing 800 kcal/day or less.

Can be liquid diets (total meal replacements) or fixed meal plans.

NICE advise that these should not be used for longer than 12 weeks.

These should not be used in Tier 1 & 2 except under guidance from a GP or Consultant Physician.

 

VLCDs have been shown in some cases to put type 2 diabetes into remission, up to 10 years after diagnosis.

Where remission is not achieved, often an improvement in HbA1c is achieved. Also reduction in medication.

VLCDs are very restrictive and can be difficult.

A specific VLCD plan should be followed.

 

The Problem with kcal & Low Fat

Research shows that most people who go on a kcal controlled diet, lose weight over a 3-6 month period. Weight loss then plateaus, and often weight is regained.

Low fat dietary advice has been around for approximately 50 years. Low fat diets usually have a high proportion of kcal from carbohydrate.

Poor outcomes in the general population.

 

 

Lower Carbohydrate Diets

These involve the reduction in the consumption of starchy carbohydrates and sugars.

Can be successful in weight loss and improving HbA1c.

Often higher in protein & sometimes fat.

Often more satiating than other dietary interventions.

 

Success may be due to the need for the body to produce less insulin.

There is a spectrum of low carbohydrate diets

Diabetes UK plan

100g or less per day of carbohydrate

Ketogenic or “keto” diets  (20g or less).

Some practical difficulties in achieving a lower carbohydrate long-term.

 

Other Interventions

Intermittent fasting

Time restricted eating

Lower glycaemic index (GI) diets

Weight loss/diabetes medications:

·         Orlistat

·         GLP-1 analogues

·         Saxenda (liraglutide)

·         SGLT2 inhibitors.

 

Machine generated alternative text: Useful Tips • Portion plate models (10 inch plate) Protein foods Veg & salad Starch/ Cåbon•/draes

 

Meal replacement products

Either as an ad-hoc tool, or as part of a partial meal replacement diet.

 

Investigate new dietary interventions and fads when patients mention them.

Some may be useful, some may be unhealthy.

 

Meet the patient where they are.in terms of their weight loss

Be flexible, there are many ways to lose weight in a healthy way

Be non-judgemental to encourage patients to talk about their weight issues

Gently but firmly correct any misunderstandings a patient may have.

 

 

 

 

 

Lifestyle Preparation For Bariatric Surgery

23 December 2020

16:01

Prerequisites for Bariatric Surgery

Engage well with a Tier 3 Specialist Weight Management Service for 12 months.

Lose 10% of excess body weight during this time.

Must be a non-smoker. Some nicotine replacement therapies will also need to have ceased prior to surgery.

Must be assessed for Obstructive Sleep Apnoea and, if diagnosed, be compliant with the appropriate treatment.

 

Checklist:

 

I eat 3 regular meals (breakfast, lunch and evening meal).

 

I eat my regular meals at about the same time every day.

 

My portion sizes have decreased.

 

I eat 5 portions of fruit and vegetables a day.

 

I have reduced the amount of fat in my diet by limiting/avoiding fried foods, choosing reduced or low fat options and now only eating lean cuts of meat.

 

I have 3 portions of dairy foods or fortified alternatives in my diet every day and choose reduced fat versions.

One portion can be:

200 ml semi-skimmed/skimmed milk

125-150g yoghurt (lower calorie)

30g reduced fat hard cheese

60g reduced fat soft cheese

100g low fat cottage cheese.

 

I no longer have fizzy drinks.

 

I aim to drink 2 litres of low calorie fluid per day (water, no added sugar drinks e.g. tea, coffee, squash, flavoured water).

 

I avoid drinking 30 minutes before, after and during eating and I am now sipping drinks throughout the day.

 

I do not drink alcohol Or I drink alcohol in moderation and do not exceed the recommendation of 14 units per week over 3 or more days.

 

I rarely eat sugary foods and can now limit myself to 1 biscuit or 2 squares of chocolate.

 

I no longer eat takeaways.

 

I take at least 20 minutes to eat a meal.

 

I chew each mouthful of food 20 times before swallowing and I wait 20 seconds between each mouthful.

 

I do not binge eat.

 

I do not graze on foods.

 

I do not comfort eat.

 

Dumping Syndrome

·         This is an unpleasant collection of symptoms that can occur post-bariatric surgery.

·         These symptoms can include: sweating, faintness, palpitations, diarrhoea, nausea (feeling sickly) and a bloated stomach.

·         Avoiding sugary and fatty foods and drinks.

·         Avoiding drinking 30 mins, before and after and during eating.

·         Eating slowly and chewing food well.

 

 

 

 

 

Bariatric Surgery / Metabolic Surgery

23 December 2020

16:09

NHS Tier 4 weight management

e 0 E Accessed via Tier 3 specialist centres in line with NHS England policy Referral to Tier 3 following suboptimal weight loss maintenance with Tiers via GPI Primary Care Primary care to advise and support lifestyle management: Diet physical activity Behavioural changes Tier 4 Bar iatric Tier 3 Specialist weight Tier 2 Lifestyle management Tier 1 Universal servtces Preoperative assessment : for specialised complex obesity services (induding bariatric surgery) Low-energy liquid diets, AOMs, assessment for bariatric surgery and/or : referral for endocrine . investigation primary care with community interventions (including referral : to commercial weight loss programmes) Primary care and community : advice to identify and reinforce healthy eating and physical activity messages

 

 

 

 

Types:

Restrictive

·         Laparoscopic adjustable gastric band

o    *Restrictive procedure  *Inflatable band  *Can be adjusted via a reservoir under the skin

·         Vertical sleeve gastrectomy

o    *Restrictive Procedure  *Part of stomach is removed  *Rest of the stomach left as a sleeve

 

Malabsorptive

·         Roux-Y-Gastric Bypass (RYGB)

*Mal-absorptive procedure: *A small pouch is made in the stomach

 *A loop of the bowel is anastomosed into small bowel

 

·         Single anastomosis Mini bypass

·         Biliary Pancreatic Diversion-Duodenal Switch (BPD-DS)

 

Who is considered for bariatric surgery:

People with BMI Of >40 without co-morbidities

People with BMI of >35 with co-morbidities

 

Before:

Work with a structured weight management program for 6 months to 1 year

Make sustainable life style changes

Confirm no major mental health problems

Stop smoking

Co-morbidities optimised

Patient keen and motivated

Prepared for a long term life style change

 

 

Bariatric surgery achieves remission of type 2 Diabetes:

Studies have shown bariatric surgery results in remission of Type 2 Diabetes-Defined as HbA1c <48 without medications for more than a year

 

 

Benefits:

Improved mobility

Hypertension improved

Sleep apnoea resolved

Quality of life improved

Mental health benefits

Improved financial and social health

 

Complications:

 

Peri-operative complications

Infection, Bleeding, anaesthetic complications

 

Long term

Nutritional deficiencies

Loose skin

Dumping syndrome

 

 

Summary:

Indications for bariatric surgery

Life style change is vital

Careful assessment of patients to assess suitability for bariatric surgery

Benefits include significant weight loss and improved co-morbidities

Helps to achieve remission of Type 2 Diabetes

Plays a major role in treating people with morbid obesity

 

 

 

Weight loss after:

Control -10 Banding Vertical-bandd gastroplasty Gastric bypass 15 Yærs

 

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Bariatric Surgery Benefits Significant weight loss Improvement of co- morbid conditions Resolution of Type Il Diabetes Improved psychological function Improved QOL Shikora SA, et al. Nutr Clin Pract. Complications Nutrient deficiencies Protein malnutrition Surgical complications Dumping syndrome

 

 

 

 

Impaired Glucose Tolerance

23 December 2020

16:20

Diagnostic Criteria
(from IDF Atlas 9th edn 2019)

FASTING PLASMA GLUCOSE TWO-HOUR PLASMA GLUCOSE (CGTT)) PLASMA GLUCOSE the of DIABETES *odd if OR MORE of be bbwi-,g cero are ret 070 11.1 48 IMPAIRED GLUCOSE IMPAIRED FASTING GLUCOSE (IFG) TOLERANCE (IGT) *odd te if tre Ee if BOTH 6.1-6.9 e 11.1 42 — 07.8 . -6.4%) (equivalent to 6 0 Sometimes termed Pre-diabetes

 

 

Bimodal distributions- DIabetes

(회 1기*Obi』』치!Iti개 (%)k)騎h囟킨삐1하개

 

 

Figure 6 Numberof ad ( 20 一 79 years)with impaired glucosetolerancebyage group, 1n2019 , 2030 and 2045 2019 2g0 2g5 20 一 24 25 一 29 333b 35 一 39 0 一 乛 5 一 9 5 5 孓 59 一 65 一 69 7874 75 一 79 Age 9 「 oups (years)

 

Figure 3.7 Prevalence of impaired glucose tolerance in adults (20—79 years) by age and 18 16 12 10 8 6 2 sex in 2019 Women Men 20-24 25-29 30-34 35-39 45-49 50-54 55-59 60-64 65-69 70-74 75-79 Age groups (years)

 

Impaired Glucose Tolerance

 

Global prevalence 2019 (age adjusted) in 20-79 yr old adults   8.6%

Projected to rise in 2045 to          9.5%

 

Prevalence nationally in UK in 2011  10.7 %

Prevalence in Malaysia in 2019 15.5 %

 

 

25 – 75 % of people with IGT will go on to develop Type 2 diabetes

Incidence of around 5 % per annum

Linked to increased cardiovascular risk (RR 1.2 for IGT & IFG)

 

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Evidence that intervention can prevent development of T2DM

Diet and exercise with modest weight loss ± Metformin was effective in the Diabetes Prevention Programme in the USA

NICE PH 38 Prevention of Type 2 Diabetes www.nice.org.uk/guidance/ph38/chapter/Glossary

 

NHS England has a National Diabetes Prevention Programme – recruited  > 380,000 by March 2019

At least 13 sessions over 9 months with health care professionals

If Lifestyle changes alone ineffective then trial of metformin or acarbose

Address all other CV Disease risk factors

·         Blood pressure

·         Plasma cholesterol

·         Smoking

·         Alcohol

 

 

 

 

 

 

 

 

Types of Diabetes

23 December 2020

16:39

Definition:

A net deficiency of insulin leading to imbalance in glucose production and utilization

·          

·          

·         Fasting plasma glucose ≥7.0 mmol/L and 2h plasma glucose ≥11.1 mmol/L

Or

·         HbA1c >48 mmol/mol 

Or

·         Random plasma glucose ≥ 11.1 mmol/L PLUS symptoms (thirst,  polyuria,weight loss) 

 

From <https://mle.ncl.ac.uk/cases/page/16226/>

 

Best non pharmacological treatment

Weight loss, DASH (Dietary Approaches to Stop Hypertension) diet, Increase potassium intake, Decrease sodium intake, Decrease alcohol consumption, Regular exercise, Increase dietary fibre.

 

In 2013, over 3.2 million adults were diagnosed with diabetes, with prevalence rates of 6% and 6.7% in England and Wales respectively. It is estimated that about 90% of adults currently diagnosed with diabetes have type 2 diabetes. Type 2 diabetes is more common in people of African, African‑Caribbean and South Asian family origin. It can occur in all age groups and is increasingly being diagnosed in children and adolescents almost always in association with obesity

FASTING PLASMA GLUCOSE TWO-HOUR PLASMA GLUCOSE (CGTT)) PLASMA GLUCOSE the of DIABETES *odd if OR MORE of be bbwi-,g cero are ret 070 11.1 48 IMPAIRED GLUCOSE IMPAIRED FASTING GLUCOSE (IFG) TOLERANCE (IGT) *odd te if tre Ee if BOTH 6.1-6.9 e 11.1 42 — 07.8 . -6.4%) (equivalent to 6 0 Sometimes termed Pre-diabetes

 

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·         Global prevalence 2019 (age adjusted) in 20-79 yr old adults 8.3%

·         Projected to rise in 2045 to  9.6%

 

·         Prevalence on Teesside around  7.0 %

·         Prevalence nationally UK around  6.5 %

·         Prevalence in 65-99 year olds around  20.1 %

·         Prevalence in Malaysia in 20 – 79 year olds > 16.0 %

 

 

Prevalence of diabetes in adults by age, 2014 Malaysia 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 Age (years)

 

·         Acute complications - metabolic comas

o    DKA accounts for > 50% deaths in people with diabetes in the USA aged < 24yrs

o    DKA listed as main cause of death in 25% of those aged < 50 yrs in Scotland

·         Chronic complications - microvascular and macrovascular

o    Diabetes commonest cause of end stage renal disease globally

o    Incidence rates in Malaysia amongst highest in world

o    Over 20% of UK dialysis population have diabetes

o    Diabetes commonest cause of visual loss globally

o    Diabetes commonest cause of non traumatic amputation

o    Diabetes doubles cardiovascular disease risk

o    Diabetes causes major pregnancy complications

 

 

Diabetes Mellitus – Type 1

·         Type 1 diabetes rare in Malaysia

·         UK incidence ~ 10 - 20 / 100,000 children

·         Usually occurs < 40 years of age

·         Peak incidence adolescence but getting younger

·         Strong genetic and auto immune basis

·         Always requires

·         Autoantibodies :

o    Glutamic acid decarboxylase (GAD 65)

o    Islet cells (not specific or sensitive)

o    Insulin

o    Tyrosine phosphatases (IA2 & IA2b)

o    Zinc transporter (ZnT8)

o    > 80% positive for GAD, IA2 or ZnT8 or all three

·         Genetics – HLA :

o    >90% have DR4, DQB*0302 and/or DR3, DQB*0201

o    Over 20 other genes identified with small effects

·          insulin therapy

 

Latent Autoimmune Diabetes in Adults - LADA

·         Up to 10% adults in Scandinavia have autoantibodies to b cell antigens

·         Share genetic features with Type 1 (HLA) and Type 2 (TCF7L2)

·         Variable phenotype

·         Many develop insulin dependence

 

Diabetes Mellitus – Type 2

 

·         Type 2 diabetes represent at least 95% of all cases

·         Incidence difficult to estimate

·         Prevalence varies with age, weight and race

·         Usually occurs > 40 yrs of age; becoming more common in young

·         Polygenic up to 50 genes with small effects (TCF7L2 most powerful)

·         Usually not insulin dependent but often becomes insulin requiring

 

Diabetes Mellitus – Other Types

 

Secondary –

due to pancreatic disease e.g. pancreatitis (acute, chronic and calcific)

 

Cystic fibrosis - now more common with increased survival

 

Haemachromatosis due to iron deposition

 

Drug induced e.g. chronic steroid use, calcineurin inhibitors, statins, major anti-psychotic agents, HAART

 

Monogenic – Maturity Onset Diabetes of the Young (MODY) (1-4% young adults with diabetes in UK). 37% glucokinase mutations; 63% transcription factors

Early onset non-insulin dependent diabetes before the age 25 yrs

Monogenic: autosomal dominance

rare (1-3% of Type 2 diabetes)

Different genes, including HNFA1 and GCK

 

 

Congenital & neonatal

 

Syndromic e.g. lipodystrophies, Prader-Willi syndrome, myotonic dystrophy, Wolfram (DIDMOAD)

 

Chromosomal e.g. Down and Turner syndrome increased Type 1 diabetes

 

Mitochondrial – maternal inheritance with deafness and cardio-neural problems ( around 1% of those with Type 2 diabetes in Japan)

 

 

 

Associated Endocrinopathies

·         Excess hormones associated with diabetes

o    Cushing’s including iatrogenic - Glucocorticoids

o    Acromegaly – Growth Hormone

o    Phaeochromocytoma – Catecholamines

o    Glucagonomas

o    Somatostatinomas

o    Hyperthyroidism (NB autoimmune link with Type 1)

 

·         Summary:

·         Diabetes is common and getting commoner

·         Diabetes is associated with significant morbidity and mortality

·         Not all diabetes is type 1 or type 2 - Consider rare but treatable causes

·         MODY is an important diagnosis (in UK)

·         it can alter treatment & prognosis

·         Understanding unusual causes of DM helps :

·         understand pancreatic beta cell function

·         understand pathophysiology of all types of DM

 

 

 

 

 

Personalised Medicine

23 December 2020

17:16

WHO Classification of Diabetes (2019)

Type 1

Insulin-dependent

Autoimmune destruction of B-cells        

Characterised by ketones and weight loss

 

Type 2

Non-insulin dependent

Both decreased insulin secretion and insulin resistance

 

Hybrid forms

      Slowly evolving immune mediated (LADA)

 

 

Maturity Onset Diabetes of the Young: MODY

Early onset non-insulin dependent diabetes before the age 25 yrs

Monogenic: autosomal dominance

rare (1-3% of Type 2 diabetes)

Different genes, including HNFA1 and GCK

 

 

Newly diagnosed diabetes: Ketone positive +1- M loss YES Type 1 DM NO Auto Ab we YES LADA NO Non-obese features of Monogenic DM YES Monogenic NO 120M

Personalised Medicine:

“ An approach for disease treatment and prevention that takes into account individual variability in environment, lifestyle and genes for each person”

 

 

Type 2 DM: Complex Trait Multiple Genes effects Diabetes Lifestyle and environmental factors (obesity, lack of exercise)

 

>400 T2D genetic loci reaching genome-wide significance - _ - "20% of variance - -"50% of heritability ISO 2013 C.ndid.te Ge G WA s Lin Whole Æque Ing *016 2018 200

 

ADOPT: Groups of Type 2 Diabetes Patients respond differently to different treatments Slim Obese females

 

Antihyperglycemic therapy in type 2 diabetes: general recommendations

 

 

 

 

Remission of Type 2 Diabetes

23 December 2020

17:57




As duration goes up its harder to put T2DM into remission

D-REcr Remissions 12 and 24 months Intervention % in 12m Lean et al Lancet Diab & Endo 2019; 7: 344

Diet for weight loss:

Simple

Practical

Spouse/partner on board

Duration limited and planned- 8 weeks max 12 weeks

No additional exercise during this time

 

Compensatory eating renders exercise counterproductive during weight loss

 

Protein mainly- satiety

 

Weight loss then weight maintenance Step ILow calorie weight loss 600kcaVday liquid fornwla diet nonstarchy vegetables (or 800kcaI/day liquid formula only) Step 2Step-wise return to normal eating step 3 Replace liquid formula with normal food, one meal at a time. Aiming for 21500kcaI/day Long term support to limit calorie intake and encourage increased physical activity

 

The Twin Cycle Hypothesis: Etiology of Type 2 diabetes blood aute irsulin Pre-existing cycle Ræistarce to irsulin cortrol of gl u coæ T plasma glucoæ Pan Teas cyde ubcutaneou es TaylorR, Diabetobgia 2008; 51: 1781

 

 

 

Lipid and Health

23 December 2020

18:17

Why should we know about lipids?

Abnormal lipid values are highly prevalent

 

Well documented relationship between total and LDL-C levels and vascular events like coronary artery disease, cerebrovascular disease and peripheral vascular disease

 

Treatment decreases the risk of  events

 

 

Early knowledge of a lipid disorder creates the best opportunity for early intervention

 

 

 

Prevalence:

About 50% of adults have an elevated total cholesterol level

 

Majority of patients with atherosclerosis have some form of dyslipidemia

 

70-80% of individuals with dyslipidemia do not meet LDL cholesterol targets despite lipid therapy

 

 

Symptoms:

 

High cholesterol does not cause any symptoms

 

Too much cholesterol may lead to a build up of plaque inside the arteries causing atherosclerosis

 

Machine generated alternative text: Artery Cholesterol particles (lipoproteins) Cholesterol deposited in lining of artery Buildup begins Plaques form (atherosclerosis) C' Rese»ch A

 

Naturall history CT the condition shoulldl be understoodln Ischemic Heart Disease Cerebrovascular Disease Peripheral Vascular Lesion: Initiation Progression ± Stable No Symptoms Reversible + Symptoms + Reversible Disease Sympto ms Non - Reversible

 

Measure:

Total Cholesterol (Desirable <5 mmol / l)

 

Low density Lipoproteins (LDL) (Desirable <2.5 mmol / l)

 

High Density lipoproteins (HDL) (Desirable > 1.2 in women and > 1 in men)

 

Triglycerides (Desirable < 2.5 mmol / l)

 

Total cholesterol/ HDL Ratio (Desirable < 4 )

 

Others: Very low density lipoproteins (VLDL), Lipoprotein A, Apolipoproteins

 

 

Total Cholesterol:

 

Total cholesterol measures the combination of LDL, HDL, and VLDL (very low density lipoprotein) in your bloodstream. VLDL is a precursor of LDL, the bad cholesterol.

 

 

 A total cholesterol of under 5 is considered healthy in most cases.

 

 

LDL:

Most of the cholesterol in the blood is carried by proteins called low density lipoproteins or LDL or the bad cholesterol

 

LDL combines with other substances to clog the arteries.

 

A diet high in saturated fats and trans fats tends to raise the level of LDL cholesterol.

 

For most people, an LDL score below 2.5 is healthy, but people with heart disease may need to aim even lower

 

HDL:

 

Up to a third of blood cholesterol is carried by high-density lipoproteins or HDL or the good cholesterol

 

HDL helps remove bad cholesterol, preventing it from building up inside the arteries.

 

The higher the level of HDL cholesterol, the better. People with too little are more likely to develop heart disease.

 

Triglyceride:

 

The body converts excess calories, sugar, and alcohol into triglycerides, a type of fat that is carried in the blood and stored in fat cells throughout the body.

 

People who are overweight, inactive, smokers, or heavy drinkers and those who eat a very high carbohydrate diet tend to have high triglycerides

 

 High triglycerides puts people at risk for metabolic syndrome,  which is linked to heart disease and diabetes.

 

Causes:

Primary Dyslipidaemia

·         Genetic dyslipidaemia

·         Familial Hypercholsterolaemia

 

Secondary

·         Type 2 Diabetes

·         Nephrotic syndrome

·         Hypothyroidism

·         Obesity, smoking, life style

 

What increases risk:

A diet high in saturated fats and cholesterol

A family history of high cholesterol

Being overweight or obese

Getting older

Secondary causes like Diabetes

Physical inactivity, smoking, alcohol will increase triglyceride level

 

Ways to lower:

 

Many National and International guidelines are in place

European Society of cardiology guidelines

NICE UK guidelines

 

Dietary Modifications:

 

Saturated fats - from animal products and tropical oils -- raise LDL cholesterol

Trans fats increase bad cholesterol and lowers the good cholesterol

 

These two bad fats are found in many baked goods, fried foods (doughnuts, french fries, chips), stick margarine, and cookies

 

Unsaturated fats may lower LDL when combined with other healthy diet changes. They're found in avocados, olive oil, and peanut oil.  

 

Moderate alcohol intake

 

 

Lifestyle Modifications:

Lose weight

Stop smoking

Increase physical activity

 

Medications/Drugs:

Statins

Fibrates, Ezetimibe, Omega 3 fatty acids

Bile acid sequestrants

PCSK 9 inhibitors, Inclisiron

 

Statins:

Lipid soluble

Atorvastatin

Simvastatin

 

Water soluble

Rosuvastatin

Pravastatin

 

 

Decrease LDL  by 18 – 55 %

 

Increase HDL by 5 – 15 %

 

Decrease TG by 7 – 30 %

 

Studies have shown siztins reduce cardio vascular events

 

 

 

 

 

 

 

 

 

 

 

 

 

Genetic dyslipideamia

23 December 2020

18:32

Familial hypercholesterolaemia

 

Dyslipidaemia Familial combined hyperlipidaemia (FCH) Heterozygous familial hypercholesterolaemia (HeFH)* Polygenic hypercholesterolaemia Familial hypertriglyceridaemia Abnormal lipids t LDL cholesterol, triglycerides (VLDL) or both T LDL cholesterol (typical range 5—10 mmoI/L in FH) tapoB Prevalence 1:100 1:500 1:50 1:100 Key: apoB = apolipoprotein B; LDL = low-density lipoprotein; VLDL = very-low-density lipoprotein * Note homozygous familial hypercholesterolaemia is very rare Pone in one million births)

 

 

o Family history of early cardiac events t LDL-C High LDL cholesterol: above 190 mg/dL in adults and 160 mg/dL in children AWARENESS DAY SEPTEMBER 24 Familial Hypercholesterolemia #FHCantWait

 

 

Familial Hypercholesterolemia:

Prevalence estimayed : 1 in 200 to 1 in 250 people

Most common inherited condition

Autosomal Dominant inheritance

 

Familial Hypercholesterolemia 50% 50% FH is different LJfe:tvIe FH is manageable 6 .5 FH is life threatening FH is undiagnosed Source: the FH Foundation

 

When to suspect:

 

High LDL > 5 mmol/l

Early Cardio vascular event

Strong family history

Stigmata

Tendon xanthoma

Arcus Lipidalis

 

Dutch lipid scoring system:

Family history F i r" degree relative with known premature coronary and/or vascular (men aged eSS pears. women aged years ) F i 'St relative with known LDL -Ch&SterOI percentile age and gender F i 'St relative with and/or a Children pears with LDL-cholesterol above the and ender Patients with premature coronary artery disease (men aged <SS years, women aged with premature cerebral or disease women years) n n ttnta Arcus rs of Stratification LDL.c 4.0—4.9 Total

 

Confirmatory test:

 

Gene sequencing

Once confirmed-Family members are screened- family cascading

 

 

Simon Broom Criteria:

Point c D Criteria DNA mutation Tendon xanthomas in patient or 1st or 2nd-degree relative Family history of myocardial infarction <50 years in 2nd-degree or <60 years in Ist-degree relative Family history of total cholesterol >7.5 mmol/L in 1st/2nd-degree relative Total cholesterol >7.5 mmol/L (adult) or >6.7 mmol/L (age <16 years) LDL-cholesterol >4.9 mmol/L (adult) or >4.0 mmol/L (age <16 years) Definite FH: Hypercholesterolaemia as defined in points E/F plus A. Probable FH: Hypercholesterolaemia as defined in points E/F plus B Possible FH: Hypercholesterolaemia as defined in points E/F plus either C or D

 

 

Management:

Life style modification

Family cascading

Statins

Ezetimibe

PCSK-9 inhibitors

·         Alirocumab

·         Evolucumab

Inclisiron

 

 

 

 

 

 

 

 

Essential Hypertension

23 December 2020

18:48

Normal Blood Pressure:

Blood pressure not normally distributed in population

Marked variation by age- higher the higher, higher distribution in elderly

Long tail of values to the right, especially in elderly

Abnormal defined largely by response to blood pressure lowering

 

Essential Hypertension:

Defined as ‘hypertension with no known cause’

Accounts for > 95% of cases (secondary causes separate resource)

Divided into stages

Stage 1 BP 140-159/90-99 mmHg clinic (135-149/85-94 mmHg average ABPM/HBPM)

Stage 2 BP 160-179/100-119 mmHg (≥ 150/95 ≤180/120 mmHg average ABPM/HBPM)

Stage 3 (severe) BP ≥ 180/120 mmHg

 

66% of patients with hypertension have a comorbidity

 

HYPERTENSION: ACT NOW! What is hypertension? Blood pressure is the force Of circulating blood against the walls of the body's arteries, the major blood vessels in the body. Hypertension is when the force Of the blood pressure is excessive. Bhost people with high blood pressure DO NOT KNOW THEY HAVE IT. 140 Hypertension is diagnosed if blood pressure readings are 140-90 or above on two different days. How many people have high blood pressure? 1.13 BILLION PEOPLE have hypertension WOMEN HAVE HYPERTENSION 1 in4 MEN HAVE HYPERTENSION

 

Recommended practice for measuring blood pressure adapted from International Society of Hypertension
 

Use a calibrated and validated instrument

Quiet room

No smoking, exercise or caffeine for 30 mins

Measure after 5 minutes in a seated position, feet on floor

Arm should be free of tight clothing and at heart level

Cuff bladder should cover >80% of arm circumference

Take 3 measurements, 1 min apart and average last 2 

Check both arms (always use the arm with higher reading)

Check standing blood pressure to detect drug-induced postural hypotension

 

 

 

What are the risk factors? Salt consumption Low intake of fruits and vegetables Saturated fat and trans fats Harmful use of alcohol Lack of physical activity Tobacco use What are the consequences? • Heart attack • Stroke • Kidney failure • Blindness Other complications Bein or o overweight

 

0—24 D 30 ; Net • S•tstouc pressure 2140 aroor pressure 290 Age-standardized prevalence of raised blood pressure* in aduls aged 18 years and over, comparable estimates, 2014

 

Age Related Prevalence of Hypertension in England in 2014

Hypertension : III III 60-64 65-69 70-74 75-79 80-84 Age 85-89 90-94 95-99 100+ Metzer O et al 2015

 

How to prevent hypertension? o Reduce salt (to less than 59 daily) • Eat fruit and vegetables regularly Avoid saturated fats and trans fats Avoid tobacco Reduce alcohol Be physically active, daily How to detect hypertension? Health workers should regularly check people's blood pressure. NO SYMPTOMS DOES NOT MEAN normal blood pressure People might have high blood pressure WITHOUT ANY WARNING SIGNS OR SYMPTOMS.

 

 

 

Impact of Non-Pharmaceutical Interventions on Blood Pressure Modification Dietary Approaches to Stop Hypertension (DASH) diet Potassium intake g/d odium intake g B g sodium chloride)/day and normal diet cohol S30 mL ethanol (3 units)/day men SIS mL ethanol (1 units)/day women xercise 3D-EO minutes moderate x 4—76week Dietary fibre supplement(ll g/day) ultiple modifications (DASH diet, weight loss, low sodium intake, hysical activity) —g week trial Systolic/diastolic blood pressure effect (mmHg) 20/1 per kg 50/27

 

 

WHO Priority Actions:

Public Health Initiatives e.g. alcohol and weight reduction; dietary salt

 

Integrated Programmes to treat hypertension and other NCDs (diabetes, atherosclerotic cardiovascular disease)

 

Education & Encouragement of populations to get tested and treated (In UK 35% identified and treated to target; 65% in Canada)

 

Promote Workplace Wellness Programmes e.g. smoking restriction, healthy food options

 

 

Assessment and investigation of the patient with hypertension :
(from NICE NG136 Hypertension in adults:diagnosis and management)

·         Measurement of height and weight (for BMI) or waist circumference

·         Examination of the:

·         heart for evidence of left ventricular hypertrophy

·         lungs for heart failure

·         abdomen for pulsatile masses, renal enlargement or bruits

·         fundi for signs of retinopathy

·         Auscultation for carotid and femoral arterial bruits

·         Examination of peripheral pulses (to exclude coarctation or peripheral vascular disease)

·         Investigations to include ECG, urinalysis (including for microalbuminuria), serum electrolytes, urea and creatinine (and calculation of eGFR), HbA1c, fasting blood lipid profile, chest X-ray or echocardiogram to confirm left ventricular hypertrophy if suspected from ECG

·         Consider referral for specialist opinion in those with signs or symptoms of possible secondary causes of hypertension.

GUIDELINE Pub ücaion First fine 2019 140/90 135/85 <140/90 •:80•,' (clinic) {138/85 {150/90 (clinic) {145/85 (A8PM/H8PM) in Afro Cåibbem) ASH/ACC 2017 130/80 <130/80 f toleraed ACEl/AR8 CC8 or Thiazide 2014 140/90 30-599' 150/90 «140/90 30-599' {ISO/So Thiazideor cca or ACEl/AR8 ACEl/AR8 if 2020 140/90 <140/90 {130/80 if high CV risk and ACEl/AR8 CC8 or Thiæide no albuminuria ACEl/AR8 f albuminuria ESHÆsc 2018 140 Eo <130/80 (65 v,' <140/80 assy ACEl/AR8. cca or Thiazide 2020 140/90 (clinic) 130/80 135/85 <130/80 (65 v,' {140/80 ACEl/AR8 cca or Thiæide

 

Medications and Behaviours that can Increase Blood Pressure Corticosteroids Cyclo-oxygenase (COX-2) inhibitors • Non-steroidal anti-inflammatory drugs Erythropoietin Oral contraceptive pill Serotonin reuptake inhibitors Monoamine oxidase inhibitors Alcohol excess • Tobacco (smoking/snuff) Liquorice • Drug abuse (amphetamine/cocaine)

 

 

 

 

Secondary Hypertension

23 December 2020

18:53






 

 

 

Life style and Cancer

23 December 2020

18:59

What is classed as life style

 

Diet

Physical activity

Smoking

Alcohol

 

 

Poor diet and reduced physical activity causes obesity

Obesity is associated with Cancer

 

 

 

 

Type of Cancer and risk of death in Obesity-Men

Men Prostate Non.H0dgkin's lym*oma @35) : All cancers (240) All other cancers (230) Kidney (235) : Multiple myeloma (235) Gallbladder (230) Colon and rectum (z35) : Esophagus (•.30) Stomach (235) : Pancreas (235) : Liver (235) 1.49 1.52 1.68* 1.70 1.71 1.76 1.84 1.91* 1.94 2.61* 3 4.52 4 6 7 Relative Risk Of Death (95% Confidence Interval)

 

 

Type of Cancer and risk of death in Obesity- Women

 

Multiple myeloma (235) Colon and rectum (240) Ovary (235) Liver (235) All cancers (240) Non-Hodgkin's lymphoma (23 S) Breast (240) Gallbladder (230) All other cancers (240) Esophagus (230) Pancreas (240) Cervix (23 S) Kidnq (240) Uterus (240) Women 1.44 1.46 1.51 1.68 1.88* 1.95 2.12 2.13 2.51. 296 3.20 4 s 6.25 6 8 9 10 11 Relative Risk of (95% Confidence Interval)

 

Tobacco causes 1 4 types of cancer outh soo esophagus ung 14600 Oancreas OJ9dder Annual UK tobacco toll: 800 Cases deaths

 

Smoking : Carcinogens to Humans

Group 1 : Definite

·         Tobacco Smoking

·         Tobacco Products, Smokeless

·         4-Aminobiphenyl (4-ABP)

·         Benzene

·         Carmium

·         Chromium

·         2-Naphthylamine (2-NA)

·         Nickel

·         Polonium-210 (Radon)

·         Vinyl Chloride

 

Group 2: Probable

·         Acrylonitrile

·         Benzo[a]pyrene

·         Benzo[a]anthracene

·         1,3-Butadiene

·         Dibenz(a,h)anthracene

·         Formaldehyde

·         N-Nitrosodiethylamine

·         N-Nitrosodimethylamine

 

Overall, 86% of cases in men and 49% in women are due to smoking.

Stop smoking apps:

Kwit

QuitNow! Quit smoking

Quit Vaping

SmokeFree

Unsmok'd

 

Type of beverage

ABV (w/w in %)

beer, cider, and Perry

4-6

wine

9-13

spirits (e.g. brandy, gin, rum, vodka, whisky) made by distilling fermented liquor

38-45

liqueurs made from distilled spirits, sweetened and flavored

20-40

fortified wines (aperitif wines, Madeira, port, sherry) made by adding spirit to wine

18-25

 

iiNI compoun Chro mu m Benz e O(amrene Cad m Nitrom Nitrom dimer.yfamine S=Suficient; L=Ljmted; 1=1nadeqLEte; ND=No data

 

 

Alcohol cancers: 7

 

Oral and pharyngeal cancer

Esophageal cancer

Stomach cancer

Liver cancer

Colorectal cancer

Lung cancer

Breast cancer

 

Nun*er of grans (drinks) per

 

I,qellæltliwe IRIi51h(5 ISzcIh• Cral cavity md pharynx 7,239 44 ,033 2,84 1,61 4,094 Rel*iæ risks 25 g 50 g no zsociabm no zsociabm 100 g Escphagus Colon and rectum Stom Prcst&e Bagnardi et al , British Journal of Cancer 2001

 

 

 

 

BMI

04 January 2021

21:23

Classification Healthy weight Overweight Obesity I Obesity Il Obesity Ill BMI (kg/m 2 ) 18.5-24.9 25-29.9 30-34.9 35-39.9 40 or more Interpret BMI with caution in highly muscular adults as it may be a less accurate measure of adiposity in this group. Some other population groups, such as people of Asian family origin and older people, have comorbidity risk factors that are of concern at different BMIs (lower for adults of an Asian family origin and higher for older people

 

 

 

 

 

Health risks in relation to BMI and waist circumference: BMI classification Overweight Obesity 1 Low No increased risk Increased risk Waist circumference High Increased risk High risk Very high High risk Very high risk For men, waist circumference of less than 94 cm is low, 94—102 cm is high and more than 102 cm is very high For women, waist circumference of less than 80 cm is low, 80—88 cm is high and more than 88 cm is very high

 

 

 

 

24 December 2020

14:11

Wilson's disease

Wilson's disease is an autosomal recessive disorder characterised by excessive copper deposition in the tissues. Metabolic abnormalities include increased copper absorption from the small intestine and decreased hepatic copper excretion. Wilson's disease is caused by a defect in the ATP7B gene located on chromosome 13.

 

The onset of symptoms is usually between 10 - 25 years. Children usually present with liver disease whereas the first sign of disease in young adults is often neurological disease

 

Features result from excessive copper deposition in the tissues, especially the brain, liver and cornea:

·         liver: hepatitis, cirrhosis

·         neurological:

o    basal ganglia degeneration: in the brain, most copper is deposited in the basal ganglia, particularly in the putamen and globus pallidus

o    speech, behavioural and psychiatric problems are often the first manifestations

o    also: asterixis, chorea, dementia, parkinsonism

·         Kayser-Fleischer rings

o    green-brown rings in the periphery of the iris

o    due to copper accumulation in Descemet membrane

o    present in around 50% of patients with isolated hepatic Wilson's disease and 90% who have neurological involvement

·         renal tubular acidosis (esp. Fanconi syndrome)

·         haemolysis

·         blue nails

Diagnosis

·         slit lamp examination for Kayser-Fleischer rings

·         reduced serum caeruloplasmin

·         reduced total serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)

o    free (non-ceruloplasmin-bound) serum copper is increased

·         increased 24hr urinary copper excretion

Management

·         penicillamine (chelates copper) has been the traditional first-line treatment

·         trientine hydrochloride is an alternative chelating agent which may become first-line treatment in the future

·         tetrathiomolybdate is a newer agent that is currently under investigation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Primary sclerosing cholangitis

Primary sclerosing cholangitis is a biliary disease of unknown aetiology characterised by inflammation and fibrosis of intra and extra-hepatic bile ducts.

 

Associations

·         ulcerative colitis: 4% of patients with UC have PSC, 80% of patients with PSC have UC

·         Crohn's (much less common association than UC)

·         HIV

Features

·         cholestasis

o    jaundice, pruritus

o    raised bilirubin + ALP

·         right upper quadrant pain

·         fatigue

Investigation

·         endoscopic retrograde cholangiopancreatography (ERCP) or magnetic resonance cholangiopancreatography (MRCP) are the standard diagnostic investigations, showing multiple biliary strictures giving a 'beaded' appearance

·         p-ANCA may be positive

·         there is a limited role for liver biopsy, which may show fibrous, obliterative cholangitis often described as 'onion skin'

Complications

·         cholangiocarcinoma (in 10%)

·         increased risk of colorectal cancer

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Variceal haemorrhage

Acute treatment of variceal haemorrhage

·         ABC: patients should ideally be resuscitated prior to endoscopy

·         correct clotting: FFP, vitamin K

·         vasoactive agents:

o    terlipressin is currently the only licensed vasoactive agent and is supported by NICE guidelines. It has been shown to be of benefit in initial haemostasis and preventing rebleeding

o    octreotide may also be used although there is some evidence that terlipressin has a greater effect on reducing mortality

·         prophylactic antibiotics have been shown to reduce mortality in patients with liver cirrhosis. Quinolones are typically used. NICE support this in their 2016 guidelines: 'Offer prophylactic intravenous antibiotics for people with cirrhosis who have upper gastrointestinal bleeding.'

·         endoscopy: endoscopic variceal band ligation is superior to endoscopic sclerotherapy. NICE recommend band ligation

·         Sengstaken-Blakemore tube if uncontrolled haemorrhage

·         Transjugular Intrahepatic Portosystemic Shunt (TIPSS) if above measures fail

o    connects the hepatic vein to the portal vein

o    exacerbation of hepatic encephalopathy is a common complication

Prophylaxis of variceal haemorrhage

·         propranolol: reduced rebleeding and mortality compared to placebo

·         endoscopic variceal band ligation (EVL) is superior to endoscopic sclerotherapy. It should be performed at two-weekly intervals until all varices have been eradicated. Proton pump inhibitor cover is given to prevent EVL-induced ulceration. This is supported by NICE who recommend: 'Offer endoscopic variceal band ligation for the primary prevention of bleeding for people with cirrhosis who have medium to large oesophageal varices.'

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Ischaemia to the lower gastrointestinal tract

Ischaemia to the lower gastrointestinal tract can result in a variety of clinical conditions. Whilst there is no standard classification it can be useful to separate cases into 3 main conditions

·         acute mesenteric ischaemia

·         chronic mesenteric ischaemia

·         ischaemic colitis

 

 

 

Venn diagram showing types of bowel ischaemia

Common features in bowel ischaemia

 

Common predisposing factors

·         increasing age

·         atrial fibrillation - particularly for mesenteric ischaemia

·         other causes of emboli: endocarditis, malignancy

·         cardiovascular disease risk factors: smoking, hypertension, diabetes

·         cocaine: ischaemic colitis is sometimes seen in young patients following cocaine use

Common features

·         abdominal pain - in acute mesenteric ischaemia this is often of sudden onset, severe and out-of-keeping with physical exam findings

·         rectal bleeding

·         diarrhoea

·         fever

·         bloods typically show an elevated white blood cell count associated with a lactic acidosis

Diagnosis

·         CT is the investigation of choice

 

Acute mesenteric ischaemia

 

Acute mesenteric ischaemia is typically caused by an embolism resulting in occlusion of an artery which supplies the small bowel, for example the superior mesenteric artery. Classically patients have a history of atrial fibrillation.

 

The abdominal pain is typically severe, of sudden onset and out-of-keeping with physical exam findings.

 

Management

·         urgent surgery is usually required

·         poor prognosis, especially if surgery delayed

 

Chronic mesenteric ischaemia

 

Chronic mesenteric ischaemia is a relatively rare clinical diagnosis due to it's non-specific features and may be thought of as 'intestinal angina'. Colickly, intermittent abdominal pain occurs.

 

 

Ischaemiac colitis

 

Ischaemic colitis describes an acute but transient compromise in the blood flow to the large bowel. This may lead to inflammation, ulceration and haemorrhage. It is more likely to occur in 'watershed' areas such as the splenic flexure that are located at the borders of the territory supplied by the superior and inferior mesenteric arteries.

 

Investigations

·         'thumbprinting' may be seen on abdominal x-ray due to mucosal oedema/haemorrhage

Management

- usually supportive

- surgery may be required in a minority of cases if conservative measures fail. Indications would include generalised peritonitis, perforation or ongoing haemorrhage

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Alcoholic liver disease

Alcoholic liver disease covers a spectrum of conditions:

·         alcoholic fatty liver disease

·         alcoholic hepatitis

·         cirrhosis

Selected investigation findings:

·         gamma-GT is characteristically elevated

·         the ratio of AST:ALT is normally > 2, a ratio of > 3 is strongly suggestive of acute alcoholic hepatitis

Selected management notes for alcoholic hepatitis:

·         glucocorticoids (e.g. prednisolone) are often used during acute episodes of alcoholic hepatitis

o    Maddrey's discriminant function (DF) is often used during acute episodes to determine who would benefit from glucocorticoid therapy

o    it is calculated by a formula using prothrombin time and bilirubin concentration

·         pentoxyphylline is also sometimes used

o    the STOPAH study (see reference) compared the two common treatments for alcoholic hepatitis, pentoxyphylline and prednisolone. It showed that prednisolone improved survival at 28 days and that pentoxyphylline did not improve outcomes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Dysphagia

The table below gives characteristic exam question features for conditions causing dysphagia. Remember that new-onset dysphagia is a red flag symptom that requires urgent endoscopy, regardless of age or other symptoms.

 

 

Causes

Notes

Oesophageal cancer

Dysphagia may be associated with weight loss, anorexia or vomiting during eating

Past history may include Barrett's oesophagus, GORD, excessive smoking or alcohol use

Oesophagitis

There may be a history of heartburn

Odynophagia but no weight loss and systemically well

Oesophageal candidiasis

There may be a history of HIV or other risk factors such as steroid inhaler use

Achalasia

Dysphagia of both liquids and solids from the start

Heartburn

Regurgitation of food - may lead to cough, aspiration pneumonia etc

Pharyngeal pouch

More common in older men

Represents a posteromedial herniation between thyropharyngeus and cricopharyngeus muscles

Usually not seen but if large then a midline lump in the neck that gurgles on palpation

Typical symptoms are dysphagia, regurgitation, aspiration and chronic cough. Halitosis may occasionally be seen

Systemic sclerosis

Other features of CREST syndrome may be present, namely Calcinosis, Raynaud's phenomenon, oEsophageal dysmotility, Sclerodactyly, Telangiectasia

 

As well as oesophageal dysmotility the lower oesophageal sphincter (LES) pressure is decreased. This contrasts to achalasia where the LES pressure is increased

Myasthenia gravis

Other symptoms may include extraocular muscle weakness or ptosis

Dysphagia with liquids as well as solids

Globus hystericus

There may be a history of anxiety

Symptoms are often intermittent and relieved by swallowing

Usually painless - the presence of pain should warrant further investigation for organic causes

 

Causes of dysphagia - by classification

 

As with many conditions, it's often useful to think about causes of a symptom in a structured way:

 

 

Classification

Examples

Extrinsic

·         Mediastinal masses

·         Cervical spondylosis

Oesophageal wall

·         Achalasia

·         Diffuse oesophageal spasm

·         Hypertensive lower oesophageal sphincter

Intrinsic

·         Tumours

·         Strictures

·         Oesophageal web

·         Schatzki rings

Neurological

·         CVA

·         Parkinson's disease

·         Multiple Sclerosis

·         Brainstem pathology

·         Myasthenia Gravis

Investigation

 

All patients require an upper GI endoscopy unless there are compelling reasons for this not to be performed. Motility disorders may be best appreciated by undertaking fluoroscopic swallowing studies.

 

A full blood count should be performed.

 

Ambulatory oesophageal pH and manometry studies will be required to evaluate conditions such as achalasia and patients with GORD being considered for fundoplication surgery.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Clostridium difficile

Clostridium difficile is a Gram positive rod often encountered in hospital practice. It produces an exotoxin which causes intestinal damage leading to a syndrome called pseudomembranous colitis. Clostridium difficile develops when the normal gut flora are suppressed by broad-spectrum antibiotics. Clindamycin is historically associated with causing Clostridium difficile but the aetiology has evolved significantly over the past 10 years. Second and third generation cephalosporins are now the leading cause of Clostridium difficile.

 

Other than antibiotics, risk factors include:

·         proton pump inhibitors

Features

·         diarrhoea

·         abdominal pain

·         a raised white blood cell count (WCC) is characteristic

·         if severe toxic megacolon may develop

The Public Health England severity scale is often used as this may determine treatment:

 

 

Mild

Moderate

Severe

life-threatening

Normal WCC

↑ WCC ( < 15 x 109/L)

Typically 3-5 loose stools per day

↑ WCC ( > 15 x 109/L)

or an acutely ↑ creatinine (> 50% above baseline)

or a temperature > 38.5°C

or evidence of severe colitis(abdominal or radiological signs)

Hypotension

Partial or complete ileus

Toxic megacolon, or CT evidence of severe disease

Diagnosis

·         is made by detecting Clostridium difficile toxin (CDT) in the stool

·         Clostridium difficile antigen positivity only shows exposure to the bacteria, rather than current infection

Management

·         first-line therapy is oral metronidazole for 10-14 days

·         if severe or not responding to metronidazole then oral vancomycin may be used

o    recurrent infection occurs in around 20% of patients, increasing to 50% after their second episode

·         fidaxomicin may also be used for patients who are not responding , particularly those with multiple co-morbidities

·         for life-threatening infections a combination of oral vancomycin and intravenous metronidazole should be used

Other therapies

·         bezlotoxumab is a monoclonal antibody which targets Clostridium difficile toxin B - it is not in widespread use

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:12

Ulcerative colitis: management

Treatment can be divided into inducing and maintaining remission. NICE updated their guidelines on the management of ulcerative colitis in 2019.

 

The severity of UC is usually classified as being mild, moderate or severe:

·         mild: < 4 stools/day, only a small amount of blood

·         moderate: 4-6 stools/day, varying amounts of blood, no systemic upset

·         severe: >6 bloody stools per day + features of systemic upset (pyrexia, tachycardia, anaemia, raised inflammatory markers)

Inducing remission

 

Treating mild-to-moderate ulcerative colitis

·         proctitis

o    topical (rectal) aminosalicylate: for distal colitis rectal mesalazine has been shown to be superior to rectal steroids and oral aminosalicylates

o    if remission is not achieved within 4 weeks, add an oral aminosalicylate

o    if remission still not achieved add topical or oral corticosteroid

·         proctosigmoiditis and left-sided ulcerative colitis

o    topical (rectal) aminosalicylate

o    if remission is not achieved within 4 weeks, add a high-dose oral aminosalicylate OR switch to a high-dose oral aminosalicylate and a topical corticosteroid

o    if remission still not achieved stop topical treatments and offer an oral aminosalicylate and an oral corticosteroid

·         extensive disease

o    topical (rectal) aminosalicylate and a high-dose oral aminosalicylate:

o    if remission is not achieved within 4 weeks, stop topical treatments and offer a high-dose oral aminosalicylate and an oral corticosteroid

Severe colitis

·         should be treated in hospital

·         intravenous steroids are usually given first-line

o    intravenous ciclosporin may be used if steroid are contraindicated

·         if after 72 hours there has been no improvement, consider adding intravenous ciclosporin to intravenous corticosteroids or consider surgery

 

Maintaining remission

 

Following a mild-to-moderate ulcerative colitis flare

·         proctitis and proctosigmoiditis

o    topical (rectal) aminosalicylate alone (daily or intermittent) or

o    an oral aminosalicylate plus a topical (rectal) aminosalicylate (daily or intermittent) or

o    an oral aminosalicylate by itself: this may not be effective as the other two options

·         left-sided and extensive ulcerative colitis

o    low maintenance dose of an oral aminosalicylate

Following a severe relapse or >=2 exacerbations in the past year

·         oral azathioprine or oral mercaptopurine

 

Other points

·         methotrexate is not recommended for the management of UC (in contrast to Crohn's disease)

·         there is some evidence that probiotics may prevent relapse in patients with mild to moderate disease

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Haemochromatosis: investigation and management

Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*.

 

There is continued debate about the best investigation to screen for haemochromatosis.

·         general population: transferrin saturation is considered the most useful marker. Ferritin should also be measured but is not usually abnormal in the early stages of iron accumulation

·         testing family members: genetic testing for HFE mutation

These guidelines may change as HFE gene analysis become less expensive

 

Diagnostic tests

·         molecular genetic testing for the C282Y and H63D mutations

·         liver biopsy: Perl's stain

Typical iron study profile in patient with haemochromatosis

·         transferrin saturation > 55% in men or > 50% in women

·         raised ferritin (e.g. > 500 ug/l) and iron

·         low TIBC

Management

·         Venesection is the first-line treatment

o    monitoring adequacy of venesection: transferrin saturation should be kept below 50% and the serum ferritin concentration below 50 ug/l

·         desferrioxamine may be used second-line

 

Joint x-rays characteristically show chondrocalcinosis

 

*there are rare cases of families with classic features of genetic haemochromatosis but no mutation in the HFE gene

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Oesophageal cancer

Until recent times oesophageal cancer was most commonly due to a squamous cell carcinoma but the incidence of adenocarcinoma is rising rapidly. Adenocarcinoma is now the most common type of oesophageal cancer and is more likely to develop in patients with a history of gastro-oesophageal reflux disease (GORD) or Barrett's.

 

The majority of adenocarcinomas are located near the gastroesophageal junction whereas squamous cell tumours are most commonly found in the upper two-thirds of the oesophagus.

 

 

 

Adenocarcinoma

Squamous cell cancer

Epidemiology

Most common type in the UK/US

Most common type in the developing world

Location

Lower third - near the gastroesophageal junction

Upper two-thirds of the oesophagus

Risk factors

·         GORD

·         Barrett's oesophagus

·         smoking

·         achalasia

·         obesity

·         smoking

·         alcohol

·         achalasia

·         Plummer-Vinson syndrome

·         diets rich in nitrosamines

Features

·         dysphagia: the most common presenting symptom

·         anorexia and weight loss

·         vomiting

·         other possible features include: odynophagia, hoarseness, melaena, cough

Diagnosis

·         Upper GI endoscopy is the first line test

·         Contrast swallow may be of benefit in classifying benign motility disorders but has no place in the assessment of tumours

·         Staging is initially undertaken with CT scanning of the chest, abdomen and pelvis. If overt metastatic disease is identified using this modality then further complex imaging is unnecessary

·         If CT does not show metastatic disease, then local stage may be more accurately assessed by use of endoscopic ultrasound

·         Staging laparoscopy is performed to detect occult peritoneal disease. PET CT is performed in those with negative laparoscopy. Thoracoscopy is not routinely performed.

Treatment

·         Operable disease is best managed by surgical resection.

·         The most standard procedure is an Ivor- Lewis type oesophagectomy. This procedure involves the mobilisation of the stomach and division of the oesophageal hiatus. The abdomen is closed and a right-sided thoracotomy performed. The stomach is brought into the chest and the oesophagus mobilised further. An intrathoracic oesophagogastric anastomosis is constructed. Alternative surgical strategies include a transhiatal resection (for distal lesions), a left thoracoabdominal resection (difficult access due to thoracic aorta) and a total oesophagectomy (McKeown) with a cervical oesophagogastric anastomosis.

·         The biggest surgical challenge is that of anastomotic leak, with an intrathoracic anastomosis this will result in mediastinitis. With high mortality. The McKeown technique has an intrinsically lower systemic insult in the event of anastomotic leakage.

·         In addition to surgical resection many patients will be treated with adjuvant chemotherapy.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Pancreatic cancer

Pancreatic cancer is often diagnosed late as it tends to present in a non-specific way. Over 80% of pancreatic tumours are adenocarcinomas which typically occur at the head of the pancreas.

 

Associations

·         increasing age

·         smoking

·         diabetes

·         chronic pancreatitis (alcohol does not appear an independent risk factor though)

·         hereditary non-polyposis colorectal carcinoma

·         multiple endocrine neoplasia

·         BRCA2 gene

·         KRAS gene mutation

Features

·         classically painless jaundice

o    pale stools, dark urine, and pruritus

o    cholestatic liver function tests

·         Courvoisier's law states that in the presence of painless obstructive jaundice, a palpable gallbladder is unlikely to be due to gallstones

·         however, patients typically present in a non-specific way with anorexia, weight loss, epigastric pain

·         loss of exocrine function (e.g. steatorrhoea)

·         loss of endocrine function (e.g. diabetes mellitus)

·         atypical back pain is often seen

·         migratory thrombophlebitis (Trousseau sign) is more common than with other cancers

Investigation

·         ultrasound has a sensitivity of around 60-90%

·         high-resolution CT scanning is the investigation of choice if the diagnosis is suspected

·         imaging may demonstrate the 'double duct' sign - the presence of simultaneous dilatation of the common bile and pancreatic ducts

Management

·         less than 20% are suitable for surgery at diagnosis

·         a Whipple's resection (pancreaticoduodenectomy) is performed for resectable lesions in the head of pancreas. Side-effects of a Whipple's include dumping syndrome and peptic ulcer disease

·         adjuvant chemotherapy is usually given following surgery

·         ERCP with stenting is often used for palliation

 

 

© Image used on license from Radiopaedia

ERCP showing invasive ductal adenocarcinoma. Note the dilation of the common bile duct due to the pancreatic lesion

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Acute upper gastrointestinal bleeding

NICE published guidelines in 2012 on the management of acute upper gastrointestinal bleeding which is most commonly due to either peptic ulcer disease or oesophageal varices. Some of the key points are detailed below.

 

Risk assessment

·         use the Blatchford score at first assessment, and

·         the full Rockall score after endoscopy

Blatchford score

 

 

Admission risk marker

Score

Urea (mmol/l)

6·5 - 8 = 2

8 - 10 = 3

10 - 25 = 4

> 25 = 6

Haemoglobin (g/l)

Men

·         12 - 13 = 1

·         10 - 12 = 3

·         < 10 = 6

Women

·         10 - 12 = 1

·         < 10 = 6

Systolic blood pressure (mmHg)

100 - 109 = 1

90 - 99 = 2

< 90 = 3

Other markers

Pulse >=100/min = 1

Presentation with melaena = 1

Presentation with syncope = 2

Hepatic disease = 2

Cardiac failure = 2

Patients with a Blatchford score of 0 may be considered for early discharge.

 

Resuscitation

·         ABC, wide-bore intravenous access * 2

·         platelet transfusion if actively bleeding platelet count of less than 50 x 10*9/litre

·         fresh frozen plasma to patients who have either a fibrinogen level of less than 1 g/litre, or a prothrombin time (international normalised ratio) or activated partial thromboplastin time greater than 1.5 times normal

·         prothrombin complex concentrate to patients who are taking warfarin and actively bleeding

Endoscopy

·         should be offered immediately after resuscitation in patients with a severe bleed

·         all patients should have endoscopy within 24 hours

Management of non-variceal bleeding

·         NICE do not recommend the use of proton pump inhibitors (PPIs) before endoscopy to patients with suspected non-variceal upper gastrointestinal bleeding although PPIs should be given to patients with non-variceal upper gastrointestinal bleeding and stigmata of recent haemorrhage shown at endoscopy

·         if further bleeding then options include repeat endoscopy, interventional radiology and surgery

Management of variceal bleeding

·         terlipressin and prophylactic antibiotics should be given to patients at presentation (i.e. before endoscopy)

·         band ligation should be used for oesophageal varices and injections of N-butyl-2-cyanoacrylate for patients with gastric varices

·         transjugular intrahepatic portosystemic shunts (TIPS) should be offered if bleeding from varices is not controlled with the above measures

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Carcinoid tumours

Carcinoid syndrome

·         usually occurs when metastases are present in the liver and release serotonin into the systemic circulation

·         may also occur with lung carcinoid as mediators are not 'cleared' by the liver

Features

·         flushing (often earliest symptom)

·         diarrhoea

·         bronchospasm

·         hypotension

·         right heart valvular stenosis (left heart can be affected in bronchial carcinoid)

·         other molecules such as ACTH and GHRH may also be secreted resulting in, for example, Cushing's syndrome

·         pellagra can rarely develop as dietary tryptophan is diverted to serotonin by the tumour

Investigation

·         urinary 5-HIAA

·         plasma chromogranin A y

Management

·         somatostatin analogues e.g. octreotide

·         diarrhoea: cyproheptadine may help

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Hepatitis B serology

Interpreting hepatitis B serology is a dying art form which still occurs at regular intervals in medical exams. It is important to remember a few key facts:

·         surface antigen (HBsAg) is the first marker to appear and causes the production of anti-HBs

·         HBsAg normally implies acute disease (present for 1-6 months)

·         if HBsAg is present for > 6 months then this implies chronic disease (i.e. Infective)

·         Anti-HBs implies immunity (either exposure or immunisation). It is negative in chronic disease

·         Anti-HBc implies previous (or current) infection. IgM anti-HBc appears during acute or recent hepatitis B infection and is present for about 6 months. IgG anti-HBc persists

·         HbeAg results from breakdown of core antigen from infected liver cells as is, therefore, a marker of infectivity

Example results

·         previous immunisation: anti-HBs positive, all others negative

·         previous hepatitis B (> 6 months ago), not a carrier: anti-HBc positive, HBsAg negative

·         previous hepatitis B, now a carrier: anti-HBc positive, HBsAg positive

HBsAg = ongoing infection, either acute or chronic if present > 6 months

 

anti-HBc = caught, i.e. negative if immunized

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Primary biliary cholangitis

Primary biliary cholangitis (previously referred to as primary biliary cirrhosis) is a chronic liver disorder typically seen in middle-aged females (female:male ratio of 9:1). The aetiology is not fully understood although it is thought to be an autoimmune condition. Interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis. The classic presentation is itching in a middle-aged woman

 

Associations

·         Sjogren's syndrome (seen in up to 80% of patients)

·         rheumatoid arthritis

·         systemic sclerosis

·         thyroid disease

Clinical features

·         early: may be asymptomatic (e.g. raised ALP on routine LFTs) or fatigue, pruritus

·         cholestatic jaundice

·         hyperpigmentation, especially over pressure points

·         around 10% of patients have right upper quadrant pain

·         xanthelasmas, xanthomata

·         also: clubbing, hepatosplenomegaly

·         late: may progress to liver failure

Diagnosis

·         anti-mitochondrial antibodies (AMA) M2 subtype are present in 98% of patients and are highly specific

·         smooth muscle antibodies in 30% of patients

·         raised serum IgM

Management

·         first-line: ursodeoxycholic acid

o    slows disease progression and improves symptoms

·         pruritus: cholestyramine

·         fat-soluble vitamin supplementation

·         liver transplantation

o    e.g. if bilirubin > 100 (PBC is a major indication)

o    recurrence in graft can occur but is not usually a problem

Complications

·         cirrhosis → portal hypertension → ascites, variceal haemorrhage

·         osteomalacia and osteoporosis

·         significantly increased risk of hepatocellular carcinoma (20-fold increased risk)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Autoimmune hepatitis

Autoimmune hepatitis is condition of unknown aetiology which is most commonly seen in young females. Recognised associations include other autoimmune disorders, hypergammaglobulinaemia and HLA B8, DR3. Three types of autoimmune hepatitis have been characterised according to the types of circulating antibodies present

 

 

Type I

Type II

Type III

Anti-nuclear antibodies (ANA) and/or anti-smooth muscle antibodies (SMA)

 

Affects both adults and children

Anti-liver/kidney microsomal type 1 antibodies (LKM1)

 

Affects children only

Soluble liver-kidney antigen

 

Affects adults in middle-age

Features

·         may present with signs of chronic liver disease

·         acute hepatitis: fever, jaundice etc (only 25% present in this way)

·         amenorrhoea (common)

·         ANA/SMA/LKM1 antibodies, raised IgG levels

·         liver biopsy: inflammation extending beyond limiting plate 'piecemeal necrosis', bridging necrosis

Management

·         steroids, other immunosuppressants e.g. azathioprine

·         liver transplantation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Coeliac disease: investigation

Coeliac disease is caused by sensitivity to the protein gluten. Repeated exposure leads to villous atrophy which in turn causes malabsorption. Conditions associated with coeliac disease include dermatitis herpetiformis (a vesicular, pruritic skin eruption) and autoimmune disorders (type 1 diabetes mellitus and autoimmune hepatitis).

 

Diagnosis is made by a combination of immunology and jejunal biopsy. Villous atrophy and immunology normally reverses on a gluten-free diet.

 

NICE issued guidelines on the investigation of coeliac disease in 2009. If patients are already taking a gluten-free diet they should be asked, if possible, to reintroduce gluten for at least 6 weeks prior to testing.

 

Immunology

·         tissue transglutaminase (TTG) antibodies (IgA) are first-choice according to NICE

·         endomyseal antibody (IgA)

o    needed to look for selective IgA deficiency, which would give a false negative coeliac result

·         anti-gliadin antibody (IgA or IgG) tests are not recommended by NICE

·         anti-casein antibodies are also found in some patients

Duodenal biopsy*

·         villous atrophy

·         crypt hyperplasia

·         increase in intraepithelial lymphocytes

·         lamina propria infiltration with lymphocytes

Rectal gluten challenge has been described but is not widely used

 

 

 

© Image used on license from PathoPic

Duodenal biopsy from a patient with coeliac disease. Complete atrophy of the villi with flat mucosa and marked crypt hyperplasia. Intraepithelial lymphocytosis. Dense mixed inflammatory infiltrate in the lamina propria.

 

 

 

© Image used on license from PathoPic

Duodenal biopsy from a patient with coeliac disease. Flat mucosa with hyperplastic crypts and dense cellular infiltrate in the lamina propria. Increased number of intraepithelial lymphocytes and vacuolated superficial epithelial cell vacuolated superficial epithelial cells. Higher magnification image on the right.

 

*these are also occasionally performed from the jejunum

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

Target cells and Howell-Jolly bodies may be seen in coeliac disease → hyposplenism

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

24 December 2020

14:13

Non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease in the developed world. It is largely caused by obesity and describes a spectrum of disease ranging from:

·         steatosis - fat in the liver

·         steatohepatitis - fat with inflammation, non-alcoholic steatohepatitis (NASH), see below

·         progressive disease may cause fibrosis and liver cirrhosis

NAFLD is thought to represent the hepatic manifestation of the metabolic syndrome and hence insulin resistance is thought to be the key mechanism leading to steatosis.

 

Non-alcoholic steatohepatitis (NASH) is a term used to describe liver changes similar to those seen in alcoholic hepatitis in the absence of a history of alcohol abuse. It is relatively common and thought to affect around 3-4% of the general population. The progression of disease in patients with NASH may be responsible for a proportion of patients previously labelled as cryptogenic cirrhosis.

 

Associated factors

·         obesity

·         type 2 diabetes mellitus

·         hyperlipidaemia

·         jejunoileal bypass

·         sudden weight loss/starvation

Features

·         usually asymptomatic

·         hepatomegaly

·         ALT is typically greater than AST

·         increased echogenicity on ultrasound

NICE produced guidelines on the investigation and management of NAFLD in 2016. Key points:

·         there is no evidence to support screening for NAFLD in adults, even in at risk groups (e.g. type 2 diabetes)

·         the guidelines are therefore based on the management of the incidental finding of NAFLD - typically asymptomatic fatty changes on liver ultrasound

·         in these patients, NICE recommends the use of the enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis

·         the ELF blood test is a combination of hyaluronic acid + procollagen III + tissue inhibitor of metalloproteinase 1. An algorithm based on these values results in an ELF blood test score, similar to triple testing for Down's syndrome

An excellent review by Byrne et Al1 in 2018 reviewed the diagnosis and monitoring of NAFLD. It made the following suggestions if the ELF blood test was not available:

·         non-invasive tests may be used to assess the severity of fibrosis

·         these include the FIB4 score or NALFD fibrosis score

·         these scores may be used in combination with a FibroScan (liver stiffness measurement assessed with transient elastography)

·         this combination has been shown to have excellent accuracy in predicting fibrosis

Patients who are likely to have advanced fibrosis should be referred to a liver specialist. They will then likely have a liver biopsy to stage the disease more accurately.

 

Management

·         the mainstay of treatment is lifestyle changes (particularly weight loss) and monitoring

·         there is ongoing research into the role of gastric banding and insulin-sensitising drugs (e.g. metformin, pioglitazone)

References

1. BMJ 2018;362:k2734

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:13

Achalasia

Failure of oesophageal peristalsis and of relaxation of the lower oesophageal sphincter (LOS) due to degenerative loss of ganglia from Auerbach's plexus i.e. LOS contracted, oesophagus above dilated. Achalasia typically presents in middle-age and is equally common in men and women.

 

Clinical features

·         dysphagia of BOTH liquids and solids

·         typically variation in severity of symptoms

·         heartburn

·         regurgitation of food

o    may lead to cough, aspiration pneumonia etc

·         malignant change in small number of patients

Investigations

·         oesophageal manometry

o    excessive LOS tone which doesn't relax on swallowing

o    considered the most important diagnostic test

·         barium swallow

o    shows grossly expanded oesophagus, fluid level

o    'bird's beak' appearance

·         chest x-ray

o    wide mediastinum

o    fluid level

Treatment

·         pneumatic (balloon) dilation is increasingly the preferred first-line option

o    less invasive and quicker recovery time than surgery

o    patients should be a low surgical risk as surgery may be required if complications occur

·         surgical intervention with a Heller cardiomyotomy should be considered if recurrent or persistent symptoms

·         intra-sphincteric injection of botulinum toxin is sometimes used in patients who are a high surgical risk

·         drug therapy (e.g. nitrates, calcium channel blockers) has a role but is limited by side-effects

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:13

Alcohol: units

In 2016 the Chief Medical Officer proposed new guidelines in relation to the safe consumption of alcohol following an expert group report. The most significant change has been a reduction in the number of units it is recommending men do not exceed from 21 to 14, in line with the recommendations for women.

 

The government now recommend the following:

·         men and women should drink no more than 14 units of alcohol per week

·         they advise 'if you do drink as much as 14 units per week, it is best to spread this evenly over 3 days or more'

·         pregnant women should not drink. The wording of the official advice is 'If you are pregnant or planning a pregnancy, the safest approach is not to drink alcohol at all, to keep risks to your baby to a minimum. Drinking in pregnancy can lead to long-term harm to the baby, with the more you drink the greater the risk.'

One unit of alcohol is equal to 10 mL of pure ethanol. The 'strength' of an alcoholic drink is determined by the 'alcohol by volume' (ABV).

 

Examples of one unit of alcohol:

·         25ml single measure of spirits (ABV 40%)

·         a third of a pint of beer (ABV 5 to 6%)

·         half a 175ml 'standard' glass of red wine (ABV 12%)

To calculate the number of units in a drink multiply the number of millilitres by the ABV and divide by 1,000. For example:

·         half a 175ml 'standard' glass of red wine = 87.5 * 12 / 1000 = 1.05 units

·         one bottle of wine = 750 * 12 / 1000 = 9 units

·         one pint of 5% beer or lager = 568 * 5 / 1000 = 2.8 units

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Ascites

The causes of ascites can be grouped into those with a serum-ascites albumin gradient (SAAG) <11 g/L or a gradient >11g/L as per the table below:

 

 

SAAG > 11g/L

SAAG <11g/L

Indicates portal hypertension

 

Cirrhosis

Alcoholic hepatitis

Cardiac ascites

Mixed ascites

Massive liver metastases

Fulminant hepatic failure

Budd-Chiari syndrome

Portal vein thrombosis

Veno-occlusive disease

Myxoedema

Fatty liver of pregnancy

Peritoneal carcinomatosis

Tuberculous peritonitis

Pancreatic ascites

Bowel obstruction

Biliary ascites

Postoperative lymphatic leak

Serositis in connective tissue diseases

Management

·         reducing dietary sodium

·         fluid restriction is sometimes recommended if the sodium is < 125 mmol/L

·         aldosterone antagonists: e.g. spironolactone

o    loop diuretics are often added. Some authorities only add loop diuretics in patients who don't respond to aldosterone agonists whereas other authorities suggest starting both types of diuretic on the first presentation of ascites

·         drainage if tense ascites (therapeutic abdominal paracentesis)

o    large-volume paracentesis for the treatment of ascites requires albumin 'cover'. Evidence suggests this reduces paracentesis-induced circulatory dysfunction and mortality

o    paracentesis induced circulatory dysfunction can occur due to large volume paracentesis (> 5 litres). It is associated with a high rate of ascites recurrence, development of hepatorenal syndrome, dilutional hyponatraemia, and high mortality rate

·         prophylactic antibiotics to reduce the risk of spontaneous bacterial peritonitis. NICE recommend: 'Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less, until the ascites has resolved'

·         a transjugular intrahepatic portosystemic shunt (TIPS) may be considered in some patients

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Diarrhoea

The table below gives characteristic features for conditions causing diarrhoea:

 

World Health Organisation definitions

·         Diarrhoea: > 3 loose or watery stool per day

·         Acute diarrhoea < 14 days

·         Chronic diarrhoea > 14 days

Usually acute

 

 

Condition

Notes

Gastroenteritis

May be accompanied by abdominal pain or nausea/vomiting

Diverticulitis

Classically causes left lower quadrant pain, diarrhoea and fever

Antibiotic therapy

More common with broad spectrum antibiotics

 

Clostridium difficile is also seen with antibiotic use

Constipation causing overflow

A history of alternating diarrhoea and constipation may be given

 

May lead to faecal incontinence in the elderly

 

Usually chronic

 

 

Condition

Notes

Irritable bowel syndrome

Extremely common. The most consistent features are abdominal pain, bloating and change in bowel habit. Patients may be divided into those with diarrhoea predominant IBS and those with constipation-predominant IBS.

 

Features such as lethargy, nausea, backache and bladder symptoms may also be present

Ulcerative colitis

Bloody diarrhoea may be seen. Crampy abdominal pain and weight loss are also common. Faecal urgency and tenesmus may be seen

Crohn's disease

Crampy abdominal pains and diarrhoea. Bloody diarrhoea less common than in ulcerative colitis. Other features include malabsorption, mouth ulcers, perianal disease and intestinal obstruction

Colorectal cancer

Symptoms depend on the site of the lesion but include diarrhoea, rectal bleeding, anaemia and constitutional symptoms e.g. Weight loss and anorexia

Coeliac disease

In children may present with failure to thrive, diarrhoea and abdominal distension

 

In adults lethargy, anaemia, diarrhoea and weight loss are seen. Other autoimmune conditions may coexist

Other conditions associated with diarrhoea include:

·         thyrotoxicosis

·         laxative abuse

·         appendicitis

·         radiation enteritis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Dyspepsia

The 2015 NICE guidelines 'Suspected cancer: recognition and referral' further updated the advice on who needs urgent referral for an endoscopy (i.e. within 2 weeks). The list below combines the advice for oesophageal and stomach cancer, with the bold added by the author, not NICE.

 

Urgent

 

All patients who've got dysphagia

 

All patients who've got an upper abdominal mass consistent with stomach cancer

 

Patients aged >= 55 years who've got weight loss, AND any of the following:

·         upper abdominal pain

·         reflux

·         dyspepsia

Non-urgent

 

Patients with haematemesis

 

Patients aged >= 55 years who've got:

·         treatment-resistant dyspepsia or

·         upper abdominal pain with low haemoglobin levels or

·         raised platelet count with any of the following: nausea, vomiting, weight loss, reflux, dyspepsia, upper abdominal pain

·         nausea or vomiting with any of the following: weight loss, reflux, dyspepsia, upper abdominal pain

 

Managing patients who do not meet referral criteria ('undiagnosed dyspepsia')

 

This can be summarised at a step-wise approach

·         1. Review medications for possible causes of dyspepsia

·         2. Lifestyle advice

·         3. Trial of full-dose proton pump inhibitor for one month OR a 'test and treat' approach for H. pylori

o    if symptoms persist after either of the above approaches then the alternative approach should be tried

Testing for H. pylori infection

·         initial diagnosis: NICE recommend using a carbon-13 urea breath test or a stool antigen test, or laboratory-based serology 'where its performance has been locally validated'

·         test of cure:

o    there is no need to check for H. pylori eradication if symptoms have resolved following test and treat

o    however, if repeat testing is required then a carbon-13 urea breath test should be used

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Gallstones

Up to 24% of women and 12% of men may have gallstones. Of these up to 30% may develop local infection and cholecystitis. In patients subjected to surgery, 12% will have stones contained within the common bile duct. The majority of gallstones are of a mixed composition (50%) with pure cholesterol stones accounting for 20% of cases.

 

The aetiology of CBD stones differs in the world, in the West most CBD stones are the result of migration. In the East, a far higher proportion arise in the CBD de novo.

 

The classical symptoms are of colicky right upper quadrant pain that occurs postprandially. The symptoms are usually worst following a fatty meal when cholecystokinin levels are highest and gallbladder contraction is maximal.

 

Investigation

 

In almost all suspected cases the standard diagnostic workup consists of abdominal ultrasound and liver function tests. Of patients who have stones within the bile duct, 60% will have at least one abnormal result on LFT's. Ultrasound is an important test, but is operator dependent and therefore may occasionally need to be repeated if a negative result is at odds with the clinical picture. Where stones are suspected in the bile duct the options lie between magnetic resonance cholangiography and intraoperative imaging. The choice between these two options is determined by the skills and experience of the surgeon. The advantages of intraoperative imaging are less useful in making therapeutic decisions if the operator is unhappy about proceeding the bile duct exploration, and in such circumstances, preoperative MRCP is probably a better option.

 

Specific gallstone and gallbladder related disease

 

 

Disease

Features

Management

Biliary colic

Colicky abdominal pain, worse postprandially, worse after fatty foods

If imaging shows gallstones and history compatible then laparoscopic cholecystectomy

Acute cholecystitis

Right upper quadrant pain

Fever

Murphys sign on examination

Occasionally mildly deranged LFT's (especially if Mirizzi syndrome)

Imaging (USS) and cholecystectomy (ideally within 48 hours of presentation) (2)

Gallbladder abscess

Usually prodromal illness and right upper quadrant pain

Swinging pyrexia

Patient may be systemically unwell

Generalised peritonism not present

Imaging with USS +/- CT Scanning

Ideally, surgery although subtotal cholecystectomy may be needed if Calot's triangle is hostile

In unfit patients, percutaneous drainage may be considered

Cholangitis

Patient severely septic and unwell

Jaundice

Right upper quadrant pain

Fluid resuscitation

Broad-spectrum intravenous antibiotics

Correct any coagulopathy

Early ERCP

Gallstone ileus

Patients may have a history of previous cholecystitis and known gallstones

Small bowel obstruction (may be intermittent)

Laparotomy and removal of the gallstone from small bowel, the enterotomy must be made proximal to the site of obstruction and not at the site of obstruction. The fistula between the gallbladder and duodenum should not be interfered with.

Acalculous cholecystitis

Patients with intercurrent illness (e.g. diabetes, organ failure)

Patient of systemically unwell

Gallbladder inflammation in absence of stones

High fever

If patient fit then cholecystectomy, if unfit then percutaneous cholecystostomy

Treatment

 

Asymptomatic gallstones which are located in the gallbladder are common and do not require treatment. However, if stones are present in the common bile duct there is an increased risk of complications such as cholangitis or pancreatitis and surgical management should be considered.

 

Patients with asymptomatic gallstones rarely develop symptoms related to them (less than 2% per year) and may, therefore, be managed expectantly. In almost all cases of symptomatic gallstones the treatment of choice is cholecystectomy performed via the laparoscopic route. In the very frail patient, there is sometimes a role for the selective use of ultrasound guided cholecystostomy.

 

During the course of the procedure, some surgeons will routinely perform either intraoperative cholangiography to either confirm anatomy or to exclude CBD stones. The latter may be more easily achieved by use of laparoscopic ultrasound. If stones are found then the options lie between early ERCP in the day or so following surgery or immediate surgical exploration of the bile duct. When performed via the trans cystic route this adds little in the way of morbidity and certainly results in faster recovery. Where transcystic exploration fails the alternative strategy is that of formal choledochotomy. The exploration of a small duct is challenging and ducts of less than 8mm should not be explored. Small stones that measure less than 5mm may be safely left and most will pass spontaneously.

 

Risks of ERCP(1)

·         Bleeding 0.9% (rises to 1.5% if sphincterotomy performed)

·         Duodenal perforation 0.4%

·         Cholangitis 1.1%

·         Pancreatitis 1.5%

References

 

1. Williams E et al. Guidelines on the management of common bile duct stones (CBDS)Gut 2008;57:10041021

 

2. Gurusamy KS, Samraj K. Early versus delayed laparoscopic cholecystectomy for acute cholecystitis. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD005440.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:13

Hepatobiliary disease and related disorders

The table below gives characteristic exam question features for conditions causing hepatobiliary disease and related disorders:

 

 

Condition

Features

Viral hepatitis

Common symptoms include:

·         nausea and vomiting, anorexia

·         myalgia

·         lethargy

·         right upper quadrant (RUQ) pain

Questions may point to risk factors such as foreign travel or intravenous drug use.

Congestive hepatomegaly

The liver only usually causes pain if stretched. One common way this can occur is as a consequence of congestive heart failure. In severe cases cirrhosis may occur.

Biliary colic

RUQ pain, intermittent, usually begins abruptly and subsides gradually. Attacks often occur after eating. Nausea is common.

 

It is sometimes taught that patients are female, forties, fat and fair although this is obviously a generalisation.

Acute cholecystitis

Pain similar to biliary colic but more severe and persistent. The pain may radiate to the back or right shoulder.

 

The patient may be pyrexial and Murphy's sign positive (arrest of inspiration on palpation of the RUQ)

Ascending cholangitis

An infection of the bile ducts commonly secondary to gallstones. Classically presents with a triad of:

·         fever (rigors are common)

·         RUQ pain

·         jaundice

Gallstone ileus

This describes small bowel obstruction secondary to an impacted gallstone. It may develop if a fistula forms between a gangrenous gallbladder and the duodenum.

 

Abdominal pain, distension and vomiting are seen.

Cholangiocarcinoma

Persistent biliary colic symptoms, associated with anorexia, jaundice and weight loss. A palpable mass in the right upper quadrant (Courvoisier sign), periumbilical lymphadenopathy (Sister Mary Joseph nodes) and left supraclavicular adenopathy (Virchow node) may be seen

Acute pancreatitis

Usually due to alcohol or gallstones

Severe epigastric pain

Vomiting is common

Examination may reveal tenderness, ileus and low-grade fever

Periumbilical discolouration (Cullen's sign) and flank discolouration (Grey-Turner's sign) is described but rare

Pancreatic cancer

Painless jaundice is the classical presentation of pancreatic cancer. However pain is actually a relatively common presenting symptom of pancreatic cancer. Anorexia and weight loss are common

Amoebic liver abscess

Typical symptoms are malaise, anorexia and weight loss. The associated RUQ pain tends to be mild and jaundice is uncommon.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:13

Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis (SBP) is a form of peritonitis usually seen in patients with ascites secondary to liver cirrhosis.

 

Features

·         ascites

·         abdominal pain

·         fever

Diagnosis

·         paracentesis: neutrophil count > 250 cells/ul

·         the most common organism found on ascitic fluid culture is E. coli

Management

·         intravenous cefotaxime is usually given

Antibiotic prophylaxis should be given to patients with ascites if:

·         patients who have had an episode of SBP

·         patients with fluid protein <15 g/l and either Child-Pugh score of at least 9 or hepatorenal syndrome

·         NICE recommend: 'Offer prophylactic oral ciprofloxacin or norfloxacin for people with cirrhosis and ascites with an ascitic protein of 15 g/litre or less until the ascites has resolved'

Alcoholic liver disease is a marker of poor prognosis in SBP.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Ulcerative colitis

Ulcerative colitis (UC) is a form of inflammatory bowel disease. Inflammation always starts at rectum (hence it is the most common site for UC), never spreads beyond ileocaecal valve and is continuous. The peak incidence of ulcerative colitis is in people aged 15-25 years and in those aged 55-65 years.

 

The initial presentation is usually following insidious and intermittent symptoms. Features include:

·         bloody diarrhoea

·         urgency

·         tenesmus

·         abdominal pain, particularly in the left lower quadrant

·         extra-intestinal features (see below)

Questions regarding the 'extra-intestinal' features of inflammatory bowel disease are common:

 

 

 

Common to both Crohn's disease (CD) and Ulcerative colitis (UC)

Notes

Related to disease activity

Arthritis: pauciarticular, asymmetric

Erythema nodosum

Episcleritis

Osteoporosis

Arthritis is the most common extra-intestinal feature in both CD and UC

Episcleritis is more common in CD

Unrelated to disease activity

Arthritis: polyarticular, symmetric

Uveitis

Pyoderma gangrenosum

Clubbing

Primary sclerosing cholangitis

Primary sclerosing cholangitis is much more common in UC

Uveitis is more common in UC

 

 

 

Venn diagram showing shared features and differences between ulcerative colitis and Crohn's disease. Note that whilst some features are present in both, some are much more common in one of the conditions, for example colorectal cancer in ulcerative colitis

Pathology

·         red, raw mucosa, bleeds easily

·         no inflammation beyond submucosa (unless fulminant disease)

·         widespread ulceration with preservation of adjacent mucosa which has the appearance of polyps ('pseudopolyps')

·         inflammatory cell infiltrate in lamina propria

·         neutrophils migrate through the walls of glands to form crypt abscesses

·         depletion of goblet cells and mucin from gland epithelium

·         granulomas are infrequent

Barium enema

·         loss of haustrations

·         superficial ulceration, 'pseudopolyps'

·         long standing disease: colon is narrow and short -'drainpipe colon'

 

 

© Image used on license from Radiopaedia

Abdominal x-ray from a patient with ulcerative colitis showing lead pipe appearance of the colon (red arrows). Ankylosis of the left sacroiliac joint and partial ankylosis on the right (yellow arrow), reinforcing the link with sacroilitis.

 

 

© Image used on license from Radiopaedia

Barium enema from a patient with ulcerative colitis. The whole colon, without skips is affected by an irregular mucosa with loss of normal haustral markings.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Helicobacter pylori: tests

Urea breath test

·         patients consume a drink containing carbon isotope 13 (13C) enriched urea

·         urea is broken down by H. pylori urease

·         after 30 mins patient exhale into a glass tube

·         mass spectrometry analysis calculates the amount of 13C CO2

·         should not be performed within 4 weeks of treatment with an antibacterial or within 2 weeks of an antisecretory drug (e.g. a proton pump inhibitor)

·         sensitivity 95-98%, specificity 97-98%

·         may be used to check for H. pylori eradication

Rapid urease test (e.g. CLO test)

·         biopsy sample is mixed with urea and pH indicator

·         colour change if H pylori urease activity

·         sensitivity 90-95%, specificity 95-98%

Serum antibody

·         remains positive after eradication

·         sensitivity 85%, specificity 80%

Culture of gastric biopsy

·         provide information on antibiotic sensitivity

·         sensitivity 70%, specificity 100%

Gastric biopsy

·         histological evaluation alone, no culture

·         sensitivity 95-99%, specificity 95-99%

Stool antigen test

·         sensitivity 90%, specificity 95%

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Acute liver failure

Acute liver failure describes the rapid onset of hepatocellular dysfunction leading to a variety of systemic complications.

 

Causes

·         paracetamol overdose

·         alcohol

·         viral hepatitis (usually A or B)

·         acute fatty liver of pregnancy

Features*

·         jaundice

·         coagulopathy: raised prothrombin time

·         hypoalbuminaemia

·         hepatic encephalopathy

·         renal failure is common ('hepatorenal syndrome')

*remember that 'liver function tests' do not always accurately reflect the synthetic function of the liver. This is best assessed by looking at the prothrombin time and albumin level.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Budd-Chiari syndrome

Budd-Chiari syndrome, or hepatic vein thrombosis, is usually seen in the context of underlying haematological disease or another procoagulant condition.

 

Causes

·         polycythaemia rubra vera

·         thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies

·         pregnancy

·         combined oral contraceptive pill: accounts for around 20% of cases

The features are classically a triad of:

·         abdominal pain: sudden onset, severe

·         ascites → abdominal distension

·         tender hepatomegaly

Investigations

·         ultrasound with Doppler flow studies is very sensitive and should be the initial radiological investigation

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:13

Coeliac disease

Coeliac disease is an autoimmune condition caused by sensitivity to the protein gluten. It is thought to affect around 1% of the UK population. Repeated exposure leads to villous atrophy which in turn causes malabsorption. Conditions associated with coeliac disease include dermatitis herpetiformis (a vesicular, pruritic skin eruption) and autoimmune disorders (type 1 diabetes mellitus and autoimmune hepatitis). It is strongly associated with HLA-DQ2 (95% of patients) and HLA-DQ8 (80%).

 

In 2009 NICE issued guidelines on the investigation of coeliac disease. They suggest that the following patients should be screened for coeliac disease:

 

 

Signs and symptoms

Conditions

·         Chronic or intermittent diarrhoea

·         Failure to thrive or faltering growth (in children)

·         Persistent or unexplained gastrointestinal symptoms including nausea and vomiting

·         Prolonged fatigue ('tired all the time')

·         Recurrent abdominal pain, cramping or distension

·         Sudden or unexpected weight loss

·         Unexplained iron-deficiency anaemia, or other unspecified anaemia

·         Autoimmune thyroid disease

·         Dermatitis herpetiformis

·         Irritable bowel syndrome

·         Type 1 diabetes

·         First-degree relatives (parents, siblings or children) with coeliac disease

Complications

·         anaemia: iron, folate and vitamin B12 deficiency (folate deficiency is more common than vitamin B12 deficiency in coeliac disease)

·         hyposplenism

·         osteoporosis, osteomalacia

·         lactose intolerance

·         enteropathy-associated T-cell lymphoma of small intestine

·         subfertility, unfavourable pregnancy outcomes

·         rare: oesophageal cancer, other malignancies

 

 

© Image used on license from PathoPic

Duodenal biopsy from a patient with coeliac disease. Complete atrophy of the villi with flat mucosa and marked crypt hyperplasia. Intraepithelial lymphocytosis. Dense mixed inflammatory infiltrate in the lamina propria.

 

 

 

© Image used on license from PathoPic

Duodenal biopsy from a patient with coeliac disease. Flat mucosa with hyperplastic crypts and dense cellular infiltrate in the lamina propria. Increased number of intraepithelial lymphocytes and vacuolated superficial epithelial cell vacuolated superficial epithelial cells. Higher magnification image on the right.

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:13

Coeliac disease: management

The management of coeliac disease involves a gluten-free diet. Gluten-containing cereals include:

·         wheat: bread, pasta, pastry

·         barley: beer

o    whisky is made using malted barley. Proteins such as gluten are however removed during the distillation process making it safe to drink for patients with coeliac disease

·         rye

·         oats

o    some patients with coeliac disease appear able to tolerate oats

Some notable foods which are gluten-free include:

·         rice

·         potatoes

·         corn (maize)

Tissue transglutaminase antibodies may be checked to check compliance with a gluten-free diet.

 

Immunisation

·         Patients with coeliac disease often have a degree of functional hyposplenism

·         For this reason, all patients with coeliac disease are offered the pneumococcal vaccine

o    Coeliac UK recommends that everyone with coeliac disease is vaccinated against pneumococcal infection and has a booster every 5 years

·         Currrent guidelines suggest giving the influenza vaccine on an individual basis.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Colorectal cancer: genetics

It is currently thought there are three types of colon cancer:

·         sporadic (95%)

·         hereditary non-polyposis colorectal carcinoma (HNPCC, 5%)

·         familial adenomatous polyposis (FAP, <1%)

Studies have shown that sporadic colon cancer may be due to a series of genetic mutations. For example, more than half of colon cancers show allelic loss of the APC gene. It is believed a further series of gene abnormalities e.g. activation of the K-ras oncogene, deletion of p53 and DCC tumour suppressor genes lead to invasive carcinoma

 

HNPCC, an autosomal dominant condition, is the most common form of inherited colon cancer. Around 90% of patients develop cancers, often of the proximal colon, which are usually poorly differentiated and highly aggressive. Currently seven mutations have been identified, which affect genes involved in DNA mismatch repair leading to microsatellite instability. The most common genes involved are:

·         MSH2 (60% of cases)

·         MLH1 (30%)

Patients with HNPCC are also at a higher risk of other cancers, with endometrial cancer being the next most common association, after colon cancer.

 

The Amsterdam criteria are sometimes used to aid diagnosis:

·         at least 3 family members with colon cancer

·         the cases span at least two generations

·         at least one case diagnosed before the age of 50 years

FAP is a rare autosomal dominant condition which leads to the formation of hundreds of polyps by the age of 30-40 years. Patients inevitably develop carcinoma. It is due to a mutation in a tumour suppressor gene called adenomatous polyposis coli gene (APC), located on chromosome 5. Genetic testing can be done by analysing DNA from a patient's white blood cells. Patients generally have a total colectomy with ileo-anal pouch formation in their twenties.

 

Patients with FAP are also at risk from duodenal tumours. A variant of FAP called Gardner's syndrome can also feature osteomas of the skull and mandible, retinal pigmentation, thyroid carcinoma and epidermoid cysts on the skin

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Crohn's disease: management

Crohn's disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus. NICE published guidelines on the management of Crohn's disease in 2012.

 

General points

·         patients should be strongly advised to stop smoking

·         some studies suggest an increased risk of relapse secondary to NSAIDs and the combined oral contraceptive pill but the evidence is patchy

Inducing remission

·         glucocorticoids (oral, topical or intravenous) are generally used to induce remission. Budesonide is an alternative in a subgroup of patients

·         enteral feeding with an elemental diet may be used in addition to or instead of other measures to induce remission, particularly if there is concern regarding the side-effects of steroids (for example in young children)

·         5-ASA drugs (e.g. mesalazine) are used second-line to glucocorticoids but are not as effective

·         azathioprine or mercaptopurine* may be used as an add-on medication to induce remission but is not used as monotherapy. Methotrexate is an alternative to azathioprine

·         infliximab is useful in refractory disease and fistulating Crohn's. Patients typically continue on azathioprine or methotrexate

·         metronidazole is often used for isolated peri-anal disease

Maintaining remission

·         as above, stopping smoking is a priority (remember: smoking makes Crohn's worse, but may help ulcerative colitis)

·         azathioprine or mercaptopurine is used first-line to maintain remission

·         methotrexate is used second-line

·         5-ASA drugs (e.g. mesalazine) should be considered if a patient has had previous surgery

Surgery

·         around 80% of patients with Crohn's disease will eventually have surgery

·         see below for further detail

 

Surgical interventions in Crohn's disease

 

The commonest disease pattern in Crohn's is stricturing terminal ileal disease and this often culminates in an ileocaecal resection. Other procedures performed include segmental small bowel resections and stricturoplasty. Colonic involvement in patients with Crohn's is not common and, where found, distribution is often segmental. However, despite this distribution segmental resections of the colon in patients with Crohn's disease are generally not advocated because the recurrence rate in the remaining colon is extremely high, as a result, the standard options of colonic surgery in Crohn's patients are generally; sub total colectomy, panproctocolectomy and staged sub total colectomy and proctectomy. Restorative procedures such as ileoanal pouch have no role in therapy.

 

Crohn's disease is notorious for the developmental of intestinal fistulae; these may form between the rectum and skin (perianal) or the small bowel and skin. Fistulation between loops of bowel may also occur and result in bacterial overgrowth and malabsorption. Management of enterocutaneous fistulae involves controlling sepsis, optimising nutrition, imaging the disease and planning definitive surgical management.

 

 

Complications of Crohn's disease

 

As well as the well-documented complications described above, patients are also at risk of:

·         small bowel cancer (standard incidence ratio = 40)

·         colorectal cancer (standard incidence ration = 2, i.e. less than the risk associated with ulcerative colitis)

·         osteoporosis

*assess thiopurine methyltransferase (TPMT) activity before offering azathioprine or mercaptopurine

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:14

Hepatic encephalopathy

Hepatic encephalopathy may be seen in liver disease of any cause. The aetiology is not fully understood but is thought to include excess absorption of ammonia and glutamine from bacterial breakdown of proteins in the gut.

 

Whilst hepatic encephalopathy is often associated with acute liver failure it may also be seen with chronic disease. It is now recognised that many patients with liver cirrhosis may develop subtle symptoms such as mild cognitive impairment before the features become more recognisable ('minimal' or 'covert' hepatic encephalopathy). It has also been noted that transjugular intrahepatic portosystemic shunting (TIPSS) may precipitate encephalopathy.

 

Features

·         confusion, altered GCS (see below)

·         asterix: 'liver flap', arrhythmic negative myoclonus with a frequency of 3-5 Hz

·         constructional apraxia: inability to draw a 5-pointed star

·         triphasic slow waves on EEG

·         raised ammonia level (not commonly measured anymore)

Grading of hepatic encephalopathy

·         Grade I: Irritability

·         Grade II: Confusion, inappropriate behaviour

·         Grade III: Incoherent, restless

·         Grade IV: Coma

Precipitating factors

·         infection e.g. spontaneous bacterial peritonitis

·         GI bleed

·         post transjugular intrahepatic portosystemic shunt

·         constipation

·         drugs: sedatives, diuretics

·         hypokalaemia

·         renal failure

·         increased dietary protein (uncommon)

Management

·         treat any underlying precipitating cause

·         NICE recommend lactulose first-line, with the addition of rifaximin for the secondary prophylaxis of hepatic encephalopathy

·         lactulose is thought to work by promoting the excretion of ammonia and increasing the metabolism of ammonia by gut bacteria

·         antibiotics such as rifaximin are thought to modulate the gut flora resulting in decreased ammonia production

·         other options include embolisation of portosystemic shunts and liver transplantation in selected patients

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the third most common cause of cancer worldwide. Chronic hepatitis B is the most common cause of HCC worldwide with chronic hepatitis C being the most common cause in Europe.

 

The main risk factor for developing HCC is liver cirrhosis, for example secondary* to hepatitis B & C, alcohol, haemochromatosis and primary biliary cirrhosis. Other risk factors include:

·         alpha-1 antitrypsin deficiency

·         hereditary tyrosinosis

·         glycogen storage disease

·         aflatoxin

·         drugs: oral contraceptive pill, anabolic steroids

·         porphyria cutanea tarda

·         male sex

·         diabetes mellitus, metabolic syndrome

Features

·         tends to present late

·         features of liver cirrhosis or failure may be seen: jaundice, ascites, RUQ pain, hepatomegaly, pruritus, splenomegaly

·         possible presentation is decompensation in a patient with chronic liver disease

·         raised AFP

Screening with ultrasound (+/- alpha-fetoprotein) should be considered for high risk groups such as:

·         patients liver cirrhosis secondary to hepatitis B & C or haemochromatosis

·         men with liver cirrhosis secondary to alcohol

Management options

·         early disease: surgical resection

·         liver transplantation

·         radiofrequency ablation

·         transarterial chemoembolisation

·         sorafenib: a multikinase inhibitor

 

*Wilson's disease is an exception

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Inflammatory bowel disease: key differences

The two main types of inflammatory bowel disease are Crohn's disease and ulcerative colitis. They have many similarities in terms of presenting symptoms, investigation findings and management options.

 

 

 

 

Venn diagram showing shared features and differences between ulcerative colitis and Crohn's disease. Note that whilst some features are present in both, some are much more common in one of the conditions, for example colorectal cancer in ulcerative colitis

There are however some key differences which are highlighted in table below:

 

 

 

Crohn's disease (CD)

Ulcerative colitis (UC)

Features

Diarrhoea usually non-bloody

Weight loss more prominent

Upper gastrointestinal symptoms, mouth ulcers, perianal disease

Abdominal mass palpable in the right iliac fossa

Bloody diarrhoea more common

Abdominal pain in the left lower quadrant

Tenesmus

Extra-intestinal

Gallstones are more common secondary to reduced bile acid reabsorption

 

Oxalate renal stones*

Primary sclerosing cholangitis more common

Complications

Obstruction, fistula, colorectal cancer

Risk of colorectal cancer high in UC than CD

Pathology

Lesions may be seen anywhere from the mouth to anus

 

Skip lesions may be present

Inflammation always starts at rectum and never spreads beyond ileocaecal valve

 

Continuous disease

Histology

Inflammation in all layers from mucosa to serosa

·         increased goblet cells

·         granulomas

No inflammation beyond submucosa (unless fulminant disease) - inflammatory cell infiltrate in lamina propria

·         neutrophils migrate through the walls of glands to form crypt abscesses

·         depletion of goblet cells and mucin from gland epithelium

·         granulomas are infrequent

Endoscopy

Deep ulcers, skip lesions - 'cobble-stone' appearance

Widespread ulceration with preservation of adjacent mucosa which has the appearance of polyps ('pseudopolyps')

Radiology

Small bowel enema

·         high sensitivity and specificity for examination of the terminal ileum

·         strictures: 'Kantor's string sign'

·         proximal bowel dilation

·         'rose thorn' ulcers

·         fistulae

Barium enema

·         loss of haustrations

·         superficial ulceration, 'pseudopolyps'

·         long standing disease: colon is narrow and short -'drainpipe colon'

*impaired bile acid rebsorption increases the loss calcium in the bile. Calcium normally binds oxalate.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Ischaemic hepatitis

Ischaemic hepatitis is a diffuse hepatic injury resulting from acute hypoperfusion (sometimes known as 'shock liver'). It is not an inflammatory process. It is diagnosed in the presence of an inciting event (e.g. a cardiac arrest) and marked increases in aminotransferase levels (exceeding 1000 international unit/L or 50 times the upper limit of normal). Often, it will occur in conjunction with acute kidney injury (tubular necrosis) or other end-organ dysfunction.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Metoclopramide

Metoclopramide is a D2 receptor antagonist* mainly used in the management of nausea. Other uses include:

·         gastro-oesophageal reflux disease

·         prokinetic action is useful in gastroparesis secondary to diabetic neuropathy

·         often combined with analgesics for the treatment of migraine (migraine attacks result in gastroparesis, slowing the absorption of analgesics)

Adverse effects

·         extrapyramidal effects: oculogyric crisis. This is particularly a problem in children and young adults

·         hyperprolactinaemia

·         tardive dyskinesia

·         parkinsonism

Metoclopramide should be avoided in bowel obstruction, but may be helpful in paralytic ileus.

 

 

*whilst metoclopramide is primarily a D2 receptor antagonist, the mechanism of action is quite complicated:

·         it is also a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist

·         the antiemetic action is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone. At higher doses the 5-HT3 receptor antagonist also has an effect

·         the gastroprokinetic activity is mediated by D2 receptor antagonist activity and 5-HT4 receptor agonist activity

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

 

 

 

 

24 December 2020

14:14

Peptic ulcer disease (uncomplicated)

Risk factors

·         Helicobacter pylori is associated with the majority of peptic ulcers:

o    95% of duodenal ulcers

o    75% of gastric ulcers

·         drugs:

o    NSAIDs

o    SSRIs

o    corticosteroids

o    bisphosphonates

·         Zollinger-Ellison syndrome: rare cause characterised by excessive levels of gastrin, usually from a gastrin secreting tumour

·         the role of alcohol and smoking is not clear

Features

·         epigastric pain

·         nausea

·         duodenal ulcers

o    more common than gastric ulcers

o    epigastric pain when hungry, relieved by eating

·         gastric ulcers

o    epigastric pain worsened by eating

Investigation

·         Helicobacter pylori should be tested for

o    either a Urea breath test or stool antigen test should be used first-line

Management

·         if Helicobacter pylori is negative then proton pump inhibitors (PPIs) should be given until the ulcer is healed

·         if Helicobacter pylori is positive then eradication therapy should be given

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Proton pump inhibitors

Proton pump inhibitors (PPI) cause irreversible blockade of H+/K+ ATPase of the gastric parietal cell.

 

Examples include omeprazole and lansoprazole.

 

Adverse effects

·         hyponatraemia, hypomagnasaemia

·         osteoporosis → increased risk of fractures

·         microscopic colitis

·         increased risk of Clostridium difficile infections

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Ulcerative colitis: flares

Most ulcerative colitis flares occur without an identifiable trigger. However, a number of factors are often linked:

·         stress

·         medications

o    NSAIDs

o    antibiotics

·         cessation of smoking

Flares of ulcerative colitis are usually classified as either mild, moderate or severe:

 

 

Mild

Moderate

Severe

Fewer than four stools daily, with or without blood

 

No systemic disturbance

 

Normal erythrocyte sedimentation rate and C-reactive protein values

Four to six stools a day, with minimal systemic disturbance

More than six stools a day, containing blood

 

Evidence of systemic disturbance, e.g.

·         fever

·         tachycardia

·         abdominal tenderness, distension or reduced bowel sounds

·         anaemia

·         hypoalbuminaemia

Patients with evidence of severe disease should be admitted to hospital.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Acute appendicitis

Acute appendicitis is the most common acute abdominal condition requiring surgery. It can occur at any age but is most common in young people aged 10-20 years.

 

Abdominal pain is seen in the vast majority of patients:

·         peri-umbilical abdominal pain (visceral stretching of appendix lumen and appendix is midgut structure) radiating to the right iliac fossa (RIF) due to localised parietal peritoneal inflammation.

·         the migration of the pain from the centre to the RIF has been shown to be one of the strongest indicators of appendicitis

·         patients often report the pain being worse on coughing or going over speed bumps. Children typically can't hop on the right leg due to the pain.

Other features:

·         vomit once or twice but marked and persistent vomiting is unusual

·         diarrhoea is rare. However, pelvic appendicitis may cause localised rectal irritation of some loose stools. A pelvic abscess may also cause diarrhoea

·         mild pyrexia is common - temperature is usually 37.5-38oC. Higher temperatures are more typical of conditions like mesenteric adenitis

·         anorexia is very common. It is very unusual for patients with appendicitis to be hungry

·         around 50% of patients have the typical symptoms of anorexia, peri-umbilical pain and nausea followed by more localised right lower quadrant pain

Examination

·         generalised peritonitis if perforation has occurred or localised peritonism

·         retrocaecal appendicitis may have relatively few signs

·         digital rectal examination may reveal boggy sensation if pelvic abscess is present, or even right-sided tenderness with a pelvic appendix

·         Rovsing's sign (palpation in the LIF causes pain in the RIF) is now thought to be of limited value

Diagnosis

·         typically raised inflammatory markers coupled with compatible history and examination findings should be enough to justify appendicectomy

·         a neutrophil-predominant leucocytosis is seen in 80-90%

·         urine analysis: useful to exclude pregnancy in women, renal colic and urinary tract infection. In patients with appendicitis, urinalysis may show mild leucocytosis but no nitrites

·         ultrasound is useful in females where pelvic organ pathology is suspected. Although it is not always possible to visualise the appendix on ultrasound, the presence of free fluid (always pathological in males) should raise suspicion

·         CT scans are widely used in patients with suspected appendicitis in the US but this practice has not currently reached the UK, due to the concerns regarding excessive ionising radiation and resource limitations

Management

·         appendicectomy which can be performed via either an open or laparoscopic approach. Laparoscopic appendicectomy is now the treatment of choice

·         administration of prophylactic intravenous antibiotics reduces wound infection rates

·         patients with perforated appendicitis (typical around 15-20%) require copious abdominal lavage.

·         patients without peritonitis who have an appendix mass should receive broad-spectrum antibiotics and consideration given to performing an interval appendicectomy.

·         be wary in the older patients who may have either an underlying caecal malignancy or perforated sigmoid diverticular disease.

·         trials have looked at the use of intravenous antibiotics alone in the treatment of appendicitis. The evidence currently suggests that whilst this is successful in the majority of patients, it is associated with a longer hospital stay and up to 20% of patients go on to have an appendicectomy within 12 months.

 

 

Image sourced from Wikipedia

Ultrasound examination may show evidence of lumenal obstruction and thickening of the appendiceal wall as shown below

 

 

Image sourced from Wikipedia

Laparoscopic appendicectomy is becoming increasing popular as demonstrated below

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:14

Alcoholic ketoacidosis

Alcoholic ketoacidosis is a non-diabetic euglycaemic form of ketoacidosis. It occurs in people who regularly drink large amounts of alcohol. Often alcoholics will not eat regularly and may vomit food that they do eat, leading to episodes of starvation. Once the person becomes malnourished, after an alcohol binge the body can start to break down body fat, producing ketones. Hence the patient develops a ketoacidosis.

 

It typically presents with a pattern of:

·         Metabolic acidosis

·         Elevated anion gap

·         Elevated serum ketone levels

·         Normal or low glucose concentration

The most appropriate treatment is an infusion of saline & thiamine. Thiamine is required to avoid Wernicke encephalopathy or Korsakoff psychosis.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Aminosalicylate drugs

5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis

 

Sulphasalazine

·         a combination of sulphapyridine (a sulphonamide) and 5-ASA

·         many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis

·         other side-effects are common to 5-ASA drugs (see mesalazine)

Mesalazine

·         a delayed release form of 5-ASA

·         sulphapyridine side-effects seen in patients taking sulphasalazine are avoided

·         mesalazine is still however associated with side-effects such as GI upset, headache, agranulocytosis, pancreatitis*, interstitial nephritis

Olsalazine

·         two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria

Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.

 

*pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Barrett's oesophagus

Barrett's refers to the metaplasia of the lower oesophageal mucosa, with the usual squamous epithelium being replaced by columnar epithelium. There is an increased risk of oesophageal adenocarcinoma, estimated at 50-100 fold. There are no screening programs for Barrett's - it's typically identified when patients have an endoscopy for evaluation of upper gastrointestinal symptoms such as dyspepsia.

 

Barrett's can be subdivided into short (<3cm) and long (>3cm). The length of the affected segment correlates strongly with the chances of identifying metaplasia. The overall prevalence of Barrett's oesophagus is difficult to determine but may be in the region of 1 in 20 and is identified in up to 12% of those undergoing endoscopy for reflux.

 

Histological features

·         the columnar epithelium may resemble that of either the cardiac region of the stomach or that of the small intestine (e.g. with goblet cells, brush border)

Risk factors

·         gastro-oesophageal reflux disease (GORD) is the single strongest risk factor

·         male gender (7:1 ratio)

·         smoking

·         central obesity

Interestingly alcohol does not seem to be an independent risk factor for Barrett's although it is associated with both GORD and oesophageal cancer.

 

Whilst Barrett's oesophagus itself is asymptomatic clearly patients will often have coexistent GORD symptoms.

 

Management

·         endoscopic surveillance with biopsies

·         high-dose proton pump inhibitor: whilst this is commonly used in patients with Barrett's the evidence base that this reduces the change of progression to dysplasia or induces regression of the lesion is limited

Endoscopic surveillance

·         for patients with metaplasia (but not dysplasia) endoscopy is recommended every 3-5 years

If dysplasia of any grade is identified endoscopic intervention is offered. Options include:

·         endoscopic mucosal resection

·         radiofrequency ablation

 

 

 

Endoscopy image showing a short segment of Barrett's oesophagus

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:14

Crohn's disease: investigation

Crohn's disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus

 

Bloods

·         C-reactive protein correlates well with disease activity

Endoscopy

·         colonoscopy is the investigation of choice

·         features suggest of Crohn's include deep ulcers, skip lesions

Histology

·         inflammation in all layers from mucosa to serosa

·         goblet cells

·         granulomas

Small bowel enema

·         high sensitivity and specificity for examination of the terminal ileum

·         strictures: 'Kantor's string sign'

·         proximal bowel dilation

·         'rose thorn' ulcers

·         fistulae

 

 

© Image used on license from Radiopaedia

Barium study is shown from a patient with worsening Crohn's disease. Long segment of narrowed terminal ileum in a 'string like' configuration in keeping with a long stricture segment. Termed 'Kantor's string sign'.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:14

Hepatomegaly

Common causes of hepatomegaly

·         Cirrhosis: if early disease, later liver decreases in size. Associated with a non-tender, firm liver

·         Malignancy: metastatic spread or primary hepatoma. Associated with a hard, irregular. liver edge

·         Right heart failure: firm, smooth, tender liver edge. May be pulsatile

Other causes

·         viral hepatitis

·         glandular fever

·         malaria

·         abscess: pyogenic, amoebic

·         hydatid disease

·         haematological malignancies

·         haemochromatosis

·         primary biliary cirrhosis

·         sarcoidosis, amyloidosis

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Liver cirrhosis

Liver cirrhosis remains a significant problem in the developed world, account for 60,000 deaths in the UK each year.

 

Causes:

·         alcohol

·         non-alcoholic fatty liver disease (NAFLD)

·         viral hepatitis (B and C)

Diagnosis

·         traditionally a liver biopsy was used. This procedure is however associated with adverse effects such as bleeding and pain

·         other techniques such as transient elastography and acoustic radiation force impulse imaging are increasingly used and were recommended by NICE in their 2016 guidelines

·         for patients with NAFLD, NICE recommend using the enhanced liver fibrosis score to screen for patients who need further testing

What is transient elastography?

·         brand name 'Fibroscan'

·         uses a 50-MHz wave is passed into the liver from a small transducer on the end of an ultrasound probe

·         measures the 'stiffness' of the liver which is a proxy for fibrosis

In terms of screening for cirrhosis NICE made a specific recommendation, suggesting to offer transient elastography to:

·         people with hepatitis C virus infection

·         men who drink over 50 units of alcohol per week and women who drink over 35 units of alcohol per week and have done so for several months

·         people diagnosed with alcohol-related liver disease

Further investigations

·         NICE recommend doing an upper endoscopy to check for varices in patient's with a new diagnosis of cirrhosis

·         liver ultrasound every 6 months (+/- alpha-feto protein) to check for hepatocellular cancer

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

 

 

24 December 2020

14:14

Oesophageal disorders

The table below lists a small group of less common oesophageal disorders.

 

 

Disorder

Notes

Plummer-Vinson syndrome

Triad of:

·         dysphagia (secondary to oesophageal webs)

·         glossitis

·         iron-deficiency anaemia

Treatment includes iron supplementation and dilation of the webs

Mallory-Weiss syndrome

Severe vomiting → painful mucosal lacerations at the gastroesophageal junction resulting in haematemesis. Common in alcoholics

Boerhaave syndrome

Severe vomiting → oesophageal rupture

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Peutz-Jeghers syndrome

Peutz-Jeghers syndrome is an autosomal dominant condition characterised by numerous hamartomatous polyps in the gastrointestinal tract. It is also associated with pigmented freckles on the lips, face, palms and soles. Although the polyps themselves don't have malignant potential, around 50% of patients will have died from another gastrointestinal tract cancer by the age of 60 years.

 

Genetics

·         autosomal dominant

·         responsible gene encodes serine threonine kinase LKB1 or STK11

Features

·         hamartomatous polyps in GI tract (mainly small bowel)

·         pigmented lesions on lips, oral mucosa, face, palms and soles

·         intestinal obstruction e.g. intussusception

·         gastrointestinal bleeding

Management

·         conservative unless complications develop

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Pharyngeal pouch

A pharyngeal pouch is a posteromedial diverticulum through Killian's dehiscence. Killian's dehiscence is a triangular area in the wall of the pharynx between the thyropharyngeus and cricopharyngeus muscles. It is more common in older patients and is 5 times more common in men

 

Features

·         dysphagia

·         regurgitation

·         aspiration

·         neck swelling which gurgles on palpation

·         halitosis

Management

·         surgery

 

 

© Image used on license from Radiopaedia

Still image taken from a barium swallow with fluoroscopy. During swallowing an outpouching of the posterior hypopharyngeal wall is visualised at the level C5-C6, right above the upper oesophageal sphincter

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Small bowel bacterial overgrowth syndrome

Small bowel bacterial overgrowth syndrome (SBBOS) is a disorder characterised by excessive amounts of bacteria in the small bowel resulting in gastrointestinal symptoms.

 

Risk factors for SBBOS

·         neonates with congenital gastrointestinal abnormalities

·         scleroderma

·         diabetes mellitus

It should be noted that many of the features overlap with irritable bowel syndrome:

·         chronic diarrhoea

·         bloating, flatulence

·         abdominal pain

Diagnosis

·         hydrogen breath test

·         small bowel aspiration and culture: this is used less often as invasive and results are often difficult to reproduce

·         clinicians may sometimes give a course of antibiotics as a diagnostic trial

Management

·         correction of underlying disorder

·         antibiotic therapy: rifaximin is now the treatment of choice due to relatively low resistance. Co-amoxiclav or metronidazole are also effective in the majority of patients.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Helicobacter pylori

Helicobacter pylori is a Gram negative bacteria associated with a variety of gastrointestinal problems, principally peptic ulcer disease

 

Associations

·         peptic ulcer disease (95% of duodenal ulcers, 75% of gastric ulcers)

·         gastric cancer

·         B cell lymphoma of MALT tissue (eradication of H pylori results causes regression in 80% of patients)

·         atrophic gastritis

The role of H pylori in Gastro-oesophageal reflux disease (GORD) is unclear - there is currently no role in GORD for the eradication of H pylori

 

Management - eradication may be achieved with a 7 day course of

·         a proton pump inhibitor + amoxicillin + clarithromycin, or

·         a proton pump inhibitor + metronidazole + clarithromycin

 

 

 

H. pylori colonized on the surface of regenerative epithelium (silver stain)

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

Since almost all Deodenal Ulcer are caused by H. pylori (HP) (in absence of NSAID therapy) there is no need to perform a CLO test.

There are many ways to make a diagnosis of HP. Non invasive tests include Urea breath test, stool for HP antigen. Invasive tests are CLO, histological examination and culture.

The Camplyobacter-like organism (CLO) test is based on the fact that mucosal biopsy specimens can be inoculated into a medium containing urea and phenol red, a dye that turns pink in a pH of 6.0 or greater.

The pH will rise above 6.0 when HP, the Campylobacter-like organism, metabolizes urea to ammonia by way of its urease activity. This test is commercially available and therefore quite inexpensive. Only one-half hour is required for diagnosis of infection, and the test has shown 98% sensitivity and 100% specificity.

 

In case of a gastric ulcer (GU), since only 65-70% are due to HP, it is recommended that the HP status be confirmed (preferably by a biopsy) before starting therapy. A biopsy will also help rule out malignancy (this is not usually a concern with DU).

 

From <https://mle.ncl.ac.uk/cases/page/15729/>

 

 

 

 

 

 

24 December 2020

14:14

Acute abdominal pain: a very basic introduction

Acute abdominal pain is one of the most common presentations encountered in clinical practice.

 

Causes

 

One of the most common ways to think about the potential causes is the location of the pain. Sometimes patients present with generalised pain but probably the most common present is pain in a particular region of the abdomen. Some conditions characteristically cause central pain before localising to a particular area. A good example is appendicitis, which typically presents with central abdominal pain before localising to the right iliac fossa.

 

 

 

 

 

Diagram showing stereotypical areas where particular conditions present. The diagram is not exhaustive and only lists the more common conditions seen in clinical practice. Note how pain from renal causes such as renal/ureteric colic and pyelonephritis may radiate and move from the loins towards the suprapubic area.

 

This approach, whilst useful, is however limited as patients commonly present with atypical findings and as mentioned previously the site of the pain can change over time.

 

Another way of classifying the causes of an acute abdomen, or any condition, is by using a surgical sieve:

 

Infective

·         gastroenteritis

·         appendicitis

·         diverticulitis

·         pyelonephritis

·         cholecystitis

·         cholangitis

·         pelvic inflammatory disease

·         hepatitis

·         pneumonia

Inflammatory

·         pancreatitis

·         peptic ulcer disease

Vascular

·         ruptured abdominal aortic aneurysm

·         mesenteric ischaemia

·         myocardial infarction

Traumatic

·         ruptured spleen

·         perforated viscus (e.g. oesophagus, stomach, bowel)

Metabolic

·         renal/ureteric stone

·         diabetic ketoacidosis

 

The tables below gives the key characteristics of common causes of abdominal pain.

 

Hepatobiliary problems

 

 

Condition

Typical location of pain

Notes

Biliary colic

Right upper quadrant

Caused by a gallstone getting lodged in the bile duct

 

Classically provoked by eating a fatty meal

 

In contrast to acute cholecystitis no fever and inflammatory markers are normal

Acute cholecystitis

Right upper quadrant

Inflammation/infection of the gallbladder secondary to impacted gallstones

 

Murphy's sign positive (arrest of inspiration on palpation of the RUQ)

 

Fever and raised inflammatory markers

Ascending cholangitis

Right upper quadrant

Ascending cholangitis is a bacterial infection of the biliary tree. The most common predisposing factor is gallstones.

 

Charcot's triad of right upper quadrant pain, fever and jaundice occurs in about 20-50% of patients

Acute pancreatitis

Epigastrium, sometimes radiating through to the back

Usually due to alcohol or gallstones

 

Pain is often very severe. Examination may reveal tenderness, ileus and low-grade fever

 

Upper gastrointestinal tract problems

 

 

Condition

Typical location of pain

Notes

Peptic ulcer disease

Epigastrium

There may be a history of NSAID use or alcohol excess.

 

Duodenal ulcers: more common than gastric ulcers, epigastric pain relieved by eating

 

Gastric ulcers: epigastric pain worsened by eating

 

Features of upper gastrointestinal haemorrhage may be seen (haematemesis, melena etc)

 

Lower gastrointestinal tract problems

 

 

Condition

Typical location of pain

Notes

Appendicitis

Right iliac fossa

Pain initial in the central abdomen before localising to the right iliac fossa (RIF).

 

Anorexia is common. Tachycardia, low-grade pyrexia, tenderness in RIF

 

Rovsing's sign: more pain in RIF than LIF when palpating LIF

Acute diverticulitis

Left lower quadrant

Colicky pain typically in the LLQ

 

Diarrhoea, sometimes bloody.

 

Fever, raised inflammatory markers and white cells

Intestinal obstruction

Central

History of malignancy (intraluminal obstruction)/previous operations (adhesions)

 

Vomiting. Not opened bowels recently

 

'Tinkling' bowel sounds

 

Urological causes

 

 

Condition

Typical location of pain

Notes

Renal colic

Loin pain radiating to the groin

Pain is often severe but intermittent. Patient's are characteristically restless.

 

Visible or non-visible haematuria may be present

Acute pyelonephritis

Loin pain

Fever and rigors are common as is vomiting

Urinary retention

Suprapubic

Caused by obstruction to the bladder outflow.

 

Much more common in men, who often have a history of benign prostatic hyperplasia

 

Gynaecological causes

 

Remember, all women of a reproductive age who present with abdominal pain should be considered pregnant until proven otherwise

 

 

Condition

Typical location of pain

Notes

Ectopic pregnancy

Right or left iliac fossa

Typically presents with pain and a history of amenorrhoea for the past 6-9 weeks. Vaginal bleeding may be present

 

Vascular causes

 

 

Condition

Typical location of pain

Notes

Ruptured abdominal aortic aneurysm

Central abdominal pain radiating to the back

Presentation may be catastrophic (e.g. Sudden collapse) or sub-acute (persistent severe central abdominal pain with developing shock)

 

Patients may be shocked (hypotension, tachycardic)

 

Patients may have a history of cardiovascular disease

Mesenteric ischaemia

Central abdominal pain

Patients often have a history of atrial fibrillation or other cardiovascular disease

 

Diarrhoea, rectal bleeding may be seen

 

A metabolic acidosis is often seen (due to 'dying' tissue)

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:14

Crohn's disease

Crohn's disease is a form of inflammatory bowel disease. It commonly affects the terminal ileum and colon but may be seen anywhere from the mouth to anus.

 

Pathology

·         cause is unknown but there is a strong genetic susceptibility

·         inflammation occurs in all layers, down to the serosa. This is why patients with Crohn's are prone to strictures, fistulas and adhesions

Crohn's disease typically presents in late adolescence or early adulthood. Features include:

·         presentation may be non-specific symptoms such as weight loss and lethargy

·         diarrhoea: the most prominent symptom in adults. Crohn's colitis may cause bloody diarrhoea

·         abdominal pain: the most prominent symptom in children

·         perianal disease: e.g. Skin tags or ulcers

·         extra-intestinal features are more common in patients with colitis or perianal disease

Investigations

·         raised inflammatory markers

·         increased faecal calprotectin

·         anaemia

·         low vitamin B12 and vitamin D

Questions regarding the 'extra-intestinal' features of inflammatory bowel disease are common:

 

 

 

Common to both Crohn's disease (CD) and Ulcerative colitis (UC)

Notes

Related to disease activity

Arthritis: pauciarticular, asymmetric

Erythema nodosum

Episcleritis

Osteoporosis

Arthritis is the most common extra-intestinal feature in both CD and UC

Episcleritis is more common in CD

Unrelated to disease activity

Arthritis: polyarticular, symmetric

Uveitis

Pyoderma gangrenosum

Clubbing

Primary sclerosing cholangitis

Primary sclerosing cholangitis is much more common in UC

Uveitis is more common in UC

 

 

 

Venn diagram showing shared features and differences between ulcerative colitis and Crohn's disease. Note that whilst some features are present in both, some are much more common in one of the conditions, for example colorectal cancer in ulcerative colitis

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:14

Drug-induced liver disease

Drug-induced liver disease is generally divided into hepatocellular, cholestatic or mixed. There is however considerable overlap, with some drugs causing a range of changes to the liver

 

The following drugs tend to cause a hepatocellular picture:

·         paracetamol

·         sodium valproate, phenytoin

·         MAOIs

·         halothane

·         anti-tuberculosis: isoniazid, rifampicin, pyrazinamide

·         statins

·         alcohol

·         amiodarone

·         methyldopa

·         nitrofurantoin

The following drugs tend to cause cholestasis (+/- hepatitis):

·         combined oral contraceptive pill

·         antibiotics: flucloxacillin, co-amoxiclav, erythromycin*

·         anabolic steroids, testosterones

·         phenothiazines: chlorpromazine, prochlorperazine

·         sulphonylureas

·         fibrates

·         rare reported causes: nifedipine

Liver cirrhosis

·         methotrexate

·         methyldopa

·         amiodarone

*risk may be reduced with erythromycin stearate

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Ferritin

Ferritin is an intracellular protein that binds iron and stores it to be released in a controlled fashion at sites where iron is required.

 

Increased ferritin levels

 

This is typically defined as > 300 µg/L in men/postmenopausal women and > 200 µµg/L in premenopausal women.

 

Ferritin is an acute phase protein and may be synthesised in increased quantities in situations where inflammatory activity is ongoing. Falsely elevated results may therefore be encountered clinically and need to be taken in the context of the clinical picture and blood results.

 

We can split the causes of increased ferritin levels into 2 distinct categories;

 

 

Without iron overload (around 90% of patients)

With iron overload (around 10% of patients)

Inflammation (due to ferritin being an acute phase reactant)

Alcohol excess

Liver disease

Chronic kidney disease

Malignancy

Primary iron overload (hereditary haemochromatosis)

 

Secondary iron overload (e.g. following repeated transfusions)

The best test to see whether iron overload is present is transferrin saturation. Typically, normal values of < 45% in females and < 50% in males exclude iron overload.

 

Reduced ferritin levels

 

Because iron and ferritin are bound the total body ferritin levels may be decreased in cases of iron deficiency anaemia.

 

Measurement of serum ferritin levels can be useful in determining whether an apparently low haemoglobin and microcytosis is truly caused by an iron deficiency state.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Gastric cancer

There are 700,000 new cases of gastric cancer worldwide each year.

 

Epidemiology

·         overall incidence is decreasing, but incidence of tumours arising from the cardia is increasing

·         peak age = 70-80 years

·         more common in Japan, China, Finland and Colombia than the West

·         more common in males, 2:1

Histology

·         signet ring cells may be seen in gastric cancer. They contain a large vacuole of mucin which displaces the nucleus to one side. Higher numbers of signet ring cells are associated with a worse prognosis

Associations

·         H. pylori infection

·         blood group A: gAstric cAncer

·         gastric adenomatous polyps

·         pernicious anaemia

·         smoking

·         diet: salty, spicy, nitrates

·         may be negatively associated with duodenal ulcer

Features

·         dyspepsia

·         nausea and vomiting

·         anorexia and weight loss

·         dysphagia

Investigation

·         diagnosis: endoscopy with biopsy

·         staging: CT or endoscopic ultrasound - endoscopic ultrasound has recently been shown to be superior to CT

Surgical aspects

 

There is some evidence of support a stepwise progression of the disease through intestinal metaplasia progressing to atrophic gastritis and subsequent dysplasia, through to cancer. The favoured staging system is TNM. The risk of lymph node involvement is related to size and depth of invasion; early cancers confined to submucosa have a 20% incidence of lymph node metastasis. Tumours of the gastro-oesophageal junction are classified as below:

 

 

Type 1

True oesophageal cancers and may be associated with Barrett's oesophagus.

Type 2

Carcinoma of the cardia, arising from cardiac type epithelium

or short segments with intestinal metaplasia at the oesophagogastric junction.

Type 3

Sub cardial cancers that spread across the junction. Involve similar nodal stations to gastric cancer.

 

 

 

Image sourced from Wikipedia

Upper GI endoscopy performed for dyspepsia. The addition of dye spraying (as shown in the bottom right) may facilitate identification of smaller tumours

Staging

·         CT scanning of the chest abdomen and pelvis is the routine first line staging investigation in most centres.

·         Laparoscopy to identify occult peritoneal disease

·         PET CT (particularly for junctional tumours)

Treatment

·         Proximally sited disease greater than 5-10cm from the OG junction may be treated by sub total gastrectomy

·         Total gastrectomy if tumour is <5cm from OG junction

·         For type 2 junctional tumours (extending into oesophagus) oesophagogastrectomy is usual

·         Endoscopic sub mucosal resection may play a role in early gastric cancer confined to the mucosa and perhaps the sub mucosa (this is debated)

·         Lymphadenectomy should be performed. A D2 lymphadenectomy is widely advocated by the Japanese, the survival advantages of extended lymphadenectomy have been debated. However, the overall recommendation is that a D2 nodal dissection be undertaken.

·         Most patients will receive chemotherapy either pre or post operatively.

Prognosis

 

UK Data

 

 

Disease extent

Percentage 5 year survival

All RO resections

54%

Early gastric cancer

91%

Stage 1

87%

Stage 2

65%

Stage 3

18%

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:15

Gilbert's syndrome

Gilbert's syndrome is an autosomal recessive* condition of defective bilirubin conjugation due to a deficiency of UDP glucuronosyltransferase. The prevalence is approximately 1-2% in the general population.

 

Features

·         unconjugated hyperbilirubinaemia (i.e. not in urine)

·         jaundice may only be seen during an intercurrent illness, exercise or fasting

Investigation and management

·         investigation: rise in bilirubin following prolonged fasting or IV nicotinic acid

·         no treatment required

*the exact mode of inheritance is still a matter of debate

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Haemochromatosis: features

Haemochromatosis is an autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation. It is caused by inheritance of mutations in the HFE gene on both copies of chromosome 6*. It is often asymptomatic in early disease and initial symptoms often non-specific e.g. lethargy and arthralgia

 

Epidemiology

·         1 in 10 people of European descent carry a mutation in the genes affecting iron metabolism, mainly HFE

·         prevalence in people of European descent = 1 in 200, making it more common than cystic fibrosis

Presenting features

·         early symptoms include fatigue, erectile dysfunction and arthralgia (often of the hands)

·         'bronze' skin pigmentation

·         diabetes mellitus

·         liver: stigmata of chronic liver disease, hepatomegaly, cirrhosis, hepatocellular deposition)

·         cardiac failure (2nd to dilated cardiomyopathy)

·         hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)

·         arthritis (especially of the hands)

Questions have previously been asked regarding which features are reversible with treatment:

 

 

Reversible complications

Irreversible complications

·         Cardiomyopathy

·         Skin pigmentation

·         Liver cirrhosis**

·         Diabetes mellitus

·         Hypogonadotrophic hypogonadism

·         Arthropathy

*there are rare cases of families with classic features of genetic haemochromatosis but no mutation in the HFE gene

**whilst elevated liver function tests and hepatomegaly may be reversible, cirrhosis is not

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

Commonly C282Y or H63D mutations HFE gene

 

MRI liver heart

Iron studies >50% transferrin sats

 

Venesection aim <100 ferritin

Refer to liver/endochronology

 

 

 

 

24 December 2020

14:15

Hepatorenal syndrome: management

The management of hepatorenal syndrome (HRS) is notoriously difficult. The ideal treatment is liver transplantation but patients are often too unwell to have surgery and there is a shortage of donors

 

The most accepted theory regarding the pathophysiology of HRS is that vasoactive mediators cause splanchnic vasodilation which in turn reduces the systemic vascular resistance. This results in 'underfilling' of the kidneys. This is sensed by the juxtaglomerular apparatus which then activates the renin-angiotensin-aldosterone system, causing renal vasoconstriction which is not enough to counterbalance the effects of the splanchnic vasodilation.

 

Hepatorenal syndrome has been categorized into two types:

 

 

Type 1 HRS

Type 2 HRS

Rapidly progressive

Doubling of serum creatinine to > 221 µmol/L or a halving of the creatinine clearance to less than 20 ml/min over a period of less than 2 weeks

Very poor prognosis

Slowly progressive

Prognosis poor, but patients may live for longer

Management options

·         vasopressin analogues, for example terlipressin, have a growing evidence base supporting their use. They work by causing vasoconstriction of the splanchnic circulation

·         volume expansion with 20% albumin

·         transjugular intrahepatic portosystemic shunt

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Irritable bowel syndrome: management

The management of irritable bowel syndrome (IBS) is often difficult and varies considerably between patients. NICE updated it's guidelines in 2015.

 

First-line pharmacological treatment - according to predominant symptom

·         pain: antispasmodic agents

·         constipation: laxatives but avoid lactulose

·         diarrhoea: loperamide is first-line

For patients with constipation who are not responding to conventional laxatives linaclotide may be considered, if:

·         optimal or maximum tolerated doses of previous laxatives from different classes have not helped and

·         they have had constipation for at least 12 months

Second-line pharmacological treatment

·         low-dose tricyclic antidepressants (e.g. amitriptyline 5-10 mg) are used in preference to selective serotonin reuptake inhibitors

Other management options

·         psychological interventions - if symptoms do not respond to pharmacological treatments after 12 months and who develop a continuing symptom profile (refractory IBS), consider referring for cognitive behavioural therapy, hypnotherapy or psychological therapy

·         complementary and alternative medicines: 'do not encourage use of acupuncture or reflexology for the treatment of IBS'

General dietary advice

·         have regular meals and take time to eat

·         avoid missing meals or leaving long gaps between eating

·         drink at least 8 cups of fluid per day, especially water or other non-caffeinated drinks such as herbal teas

·         restrict tea and coffee to 3 cups per day

·         reduce intake of alcohol and fizzy drinks

·         consider limiting intake of high-fibre food (for example, wholemeal or high-fibre flour and breads, cereals high in bran, and whole grains such as brown rice)

·         reduce intake of 'resistant starch' often found in processed foods

·         limit fresh fruit to 3 portions per day

·         for diarrhoea, avoid sorbitol

·         for wind and bloating consider increasing intake of oats (for example, oat-based breakfast cereal or porridge) and linseeds (up to one tablespoon per day).

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Malnutrition

Malnutrition is an important consequence of and contributor to chronic disease. It is clearly a complex and multifactorial problem that can be difficult to manage but there are a number of key points to remember for the exam.

 

NICE define malnutrition as the following:

·         a Body Mass Index (BMI) of less than 18.5; or

·         unintentional weight loss greater than 10% within the last 3-6 months; or

·         a BMI of less than 20 and unintentional weight loss greater than 5% within the last 3-6 months

Around 10% of patients aged over 65 years are malnourished, the vast majority of those living independently, i.e. not in hospital or care/nursing homes.

 

Screening for malnutrition if mostly done using MUST (Malnutrition Universal Screen Tool). A link is provided to a copy of the MUST score algorithm.

·         it should be done on admission to care/nursing homes and hospital, or if there is concern. For example an elderly, thin patient with pressure sores

·         it takes into account BMI, recent weight change and the presence of acute disease

·         categorises patients into low, medium and high risk

Management of malnutrition is difficult. NICE recommend the following points:

·         dietician support if the patient is high-risk

·         a 'food-first' approach with clear instructions (e.g. 'add full-fat cream to mashed potato'), rather than just prescribing oral nutritional supplements (ONS) such as Ensure

·         if ONS are used they should be taken between meals, rather than instead of meals

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Melanosis coli

Melanosis coli is a disorder of pigmentation of the bowel wall. Histology demonstrates pigment-laden macrophages

 

It is associated with laxative abuse, especially anthraquinone compounds such as senna

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Pyogenic liver abscess

The most common organisms found in pyogenic liver abscesses are Staphylococcus aureus in children and Escherichia coli in adults.

 

Management

·         drainage (typically percutaneous) and antibiotics

·         amoxicillin + ciprofloxacin + metronidazole

·         if penicillin allergic: ciprofloxacin + clindamycin

 

 

© Image used on license from Radiopaedia

CT showing a pyogenic liver abscess in the right lobe of the liver.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Refeeding syndrome

Refeeding syndrome describes the metabolic abnormalities which occur on feeding a person following a period of starvation. It occurs when an extended period of catabolism ends abruptly with switching to carbohydrate metabolism. The metabolic consequences include:

·         hypophosphataemia

·         hypokalaemia

·         hypomagnesaemia: may predispose to torsades de pointes

·         abnormal fluid balance

These abnormalities can lead to organ failure.

 

Prevention

 

NICE produced guidelines in 2006 on nutritional support. Refeeding syndrome may avoided by identifying patients at a high-risk of developing refeeding syndrome:

 

Patients are considered high-risk if one or more of the following:

·         BMI < 16 kg/m2

·         unintentional weight loss >15% over 3-6 months

·         little nutritional intake > 10 days

·         hypokalaemia, hypophosphataemia or hypomagnesaemia prior to feeding (unless high)

If two or more of the following:

·         BMI < 18.5 kg/m2

·         unintentional weight loss > 10% over 3-6 months

·         little nutritional intake > 5 days

·         history of: alcohol abuse, drug therapy including insulin, chemotherapy, diuretics and antacids

NICE recommend that if a patient hasn't eaten for > 5 days, aim to re-feed at no more than 50% of requirements for the first 2 days.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Scoring systems for liver cirrhosis

For many years the Child-Pugh classification was used to classify the severity of liver cirrhosis. However, in recent years the Model for End-Stage Liver Disease (MELD) has been increasingly used, particularly patient's who are on a liver transplant waiting list

 

 

Child-Pugh classification

 

 

Score

1

2

3

Bilirubin (µmol/l)

<34

34-50

>50

Albumin (g/l)

>35

28-35

<28

Prothrombin time,

prolonged by (s)

<4

4-6

>6

Encephalopathy

none

mild

marked

Ascites

none

mild

marked

Summation of the scores allows the severity to be graded either A, B or C:

·         < 7 = A

·         7-9 = B

·         > 9 = C

 

MELD

 

Uses a combination of a patient's bilirubin, creatinine, and the international normalized ratio (INR) to predict survival. A formula is used to calculate the score:

 

MELD = 3.78×ln[serum bilirubin (mg/dL)] + 11.2×ln[INR] + 9.57×ln[serum creatinine (mg/dL)] + 6.43

 

The 3-month mortality based on MELD scores:

·         40 or more: 71.3% mortality

·         30 - 39: 52.6% mortality

·         20 - 29: 19.6% mortality

·         10 - 19: 6.0% mortality

·         < 9: 1.9% mortality

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Vitamin C deficiency (scurvy)

Vitamin C (ascorbic acid) is found in citrus fruits, tomatoes, potatoes, Brussel sprouts, cauliflower, broccoli, cabbage and spinach. Deficiency (commonly called scurvy) leads to impaired collagen synthesis and disordered connective tissue as ascorbic acid is a cofactor for enzymes used in the production of proline and lysine. It is associated with severe malnutrition as well as drug and alcohol abuse, and those living in poverty with limited access to fruits and vegetables.

 

Symptoms and signs include:

·         Follicular hyperkeratosis and perifollicular haemorrhage

·         Ecchymosis, easy bruising

·         Poor wound healing

·         Gingivitis with bleeding and receding gums

·         Sjogren's syndrome

·         Arthralgia

·         Oedema

·         Impaired wound healing

·         Generalised symptoms such as weakness, malaise, anorexia and depression

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Abdominal incisions

Midline incision

·         Commonest approach to the abdomen

·         Structures divided: linea alba, transversalis fascia, extraperitoneal fat, peritoneum (avoid falciform ligament above the umbilicus)

·         Bladder can be accessed via an extraperitoneal approach through the space of Retzius

Paramedian incision

·         Parallel to the midline (about 3-4cm)

·         Structures divided/retracted: anterior rectus sheath, rectus (retracted), posterior rectus sheath, transversalis fascia, extraperitoneal fat, peritoneum

·         Incision is closed in layers

Battle

·         Similar location to paramedian but rectus displaced medially (and thus denervated)

·         Now seldom used

Kocher's

Incision under right subcostal margin e.g. Cholecystectomy (open)

Lanz

Incision in right iliac fossa e.g. Appendicectomy

Gridiron

Oblique incision centered over McBurneys point- usually appendicectomy (less cosmetically acceptable than Lanz

Gable

Rooftop incision

Pfannenstiel's

Transverse supra pubic, primarily used to access pelvic organs

McEvedy's

Groin incision e.g. Emergency repair strangulated femoral hernia

Rutherford Morrison

Extraperitoneal approach to left or right lower quadrants. Gives excellent access to iliac vessels and is the approach of choice for first time renal transplantation.

 

 

Image sourced from Wikipedia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:15

Antidiarrhoeal agents

Opioid agonists include

·         loperamide

·         diphenoxylate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Bile-acid malabsorption

Bile-acid malabsorption is a cause of chronic diarrhoea. This may be primary, due to excessive production of bile acid, or secondary to an underlying gastrointestinal disorder causing reduced bile acid absorption. It can lead to steatorrhoea and vitamin A, D, E, K malabsorption.

 

Secondary causes are often seen in patients with ileal disease, such as with Crohn's. Other secondary causes include:

·         cholecystectomy

·         coeliac disease

·         small intestinal bacterial overgrowth

Investigation

·         the test of choice is SeHCAT

·         nuclear medicine test using a gamma-emitting selenium molecule in selenium homocholic acid taurine or tauroselcholic acid (SeHCAT)

·         scans are done 7 days apart to assess the retention/loss of radiolabelled 75SeHCAT

Management

·         bile acid sequestrants e.g. cholestyramine

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Bilirubin

Bilirubin is a chemical by-product of the breakdown of heme, a component of red blood cells, and other hepatic heme-containing proteins, for example, myoglobin. The released heme is processed within macrophages and oxidized to form biliverdin and iron. Biliverdin is then reduced to form unconjugated bilirubin, which is released into the bloodstream.

 

Unconjugated bilirubin is bound to albumin in the blood and then taken up by hepatocytes, where it is conjugated, thus rendering it water-soluble. From hepatocytes, it is excreted into bile and thus enters the intestines to be broken down by intestinal bacteria. Bacterial proteases produce urobilinogen from bilirubin within the intestinal lumen, the majority of which is further processed by intestinal bacteria to form urobilin and stercobilin and excreted via the faeces. Around 10% of the bilirubin entering the intestinal system re-enters the portal circulation to be finally excreted via the kidneys in urine.

 

Raised levels of unconjugated bilirubin may occur as a result of haemolysis, which is to say a pre-hepatic source, for example, autoimmune-mediated haemolytic anaemia. Red blood cell breakdown exposes heme-containing proteins and, as discussed above, these are then processed to form unconjugated bilirubin.

 

Hepatocyte defects, such as a compromised hepatocyte uptake of unconjugated bilirubin and/or defective conjugation may occur in liver disease, or deficiency of glucuronyl transferase.

 

A mild glucuronyl transferase deficiency results in Gilbert's Syndrome, whilst a moderate to severe glucuronyl transferase deficiency may be seen in Crigler-Najjar Syndrome types I and II respectively. A transient glucuronyl transferase deficiency may also contribute to physiological neonatal jaundice.

 

Raised levels of conjugated bilirubin can result from defective excretion of bilirubin, for example, Dubin-Johnson Syndrome, or cholestasis.

 

Jaundice starts to appear when bilirubin reaches an excess of 35umol/l.

 

Cholestasis can result from a wide range of pathologies, which can be largely divided into physical causes, for example, gallstones, pancreatic and cholangiocarcinoma, or functional causes, for example, drug-induced, pregnancy-related and post-operative cholestasis.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:15

Constipation

Constipation is a common primary functional disorder of the bowel but may, of course, develop secondary to another condition. It may be defined as defecation that is unsatisfactory because of infrequent stools (< 3 times weekly), difficult stool passage (with straining or discomfort), or seemingly incomplete defecation.

 

Features

·         the passage of infrequent hard stools

Complications

·         overflow diarrhoea

·         acute urinary retention

·         haemorrhoids

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Diverticulosis

Diverticulosis is an extremely common disorder characterised by multiple outpouchings of the bowel wall, most commonly in the sigmoid colon. Strictly speaking the term diverticular disease is reserved for patients who are symptomatic - diverticulosis is the more accurate term for diverticula being present.

 

Risk factors

·         increasing age

·         low-fibre diet

Diverticulosis can present in a number of ways:

·         painful diverticular disease: altered bowel habit, colicky left sided abdominal pain. A high fibre diet is usually recommended to minimise symptoms

·         diverticulitis: see below for more details

Diverticulitis

 

One of the diverticular become infected. The classical presentation is:

·         left iliac fossa pain and tenderness

·         anorexia, nausea and vomiting

·         diarrhoea

·         features of infection (pyrexia, raised WBC and CRP)

Management:

·         mild attacks can be treated with oral antibiotics

·         more significant episodes are managed in hospital. Patients are made nil by mouth, intravenous fluids and intravenous antibiotics (typical a cephalosporin + metronidazole) are given

Complications of diverticulitis include:

·         abscess formation

·         peritonitis

·         obstruction

·         perforation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:16

Gastro-oesophageal reflux disease: investigation

Overview

·         poor correlation between symptoms and endoscopy appearance

Indications for upper GI endoscopy:

·         age > 55 years

·         symptoms > 4 weeks or persistent symptoms despite treatment

·         dysphagia

·         relapsing symptoms

·         weight loss

If endoscopy is negative consider 24-hr oesophageal pH monitoring (the gold standard test for diagnosis)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Gastro-oesophageal reflux disease: management

Gastro-oesophageal reflux disease (GORD) may be defined as symptoms of oesophagitis secondary to refluxed gastric contents

 

NICE recommend that GORD which has not been investigated with endoscopy should be treated as per the dyspepsia guidelines

 

Endoscopically proven oesophagitis

·         full dose proton pump inhibitor (PPI) for 1-2 months

·         if response then low dose treatment as required

·         if no response then double-dose PPI for 1 month

Endoscopically negative reflux disease

·         full dose PPI for 1 month

·         if response then offer low dose treatment, possibly on an as-required basis, with a limited number of repeat prescriptions

·         if no response then H2RA or prokinetic for one month

Complications

·         oesophagitis

·         ulcers

·         anaemia

·         benign strictures

·         Barrett's oesophagus

·         oesophageal carcinoma

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Hepatitis D

Hepatitis D is a single stranded RNA virus that is transmitted parenterally. It is an incomplete RNA virus that requires hepatitis B surface antigen to complete its replication and transmission cycle.

 

It is transmitted in a similar fashion to hepatitis B (exchange of bodily fluids) and patients may be infected with hepatitis B and hepatitis D at the same time.

 

Hepatitis D terminology:

·         Co-infection: Hepatitis B and Hepatitis D infection at the same time.

·         Superinfection: A hepatitis B surface antigen positive patient subsequently develops a hepatitis D infection.

Superinfection is associated with high risk of fulminant hepatitis, chronic hepatitis status and cirrhosis.

 

Diagnosis is made via reverse polymerase chain reaction of hepatitis D RNA. Interferon is currently used as treatment, but with a poor evidence base.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

14:16

Inferior mesenteric artery

The IMA is the main arterial supply of the embryonic hindgut and originates approximately 3-4 cm superior to the aortic bifurcation. From its aortic origin it passes immediately inferiorly across the anterior aspect of the aorta to eventually lie on its left hand side. At the level of the left common iliac artery it becomes the superior rectal artery.

 

Branches

The left colic artery arises from the IMA near its origin. More distally up to three sigmoid arteries will exit the IMA to supply the sigmoid colon.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Iron studies

Serum iron

 

Total iron binding capacity (TIBC)

·         transferrin

·         raised in iron deficiency anaemia (IDA)

·         raised in pregnancy and by oestrogen

Transferrin saturation

·         calculated by serum iron / TIBC

Ferritin

·         raised in inflammatory disorders

·         low in IDA

Rarer tests

·         transferrin receptors increased in IDA

Anaemia of chronic disease

·         normochromic/hypochromic, normocytic anaemia

·         reduced serum and TIBC

·         normal or raised ferritin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Irritable bowel syndrome

NICE published clinical guidelines on the diagnosis and management of irritable bowel syndrome (IBS) in 2008

 

The diagnosis of IBS should be considered if the patient has had the following for at least 6 months:

·         abdominal pain, and/or

·         bloating, and/or

·         change in bowel habit

A positive diagnosis of IBS should be made if the patient has abdominal pain relieved by defecation or associated with altered bowel frequency stool form, in addition to 2 of the following 4 symptoms:

·         altered stool passage (straining, urgency, incomplete evacuation)

·         abdominal bloating (more common in women than men), distension, tension or hardness

·         symptoms made worse by eating

·         passage of mucus

Features such as lethargy, nausea, backache and bladder symptoms may also support the diagnosis

 

Red flag features should be enquired about:

·         rectal bleeding

·         unexplained/unintentional weight loss

·         family history of bowel or ovarian cancer

·         onset after 60 years of age

Suggested primary care investigations are:

·         full blood count

·         ESR/CRP

·         coeliac disease screen (tissue transglutaminase antibodies)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Peptic ulcer disease (perforation)

The symptoms of perforation secondary to peptic ulcer disease typically develop suddenly

·         epigastric pain, later becoming more generalised

·         patients may describe syncope

Investigations

·         Although the diagnosis is largely clinical, UptoDate recommend that plain x-rays are the first form of imaging to obtain

·         An upright ('erect') chest x-ray is usually required when a patient presents with acute upper abdominal pain

·         This is a useful test, as approximately 75% of patients with a perforated peptic ulcer will have free air under the diaphragm

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Pernicious anaemia

Pernicious anaemia is an autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency. It is helpful to remember that pernicious means 'causing harm, especially in a gradual or subtle way' - the symptoms of signs are often subtle and diagnose is often delayed.

 

Whilst pernicious anaemia is the most common cause of vitamin B12 deficiency, it's not the only cause. Other causes include atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism).

 

Pathophysiology

·         antibodies to intrinsic factor +/- gastric parietal cells

o    intrinsic factor antibodies → bind to intrinsic factor blocking the vitamin B12 binding site

o    gastric parietal cell antibodies → reduced acid production and atrophic gastritis. Reduced intrinsic factor production → reduced vitamin B12 absorption

·         vitamin B12 is important in both the production of blood cells and the myelination of nerves → megaloblastic anaemia and neuropathy

Risk factors

·         more common in females (F:M = 1.6:1) and typically develops in middle to old age

·         associated with other autoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison's, rheumatoid and vitiligo

·         more common if blood group A

Features

·         anaemia features

o    lethargy

o    pallor

o    dyspnoea

·         neurological features

o    peripheral neuropathy: 'pins and needles', numbness. Typically symmetrical and affects the legs more than the arms

o    subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia

o    neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy

·         other features

o    mild jaundice: combined with pallor results in a 'lemon tinge'

o    glossitis → sore tongue

Investigation

·         full blood count

o    macrocytic anaemia: macrocytosis may be absent in around of 30% of patients

o    hypersegmented polymorphs on blood film

o    low WCC and platelets may also be seen

·         vitamin B12 and folate levels

o    a vitamin B12 level of >= 200 nh/L is generally considered to be normal

·         antibodies

o    anti intrinsic factor antibodies: sensivity is only 50% but highly specific for pernicious anaemia (95-100%)

o    anti gastric parietal cell antibodies in 90% but low specificity so often not useful clinically

·         Schilling test is no longer routinely done

o    radiolabelled B12 given on two occasions, firstly on its own, secondly with oral IF. Urine B12 levels are then measured

Management

·         vitamin B12 replacement

o    usually given intramuscularly

o    no neurological features: 3 injections per week for 2 weeks followed by 3 monthly treatment of vitamin B12 injections

o    more frequent doses are given for patients with neurological features

o    there is some evidence that oral vitamin B12 may be effective for providing maintenance levels of vitamin B12 but it is not yet common practice

·         folic acid supplementation may also be required

Complications other than the haematological and neurological features detailed above

·         increased risk of gastric cancer

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Vitamin A (retinol)

Vitamin A is a fat soluble vitamin.

 

Functions

·         converted into retinal, an important visual pigment

·         important in epithelial cell differentiation

·         antioxidant

Consequences of vitamin A deficiency

·         night blindness

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Vitamin B3 (niacin)

Niacin is a water soluble vitamin of the B complex group. It is a precursor to NAD+ and NADP+ and hence plays an essential metabolic role in cells.

 

Biosynthesis

·         Hartnup's disease: hereditary disorder which reduces absorption of tryptophan

·         carcinoid syndrome: increased tryptophan metabolism to serotonin

Consequences of niacin deficiency:

·         pellagra: dermatitis, diarrhoea, dementia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Vitamin B6 (pyridoxine)

Vitamin B6 is a water soluble vitamin of the B complex group. It is converted to pyridoxal phosphate (PLP) which is a cofactor for many reactions including transamination, deamination and decarboxylation.

 

Causes of vitamin B6 deficiency

·         isoniazid therapy

Consequences of vitamin B6 deficiency

·         peripheral neuropathy

·         sideroblastic anemia

 

 

 

Diagram showing the biochemical role of vitamin B12 and vitamin B6

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Vitamin C (ascorbic acid)

Vitamin C is a water soluble vitamin.

 

Functions

·         antioxidant

·         collagen synthesis: acts as a cofactor for enzymes that are required for the hydroxylation proline and lysine in the synthesis of collagen

·         facilitates iron absorption

·         cofactor for norepinephrine synthesis

Vitamin C deficiency (scurvy) leads to defective synthesis of collagen resulting in capillary fragility (bleeding tendency) and poor wound healing

 

Features vitamin C deficiency

·         gingivitis, loose teeth

·         poor wound healing

·         bleeding from gums, haematuria, epistaxis

·         general malaise

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

14:16

Zollinger-Ellison syndrome

Zollinger-Ellison syndrome is condition characterised by excessive levels of gastrin, usually from a gastrin secreting tumour usually of the duodenum or pancreas. Around 30% occur as part of MEN type I syndrome

 

Features

·         multiple gastroduodenal ulcers

·         diarrhoea

·         malabsorption

Diagnosis

·         fasting gastrin levels: the single best screen test

·         secretin stimulation test

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

Liver function tests

04 January 2021

23:14

 

 

ALP (Isolated) is physiologically raised in the 3rd trimester of pregnancy

 

plasma half-life of prothrombin  factor 7 is approximately 6 hours

 

90% of Liver disease is preventable, with three quarters of people being diagnosed at a late stage.

 

 

Where Transferases (ALT/AST) >> ALP and GGT

·         Consider a Hepatic cause

 

Where ALP and GGT >> Transferases (ALT/AST)

·         Consider a Biliary / Obstructive cause

 

 

 

 

A standardised serum liver function test usually includes:

 

Bilirubin

Albumin

Transferases (alanine transferase (ALT); aspartate transferase (AST)

Alkaline phosphatase (ALP)

Gamma Glutamyltransferase (GGT)

 

On some testing panels GGT and AST have to been added on in addition to the  standard panel. It is  also useful to include a serum coagulation or INR when assessing liver function

 

 

 

 

Bilirubin is formed by the breakdown of haemoglobin within the reticuloendothelial system. This forms unconjugated bilirubin, which is water-insoluble and therefore needs to be bound to albumin, where it is taken up by the liver.

 

In the Liver bilirubin is conjugated to make it water-soluble. The majority of Conjugated bilirubin is excreted as bile acid via the bile ducts of the Liver. It is stored within the gallbladder and released into the small intestine where it aids in the breakdown of lipids. 95% of bile is reabsorbed in the terminal ileum to the Entrohepatic circulation.

 

From <https://mle.ncl.ac.uk/cases/page/16351/>

 

In general the total serum bilirubin is usually measured, but you can measure both the indirect (unconjugated) and direct (conjugated) portions.

 

 The normal range is usually <21umol/L

 

 

From <https://mle.ncl.ac.uk/cases/page/16351/>

 

 

Unconjugated bilirubin

This usually is elevated due to increased bilirubin production OR decreased hepatic uptake/conjugation:

The commonest causes of raised unconjugated bilirubin in adults are:

·         Gilbert’s syndrome:

o    A genetic disorder where less of the enzyme that breaks down Bilirubin (UDP-glucuronyltransferase) is produced. It affects 5% of the population. There is an increase in the bilirubin often with fasting or concurrent illness.

o    Confirmation of just a predominant unconjugated hyperbilirubinaemia makes the diagnosis of Gilbert’s syndrome virtually certain. This does not require any treatment and the patient can be completely reassured.

o    Rarely does it cause a bilirubin above 68umol/L

·         Haemolysis:

o    The breakdown of red blood cells. There can by many causes for this and standard investigations for this would include: reticulocyte count, LDH, blood film, Haptoglobin, Direct coombs test

·         Drug related, for example, the antibiotic Rifampicin impairs the uptake of Bilirubin

 

 

 

 

 

 

 

Conjugated Bilirubin

In healthy adults conjugated bilirubin is virtually absent. Levels usually start to become increased when the liver has lost approximately ½ of its excretory capacity. It is therefore usually a sign of liver disease, which may be acute or chronic in nature.

 

Common causes for elevated conjugated bilirubin include:

·         Biliary obstruction at any level of the bile ducts

o    Often secondary to gallstones in the common bile duct, but also from malignancy – commonly Cholangiocarcinoma or Pancreatic cancer

·         Cholestatic drug reactions

o    Potentially any drug, but commonly antibiotics such as Nitrofuratoin and Penicillin

·         Autoimmune Cholestatic disease e.g. Primary Sclerosing Cholangitis (may occur at any level) and Primary Biliary Cirrhosis (intrahepatic ducts)

·         Hepatitis of any origin where there is significant impairment in liver function

·         Cirrhosis

 

 

 

ALT and AST

Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is measured in a liver function test profile. Both these enzymes live predominately in hepatocytes, whilst AST may also be found diffusely in cardiac and skeletal muscle, renal tissue, along with red blood cells. This means that ALT is in general more specific to the liver.

Injury to the liver, whether acute or chronic, will cause inflammation or damage to hepatocytes (but not necessarily cell death), leading to a release of these enzymes into the blood stream and resulting in a measureable increase in serum concentration of aminotransferases.

Therefore elevated transferase usually reflects a hepatitis of which there could be many causes.

 

Common causes of acute and chronic hepatitis are:

·         Alcohol – including chronic alcohol abuse and Alcoholic hepatitis

·         Non-alcoholic fatty liver disease (NAFLD)

·         Viral Hepatitis – both acute and chronic

·         Autoimmune Hepatitis

·         Drug toxicity

·         Ischaemia – this can be due to anything which suddenly causes a patient’s blood pressure to drop

·         Metabolic liver disease (Wilson’s / Haemochromatosis)

 

Upper limits may vary between labs and the units that are used, but normal is usually considered to be less than 40IU/L.

There is no internationally recognised criteria but generally rises in aminotransferase can be thought as:

·      Mild (<5 upper limit of normal)

·      Moderate (5-10 upper limit of normal)  

·      Marked (> 10 upper limit of normal)

 

The degree of rise in transferase can help guide the underlying aetiology, although there is often significant overlap.

 The diagram below illustrates the degree of ALT rise with associated disease.

 

10000 1000 100 10 Ischemic or toxic liver injury Acute viral hepatitis Autoimmune Alcoholic hepatitis liver disease Chronic hepatitis cirrhosis Reference range

A useful rule of thumb is that an ALT rise of greater than 1,000 IU/L reflects a significant acute liver injury and is typically only caused by the following:

·         Ischaemia

·         Drugs (Most commonly Paracetamol)

·         Viruses (Hepatitis A, B, C and E)

 

Examining the ratio of AST to ALT can also be helpful in determining the underlying cause. In alcohol related liver disease patients are often nutritionally deficient in vitamin B6. This effects the activity of ALT, resulting in reduced concentrations, thus typically resulting in an AST/ALT ratio of >2 in alcoholic liver disease; whilst an AST/ALT ratio of <1.0 would be more suggestive of non-alcoholic liver disease.

 

The circulation half-life for ALT is around 47 hours.

 

From <https://mle.ncl.ac.uk/cases/page/16748/>

 

ALP

Alkaline phosphatase (ALP) is another enzyme, but which predominately comes from cells that line the biliary tract, however it is also present in bone and the placenta. Therefore it may be elevated physiologically or pathologically.

 

 

A normal ALP is generally <130 IU/L 

 

Physiological causes include:

·         3rd Trimester of pregnancy

·         Increase bone turnover – adolescents during periods of growth

 

 

Pathological causes include:

·         Hepatic:

o    Bile duct obstruction – stones, malignancy

o    Primary Sclerosing Cholangitis (PSC)

o    Primary Biliary Cirrhosis (PBC)

o    Drug induced cholestasis (antibiotics, anabolic steroids)

·         Extra-hepatic:

o    Bone disease: Factures, Pagets disease and bone metastasis 

 

 

 

GGT

 

 

The enzyme Gamma-glutamyltransferase (GGT) is present in cell membranes of bile ducts, gallbladder, kidneys, pancreas, spleen and heart. It may be raised in all types of liver disease, however when paired with an elevated ALP it is highly suggestive of hepatobiliary source.

 

A normal GGT is usually < 70 unit/L

 

Isolated ALP rises can and do occur in PSC and PBC. However you should also be alert for other sources, in particular for bone metastasis. Isolated GGT is seen in alcohol abuse, as well as COPD and renal failure.

 

Cholestasis enhances the synthesis and release of ALP. The half-life of ALP is around a week; therefore levels may rise quickly in bile duct obstruction and decrease slowly following resolution.

 

 

 

 

Prothrombin

 

 

The Prothrombin Time (PT) is a measure of the function of the extrinsic and common coagulation pathways. It represents the time in seconds for the patient’s plasma to clot after the addition of calcium and thromboplastin (an activator in the extrinsic pathway).  Another way to represent this is the Internationalised Normalised Ratio, which standardises how the PT is measured - difficult labs have different ways of measuring PT, meaning it is difficult to compare PT’s across different laboratories.

 

The PT and Internationalised Normalised Ratio (INR) are both useful for measuring Liver synthetic function because clotting factors II, V, VII, IX, and X are produced in the Liver.  Therefore if the liver is not able to produce these clotting factors due to dysfunction this is reflected in a prolonged PT/INR.

 

Intrinsic pathway Xll IX Xia Villa Extrinsic pathway Vil Prothrombin Thrombin Common pathway Fibrinogen Fibrin Xllla Cross-linked fibrin clot Clot formation

 

 

The PT/INR is particularly useful in acute liver injury as factor VII has a short half-life – around 6 hours. Therefore it is useful in acute or fulminant liver failure as a way to monitor the progression of damage or impairment to the liver.

 

PT and INR may be prolonged in chronic liver disease but not until approximately 80% of the livers synthetic function is compromised. It is therefore a useful indicator of advanced liver disease, particularly in decompensated liver cirrhosis and is often included in prognostic scoring systems.

 

 

 

One important thing to consider is that while a prolonged PT may indicate liver synthetic dysfunction, it can be prolonged for other reasons. In particular deficiency in fat-soluble vitamin k, which is used in the generation of factors II, VII, IX, and X, can be responsible.  This is particularly true in cases of obstructive jaundice where reduced bile acid excretion impairs intestinal absorption of fat-soluble vitamins.

 

 

 

Acute liver failure (ALF) is loss of liver function at that occurs rapidly in days or weeks in the absence of any underlying chronic liver disease. It is characterized by jaundice, coagulopathy (prolonged PT/INR) and hepatic encephalopathy. Hepatic Encephalopathy is essential to fulfil the diagnosis of ALF.

 

ALF can be further subdivided into Hyperacute, Acute or Subacute.

·         Hyperacute - Encephalopathy occurs within 7 days of onset of jaundice

·         Acute liver failure – 8 to 28 days from jaundice to encephalopathy

·         Sub acute failure - Hepatic encephalopathy occurs within 5-12 weeks of onset of jaundice.

·         Severe Acute liver injury – Elevated transferases, prolonged PT and jaundice. But NO hepatic encephalopathy

 

 

 

 

 

Weeks from development Of jaundice to development Of HEI >28 weeks = chronic liver disease Hyperaeute' Paraætarnol HAV. HEV 4 Acute' HBV Subacutel Norrparacetamol drug-induced 12 Severity of coagulopathy2 Severity of jaundice2 Degree of intracranial hypertension2 Chance of spontaneous recovery* Typical cause' HO' severity; Medium severity; • LTN severity; Present or absent JG. et 2 W. et al. Lance EASL CPGALK J EASL

 

In chronic liver disease there is a duration of greater than 28 weeks before the onset of hepatic encephalopathy.

 

Acute on chronic liver disease, or decompensating liver disease share features of acute liver failure clinically – we know that ¾ of patients present with advanced liver disease, their first presentation may therefore be with jaundice, coagulopathy and hepatic encephalopathy.

 

Clues to suggest underlying chronic liver disease rely on a thorough clinical assessment, which includes a full history.  Clinical examination to look for signs secondary to chronic liver disease is particularly helpful (see later).  Portal hypertension is more common in advanced chronic liver disease (but may also occur in the acute setting), these may be evident clinically, biochemically (Platelets  < 150 due to hypersplenism) or radiologically.

 

From <https://mle.ncl.ac.uk/cases/page/16558/>

 

Consequences of portal hypertension include:

 

Oesophageal and Gastric Varices

Abdominal Ascites

Peripheral oedema

Hepatic Encephalopathy

Low Platelets (due to hypersplenism)

 

 

 

         Antimitochondrial antibody - PBC

         Anti-smooth muscle antibody / anti LKM1 / Antinuclear antibody – Autoimmune Hepatitis

         pANCA – PSC

 

From <https://mle.ncl.ac.uk/cases/page/16583/>

         Elevated IgA – often associated with fatty liver disease -such as alcohol or NAFLD (Non-Alcoholic Fatty Liver Disease)

         Elevated IgM – often associated with Primary Biliary Cirrhosis

         Elevated IgG – often associated with Autoimmune Hepatitis

 

 

From <https://mle.ncl.ac.uk/cases/page/16583/>

 

 

¡  Serum ferritin and transferrin saturation – elevated in Haemochromatosis

 

¡  Copper/Caeruloplasmin – Wilson's disease

 

¡  Alpha-1 antitrypsin (A1AT) – Hereditary disorder

 

Alpha-fetoprotein (AFP) – this should not form part of the liver screen but instead is used in screening for Hepatocellular Carcinoma – a common sequelae of Cirrhosis, and chronic Hepatitis B and C infection.

 

From <https://mle.ncl.ac.uk/cases/page/16583/>

 

 

 

 

 

Haemochromatosis

04 January 2021

23:52

Haemochromatosis

A disorder that results in iron overload, which may affect many organs. There are two types – primary and secondary.

Primary

An inherited disorder, the most common being autosomal recessive caused by a defect in the HFE gene, sometimes called HFE Haemochromatosis. It was thought this was the only gene associated with Haemochromatosis, however it is now know that there are other gene associations.

 

 

Haemochromatosis.org.uk

 

This is the UK’s most common genetic condition.

 

The two known mutations of HFE are C282Y and H63D. Testing for these is simple and cheap. But there are other rare genes that may cause disease

 

Whilst this is an autosomal recessive condition, clinically things can be a bit more complex – this is because gene expression (penetrance) varies. E.g. just because you have two copies of the defective gene does not mean you will definitely develop the clinical condition.

·         C282Y/C282Y Homozygous gives a 95% risk of iron overload

·         C282Y/H63D compound heterozygotes gives around 4% risk (increased risk with increased alcohol intake, viral hepatitis) 

·         H63D/H63D Homozygous is least likely to cause iron overload

 

All these genes lead to increased intestinal absorption of iron.

 

Patients are often identified incidentally due to abnormal liver tests (elevated ALT), abnormal imaging (fatty liver, iron overload in liver) or elevated serum ferritin (see later). They can  present with vague symptoms or advanced disease 

 

The main symptoms patients may present with are:

1.       Joint pain – especially of the hands and fingers

2.       Fatigue

3.       Mood disorders – depression / anxiety / mood swings

 

Other symptoms include abdominal pain, palpations, shortness of breath, infertility, hair loss and amenorrhoea.

 

These symptoms usually appear later on in the disease – around age 40-60 in males, and post menopausal for females.

 

Advanced disease may present with diabetes, bronzing of the skin, hepatomegaly/cirrhosis and arthropathy of the 2nd and 3rd metacarpophalangeal joints 

 

If there is genetic expression then this is likely to be reflected in elevated serum ferritin and transferrin saturations.

 

 

 

Secondary

Iron overload due to parental iron-overload e.g. multiple blood transfusions or IV iron replacement. It can be from several haematological disorders e.g. myelodysplastic syndrome

 

Serum Ferritin (SF)

This is a measurement of the protein ferritin in the blood. SF usually correlates well with iron storage.

 

The normal range males is 15-300 µg/l and females 15-200 µg/l

 

In Haemochromatosis the ferritin is often (but not always) in 1000’s

 

It is however important to note that ferritin can also be significantly raised in those with chronic alcohol abuse or have NAFLD as part of the metabolic syndrome. It is also an acute phase protein and can be raised in inflammatory conditions and malignancy.   Therefore an additional blood test called transferrin saturations is also tested.

 

Transferrin Saturation (TS)

A glycoprotein that binds free iron in the bloodstream. When low it means that there is not much iron available. Conversely when high it indicates that the free iron levels are high.

 

The normal range for males is 16-50%, for females this is 16-45%

 

Diagnosis

Patients with elevated SF and T/S should undergo genetic screening for the above genes; those with a ferritin greater than 1000 µg/l should be referred urgently to secondary care to exclude Cirrhosis.

 

Liver function tests, imaging such as ultrasound and/or fibroscan should be used to assess degree of liver damage.

 

Diagnosis of HFE Haemochromatosis should not be based on C282Y homozygosity. It requires evidence of increased iron stores.

 

Those with HFE genotype, but not gene expression, e.g. normal SF and TS should have annual iron studies.

 

Treatment

There are two main phases to treatment:

 

1.     Acute iron removal – this is done via venesection (approx. 450ml of blood is removed). This will reduce the SF by approx. 20-25 µg/l. This is continued until SF are 50-100 µg/l.. Treatment may be required for 12 to 18months, weekly to 2 weekly.

 

2.     Maintenance phase – 2-4 venesections a year to keep SF 50-100 µg/l

 

Some symptoms may improve with venesection 

 

Patients with Cirrhosis and haemochromatosis are at a significant increased risk of Hepatocellular Carcinoma and should be screened every 6 months with ultrasound imaging and serum AFP.

 

Haemochromatosis.org.uk

 

 

A patient with confirmed genetic haemochromatosis should be offered genetic counselling and also genetic screening for any first-degree relatives – siblings will have a ¼ chance of being homozygote. If the patient has children, then assuming a patients partner does not carry the gene then any children will be carriers.

 

From <https://mle.ncl.ac.uk/cases/page/16603/>

 

 

 

 

Wilson's disease

04 January 2021

23:53

 

Wilson’s disease is a rare progressive genetic disorder, which results in accumulation of copper in the body’s tissues. In particular it affects the brain, liver and cornea of the eyes.  Untreated it may lead to liver fibrosis and cirrhosis, along with central nervous system dysfunction.

 

There are 500 gene mutations known about. These result in dysfunction in Wilson’s ATPase, which usually moves copper from along intracellular membranes in the liver. The defective ATPase results in accumulation of copper in the liver, resulting in damage. Over time as the liver becomes damaged the copper is released into the blood and causes other end organ damage.

 

Damage may begin to occur as early as age 6, but often does not become apparent until teenage years (range 5 to 35).

 

Patients may present with:

 

Liver dysfunction (most common presentation):

·      Decompensated liver cirrhosis

·      Acute liver failure  (often associated with renal failure and haemolytic anaemia)

 

Central nervous system (usually have established liver disease):

·      Asymmetrical tremor in ½ patients with CNS dysfunction

·      Poor co-ordination and clumsiness

·      Speech and language problems

·      Neuropsychiatric illness – commonly severe depression or neurotic behaviours

 

Ophthalmological

·      Kayser-Fleischer ring present in 95% of those with neurological disease (seen on slit-lamp), 50% of those without. May occur in other diseases.

·      Sun-flower cataracts – seen on slit lamp. Do not impair vision

 

 

Diagnosis.

Consider in any patient of any age with unusual liver or neurological abnormalities. There is no one best test for diagnosis.

 

Presence of Kayser-Felischer ring and low serum caeruloplasmin (<0.1g/L) is enough to establish diagnosis.

Caeruloplasmin is a protein made in the liver that stores and carries copper around the blood. This may be low in Wilson’s as copper is not able to bind to the protein causing instability. Serum Caeruloplasmin is can be affected by many factors and is not diagnostic on it’s own.

 

Other markers of disease include 24hour urinary copper, serum free copper and hepatic copper (liver biopsy). 

 

A scoring system also exists to help with diagnosis.

 

Genetic screening is complex, many patients are compound heterozygotes (carry two different defective genes) and it can take many months to complete.

 

Treatment

Treatment is life-long. It involves using medication to either promote urinary excretion or to decrease intestinal absorption. The commonest medication used is D-Penicillamine. 

 

Genetics are complex due to the number of gene variations, but essentially siblings (25% risk) and any offspring (0.5% risk) should be offered genetic screening.

 

 

From <https://mle.ncl.ac.uk/cases/page/16604/>

 

 

 

 

SAAG serum to ascites albumin gradient 

05 January 2021

00:02

A serum to ascites albumin gradient (SAAG) can help you differentiate the underlying cause of ascites.

·         The serum-to-ascites albumin gradient (SAAG) accurately identifies the presence of portal hypertension and is more useful than the protein-based exudate/transudate concept

·         The SAAG is easily calculated by subtracting the ascitic fluid albumin value from the serum albumin value, which should be obtained the same day. The SAAG generally does not need to be repeated after the initial measurement.

·         The presence of a gradient ≥11 g/L predicts that the patient has portal hypertension with 97 percent accuracy

·         This is due to increased hydrostatic pressure within the blood vessels of the hepatic portal system, which in turn forces water into the peritoneal cavity but leaves proteins such as albumin within the vasculature.

·         A gradient <11 g/L indicates that portal hypertension is not the primary cause of ascites

·         The following table illustrates some different causes of ascites which are associated with a high or low SAAG:

 

From <https://mle.ncl.ac.uk/cases/page/17267/>

 

 

 

Child Pugh score

05 January 2021

00:07

Child Pugh score is a grading system of cirrhosis and risk of variceal bleeding, ranging from 5-15. The grading can be used to predict mortality and quantify need for liver transplantation. Risk of variceal bleeding is much higher if the score is >8.

Mr Wilson’s Child-Pugh score is 11, which means he has Child-Pugh class C cirrhosis. This signifies he has a higher risk of variceal bleeding and higher mortality rate (1 year survival is 45% compared with 100% & 80% for Child-Pugh A & B respectively).

 

From <https://mle.ncl.ac.uk/cases/page/17271/>

 

 

 

 

 Glasgow-Blatchford score

05 January 2021

00:10

Glasgow-Blatchford score. This is a prognostic score to assess the likelihood that Mr Wilson will require an intervention such as endoscopy or blood transfusion following his upper GI bleed.

Patients with a Glasgow-Blatchford score of 0 should be considered for discharge and subsequent outpatient endoscopy. Patients with a score >0 should be considered for endoscopy. This is shown below:

This patients scores 10 (4 for urea of 12.1, 3 for Hb 104, 0 for BP, score 1 for malaena and 2 for hepatic disease).

 

From <https://mle.ncl.ac.uk/cases/page/17274/>

 

 

 

Summary

05 January 2021

12:46

After blood tests

 

most important next step in NAFLD is to stage the disease; this helps stratify severity and those that should be managed in primary or secondary care. Most commonly in primary care this is done using either: FIB 4 score NAFLD score Tend to use FIB 4 in Newcastle; get students to calculate FIB 4 https://www.mdcalc.com/fibrosis-4-fib-4-index-liver-fibrosis Answer =1.24 Those with a FIB 4 65) have a low risk of advanced fibrosis and therefore can be managed in primary care. Management from the GP should concentrate on weight loss and management of metabolic risk factors including good diabetic control. Weight loss may include increasing exercise, decrease calories, use of a Mediterranean diet. Patients may find groups or apps helpful in this (this is covered in more detail in the NAFLD lecture). Also emphasis that if patient loses >10% of body weight can have complete resolution of inflammation Bloods should be repeated at least 3 yearly (but normally performed on an annual basis) and a FIB 4 recalculated

 

 

 

 

 

 

NICE guidelines suggest any patient who drinks > 50 units a week should be screened for significant liver disease with a fibroscan or bloods such as ELF test (estimation of liver fibrosis – blood test which looks for markers of fibrosis in the blood and gives an estimation of overall scarring)

 

 

 

 

 

 

Suspected NAFLD More tha .3 (<65yrs) T2DM/Meub•Q syndrome Stet-Eis •n Reed enzymes + lessthan or equal 1.30 (<65yrs) 2.0 (265 yrs) O KPa Low risk NAFL Pri ma ry care: lifestyle advice, treat metabolic Re-assess FIB-4/TE in 3 yrs ra nsiert elastograØy (TE) ver Lifestyle advice Treat metabolic risk Lifestyle advice Treat metabolic NAFLD directed therapi NAFLD HCC + Varices screen

 

 

Cirrhosis:

All patients with cirrhosis should be screened for osteoporosis with a DEXA scan

 - Screened for varices with an OGD

 - All patients (who would be fit enough to be considered for treatment) require 6 monthly HCC surveillance with USS (and most also measure alpha-feto protein

 

ascites/ peripheral oedema -

 This is normally done with diuretics, usually introduce spironolactone first and then add in furosemide if not relieved on spironolactone alone

 - This requires close monitoring of renal function and particularly sodium between increments of diuretics

- Some patients develop refractory ascites (persistent ascites despite maximal doses of diuretics) or renal function/ hyponatraemia preclude increasing diuretic dose further

- An option in these patients is large volume paracentesis (drainage of ascites) done as a day case procedure and can be repeated every few weeks

 - If requiring regular paracentesis can consider TIPSS (transjugular intrahepatic portosystemic shunt) as long as liver synthetic function good and not had episodes of encephalopathy (as risk of encephalopathy significantly increases post TIPSS). If TIPSS contraindicated alternative would be to consider liver transplant

 

Liver transplantation criteria for chronic liver disease include:

 

 - Poor synthetic function; this is assessed by the use of UKELD; this is a score that takes into account bilirubin, INR, creatinine and sodium https://www.mdcalc.com/unitedkingdom-model-end-stage-liver-disease-ukeld A UKELD of 49 or more is used as a threshold for eligibility; this confers a 9% chance of death within a year without transplant

- Persistent encephalopathy

- Refractory ascites (not suitable for TIPSS)

 - Hepatocellular cancer – there are size criteria for this to be eligible must be 1 lesion < 5cm or can have up to 5 lesions with all lesions < 3cm

 

If considering transplant, patients are put forward for an assessment where lots of factors are taken

into account including overall fitness, other co-morbidities etc. If accepted for transplant they are

then placed on the transplant waiting list.

 

 

 

 

 

24 December 2020

14:09

Degenerative cervical myelopathy

Degenerative cervical myelopathy (DCM) has a number of risk factors, which include smoking due to its effects on the intervertebral discs, genetics and occupation - those exposing patients to high axial loading [1].

 

The presentation of DCM is very variable. Early symptoms are often subtle and can vary in severity day to day, making the disease difficult to detect initially. However as a progressive condition, worsening, deteriorating or new symptoms should be a warning sign.

 

DCM symptoms can include any combination of [1]:

·         Pain (affecting the neck, upper or lower limbs)

·         Loss of motor function (loss of digital dexterity, preventing simple tasks such as holding a fork or doing up their shirt buttons, arm or leg weakness/stiffness leading to impaired gait and imbalance

·         Loss of sensory function causing numbness

·         Loss of autonomic function (urinary or faecal incontinence and/or impotence) - these can occur and do not necessarily suggest cauda equina syndrome in the absence of other hallmarks of that condition

·         Hoffman's sign: is a reflex test to assess for cervical myelopathy. It is performed by gently flicking one finger on a patient's hand. A positive test results in reflex twitching of the other fingers on the same hand in response to the flick.

The most common symptoms at presentation of DCM are unknown, but in one series 50% of patients were initially incorrectly diagnosed and sometimes treated for carpal tunnel syndrome [2].

 

An MRI of the cervical spine is the gold standard test where cervical myelopathy is suspected. It may reveal disc degeneration and ligament hypertrophy, with accompanying cord signal change.

 

All patients with degenerative cervical myelopathy should be urgently referred for assessment by specialist spinal services (neurosurgery or orthopaedic spinal surgery). This is due to the importance of early treatment. The timing of surgery is important, as any existing spinal cord damage can be permanent. Early treatment (within 6 months of diagnosis) offers the best chance of a full recovery but at present, most patients are presenting too late. In one study, patients averaged over 5 appointments before diagnosis, representing >2 years.

 

Currently, decompressive surgery is the only effective treatment. It has been shown to prevent disease progression. Close observation is an option for mild stable disease, but anything progressive or more severe requires surgery to prevent further deterioration. Physiotherapy should only be initiated by specialist services, as manipulation can cause more spinal cord damage.

 

References

1. Baron EM, Young WF. Cervical spondylotic myelopathy: a brief review of its pathophysiology, clinical course, and diagnosis. Neurosurgery. 2007 Jan;60(1 Supp1 1):S35-41.

2. Behrbalk E, Salame K, Regev GJ, Keynan O, Boszczyk B, Lidar Z. Delayed diagnosis of cervical spondylotic myelopathy by primary care physicians. Neurosurg Focus. 2013 Jul;35(1):E1.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Cluster headache

Cluster headaches are known to be one of the most painful conditions that patients can have the misfortune to suffer. The name relates to the pattern of the headaches - they typically occur in clusters lasting several weeks, with the clusters themselves typically once a year.

 

Cluster headaches are more common in men (3:1) and smokers. Alcohol may trigger an attack and there also appears to be a relation to nocturnal sleep.

 

Features

·         pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours

·         clusters typically last 4-12 weeks

·         intense sharp, stabbing pain around one eye (recurrent attacks 'always' affect same side)

·         patient is restless and agitated during an attack

·         accompanied by redness, lacrimation, lid swelling

·         nasal stuffiness

·         miosis and ptosis in a minority

Management

·         acute: 100% oxygen (80% response rate within 15 minutes), subcutaneous triptan (75% response rate within 15 minutes)

·         prophylaxis: verapamil is the drug of choice. There is also some evidence to support a tapering dose of prednisolone

·         NICE recommend seeking specialist advice from a neurologist if a patient develops cluster headaches with respect to neuroimaging

Some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Status epilepticus

This is a medical emergency. The priority is termination of seizure activity, which if prolonged will lead to irreversible brain damage.

 

Management

·         ABC

o    airway adjunct

o    oxygen

o    check blood glucose

·         First-line drugs are benzodiazepines such as diazepam or lorazepam

o    in the prehospital setting diazepam may be given rectally

o    in hospital IV lorazepam is generally used. This may be repeated once after 10-20 minutes

·         If ongoing (or 'established') status it is appropriate to start a second-line agent such as phenytoin or phenobarbital infusion

·         If no response ('refractory status') within 45 minutes from onset, then the best way to achieve rapid control of seizure activity is induction of general anaesthesia.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Parkinson's disease: management

Parkinsons disease should only be diagnosed, and management initiated, by a specialist with expertise in movement disorders. However, it is important for all doctors to be aware of the medications used in Parkinson's given the prevalence of this condition. NICE published guidelines in 2017 regarding the management of Parkinson's disease.

 

For first-line treatment:

·         if the motor symptoms are affecting the patient's quality of life: levodopa

·         if the motor symptoms are not affecting the patient's quality of life: dopamine agonist (non-ergot derived), levodopa or monoamine oxidase B (MAO‑B) inhibitor

Whilst all drugs used to treat Parkinson's can cause a wide variety of side-effects NICE produced tables to help with decision making:

 

 

 

Levodopa

Dopamine agonists

MAO‑B inhibitors

Motor symptoms

More improvement in motor symptoms

Less improvement in motor symptoms

Less improvement in motor symptoms

Activities of daily living

More improvement in activities of daily living

Less improvement in activities of daily living

Less improvement in activities of daily living

Motor complications

More motor complications

Fewer motor complications

Fewer motor complications

Adverse events

Fewer specified adverse events*

More specified adverse events*

Fewer specified adverse events*

* excessive sleepiness, hallucinations and impulse control disorders

 

If a patient continues to have symptoms despite optimal levodopa treatment or has developed dyskinesia then NICE recommend the addition of a dopamine agonist, MAO‑B inhibitor or catechol‑O‑methyl transferase (COMT) inhibitor as an adjunct. Again, NICE summarise the main points in terms of decision making:

 

 

 

Dopamine agonists

MAO‑B inhibitors

COMT inhibitors

Amantadine

Motor symptoms

Improvement in motor symptoms

Improvement in motor symptoms

Improvement in motor symptoms

No evidence of improvement in motor symptoms

Activities of daily living

Improvement in activities of daily living

Improvement in activities of daily living

Improvement in activities of daily living

No evidence of improvement in activities of daily living

Off time

More off‑time reduction

Off‑time reduction

Off‑time reduction

No studies reporting this outcome

Adverse events

Intermediate risk of adverse events

Fewer adverse events

More adverse events

No studies reporting this outcome

Hallucinations

More risk of hallucinations

Lower risk of hallucinations

Lower risk of hallucinations

No studies reporting this outcome

 

Specific points regarding Parkinson's medication

 

NICE reminds us of the risk of acute akinesia or neuroleptic malignant syndrome if medication is not taken/absorbed (for example due to gastroenteritis) and advise against giving patients a 'drug holiday' for the same reason.

 

Impulse control disorders have become a significant issue in recent years. These can occur with any dopaminergic therapy but are more common with:

·         dopamine agonist therapy

·         a history of previous impulsive behaviours

·         a history of alcohol consumption and/or smoking

If excessive daytime sleepiness develops then patients should not drive. Medication should be adjusted to control symptoms. Modafinil can be considered if alternative strategies fail.

 

If orthostatic hypotension develops then a medication review looking at potential causes should be done. If symptoms persist then midodrine (acts on peripheral alpha-adrenergic receptors to increase arterial resistance) can be considered.

 

Consider glycopyrronium bromide to manage drooling of saliva in people with Parkinson's disease.

 

Further information regarding specific anti-Parkinson's medication

 

 

Levodopa

·         usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of levodopa to dopamine

·         reduced effectiveness with time (usually by 2 years)

·         unwanted effects: dyskinesia (involuntary writhing movements), 'on-off' effect, dry mouth, anorexia, palpitations, postural hypotension, psychosis, drowsiness

·         no use in neuroleptic induced parkinsonism

·         it is important not to acutely stop levodopa, for example if a patient is admitted to hospital. If a patient with Parkinson's disease cannot take levodopa orally, they can be given a dopamine agonist patch as rescue medication to prevent acute dystonia

Dopamine receptor agonists

·         e.g. bromocriptine, ropinirole, cabergoline, apomorphine

·         ergot-derived dopamine receptor agonists (bromocriptine, cabergoline) have been associated with pulmonary, retroperitoneal and cardiac fibrosis. The Committee on Safety of Medicines advice that an echocardiogram, ESR, creatinine and chest x-ray should be obtained prior to treatment and patients should be closely monitored

·         patients should be warned about the potential for dopamine receptor agonists to cause impulse control disorders and excessive daytime somnolence

·         more likely than levodopa to cause hallucinations in older patients. Nasal congestion and postural hypotension are also seen in some patients

MAO-B (Monoamine Oxidase-B) inhibitors

·         e.g. selegiline

·         inhibits the breakdown of dopamine secreted by the dopaminergic neurons

Amantadine

·         mechanism is not fully understood, probably increases dopamine release and inhibits its uptake at dopaminergic synapses

·         side-effects include ataxia, slurred speech, confusion, dizziness and livedo reticularis

COMT (Catechol-O-Methyl Transferase) inhibitors

·         e.g. entacapone, tolcapone

·         COMT is an enzyme involved in the breakdown of dopamine, and hence may be used as an adjunct to levodopa therapy

·         used in conjunction with levodopa in patients with established PD

Antimuscarinics

·         block cholinergic receptors

·         now used more to treat drug-induced parkinsonism rather than idiopathic Parkinson's disease

·         help tremor and rigidity

·         e.g. procyclidine, benzotropine, trihexyphenidyl (benzhexol)

 

 

Image sourced from Wikipedia

Diagram showing the mechanism of action of Parkinson's drugs

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Stroke: types

The Bamford/Oxford Stroke Classification (also known as the Bamford Classification) classifies strokes based on the initial symptoms. A summary is as follows:

 

The following criteria should be assessed:

·         1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg

·         2. homonymous hemianopia

·         3. higher cognitive dysfunction e.g. dysphasia

Total anterior circulation infarcts (TACI, c. 15%)

·         involves middle and anterior cerebral arteries

·         all 3 of the above criteria are present

Partial anterior circulation infarcts (PACI, c. 25%)

·         involves smaller arteries of anterior circulation e.g. upper or lower division of middle cerebral artery

·         2 of the above criteria are present

Lacunar infarcts (LACI, c. 25%)

·         involves perforating arteries around the internal capsule, thalamus and basal ganglia

·         presents with 1 of the following:

·         1. unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.

·         2. pure sensory stroke.

·         3. ataxic hemiparesis

Posterior circulation infarcts (POCI, c. 25%)

·         involves vertebrobasilar arteries

·         presents with 1 of the following:

·         1. cerebellar or brainstem syndromes

·         2. loss of consciousness

·         3. isolated homonymous hemianopia

Other recognised patterns of stroke:

 

Lateral medullary syndrome (posterior inferior cerebellar artery)

·         aka Wallenberg's syndrome

·         ipsilateral: ataxia, nystagmus, dysphagia, facial numbness, cranial nerve palsy e.g. Horner's

·         contralateral: limb sensory loss

Weber's syndrome

·         ipsilateral III palsy

·         contralateral weakness

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Migraine: management

It should be noted that as a general rule 5-HT receptor agonists are used in the acute treatment of migraine whilst 5-HT receptor antagonists are used in prophylaxis. NICE produced guidelines in 2012 on the management of headache, including migraines.

 

Acute treatment

·         first-line: offer combination therapy with an oral triptan and an NSAID, or an oral triptan and paracetamol

·         for young people aged 12-17 years consider a nasal triptan in preference to an oral triptan

·         if the above measures are not effective or not tolerated offer a non-oral preparation of metoclopramide* or prochlorperazine and consider adding a non-oral NSAID or triptan

Prophylaxis

·         prophylaxis should be given if patients are experiencing 2 or more attacks per month. Modern treatment is effective in about 60% of patients.

·         NICE advise either topiramate or propranolol 'according to the person's preference, comorbidities and risk of adverse events'. Propranolol should be used in preference to topiramate in women of child bearing age as it may be teratogenic and it can reduce the effectiveness of hormonal contraceptives

·         if these measures fail NICE recommend 'a course of up to 10 sessions of acupuncture over 5-8 weeks'

·         NICE recommend: 'Advise people with migraine that riboflavin (400 mg once a day) may be effective in reducing migraine frequency and intensity for some people'

·         for women with predictable menstrual migraine treatment NICE recommend either frovatriptan (2.5 mg twice a day) or zolmitriptan (2.5 mg twice or three times a day) as a type of 'mini-prophylaxis'

·         pizotifen is no longer recommend. Adverse effects such as weight gain & drowsiness are common

 

*caution should be exercised with young patients as acute dystonic reactions may develop

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Motor neuron disease: features

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy.

 

There are a number of clues which point towards a diagnosis of motor neuron disease:

·         fasciculations

·         the absence of sensory signs/symptoms*

·         the mixture of lower motor neuron and upper motor neuron signs

·         wasting of the small hand muscles/tibialis anterior is common

Other features

·         doesn't affect external ocular muscles

·         no cerebellar signs

·         abdominal reflexes are usually preserved and sphincter dysfunction if present is a late feature

The diagnosis of motor neuron disease is clinical, but nerve conduction studies will show normal motor conduction and can help exclude a neuropathy. Electromyography shows a reduced number of action potentials with increased amplitude. MRI is usually performed to exclude the differential diagnosis of cervical cord compression and myelopathy

 

*vague sensory symptoms may occur early in the disease (e.g. limb pain) but 'never' sensory signs

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Myasthenia gravis

Myasthenia gravis is an autoimmune disorder resulting in insufficient functioning acetylcholine receptors. Antibodies to acetylcholine receptors are seen in 85-90% of cases*. Myasthenia is more common in women (2:1)

 

The key feature is muscle fatigability - muscles become progressively weaker during periods of activity and slowly improve after periods of rest:

·         extraocular muscle weakness: diplopia

·         proximal muscle weakness: face, neck, limb girdle

·         ptosis

·         dysphagia

Associations

·         thymomas in 15%

·         autoimmune disorders: pernicious anaemia, autoimmune thyroid disorders, rheumatoid, SLE

·         thymic hyperplasia in 50-70%

Investigations

·         single fibre electromyography: high sensitivity (92-100%)

·         CT thorax to exclude thymoma

·         CK normal

·         autoantibodies: around 85-90% of patients have antibodies to acetylcholine receptors. In the remaining patients, about about 40% are positive for anti-muscle-specific tyrosine kinase antibodies

·         Tensilon test: IV edrophonium reduces muscle weakness temporarily - not commonly used anymore due to the risk of cardiac arrhythmia

Management

·         long-acting acetylcholinesterase inhibitors

o    pyridostigmine is first-line

·         immunosuppression may be used if

o    prednisolone initially

o    azathioprine, cyclosporine, mycophenolate mofetil may also be used

·         thymectomy

Management of myasthenic crisis

·         plasmapheresis

·         intravenous immunoglobulins

*antibodies are less commonly seen in disease limited to the ocular muscles

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome is a rare but dangerous condition seen in patients taking antipsychotic medication. It carries a mortality of up to 10% and can also occur with atypical antipsychotics. It may also occur with dopaminergic drugs (such as levodopa) for Parkinson's disease, usually when the drug is suddenly stopped or the dose reduced.

 

The pathophysiology is unknown but one theory is that the dopamine blockade induced by antipsychotics triggers massive glutamate release and subsequent neurotoxicity and muscle damage.

 

It occurs within hours to days of starting an antipsychotic (antipsychotics are also known as neuroleptics, hence the name) and the typical features are:

·         pyrexia

·         muscle rigidity

·         autonomic lability: typical features include hypertension, tachycardia and tachypnoea

·         agitated delirium with confusion

A raised creatine kinase is present in most cases. Acute kidney injury (secondary to rhabdomyolysis) may develop in severe cases. A leukocytosis may also be seen

 

Management

·         stop antipsychotic

·         patients should be transferred to a medical ward if they are on a psychiatric ward and often they are nursed in intensive care units

·         IV fluids to prevent renal failure

·         dantrolene may be useful in selected cases

o    thought to work by decreasing excitation-contraction coupling in skeletal muscle by binding to the ryanodine receptor, and decreasing the release of calcium from the sarcoplasmic reticulum

·         bromocriptine, dopamine agonist, may also be used

 

 

 

Venn diagram showing contrasting serotonin syndrome with neuroleptic malignant syndrome. Note that both conditions can cause a raised creatine kinase (CK) but it tends to be more associated with NMS.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Parkinson's disease: features

Parkinson's disease is a progressive neurodegenerative condition caused by degeneration of dopaminergic neurons in the substantia nigra. This results in a classic triad of features: bradykinesia, tremor and rigidity. The symptoms of Parkinson's disease are characteristically asymmetrical.

 

Epidemiology

·         around twice as common in men

·         mean age of diagnosis is 65 years

Bradykinesia

·         poverty of movement also seen, sometimes referred to as hypokinesia

·         short, shuffling steps with reduced arm swinging

·         difficulty in initiating movement

Tremor

·         most marked at rest, 3-5 Hz

·         worse when stressed or tired, improves with voluntary movement

·         typically 'pill-rolling', i.e. in the thumb and index finger

Rigidity

·         lead pipe

·         cogwheel: due to superimposed tremor

Other characteristic features

·         mask-like facies

·         flexed posture

·         micrographia

·         drooling of saliva

·         psychiatric features: depression is the most common feature (affects about 40%); dementia, psychosis and sleep disturbances may also occur

·         impaired olfaction

·         REM sleep behaviour disorder

·         fatigue

·         autonomic dysfunction:

o    postural hypotension

Drug-induced parkinsonism has slightly different features to Parkinson's disease:

·         motor symptoms are generally rapid onset and bilateral

·         rigidity and rest tremor are uncommon

Diagnosis is usually clinical. However, if there is difficulty differentiating between essential tremor and Parkinson's disease NICE recommend considering 123I‑FP‑CIT single photon emission computed tomography (SPECT).

 

 

 

Image sourced from Wikipedia

A Lewy body (stained brown) in a brain cell of the substantia nigra in Parkinson's disease. The brown colour is positive immunohistochemistry staining for alpha-synuclein.

 

 

 

Image sourced from Wikipedia

Discoloration of the substantia nigra due to loss of pigmented nerve cells.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:17

Tuberous sclerosis

Tuberous sclerosis (TS) is a genetic condition of autosomal dominant inheritance. Like neurofibromatosis, the majority of features seen in TS are neurocutaneous.

 

Cutaneous features

·         depigmented 'ash-leaf' spots which fluoresce under UV light

·         roughened patches of skin over lumbar spine (Shagreen patches)

·         adenoma sebaceum (angiofibromas): butterfly distribution over nose

·         fibromata beneath nails (subungual fibromata)

·         café-au-lait spots* may be seen

Neurological features

·         developmental delay

·         epilepsy (infantile spasms or partial)

·         intellectual impairment

Also

·         retinal hamartomas: dense white areas on retina (phakomata)

·         rhabdomyomas of the heart

·         gliomatous changes can occur in the brain lesions

·         polycystic kidneys, renal angiomyolipomata

·         lymphangioleiomyomatosis: multiple lung cysts

 

 

 

Comparison of neurofibromatosis and tuberous sclerosis. Note that whilst they are both autosomal dominant neurocutaneous disorders there is little overlap otherwise

 

*these of course are more commonly associated with neurofibromatosis. However a 1998 study of 106 children with TS found café-au-lait spots in 28% of patients

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Brachial plexus

Origin

Anterior rami of C5 to T1

Sections of the plexus

·         Roots, trunks, divisions, cords, branches

·         Mnemonic:Real Teenagers Drink Cold Beer

Roots

·         Located in the posterior triangle

·         Pass between scalenus anterior and medius

Trunks

·         Located posterior to middle third of clavicle

·         Upper and middle trunks related superiorly to the subclavian artery

·         Lower trunk passes over 1st rib posterior to the subclavian artery

Divisions

Apex of axilla

Cords

Related to axillary artery

Diagram illustrating the branches of the brachial plexus

 

 

 

Image sourced from Wikipedia

Cutaneous sensation of the upper limb

 

 

Image sourced from Wikipedia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Multiple system atrophy

There are 2 predominant types of multiple system atrophy

·         1) MSA-P - Predominant Parkinsonian features

·         2) MSA-C - Predominant Cerebellar features

Shy-Drager syndrome is a type of multiple system atrophy.

 

Features

·         parkinsonism

·         autonomic disturbance

o    erectile dysfunction: often an early feature

o    postural hypotension

o    atonic bladder

·         cerebellar signs

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Psychogenic non-epileptic seizures

Psychogenic nonepileptic seizures are sometimes referred to as pseudoseizures.

 

Factors favouring pseudoseizures

·         pelvic thrusting

·         family member with epilepsy

·         much more common in females

·         crying after seizure

·         don't occur when alone

·         gradual onset

Factors favouring true epileptic seizures

·         tongue biting

·         raised serum prolactin*

Video telemetry is useful for differentiating

 

*why prolactin is raised following seizures is not fully understood. It is hypothesised that there is spread of electrical activity to the ventromedial hypothalamus, leading to release of a specific prolactin regulator into the hypophyseal portal system

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Subdural haemorrhage

A subdural haematoma is a collection of blood deep to the dural layer of the meninges. The blood is not within the substance of the brain and is therefore called an ‘extra-axial’ or ‘extrinsic’ lesion. They can be unilateral or bilateral.

 

Subdural haematomas can be classified in terms of their age:

·         Acute

·         Subacute

·         Chronic

Although the collection of blood is within the same anatomical compartment, acute and chronic subdurals have important differences in terms of their mechanisms, associated clinical features and management:

 

Acute subdural haematoma

 

An acute subdural haematoma is a collection of fresh blood within the subdural space and is most commonly caused by high-impact trauma. Since it is associated with high-impact injuries, there is often other brain underlying brain injuries.

 

There is a spectrum of severity of symptoms and presentation depending on the size of the compressive acute subdural haematoma and the associated injuries. Presentation ranges from an incidental finding in trauma to severe coma and coning due to herniation.

 

CT imaging is the first-line investigation and will show a crescentic collection, not limited by suture lines. They will appear hyperdense (bright) in comparison to the brain. Large acute subdural haematomas will push on the brain (‘mass effect’) and cause midline shift or herniation.

 

Small or incidental acute subdurals can be observed conservatively. Surgical options include monitoring of intracranial pressure and decompressive craniectomy.

 

 

Chronic subdural haematoma

 

A chronic subdural haematoma is a collection of blood within the subdural space that has been present for weeks to months.

 

Rupture of the small bridging veins within the subdural space rupture and cause slow bleeding. Elderly and alcoholic patients are particularly at risk of subdural haematomas since they have brain atrophy and therefore fragile or taut bridging veins.

 

Presentation is typically a several week to month progressive history of either confusion, reduced consciousness or neurological deficit.

 

Infants also have fragile bridging veins and can rupture in shaken baby syndrome.

 

On CT imaging they similarly are crescentic in shape, not restricted by suture lines and compress the brain (‘mass effect’). In contrast to acute subdurals, chronic subdurals are hypodense (dark) compared to the substance of the brain.

 

If the chronic subdural is an incidental finding or if it is small in size with no associated neurological deficit then it can be managed conservatively with the hope that it will dissolve with time. If the patient is confused, has an associated neurological deficit or has severe imaging findings then surgical decompression with burr holes is required.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Third nerve palsy

Features

·         eye is deviated 'down and out'

·         ptosis

·         pupil may be dilated (sometimes called a 'surgical' third nerve palsy)

Causes

·         diabetes mellitus

·         vasculitis e.g. temporal arteritis, SLE

·         false localizing sign* due to uncal herniation through tentorium if raised ICP

·         posterior communicating artery aneurysm

o    pupil dilated

o    often associated pain

·         cavernous sinus thrombosis

·         Weber's syndrome: ipsilateral third nerve palsy with contralateral hemiplegia -caused by midbrain strokes

·         other possible causes: amyloid, multiple sclerosis

*this term is usually associated with sixth nerve palsies but it may be used for a variety of neurological presentations

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Trigeminal neuralgia

Trigeminal neuralgia is a pain syndrome characterised by severe unilateral pain. The vast majority of cases are idiopathic but compression of the trigeminal roots by tumours or vascular problems may occur.

 

The International Headache Society defines trigeminal neuralgia as:

·         a unilateral disorder characterised by brief electric shock-like pains, abrupt in onset and termination, limited to one or more divisions of the trigeminal nerve

·         the pain is commonly evoked by light touch, including washing, shaving, smoking, talking, and brushing the teeth (trigger factors), and frequently occurs spontaneously

·         small areas in the nasolabial fold or chin may be particularly susceptible to the precipitation of pain (trigger areas)

·         the pains usually remit for variable periods

NICE Clinical Knowledge Summaries list the following as red flag symptoms and signs suggesting a serious underlying cause:

·         Sensory changes

·         Deafness or other ear problems

·         History of skin or oral lesions that could spread perineurally

·         Pain only in the ophthalmic division of the trigeminal nerve (eye socket, forehead, and nose), or bilaterally

·         Optic neuritis

·         A family history of multiple sclerosis

·         Age of onset before 40 years

Management

·         carbamazepine is first-line

·         failure to respond to treatment or atypical features (e.g. < 50 years old) should prompt referral to neurology

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Epilepsy: localising features of focal seizures

Location

Typical seizure type

Temporal lobe (HEAD)

Hallucinations (auditory/gustatory/olfactory), Epigastric rising/Emotional, Automatisms (lip smacking/grabbing/plucking), Deja vu/Dysphasia post-ictal)

Frontal lobe (motor)

Head/leg movements, posturing, post-ictal weakness, Jacksonian march

Parietal lobe (sensory)

Paraesthesia

Occipital lobe (visual)

Floaters/flashes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Facial nerve palsy

The facial nerve is the main nerve supplying the structures of the second embryonic branchial arch. It is predominantly an efferent nerve to the muscles of facial expression, digastric muscle and also to many glandular structures. It contains a few afferent fibres which originate in the cells of its genicular ganglion and are concerned with taste.

 

Supply - 'face, ear, taste, tear'

·         face: muscles of facial expression

·         ear: nerve to stapedius

·         taste: supplies anterior two-thirds of tongue

·         tear: parasympathetic fibres to lacrimal glands, also salivary glands

Causes of bilateral facial nerve palsy

·         sarcoidosis

·         Guillain-Barre syndrome

·         Lyme disease

·         bilateral acoustic neuromas (as in neurofibromatosis type 2)

·         as Bell's palsy is relatively common it accounts for up to 25% of cases f bilateral palsy, but this represents only 1% of total Bell's palsy cases

Causes of unilateral facial nerve palsy - as above plus

 

 

Lower motor neuron

·         Bell's palsy

·         Ramsay-Hunt syndrome (due to herpes zoster)

·         acoustic neuroma

·         parotid tumours

·         HIV

·         multiple sclerosis*

·         diabetes mellitus

Upper motor neuron

·         stroke

LMN vs. UMN

·         upper motor neuron lesion 'spares' upper face i.e. forehead

·         lower motor neuron lesion affects all facial muscles

*may also cause an UMN palsy

 

Path

 

Subarachnoid path

·         Origin: motor- pons, sensory- nervus intermedius

·         Pass through the petrous temporal bone into the internal auditory meatus with the vestibulocochlear nerve. Here they combine to become the facial nerve.

Facial canal path

·         The canal passes superior to the vestibule of the inner ear

·         At the medial aspect of the middle ear, it becomes wider and contains the geniculate ganglion.

- 3 branches:

·         1. greater petrosal nerve

·         2. nerve to stapedius

·         3. chorda tympani

Stylomastoid foramen

·         Passes through the stylomastoid foramen (tympanic cavity anterior and mastoid antrum posteriorly)

·         Posterior auricular nerve and branch to posterior belly of digastric and stylohyoid muscle

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Neuropathic pain

Neuropathic pain may be defined as pain which arises following damage or disruption of the nervous system. It is often difficult to treat and responds poorly to standard analgesia.

 

Examples include:

·         diabetic neuropathy

·         post-herpetic neuralgia

·         trigeminal neuralgia

·         prolapsed intervertebral disc

NICE updated their guidance on the management of neuropathic pain in 2013:

·         first-line treatment*: amitriptyline, duloxetine, gabapentin or pregabalin

o    if the first-line drug treatment does not work try one of the other 3 drugs

o    in contrast to standard analgesics, drugs for neuropathic pain are typically used as monotherapy, i.e. if not working then drugs should be switched, not added

·         tramadol may be used as 'rescue therapy' for exacerbations of neuropathic pain

·         topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)

·         pain management clinics may be useful in patients with resistant problems

*please note that for some specific conditions the guidance may vary. For example carbamazepine is used first-line for trigeminal neuralgia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Peripheral neuropathy

Peripheral neuropathy may be divided into conditions which predominately cause a motor or sensory loss

 

Predominately motor loss

·         Guillain-Barre syndrome

·         porphyria

·         lead poisoning

·         hereditary sensorimotor neuropathies (HSMN) - Charcot-Marie-Tooth

·         chronic inflammatory demyelinating polyneuropathy (CIDP)

·         diphtheria

Predominately sensory loss

·         diabetes

·         uraemia

·         leprosy

·         alcoholism

·         vitamin B12 deficiency

·         amyloidosis

Alcoholic neuropathy

·         secondary to both direct toxic effects and reduced absorption of B vitamins

·         sensory symptoms typically present prior to motor symptoms

Vitamin B12 deficiency

·         subacute combined degeneration of spinal cord

·         dorsal column usually affected first (joint position, vibration) prior to distal paraesthesia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Phenytoin

Phenytoin is used in the management of seizures.

 

Mechanism of action

·         binds to sodium channels increasing their refractory period

Adverse effects

 

Phenytoin is associated with a large number of adverse effects. These may be divided into acute, chronic, idiosyncratic and teratogenic. Phenytoin is also an inducer of the P450 system.

 

Acute

·         initially: dizziness, diplopia, nystagmus, slurred speech, ataxia

·         later: confusion, seizures

Chronic

·         common: gingival hyperplasia (secondary to increased expression of platelet derived growth factor, PDGF), hirsutism, coarsening of facial features, drowsiness

·         megaloblastic anaemia (secondary to altered folate metabolism)

·         peripheral neuropathy

·         enhanced vitamin D metabolism causing osteomalacia

·         lymphadenopathy

·         dyskinesia

Idiosyncratic

·         fever

·         rashes, including severe reactions such as toxic epidermal necrolysis

·         hepatitis

·         Dupuytren's contracture*

·         aplastic anaemia

·         drug-induced lupus

Teratogenic

·         associated with cleft palate and congenital heart disease

Monitoring

 

Phenytoin levels do not need to be monitored routinely but trough levels, immediately before dose should be checked if:

·         adjustment of phenytoin dose

·         suspected toxicity

·         detection of non-adherence to the prescribed medication

*although not listed in the BNF

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Stroke by anatomy

Site of the lesion

Associated effects

Anterior cerebral artery

Contralateral hemiparesis and sensory loss, lower extremity > upper

Middle cerebral artery

Contralateral hemiparesis and sensory loss, upper extremity > lower

Contralateral homonymous hemianopia

Aphasia

Posterior cerebral artery

Contralateral homonymous hemianopia with macular sparing

Visual agnosia

Weber's syndrome (branches of the posterior cerebral artery that supply the midbrain)

Ipsilateral CN III palsy

Contralateral weakness of upper and lower extremity

Posterior inferior cerebellar artery (lateral medullary syndrome, Wallenberg syndrome)

Ipsilateral: facial pain and temperature loss

Contralateral: limb/torso pain and temperature loss

Ataxia, nystagmus

Anterior inferior cerebellar artery (lateral pontine syndrome)

Symptoms are similar to Wallenberg's (see above), but:

Ipsilateral: facial paralysis and deafness

Retinal/ophthalmic artery

Amaurosis fugax

Basilar artery

'Locked-in' syndrome

 

Lacunar strokes

·         present with either isolated hemiparesis, hemisensory loss or hemiparesis with limb ataxia

·         strong association with hypertension

·         common sites include the basal ganglia, thalamus and internal capsule

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Syringomyelia

Syringomyelia (‘syrinx’ for short) describes a collection of cerebrospinal fluid within the spinal cord.

 

Syringobulbia is a similar phenomenon in which there is a fluid-filled cavity within the medulla of the brainstem. This is often an extension of the syringomyelia but in rare cases can be an isolated finding.

 

Causes include:

·         a Chiari malformation: strong association

·         trauma

·         tumours

·         idiopathic

The classical presentation of a syrinx is a patient who has a ‘cape-like’ (neck and arms) loss of sensation to temperature but preservation of light touch, proprioception and vibration. Classic examples are of patients who accidentally burn their hands without realising. This is due to the crossing spinothalamic tracts in the anterior commissure of the spinal cord being the first tracts to be affected. Other symptoms and signs include spastic weakness (predominantly of the upper limbs), paraesthesia, neuropathic pain, upgoing plantars and bowel and bladder dysfunction. Scoliosis will occur over a matter of years if the syrinx is not treated. It may cause a Horner’s syndrome due to compression of the sympathetic chain, but this is rare.

 

Investigation requires a full spine MRI with contrast to exclude a tumour or tethered cord. A brain MRI is also needed to exclude a Chiari malformation.

 

Treatment will be directed at treating the cause of the syrinx. In patients with a persistent or symptomatic syrinx, a shunt into the syrinx can be placed.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Wernicke's encephalopathy

Wernicke's encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion may occur. In Wernicke's encephalopathy petechial haemorrhages occur in a variety of structures in the brain including the mamillary bodies and ventricle walls.

 

Features

·         nystagmus (the most common ocular sign)

·         ophthalmoplegia

·         ataxia

·         confusion, altered GCS

·         peripheral sensory neuropathy

Investigations

·         decreased red cell transketolase

·         MRI

Treatment is with urgent replacement of thiamine

 

Relationship with Korsakoff syndrome

 

If not treated Korsakoff's syndrome may develop as well. This is termed Wernicke-Korsakoff syndrome and is characterised by the addition of antero- and retrograde amnesia and confabulation in addition to the above symptoms.

 

 

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

5-HT3 antagonists

5-HT3 antagonists are antiemetics used mainly in the management of chemotherapy-related nausea. They mainly act in the chemoreceptor trigger zone area of the medulla oblongata.

 

Examples

·         ondansetron

·         granisetron

Adverse effects

·         constipation is common

·         prolonged QT interval

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Brain tumours

The majority of adult tumours are supratentorial, where as the majority of childhood tumours are infratentorial.

 

 

Type of tumour

Features

Metastases

Metastatic brain cancer is the most common form of brain tumours. They are often multiple and not treatable with surgical intervention.

 

Tumours that most commonly spread to the brain include:

·         lung (most common)

·         breast

·         bowel

·         skin (namely melanoma)

·         kidney

Gliolastoma multiforme

• Glioblastoma is the most common primary tumour in adults and is associated with a poor prognosis (~ 1yr).

 

• On imaging they are solid tumours with central necrosis and a rim that enhances with contrast. Disruption of the blood-brain barrier and therefore are associated with vasogenic oedema.

 

• Histology: Pleomorphic tumour cells border necrotic areas

 

• Treatment is surgical with postoperative chemotherapy and/or radiotherapy. Dexamethasone is used to treat the oedema.

Meningioma

• The second most common primary brain tumour in adults

 

• Meningiomas are typically benign, extrinsic tumours of the central nervous system. They arise from the dura mater of the meninges and cause symptoms by compression rather than invasion.

 

• They typically are located at the falx cerebri, superior sagittal sinus, convexity or skull base.

 

• Histology: Spindle cells in concentric whorls and calcified psammoma bodies

 

• Investigation is with CT (will show contrast enhancement) and MRI, and treatment will involve either observation, radiotherapy or surgical resection.

Vestibular schwannoma

• A vestibular schwannoma (previously termed acoustic neuroma) is a benign tumour arising from the eighth cranial nerve (vestibulocochlear nerve). Often seen in the cerebellopontine angle. It presents with hearing loss, facial nerve palsy (due to compression of the nearby facial nerve) and tinnitus.

 

• Neurofibromatosis type 2 is associated with bilateral vestibular schwannomas.

 

• Histology: Antoni A or B patterns are seen. Verocay bodies (acellular areas surrounded by nuclear palisades)

 

• Treatment may involve observation, radiotherapy or surgery.

Pilocytic astrocytoma

• The most common primary brain tumour in children

• Histology: Rosenthal fibres (corkscrew eosinophilic bundle)

Medulloblastoma

• A medulloblastoma is an aggressive paediatric brain tumour that arises within the infratentorial compartment. It spreads through the CSF system. Treatment is surgical resection and chemotherapy.

 

• Histology: Small, blue cells. Rosette pattern of cells with many mitotic figures

Ependymoma

• Commonly seen in the 4th ventricle

• May cause hydrocephalus

• Histology: perivascular pseudorosettes

Oligodendroma

• Benign, slow-growing tumour common in the frontal lobes

• Histology: Calcifications with 'fried-egg' appearance

Haemangioblastoma

• Vascular tumour of the cerebellum

• Associated with von Hippel-Lindau syndrome

• Histology: foam cells and high vascularity

Pituitary adenoma

• Pituitary adenomas are benign tumours of the pituitary gland. They are either secretory (producing a hormone in excess) or non-secretory. They may be divided into microadenomas (smaller than 1cm) or macroadenoma (larger than 1cm).

 

• Patients will present with the consequences of hormone excess (e.g. Cushing’s due to ACTH, or acromegaly due to GH) or depletion. Compression of the optic chiasm will cause a bitemporal hemianopia due to the crossing nasal fibers.

 

• Investigation requires a pituitary blood profile and MRI. Treatment can either be hormonal or surgical (e.g. transphenoidal resection).

Craniopharyngioma

• Most common paediatric supratentorial tumour

 

• A craniopharyngioma is a solid/cystic tumour of the sellar region that is derived from the remnants of Rathke’s pouch. It is common in children, but can present in adults also. It may present with hormonal disturbance, symptoms of hydrocephalus or bitemporal hemianopia.

 

• Histology: Derived from remnants of Rathke pouch

 

• Investigation requires pituitary blood profile and MRI. Treatment is typically surgical with or without postoperative radiotherapy.

 

 

© Image used on license from Radiopaedia

Meningioma - MRI showing the typical well-circumscribed appearance. A dural tail can be where the tumour 'connects' to the dura. It is seen in around 65% of meningiomas.

 

 

© Image used on license from Radiopaedia

Glioblastoma multiforme - CT showing a peripherally enhancing lesion within the left frontal lobe. Note the contrast to the more homogenous meningioma above.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Carbamazepine

Carbamazepine is chemically similar to the tricyclic antidepressant drugs. It is most commonly used in the treatment of epilepsy, particularly partial seizures, where carbamazepine remains a first-line medication. Other uses include

·         trigeminal neuralgia

·         bipolar disorder

Mechanism of action

·         binds to sodium channels increases their refractory period

Adverse effects

·         P450 enzyme inducer

·         dizziness and ataxia

·         drowsiness

·         headache

·         visual disturbances (especially diplopia)

·         Steven-Johnson syndrome

·         leucopenia and agranulocytosis

·         hyponatraemia secondary to syndrome of inappropriate ADH secretion

Carbamazepine is known to exhibit autoinduction, hence when patients start carbamazepine they may see a return of seizures after 3-4 weeks of treatment.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:18

Common peroneal nerve lesion

The sciatic nerve divides into the tibial and common peroneal nerves. Injury often occurs at the neck of the fibula

 

The most characteristic feature of a common peroneal nerve lesion is foot drop.

 

Other features include:

·         weakness of foot dorsiflexion

·         weakness of foot eversion

·         weakness of extensor hallucis longus

·         sensory loss over the dorsum of the foot and the lower lateral part of the leg

·         wasting of the anterior tibial and peroneal muscles

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

Meningitis

Most common adult cause (mortality)

·         meningococcus (10%)

·         pneumococcus (25%)

Diagnosis

·         if partially treated with antibiotics, negative CSF culture, but glucose, protein and white cells unchanged

Neurological sequalae

·         sensorineural hearing loss (most common)

·         other neurological: epilepsy, paralysis

·         infective: sepsis, intracerebral abscess

·         pressure: brain herniation, hydrocephalus

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

 

24 December 2020

17:18

Meningitis

Most common adult cause (mortality)

·         meningococcus (10%)

·         pneumococcus (25%)

Diagnosis

·         if partially treated with antibiotics, negative CSF culture, but glucose, protein and white cells unchanged

Neurological sequalae

·         sensorineural hearing loss (most common)

·         other neurological: epilepsy, paralysis

·         infective: sepsis, intracerebral abscess

·         pressure: brain herniation, hydrocephalus

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Migraine: diagnostic criteria

The International Headache Society has produced the following diagnostic criteria for migraine without aura:

 

 

Point

Criteria

A

At least 5 attacks fulfilling criteria B-D

B

Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)

C

Headache has at least two of the following characteristics:

·         1. unilateral location*

·         2. pulsating quality (i.e., varying with the heartbeat)

·         3. moderate or severe pain intensity

·         4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)

D

During headache at least one of the following:

·         1. nausea and/or vomiting*

·         2. photophobia and phonophobia

E

Not attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder)

*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.

 

Migraine with aura (seen in around 25% of migraine patients) tends to be easier to diagnose with a typical aura being progressive in nature and may occur hours prior to the headache. Typical aura include a transient hemianopic disturbance or a spreading scintillating scotoma ('jagged crescent'). Sensory symptoms may also occur

 

If we compare these guidelines to the NICE criteria the following points are noted:

·         NICE suggests migraines may be unilateral or bilateral

·         NICE also give more detail about typical auras:

Auras may occur with or without headache and:

·         are fully reversible

·         develop over at least 5 minutes

·         last 5-60 minutes

The following aura symptoms are atypical and may prompt further investigation/referral;

·         motor weakness

·         double vision

·         visual symptoms affecting only one eye

·         poor balance

·         decreased level of consciousness.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Multiple sclerosis

Multiple sclerosis is chronic cell-mediated autoimmune disorder characterised by demyelination in the central nervous system.

 

Epidemiology

·         3 times more common in women

·         most commonly diagnosed in people aged 20-40 years

·         much more common at higher latitudes (5 times more common than in tropics)

Genetics

·         monozygotic twin concordance = 30%

·         dizygotic twin concordance = 2%

A variety of subtypes have been identified:

 

Relapsing-remitting disease

·         most common form, accounts for around 85% of patients

·         acute attacks (e.g. last 1-2 months) followed by periods of remission

Secondary progressive disease

·         describes relapsing-remitting patients who have deteriorated and have developed neurological signs and symptoms between relapses

·         around 65% of patients with relapsing-remitting disease go on to develop secondary progressive disease within 15 years of diagnosis

·         gait and bladder disorders are generally seen

Primary progressive disease

·         accounts for 10% of patients

·         progressive deterioration from onset

·         more common in older people

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Neurofibromatosis

There are two types of neurofibromatosis, NF1 and NF2. Both are inherited in an autosomal dominant fashion

 

NF1 is also known as von Recklinghausen's syndrome. It is caused by a gene mutation on chromosome 17 which encodes neurofibromin and affects around 1 in 4,000

 

NF2 is caused by gene mutation on chromosome 22 and affects around 1 in 100,000

 

Features

 

 

NF1

NF2

Café-au-lait spots (>= 6, 15 mm in diameter)

Axillary/groin freckles

Peripheral neurofibromas

Iris hamatomas (Lisch nodules) in > 90%

Scoliosis

Pheochromocytomas

Bilateral vestibular schwannomas

Multiple intracranial schwannomas, mengiomas and ependymomas

 

 

 

Comparison of neurofibromatosis and tuberous sclerosis. Note that whilst they are both autosomal dominant neurocutaneous disorders there is little overlap otherwise

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Normal pressure hydrocephalus

Normal pressure hydrocephalus is a reversible cause of dementia seen in elderly patients. It is thought to be secondary to reduced CSF absorption at the arachnoid villi. These changes may be secondary to head injury, subarachnoid haemorrhage or meningitis.

 

A classical triad of features is seen

·         urinary incontinence

·         dementia and bradyphrenia

·         gait abnormality (may be similar to Parkinson's disease)

It is thought around 60% of patients will have all 3 features at the time of diagnosis. Symptoms typically develop over a few months.

 

Imaging

·         hydrocephalus with an enlarged fourth ventricle

·         in addition to the ventriculomegaly there is typically an absence of substantial sulcal atrophy

Management

·         ventriculoperitoneal shunting

·         around 10% of patients who have shunts experience significant complications such as seizures, infection and intracerebral haemorrhages

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Radial nerve

Continuation of posterior cord of the brachial plexus (root values C5 to T1)

 

Path

·         In the axilla: lies posterior to the axillary artery on subscapularis, latissimus dorsi and teres major.

·         Enters the arm between the brachial artery and the long head of triceps (medial to humerus).

·         Spirals around the posterior surface of the humerus in the groove for the radial nerve.

·         At the distal third of the lateral border of the humerus it then pierces the intermuscular septum and descends in front of the lateral epicondyle.

·         At the lateral epicondyle it lies deeply between brachialis and brachioradialis where it then divides into a superficial and deep terminal branch.

·         Deep branch crosses the supinator to become the posterior interosseous nerve.

 

 

Image sourced from Wikipedia

In the image above the relationships of the radial nerve can be appreciated

Regions innervated

 

 

Motor (main nerve)

·         Triceps

·         Anconeus

·         Brachioradialis

·         Extensor carpi radialis

Motor (posterior interosseous branch)

·         Supinator

·         Extensor carpi ulnaris

·         Extensor digitorum

·         Extensor indicis

·         Extensor digiti minimi

·         Extensor pollicis longus and brevis

·         Abductor pollicis longus

Sensory

The area of skin supplying the proximal phalanges on the dorsal aspect of the hand is supplied by the radial nerve (this does not apply to the little finger and part of the ring finger)

Muscular innervation and effect of denervation

 

Anatomical location

Muscle affected

Effect of paralysis

Shoulder

Long head of triceps

Minor effects on shoulder stability in abduction

Arm

Triceps

Loss of elbow extension

Forearm

Supinator

Brachioradialis

Extensor carpi radialis longus and brevis

Weakening of supination of prone hand and elbow flexion in mid prone position

Patterns of damage

·         wrist drop

·         sensory loss to small area between the dorsal aspect of the 1st and 2nd metacarpals

Axillary damage

·         as above

·         paralysis of triceps

 

 

Image sourced from Wikipedia

The cutaneous sensation of the upper limb- illustrating the contribution of the radial nerve

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Thoracic outlet syndrome

Thoracic outlet syndrome (TOS) is a disorder involving compression of brachial plexus, subclavian artery or vein at the site of the thoracic outlet. TOS can be neurogenic or vascular; the former accounts for 90% of the cases.

 

Epidemiology

·         given the lack of widely agreed diagnostic criteria, the epidemiology of TOS is not well documented

·         patients are typically young thin women possessing long neck and drooping shoulders

·         peak onset occurs in the 4th decade

Aetiology

·         TOS develops when neck trauma occurs to individuals with anatomical predispositions

·         neck trauma can either be a single acute incident or repeated stresses

·         anatomical anomalies can either be in the form of soft tissue (70%) or osseous structures (30%)

·         a well-known osseous anomaly is the presence of cervical rib

·         examples of soft tissue causes are scalene muscle hypertrophy and anomalous bands

·         there is usually a history of neck trauma preceding TOS

Clinical presentation of neurogenic TOS

·         painless muscle wasting of hand muscles, with patients complaining of hand weakness e.g. grasping

·         sensory symptoms such as numbness and tingling may be present

·         if autonomic nerves are involved, the patient may experience cold hands, blanching or swelling

Clinical presentation of vascular TOS:

·         subclavian vein compression leads to painful diffuse arm swelling with distended veins

·         subclavian artery compression leads to painful arm claudication and in severe cases, ulceration and gangrene

Examinations:

·         neurological examination and musculoskeletal examination are necessary

·         stress manoeuvres such as Adson's manoeuvres may be attempted although they have limited utility

·         careful examinations should aim to rule out other pathologies of the cervical spine, the shoulder or peripheral nerves. For instance, cervical radiculopathy, shoulder injuries and carpal tunnel syndrome

Investigations:

·         chest and cervical spine plain radiographs to check for any obvious osseous abnormalities e.g. cervical ribs, exclude malignant tumours or other differentials e.g. cervical spine degenerative changes

·         other imaging modalities may be helpful e.g. CT or MRI to rule out cervical root lesions

·         venography or angiography may be helpful in vascular TOS

·         an anterior scalene block may be used to confirm neurogenic TOS and check the likelihood of successful surgical treatment

Treatment:

·         there is a limited evidence base

·         conservative management with education, rehabilitation, physiotherapy, or taping is typically the first-line management for neurogenic TOS

·         surgical decompression is warranted where conservative management has failed especially if there is a physical anomaly. Early intervention may prevent brachial plexus degeneration

·         in vascular TOS, surgical treatment may be preferred

·         other therapies being investigated include botox injection

Further reading

1. Huang JH, Zager EL; Thoracic outlet syndrome. Neurosurgery. 2004 Oct55(4):897-902

2. Al-Hashel JY, El Shorbgy AA, Ahmed SF, et al; Early versus Late Surgical Treatment for Neurogenic Thoracic Outlet Syndrome. ISRN Neurol. 2013 Sep 102013:673020. doi: 10.1155/2013/673020.

3. Kuhn, J. E., Lebus V, G. F., & Bible, J. (2015). Thoracic outlet syndrome. Journal of the American Academy of Orthopaedic Surgeons, 23(4), 222-232. https://doi.org/10.5435/JAAOS-D-13-00215

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Aphasia

The table below lists the major types of aphasia. Remember that dysarthria is different and refers to a motor speech disorder.

 

 

Type of aphasia

Notes

Wernicke's (receptive) aphasia

Due to a lesion of the superior temporal gyrus. It is typically supplied by the inferior division of the left MCA

 

This area 'forms' the speech before 'sending it' to Broca's area. Lesions result in sentences that make no sense, word substitution and neologisms but speech remains fluent

 

Comprehension is impaired

Broca's (expressive) aphasia

Due to a lesion of the inferior frontal gyrus. It is typically supplied by the superior division of the left MCA

 

Speech is non-fluent, laboured, and halting

 

Comprehension is normal

Conduction aphasia

Classically due to a stroke affecting the arcuate fasiculus - the connection between Wernicke's and Broca's area

 

Speech is fluent but repetition is poor. Aware of the errors they are making

 

Comprehension is normal

Global aphasia

Large lesion affecting all 3 of the above areas resulting in severe expressive and receptive aphasia

 

May still be able to communicate using gestures

 

 

 

Diagram showing the main types of aphasia

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Arnold-Chiari malformation

Arnold-Chiari malformation describes the downward displacement, or herniation, of the cerebellar tonsils through the foramen magnum. Malformations may be congenital or acquired through trauma.

 

Features

·         non-communicating hydrocephalus may develop as a result of obstruction of cerebrospinal fluid (CSF) outflow

·         headache

·         syringomyelia

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Autonomic dysreflexia

This clinical syndrome occurs in patients who have had a spinal cord injury at, or above T6 spinal level. Briefly, afferent signals, most commonly triggered by faecal impaction or urinary retention (but many other triggers have been reported) cause a sympathetic spinal reflex via thoracolumbar outflow. The usual, centrally mediated, parasympathetic response however is prevented by the cord lesion. The result is an unbalanced physiological response, characterised by extreme hypertension, flushing and sweating above the level of the cord lesion, agitation, and in untreated cases severe consequences of extreme hypertension have been reported, e.g. haemorrhagic stroke.

 

Management of autonomic dysreflexia involves removal/control of the stimulus and treatment of any life-threatening hypertension and/or bradycardia.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Dermatomes

The table below lists the major dermatome landmarks:

 

 

Nerve root

Landmark

Mnemonics

C2

Posterior half of the skull (cap)

 

C3

High turtleneck shirt

 

C4

Low-collar shirt

 

C5

Ventral axial line of upper limb

 

C6

Thumb + index finger

Make a 6 with your left hand by touching the tip of the thumb & index finger together - C6

C7

Middle finger + palm of hand

 

C8

Ring + little finger

 

T4

Nipples

T4 at the Teat Pore

T5

Inframammary fold

 

T6

Xiphoid process

 

T10

Umbilicus

BellybuT-TEN

L1

Inguinal ligament

L for ligament, 1 for 1nguinal

L4

Knee caps

Down on aLL fours - L4

L5

Big toe, dorsum of foot (except lateral aspect)

L5 = Largest of the 5 toes

S1

Lateral foot, small toe

S1 = the smallest one

S2, S3

Genitalia

 

 

 

 

 

 

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

17:19

Epilepsy: a very basic introduction

Epilepsy is a common neurological condition characterised by recurrent seizures. There are around 500,000 people in the UK with epilepsy, of whom around two-thirds achieve satisfactory seizure control with antiepileptic medication.

 

Epilepsy most commonly occurs in isolation although certain conditions have an association with epilepsy:

·         cerebral palsy: around 30% have epilepsy

·         tuberous sclerosis

·         mitochondrial diseases

It should be remembered that epilepsy is not the only reason people have seizures. The table below shows some of the more common causes of recurrent seizures seen in clinical practice. Patients may of course develop one-off seizures following any insult to the brain, for example infection, trauma or metabolic disturbance.

 

 

Disorder

Notes

Febrile convulsions

·         typically occur in children between the ages of 6 months and 5 years

·         around 3% of children will have at least one febrile convulsion

·         usually occur early in a viral infection as the temperature rises rapidly

·         seizures are typically brief and generalised tonic/tonic-clonic in nature

Alcohol withdrawal seizures

·         occur in patients with a history of alcohol excess who suddenly stop drinking, for example following admission to hospital

·         chronic alcohol consumption enhances GABA mediated inhibition in the CNS (similar to benzodiazepines) and inhibits NMDA-type glutamate receptors.Alcohol withdrawal is thought to be lead to the opposite (decreased inhibitory GABA and increased NMDA glutamate transmission)

·         the peak incidence of seizures is at around 36 hours following cessation of drinking

·         patients are often given benzodiazepines following cessation of drinking to reduce the risk

Psychogenic non-epileptic seizures

·         previously termed pseudoseizures, this term describes patients who present with epileptic-like seizures but do not have characteristic electrical discharges

·         patients may have a history of mental health problems or a personality disorder

Classification of seizures

 

The basic classification of epilepsy has changed in recent years. The new basic seizure classification is based on 3 key features:

·         1. Where seizures begin in the brain

·         2. Level of awareness during a seizure (important as can affect safety during seizure)

·         3. Other features of seizures

Focal seizures

·         previously termed partial seizures

·         these start in a specific area, on one side of the brain

·         the level of awareness can vary in focal seizures. The terms focal aware (previously termed 'simple partial'), focal impaired awareness (previously termed 'complex partial') and awareness unknown are used to further describe focal seizures

·         further to this, focal seizures can be classified as being motor (e.g. Jacksonian march), non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura

Generalised

·         these engage or involve networks on both sides of the brain at the onset

·         consciousness lost immediately. The level of awareness in the above classification is therefore not needed, as all patients lose consciousness

·         generalised seizures can be further subdivided into motor (e.g. tonic-clonic) and non-motor (e.g. absence)

·         specific types include:

·         → tonic-clonic (grand mal)

·         → tonic

·         → clonic

·         → typical absence (petit mal)

·         → myoclonic: brief, rapid muscle jerks

·         → atonic

Unknown onset

·         this termed is reserved for when the origin of the seizure is unknown

Focal to bilateral seizure

·         starts on one side of the brain in a specific area before spreading to both lobes

·         previously termed secondary generalized seizures

In addition a number of special forms of epilepsy are recognised in children:

 

 

Syndrome

Notes

Infantile spasms (West's syndrome)

Brief spasms beginning in first few months of life

·         1. Flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs, repeat up to 50 times

·         2. Progressive mental handicap

·         3. EEG: hypsarrhythmia

·         usually 2nd to serious neurological abnormality (e.g. TS, encephalitis, birth asphyxia) or may be cryptogenic

·         poor prognosis

Lennox-Gastaut syndrome

May be extension of infantile spasms (50% have hx)

·         onset 1-5 yrs

·         atypical absences, falls, jerks

·         90% moderate-severe mental handicap

·         EEG: slow spike

·         ketogenic diet may help

Benign rolandic epilepsy

·         paraesthesia (e.g. unilateral face), usually on waking up

Juvenile myoclonic epilepsy (Janz syndrome)

Typical onset in the teens, more common in girls

·         1. Infrequent generalized seizures, often in morning

·         2. Daytime absences

·         3. Sudden, shock like myoclonic seizure

·         usually good response to sodium valproate

 

Symptoms and signs

 

As well as the seizure activity described above patients who have had generalised seizures may

·         bite their tongue

·         experience incontinence of urine

Asking about such features can be useful way of detecting epileptic seizures when taking a history from a patient who presents with a 'blackout' or 'collapse'.

 

Following a seizure patients typically have a postictal phase where they feel drowsy and tired for around 15 minutes.

 

 

Investigations

 

Following their first seizure patients generally have both an electroencephalogram (EEG) and neuroimaging (usually a MRI).

 

 

Management

 

Most neurologists now start antiepileptics following a second epileptic seizure.

 

As a general rule:

·         sodium valproate is used first-line for patients with generalised seizures

·         carbamazepine is used first-line for patients with partial seizures

Antiepileptics are one of the few drugs where it is recommended that we prescribe by brand, rather than generically, due to the risk of slightly different bioavailability resulting in a lowered seizure threshold.

 

It is useful when thinking about the management of epilepsy to consider certain groups of patients:

·         patients who drive: generally patients cannot drive for 6 months following a seizure. For patients with established epilepsy they must be fit free for 12 months before being able to drive

·         patients taking other medications: antiepileptics can induce/inhibit the P450 system resulting in varied metabolism of other medications, for example warfarin

·         women wishing to get pregnant: antiepileptics are generally teratogenic, particularly sodium valproate. It is important that women take advice from a neurologist prior to becoming pregnant, to ensure they are on the most suitable antiepileptic medication. Breastfeeding is generally considered safe for mothers taking antiepileptics with the possible exception of the barbiturates

·         women taking contraception: both the effect of the contraceptive on the effectiveness of the anti-epileptic medication and the effect of the anti-epileptic on the effectiveness of the contraceptive need to be considered

The table below looks at some of the more commonly used antiepileptics:

 

 

Drug

Mechanism of action

Uses

Adverse effects

Sodium valproate

Increases GABA activity

First-line for generalised seizures

·         increased appetite and weight gain

·         alopecia: regrowth may be curly

·         P450 enzyme inhibitor

·         ataxia

·         tremor

·         hepatitis

·         pancreatitis

·         thrombocytopaenia

·         teratogenic (neural tube defects)

Carbamazepine

Binds to sodium channels increasing their refractory period

First-line for partial seizures

·         P450 enzyme inducer

·         dizziness and ataxia

·         drowsiness

·         leucopenia and agranulocytosis

·         syndrome of inappropriate ADH secretion

·         visual disturbances (especially diplopia)

Lamotrigine

Sodium channel blocker

Used second-line for a variety of generalised and partial seizures

·         Stevens-Johnson syndrome

Phenytoin

Binds to sodium channels increasing their refractory period

No longer used first-line due to side-effect profile

·         P450 enzyme inducer

·         dizziness and ataxia

·         drowsiness

·         gingival hyperplasia, hirsutism, coarsening of facial features

·         megaloblastic anaemia

·         peripheral neuropathy

·         enhanced vitamin D metabolism causing osteomalacia

·         lymphadenopathy

Acute management of seizures

 

Most seizures terminate spontaneously. When seizures don't terminate after 5-10 minutes then it is often appropriate to administer medication to terminate the seizure. Patients are often prescribed these so family members may administer them in this eventuality, often termed 'rescue medication'. Benzodiazepines such as diazepam are typically used are may be administered rectally or intranasally/under the tongue.

 

If a patient continues to fit despite such measures then they are termed to have status epilepticus. This is a medical emergency requiring hospital treatment. Management options include further benzodiazepine medication, infusions of antiepileptics or even the use of general anaesthetic agents.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Fourth nerve palsy

Overview

·         supplies superior oblique (depresses eye, moves inward)

Features

·         vertical diplopia

o    classically noticed when reading a book or going downstairs

·         subjective tilting of objects (torsional diplopia)

·         the patient may develop a head tilt, which they may or may not be aware of

·         when looking straight ahead, the affected eye appears to deviate upwards and is rotated outwards

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:19

Headache

Headache accounts for a large proportion of medical consultations. The table below summarises the main characteristics of common or important causes:

 

 

Condition

Notes

Migraine

Recurrent, severe headache which is usually unilateral and throbbing in nature

May be be associated with aura, nausea and photosensitivity

Aggravated by, or causes avoidance of, routine activities of daily living. Patients often describe 'going to bed'.

In women may be associated with menstruation

Tension headache

Recurrent, non-disabling, bilateral headache, often described as a 'tight-band'

Not aggravated by routine activities of daily living

Cluster headache*

Pain typical occurs once or twice a day, each episode lasting 15 mins - 2 hours with clusters typically lasting 4-12 weeks

Intense pain around one eye (recurrent attacks 'always' affect same side)

Patient is restless during an attack

Accompanied by redness, lacrimation, lid swelling

More common in men and smokers

Temporal arteritis

Typically patient > 60 years old

Usually rapid onset (e.g. < 1 month) of unilateral headache

Jaw claudication (65%)

Tender, palpable temporal artery

Raised ESR

Medication overuse headache

Present for 15 days or more per month

Developed or worsened whilst taking regular symptomatic medication

Patients using opioids and triptans are at most risk

May be psychiatric co-morbidity

Other causes of headache

 

Acute single episode

·         meningitis

·         encephalitis

·         subarachnoid haemorrhage

·         head injury

·         sinusitis

·         glaucoma (acute closed-angle)

·         tropical illness e.g. Malaria

Chronic headache

·         chronically raised ICP

·         Paget's disease

·         psychological

*some neurologists use the term trigeminal autonomic cephalgia to group a number of conditions including cluster headache, paroxysmal hemicrania and short-lived unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). It is recommended such patients are referred for specialist assessment as specific treatment may be required, for example it is known paroxysmal hemicrania responds very well to indomethacin

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

HSMN

Hereditary sensorimotor neuropathy (HSMN) is a relatively new term which encompasses Charcot-Marie-Tooth disease (also known as peroneal muscular atrophy). Over 7 types have been characterised - however only 2 are common to clinical practice

·         HSMN type I: primarily due to demyelinating pathology

·         HSMN type II: primarily due to axonal pathology

HSMN type I

·         autosomal dominant

·         due to defect in PMP-22 gene (which codes for myelin)

·         features often start at puberty

·         motor symptoms predominate

·         distal muscle wasting, pes cavus, clawed toes

·         foot drop, leg weakness often first features

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Lambert-Eaton syndrome

Lambert-Eaton myasthenic syndrome is seen in association with small cell lung cancer and to a lesser extent breast and ovarian cancer. It may also occur independently as an autoimmune disorder. Lambert-Eaton myasthenic syndrome is caused by an antibody directed against presynaptic voltage-gated calcium channel in the peripheral nervous system.

 

Features

·         repeated muscle contractions lead to increased muscle strength (in contrast to myasthenia gravis)

o    in reality, this is seen in only 50% of patients and following prolonged muscle use muscle strength will eventually decrease

·         limb-girdle weakness (affects lower limbs first)

·         hyporeflexia

·         autonomic symptoms: dry mouth, impotence, difficulty micturating

·         ophthalmoplegia and ptosis not commonly a feature (unlike in myasthenia gravis)

EMG

·         incremental response to repetitive electrical stimulation

Management

·         treatment of underlying cancer

·         immunosuppression, for example with prednisolone and/or azathioprine

·         3,4-diaminopyridine is currently being trialled

o    works by blocking potassium channel efflux in the nerve terminal so that the action potential duration is increased. Calcium channels can then be open for a longer time and allow greater acetylcholine release to the stimulate muscle at the end plate

·         intravenous immunoglobulin therapy and plasma exchange may be beneficial

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Median nerve

The median nerve is formed by the union of a lateral and medial root respectively from the lateral (C5,6,7) and medial (C8 and T1) cords of the brachial plexus; the medial root passes anterior to the third part of the axillary artery. The nerve descends lateral to the brachial artery, crosses to its medial side (usually passing anterior to the artery). It passes deep to the bicipital aponeurosis and the median cubital vein at the elbow.

 

It passes between the two heads of the pronator teres muscle, and runs on the deep surface of flexor digitorum superficialis (within its fascial sheath).

 

Near the wrist it becomes superficial between the tendons of flexor digitorum superficialis and flexor carpi radialis, deep to palmaris longus tendon. It passes deep to the flexor retinaculum to enter the palm, but lies anterior to the long flexor tendons within the carpal tunnel.

 

Branches

 

 

Region

Branch

Upper arm

No branches, although the nerve commonly communicates with the musculocutaneous nerve

Forearm

Pronator teres

Flexor carpi radialis

Palmaris longus

Flexor digitorum superficialis

Flexor pollicis longus

Flexor digitorum profundus (only the radial half)

Distal forearm

Palmar cutaneous branch

Hand (Motor)

Motor supply (LOAF)

·         Lateral 2 lumbricals

·         Opponens pollicis

·         Abductor pollicis brevis

·         Flexor pollicis brevis

Hand (Sensory)

·         Over thumb and lateral 2 ½ fingers

·         On the palmar aspect this projects proximally, on the dorsal aspect only the distal regions are innervated with the radial nerve providing the more proximal cutaneous innervation.

Patterns of damage

 

Damage at wrist

·         e.g. carpal tunnel syndrome

·         paralysis and wasting of thenar eminence muscles and opponens pollicis (ape hand deformity)

·         sensory loss to palmar aspect of lateral (radial) 2 ½ fingers

Damage at elbow, as above plus:

·         unable to pronate forearm

·         weak wrist flexion

·         ulnar deviation of wrist

Anterior interosseous nerve (branch of median nerve)

·         leaves just below the elbow

·         results in loss of pronation of forearm and weakness of long flexors of thumb and index finger

Topography of the median nerve

 

 

Image sourced from Wikipedia

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Migraine: pregnancy, contraception and other hormonal factors

SIGN produced guidelines in 2008 on the management of migraine, the following is selected highlights:

 

Migraine during pregnancy

·         paracetamol 1g is first-line

·         NSAIDs can be used second-line in the first and second trimester

·         avoid aspirin and opioids such as codeine during pregnancy

Migraine and the combined oral contraceptive (COC) pill

·         if patients have migraine with aura then the COC is absolutely contraindicated due to an increased risk of stroke (relative risk 8.72)

Migraine and menstruation

·         many women find that the frequency and severity of migraines increase around the time of menstruation

·         SIGN recommends that women are treated with mefanamic acid or a combination of aspirin, paracetamol and caffeine. Triptans are also recommended in the acute situation

Migraine and hormone replacement therapy (HRT)

·         safe to prescribe HRT for patients with a history of migraine but it may make migraines worse

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Myasthenia gravis: exacerbating factors

The most common exacerbating factor is exertion resulting in fatigability, which is the hallmark feature of myasthenia gravis . Symptoms become more marked during the day

 

The following drugs may exacerbate myasthenia:

·         penicillamine

·         quinidine, procainamide

·         beta-blockers

·         lithium

·         phenytoin

·         antibiotics: gentamicin, macrolides, quinolones, tetracyclines

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Reflexes

The common reflexes are listed below:

 

 

Reflex

Root

Ankle

S1-S2

Knee

L3-L4

Biceps

C5-C6

Triceps

C7-C8

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Sodium valproate

Sodium valproate is used in the management of epilepsy and is first-line therapy for generalised seizures. It works by increasing GABA activity.

 

Adverse effects

·         teratogenic

o    maternal use of sodium valproate is associated with a significant risk of neurodevelopmental delay in children

o    guidance is now clear that sodium valproate should not be used during pregnancy and in women of childbearing age unless clearly necessary. Women of childbearing age should not start treatment without specialist neurological or psychiatric advice.

·         P450 inhibitor

·         gastrointestinal: nausea

·         increased appetite and weight gain

·         alopecia: regrowth may be curly

·         ataxia

·         tremor

·         hepatotoxicity

·         pancreatitis

·         thrombocytopaenia

·         hyponatraemia

·         hyperammonemic encephalopathy: L-carnitine may be used as treatment if this develops

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Spinal cord lesions

The diagram belows shows cross-section view of the spinal cord:

 

 

 

Image sourced from Wikipedia

Motor lesions

 

Amyotrophic lateral sclerosis (motor neuron disease)

·         affects both upper (corticospinal tracts) and lower motor neurons

·         results in a combination of upper and lower motor neuron signs

Poliomyelitis

·         affects anterior horns resulting in lower motor neuron signs

Combined motor and sensory lesions

 

 

Disorder

Tracts affected

Clinical notes

Brown-Sequard syndrome (spinal cord hemisection)

1. Lateral corticospinal tract

2. Dorsal columns

3. Lateral spinothalamic tract

1. Ipsilateral spastic paresis below lesion

2. Ipsilateral loss of proprioception and vibration sensation

3. Contralateral loss of pain and temperature sensation

Subacute combined degeneration of the spinal cord (vitamin B12 & E deficiency)

1. Lateral corticospinal tracts

2. Dorsal columns

3. Spinocerebellar tracts

1. Bilateral spastic paresis

2. Bilateral loss of proprioception and vibration sensation

3. Bilateral limb ataxia

Friedrich's ataxia

Same as subacute combined degeneration of the spinal cord (see above)

Same as subacute combined degeneration of the spinal cord (see above)

 

In addition cerebellar ataxia → other features e.g. intention tremor

Anterior spinal artery occlusion

1. Lateral corticospinal tracts

2. Lateral spinothalamic tracts

1. Bilateral spastic paresis

2. Bilateral loss of pain and temperature sensation

Syringomyelia

1. Ventral horns

2. Lateral spinothalamic tract

1. Flacid paresis (typically affecting the intrinsic hand muscles)

2. Loss of pain and temperature sensation

Multiple sclerosis

Asymmetrical, varying spinal tracts involved

Combination of motor, sensory and ataxia symptoms

Sensory lesions

 

 

Disorder

Tracts affected

Clinical notes

Neurosyphilis (tabes dorsalis)

1. Dorsal columns

1. Loss of proprioception and vibration sensation

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Stroke management: other issues

This background note focuses on other issues in acute stroke management, particularly management of fluids, glycaemic control, blood pressure management, feeding assessment/management and disability scales.

 

Fluid management

·         As in all patients in hospital, regular assessment for fluid status must be undertaken to ensure patients remain normovolaemic

·         The NICE guidelines recommend assessing the hydration of all patients with acute stroke on admission, with regular review during their stay

·         Greater than 80% of patients who cannot swallow post stroke will recover within 2-4 weeks

·         However, it is important to manage fluids in this immediate post-event period as hypovolaemia can worsen the ischaemic penumbra, as well as increase risk of other complications such as infection, deep vein thrombosis, constipation and delirium

·         Conversely, over-hydration can also complicate matters by leading to cerebral oedema, cardiac failure and hyponatraemia, therefore it is important to regularly review fluid status in these patients

·         Recommendations for management:

o    Oral hydration is preferable in all patients who are able to safely swallow

o    Intravenous hydration may be necessary otherwise, and although studies have remained contentious regarding choice of intravenous fluid, UptoDate currently recommend isotonic saline without dextrose as the agent of choice in most patients

o    Other factors to take into consideration when choosing fluid agent include electrolyte disturbances and/or cardiovascular status

Glycaemic control

·         It is important to closely monitor and control blood sugar, particularly if they are nil by mouth due to concerns regarding swallowing safety post stroke, and/or in diabetics

·         Post stroke, patients with hyperglycaemia have increased mortality independent from their age and the severity of stroke

o    This is likely due to increased tissue acidosis from anaerobic metabolism, free radical generation, and increased blood brain barrier permeability post injury

·         The NICE guidelines recommend maintaining a blood sugar level between 4 and 11 mmol/L in people with acute stroke

·         Diabetic patients

o    It is important to provide intensive management for diabetics post acute stroke

o    The NICE guidelines suggest optimising insulin treatment using intravenous insulin and glucose infusions

o    Hypoglycaemia also needs to be managed appropriately, as alone it can cause neuronal injury as well as mimic stroke-related neurological deficits

Blood pressure management

·         Use of anti-hypertensive medications should only be used for blood pressure control in patients post ischaemic stroke if there is a hypertensive emergency with one or more of the following serious concomitant medical issues (according to the NICE guidelines):

o    Hypertensive encephalopathy

o    Hypertensive nephropathy

o    Hypertensive cardiac failure/myocardial infarction

o    Aortic dissection

o    Pre-eclampsia/eclampsia

·         This is because lowering blood pressure too much can potentially compromise collateral blood flow to the affected region, and possibly hasten the time to complete and irreversible tissue infarction

·         If if treatment is indicated, UptoDate recommend cautious lowering of blood pressure by approximately 15% in the first 24-hours after stroke onset

·         UptoDate suggest using intravenous labetalol, nicardipine and clevidipine as first-line agents, due to the possibility for rapid and safe titration to control blood pressure

·         However, in patients who are candidates for thrombolytic therapy for acute stroke, blood pressure should be reduced to 185/110mmHg or lower

o    Elevated BP can affect thrombolytic eligibility and delay treatment

o    Timely management of elevated BP is crucial when patients are otherwise eligible for intravenous thrombolysis

o    After thrombolytic therapy, UptoDate recommend ensuring that the blood pressure is stabilised and maintained at or below 180/105mmHg for at least 24 hours after treatment

Feeding assessment and management

·         All patients presenting with acute stroke must be screened for safe swallowing function prior to further oral intake, as dysphagia is common after stroke

o    This is to reduce the risk of aspiration and subsequent complications

o    This includes prior to any oral intake of food, fluids, and/or medications

·         If there are any concerns regarding swallowing, the NICE guidelines recommend specialist assessment of swallowing

o    This should preferably within 24 hours of admission and not greater than 72 hours after

o    Prior to assessment is undertaken, a patient should remain nil by mouth to prevent complications

·         Recommendations for patients deemed unsafe for oral intake:

o    Patients should receive nasogastric tube feeding, ideally within 24 hours of admission, unless they have had thrombolytic therapy

o    If nasogastric tube feeding is not tolerated, patients should be considered for a nasal bridle tube/gastrostomy instead

o    Medications need to be assessed to determine if formulations are available for nasogastric feeding, or if conversion to subcutaneous or intravenous forms are required

·         Nutritional support may be required for patients at risk of malnutrition post stroke, whether a result from dysphagia, poor oral health or reduced ability to self-feed due to weakness or paralysis

Disability scales

·         Stroke can result in a number of complications and subsequent disability, therefore disability scales are often used as a measure of functional decline post event and subsequent improvement after medical intervention

·         Disability, often measured in terms of functional status (notably, basic activities of daily living), is often the leading cause of morbidity after stroke

·         After a patient is medically stabilised after a stroke, they may require transfer to a rehabilitation team for ongoing treatment depending on their level of disability

·         Disability is most commonly measured using the Barthel index (BI), an outcome measure for stroke

o    Describes 10 tasks, and is scored according to amount of time or assistance required by the patient for each given task

o    Tasks: feeding, moving from wheelchair to bed, personal toileting, getting on/off toilet, bathing, walking on level surface, ascending/descending stairs, dressing, controlling bowels and controlling bladder

o    The total score is from 0 to 100, with 0 being completely dependent, and 100 being completely independent

·         This index should be used to assess the functional status of a patient post stroke, and to monitor their improvement with ongoing rehabilitation to regain independence after the event

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Ulnar nerve

Overview

·         arises from medial cord of brachial plexus (C8, T1)

Motor to

·         medial two lumbricals

·         aDductor pollicis

·         interossei

·         hypothenar muscles: abductor digiti minimi, flexor digiti minimi

·         flexor carpi ulnaris

Sensory to

·         medial 1 1/2 fingers (palmar and dorsal aspects)

Path

·         the ulnar nerve travels through the posteromedial aspect of the upper arm to the flexor compartment of the forearm

·         it then enters the palm of the hand via the Guyon's canal, superficial to the flexor retinaculum and lateral to the pisiform bone

 

 

Image sourced from Wikipedia

Branches

 

 

Branch

Supplies

Muscular branch

Flexor carpi ulnaris

Medial half of the flexor digitorum profundus

Palmar cutaneous branch (Arises near the middle of the forearm)

Skin on the medial part of the palm

Dorsal cutaneous branch

Dorsal surface of the medial part of the hand

Superficial branch

Cutaneous fibres to the anterior surfaces of the medial one and one-half digits

Deep branch

Hypothenar muscles

All the interosseous muscles

Third and fourth lumbricals

Adductor pollicis

Medial head of the flexor pollicis brevis

Patterns of damage

 

Damage at wrist

·         'claw hand' - hyperextension of the metacarpophalangeal joints and flexion at the distal and proximal interphalangeal joints of the 4th and 5th digits

·         wasting and paralysis of intrinsic hand muscles (except lateral two lumbricals)

·         wasting and paralysis of hypothenar muscles

·         sensory loss to the medial 1 1/2 fingers (palmar and dorsal aspects)

Damage at elbow

·         as above (however, ulnar paradox - clawing is more severe in distal lesions)

·         radial deviation of wrist

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

17:20

Absence seizures

Absence seizures (petit mal) are a form of generalised epilepsy that is mostly seen in children. The typical age of onset of 3-10 years old and girls are affected twice as commonly as boys

 

Features

·         absences last a few seconds and are associated with a quick recovery

·         seizures may be provoked by hyperventilation or stress

·         the child is usually unaware of the seizure

·         they may occur many times a day

·         EEG: bilateral, symmetrical 3Hz spike and wave pattern

Management

·         sodium valproate and ethosuximide are first-line treatment

·         good prognosis - 90-95% become seizure free in adolescence

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Brachial plexus injuries

Erb-Duchenne paralysis

·         damage to C5,6 roots

·         winged scapula

·         may be caused by a breech presentation

Klumpke's paralysis

·         damage to T1

·         loss of intrinsic hand muscles

·         due to traction

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Brown-Sequard syndrome

Overview

·         caused by lateral hemisection of the spinal cord

Features

·         ipsilateral weakness below lesion

·         ipsilateral loss of proprioception and vibration sensation

·         contralateral loss of pain and temperature sensation

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Cataplexy

Cataplexy describes the sudden and transient loss of muscular tone caused by strong emotion (e.g. laughter, being frightened). Around two-thirds of patients with narcolepsy have cataplexy.

 

Features range from buckling knees to collapse.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Cavernous sinus

The cavernous sinuses are paired and are situated on the body of the sphenoid bone. It runs from the superior orbital fissure to the petrous temporal bone.

 

Relations

 

Medial

Lateral

Pituitary fossa

Sphenoid sinus

Temporal lobe

Contents

 

Lateral wall components

(from top to bottom:)

Oculomotor nerve

Trochlear nerve

Ophthalmic nerve

Maxillary nerve

Contents of the sinus

(from medial to lateral:)

Internal carotid artery (and sympathetic plexus)

Abducens nerve

Blood supply

Ophthalmic vein, superficial cortical veins, basilar plexus of veins posteriorly.

 

Drains into the internal jugular vein via: the superior and inferior petrosal sinuses

 

 

 

Image sourced from Wikipedia

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Cerebellar syndrome

Unilateral cerebellar lesions cause ipsilateral signs.

 

Useful and well-known mnemonic to remember symptoms of cerebellar disease is DANISH:

·         D - Dysdiadochokinesia, Dysmetria (past-pointing), patients may appear 'Drunk'

·         A - Ataxia (limb, truncal)

·         N - Nystamus (horizontal = ipsilateral hemisphere)

·         I - Intention tremour

·         S - Slurred staccato speech, Scanning dysarthria

·         H - Hypotonia

Causes

·         Friedreich's ataxia, ataxic telangiectasia

·         neoplastic: cerebellar haemangioma

·         stroke

·         alcohol

·         multiple sclerosis

·         hypothyroidism

·         drugs: phenytoin, lead poisoning

·         paraneoplastic e.g. secondary to lung cancer

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Cerebral perfusion pressure

The cerebral perfusion pressure (CPP) is defined as being the net pressure gradient causing blood flow to the brain. The CPP is tightly autoregulated to maximise cerebral perfusion. A sharp rise in CPP may result in a rising ICP, a fall in CPP may result in cerebral ischaemia. It may be calculated by the following equation:

 

CPP= Mean arterial pressure - Intra cranial pressure

 

Following trauma, the CPP has to be carefully controlled and the may require invasive monitoring of the ICP and MAP.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Cerebrospinal fluid

The CSF fills the space between the arachnoid mater and pia mater (covering surface of the brain). The total volume of CSF in the brain is approximately 150ml. Approximately 500 ml is produced by the ependymal cells in the choroid plexus (70%), or blood vessels (30%). It is reabsorbed via the arachnoid granulations which project into the venous sinuses.

 

Circulation

1. Lateral ventricles (via foramen of Munro)

2. 3rd ventricle

3. Cerebral aqueduct (aqueduct of Sylvius)

4. 4th ventricle (via foramina of Magendie and Luschka)

5. Subarachnoid space

6. Reabsorbed into the venous system via arachnoid granulations into superior sagittal sinus

 

Composition

·         Glucose: 50-80mg/dl

·         Protein: 15-40 mg/dl

·         Red blood cells: Nil

·         White blood cells: 0-3 cells/ mm3

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Charcot-Marie-Tooth disease

Charcot-Marie-Tooth Disease is the most common hereditary peripheral neuropathy. It results in a predominantly motor loss. There is no cure, and management is focused on physical and occupational therapy.

 

Features:

·         There may be a history of frequently sprained ankles

·         Foot drop

·         High-arched feet (pes cavus)

·         Hammer toes

·         Distal muscle weakness

·         Distal muscle atrophy

·         Hyporeflexia

·         Stork leg deformity

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

CNS tumours

- 60% = Glioma and metastatic disease

·         20% = Meningioma

·         10% = Pituitary lesions

In paediatric practice medulloblastomas (neuroectodermal tumours) were the commonest lesions, astrocytomas now account for the majority.

Tumours arising in right temporal and frontal lobe may reach considerable size before becoming symptomatic. Whereas tumours in the speech and visual areas will typically produce early symptoms.

 

Diagnosis

MRI Scanning provides the best resolution.

 

Treatment

Usually surgery, even if tumour cannot be completely resected conditions such as rising ICP can be addressed with tumour debulking and survival and quality of life prolonged.

Curative surgery can usually be undertaken with lesions such as meningiomas. Gliomas have a marked propensity to invade normal brain and resection of these lesions is nearly always incomplete.

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Complex regional pain syndrome

Complex regional pain syndrome (CRPS) is the modern, umbrella term for a number of conditions such as reflex sympathetic dystrophy and causalgia. It describes a number of neurological and related symptoms which typically occur following surgery or a minor injury. CRPS is 3 times more common in women.

 

There are two types of CRPS:

·         type I (most common): there is no demonstrable lesion to a major nerve

·         type II: there is a lesion to a major nerve

Features

·         progressive, disproportionate symptoms to the original injury/surgery

·         allodynia

·         temperature and skin colour changes

·         oedema and sweating

·         motor dysfunction

·         the Budapest Diagnostic Criteria are commonly used in the UK

Management

·         early physiotherapy is important

·         neuropathic analgesia in-line with NICE guidelines

·         specialist management (e.g. Pain team) is required

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Dystrophinopathies

Overview

·         X-linked recessive

·         due to mutation in the gene encoding dystrophin, dystrophin gene on Xp21

·         dystrophin is part of a large membrane associated protein in muscle which connects the muscle membrane to actin, part of the muscle cytoskeleton

·         in Duchenne muscular dystrophy there is a frameshift mutation resulting in one or both of the binding sites are lost leading to a severe form

·         in Becker muscular dystrophy there is a non-frameshift insertion in the dystrophin gene resulting in both binding sites being preserved leading to a milder form

Duchenne muscular dystrophy

·         progressive proximal muscle weakness from 5 years

·         calf pseudohypertrophy

·         Gower's sign: child uses arms to stand up from a squatted position

·         30% of patients have intellectual impairment

Becker muscular dystrophy

·         develops after the age of 10 years

·         intellectual impairment much less common

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Electromyography

Electromyography (EMG) is used to evaluate the physiological properties of muscles at rest and whilst contracting

 

General characteristics of an abnormal EMG are listed below

 

 

Condition

Characteristic

Neuropathy

• Increased action potential duration

• Increased action potential amplitude

Myopathy

• Decreased action potential duration

• Decreased action potential amplitude

Specific characteristics of abnormal EMGs are shown in the table below

 

 

Condition

Characteristic

Myasthenia gravis

Diminished response to repetitive stimulation

Lambert-Eaton syndrome

Incremental response to repetitive stimulation

Myotonic syndromes

extended series of repetitive discharges lasting up to 30 seconds

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Encephalitis

Features

·         fever, headache, psychiatric symptoms, seizures, vomiting

·         focal features e.g. aphasia

·         peripheral lesions (e.g. cold sores) have no relation to presence of HSV encephalitis

Pathophysiology

·         HSV-1 responsible for 95% of cases in adults

·         typically affects temporal and inferior frontal lobes

Investigation

·         CSF: lymphocytosis, elevated protein

·         PCR for HSV

·         CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients

·         MRI is better

·         EEG pattern: lateralised periodic discharges at 2 Hz

Management

·         intravenous aciclovir should be started in all cases of suspected encephalitis

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:20

Epilepsy in children: syndromes

Infantile spasms (West's syndrome)

·         brief spasms beginning in first few (4-6) months of life; M>F

·         1. Flexion of head, trunk, limbs → extension of arms (Salaam attack); last 1-2 secs, repeat up to 50 times

·         2. Progressive mental handicap

·         3. EEG: hypsarrhythmia

·         usually 2nd to serious neurological abnormality (e.g. TS, encephalitis, birth asphyxia) or may be cryptogenic

·         poor prognosis

·         vigabatrin/steroids

Typical (petit mal) absence seizures

·         onset 4-8 yrs

·         duration few-30 secs; no warning, quick recovery; often many per day

·         EEG: 3Hz generalized, symmetrical

·         sodium valproate, ethosuximide

·         good prognosis: 90-95% become seizure free in adolescence

Lennox-Gastaut syndrome

·         may be extension of infantile spasms (50% have hx)

·         onset 1-5 yrs

·         atypical absences, falls, jerks

·         90% moderate-severe mental handicap

·         EEG: slow spike

·         ketogenic diet may help

Benign rolandic epilepsy

·         most common in childhood, M>F

·         paraesthesia (e.g. unilateral face), usually on waking up

Juvenile myoclonic epilepsy (Janz syndrome)

·         onset: teens; F:M = 2:1

·         1. Infrequent generalized seizures, often in morning

·         2. Daytime absences

·         3. Sudden, shock like myoclonic seizure (these may develop before seizures)

·         usually good response to sodium valproate

 

Neonatal period - try vitamin B6

·         2nd: hypoglycaemia, meningitis, head trauma

·         pyridoxine dependency (AR, IV B6)

·         benign familial neonatal seizures (AD)

·         benign neonatal convulsions (5th day)

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:21

Extradural haematoma

An extradural (or ‘epidural’) haematoma is a collection of blood that is between the skull and the dura. It is almost always caused by trauma and most typically by ‘low-impact’ trauma (e.g. a blow to the head or a fall). The collection is often in the temporal region since the thin skull at the pterion overlies the middle meningeal artery and is therefore vulnerable to injury.

 

The classical presentation is of a patient who initially loses, briefly regains and then loses again consciousness after a low-impact head injury. The brief regain in consciousness is termed the ‘lucid interval’ and is lost eventually due to the expanding haematoma and brain herniation. As the haematoma expands the uncus of the temporal lobe herniates around the tentorium cerebelli and the patient develops a fixed and dilated pupil due to the compression of the parasympathetic fibers of the third cranial nerve.

 

On imaging, an extradural haematoma appears as a biconvex (or lentiform), hyperdense collection around the surface of the brain. They are limited by the suture lines of the skull.

 

In patients who have no neurological deficit, cautious clinical and radiological observation is appropriate. The definitive treatment is craniotomy and evacuation of the haematoma.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:21

Foot drop

Foot drop is a result of weakness of the foot dorsiflexors.

 

Possible causes include:

·         common peroneal nerve lesion - the most common cause

·         L5 radiculopathy

·         sciatic nerve lesion

·         superficial or deep peroneal nerve lesion

·         other possible includes central nerve lesions (e.g. stroke) but other features are usually present

A common peroneal nerve lesion is the most common cause . This is often secondary to compression at the neck of the fibula. This may be caused by certain positions such as leg crossing, squatting or kneeling. Prolonged confinement, recent weight loss, Baker's cysts and plaster casts to the lower leg are also known to be precipitating factors.

 

Examination

·         if the patient has an isolated peroneal neuropathy there will be weakness of foot dorsiflexion and eversion. Reflexes will be normal

·         weakness of hip abduction is suggestive of a L5 radiculopathy

Bilateral symptoms, fasiculations or other abnormal neurological findings (e.g. hyperreflexia) are indications for specialist referral.

 

If the examination suggests a peroneal neuropathy then conservative management is appropriate. Leg crossing, squatting and kneeling should be avoided. Symptoms typically improve over 2-3 months.*

 

*BMJ 2015;350:h1736 - Foot drop

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:21

Guillain-Barre syndrome

Guillain-Barre syndrome describes an immune mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni)

 

Pathogenesis

·         cross reaction of antibodies with gangliosides in the peripheral nervous system

·         correlation between anti-ganglioside antibody (e.g. anti-GM1) and clinical features has been demonstrated

·         anti-GM1 antibodies in 25% of patients

Miller Fisher syndrome

·         variant of Guillain-Barre syndrome

·         associated with ophthalmoplegia, areflexia and ataxia. The eye muscles are typically affected first

·         usually presents as a descending paralysis rather than ascending as seen in other forms of Guillain-Barre syndrome

·         anti-GQ1b antibodies are present in 90% of cases

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

Guillian-Barré Syndrome

GBS is a rare condition, but is important to recognise as it can be life-threatening. GBS will be covered in more detail in another tutorial.

The take-home points for GBS are:

·         Often triggered by a viral illness, commonly campylobacter gastroenteritis

·         Driven by an auto-immune process causing demyelination of the nerves

·         Motor function and muscle weakness is the most prominent feature

·         Pattern starts distally and ascends inwards towards the body

·         Progresses for up to 4 weeks

·         The big threat is weakness to the breathing and swallowing muscles

·         Treated with immune modifying therapies

·         Recovery takes a LONG time ("GBS - Gets Better Slowly")

The Time Place Type description for this disease would be:

Acute symmetrical diffuse sensorimotor polyneuropathy. 

 

From <https://mle.ncl.ac.uk/cases/page/17650/>

 

 

 

 

 

 

24 December 2020

17:21

Internuclear ophthalmoplegia

Overview

·         a cause of horizontal disconjugate eye movement

·         due to a lesion in the medial longitudinal fasciculus (MLF)

o    controls horizontal eye movements by interconnecting the IIIrd, IVth and VIth cranial nuclei

o    located in the paramedian area of the midbrain and pons

Features

·         impaired adduction of the eye on the same side as the lesion

·         horizontal nystagmus of the abducting eye on the contralateral side

Causes

·         multiple sclerosis

·         vascular disease

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:21

Intracranial venous thrombosis

Overview

·         can cause cerebral infarction, much lesson common than arterial causes

·         50% of patients have isolated sagittal sinus thromboses - the remainder have coexistent lateral sinus thromboses and cavernous sinus thromboses

Features

·         headache (may be sudden onset)

·         nausea & vomiting

Sagittal sinus thrombosis

·         may present with seizures and hemiplegia

·         parasagittal biparietal or bifrontal haemorrhagic infarctions are sometimes seen

Cavernous sinus thrombosis

·         other causes of cavernous sinus syndrome: local infection (e.g. sinusitis), neoplasia, trauma

·         periorbital oedema

·         ophthalmoplegia: 6th nerve damage typically occurs before 3rd & 4th

·         trigeminal nerve involvement may lead to hyperaesthesia of upper face and eye pain

·         central retinal vein thrombosis

Lateral sinus thrombosis

·         6th and 7th cranial nerve palsies

 

 

© Image used on license from Radiopaedia

CT with contrast demonstrating a superior sagittal sinus thrombosis showing the typical empty delta sign. Look at the 'bottom' of the scan for the triangular shaped dural sinus. This should normally be white due to it being filled with contrast. The empty delta sign occurs when the thrombus fails to enhance within the dural sinus and is outlined by enhanced collateral channels in the falx. This sign is seen in only about 25%-30% of cases but is highly diagnostic for sagittal sinus thrombosis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:21

Lamotrigine

Lamotrigine is an antiepileptic used second-line for a variety of generalised and partial seizures.

 

Mechanism of action

·         sodium channel blocker

Adverse effects

·         Stevens-Johnson syndrome

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Levodopa

Overview

·         usually combined with a decarboxylase inhibitor (e.g. carbidopa or benserazide) to prevent peripheral metabolism of L-dopa to dopamine

·         reduced effectiveness with time (usually by 2 years)

·         no use in neuroleptic induced parkinsonism

Adverse effects

·         dyskinesia

·         'on-off' effect

·         postural hypotension

·         cardiac arrhythmias

·         nausea & vomiting

·         psychosis

·         reddish discolouration of urine upon standing

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Migraine

Migraine is a common type of primary headache. It is characterised typically by:

·         a severe, unilateral, throbbing headache

·         associated with nausea, photophobia and phonophobia

·         attacks may last up to 72 hours

·         patients characteristically go to a darkened, quiet room during an attack

·         'classic' migraine attacks are precipitated by an aura. These occur in around one-third of migraine patients

·         typical aura are visual, progressive, last 5-60 minutes and are characterised by transient hemianopic disturbance or a spreading scintillating scotoma

·         formal diagnostic criteria are produced by the International Headache Society (see below)

Epidemiology

·         3 times more common in women

·         prevalence in men is around 6%, in women 18%

Common triggers for a migraine attack

·         tiredness, stress

·         alcohol

·         combined oral contraceptive pill

·         lack of food or dehydration

·         cheese, chocolate, red wines, citrus fruits

·         menstruation

·         bright lights

Migraine diagnostic criteria

 

 

A

At least 5 attacks fulfilling criteria B-D

B

Headache attacks lasting 4-72 hours* (untreated or unsuccessfully treated)

C

Headache has at least two of the following characteristics:

·         1. unilateral location*

·         2. pulsating quality (i.e., varying with the heartbeat)

·         3. moderate or severe pain intensity

·         4. aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs)

D

During headache at least one of the following:

·         1. nausea and/or vomiting*

·         2. photophobia and phonophobia

E

Not attributed to another disorder (history and examination do not suggest a secondary headache disorder or, if they do, it is ruled out by appropriate investigations or headache attacks do not occur for the first time in close temporal relation to the other disorder)

*In children, attacks may be shorter-lasting, headache is more commonly bilateral, and gastrointestinal disturbance is more prominent.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

The mnemonic CHOCOLATE is useful for remembering the common precipitants.

·         Chocolate

·         Hangovers

·         Orgasms

·         Cheese

·         Caffeine

·         The oral contraceptive pill

·         Lie-ins

·         Alcohol

·         Travel

·         Exercise

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

 

24 December 2020

17:22

Motor neuron disease: management

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, progressive muscular atrophy and bulbar palsy

 

Riluzole

·         prevents stimulation of glutamate receptors

·         used mainly in amyotrophic lateral sclerosis

·         prolongs life by about 3 months

Respiratory care

·         non-invasive ventilation (usually BIPAP) is used at night

·         studies have shown a survival benefit of around 7 months

Prognosis

·         poor: 50% of patients die within 3 years

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Multiple sclerosis: investigation

Diagnosis requires demonstration of lesions disseminated in time and space

MRI with contrast should be used to view demyelinating lesions

MRI

·         high signal T2 lesions

·         periventricular plaques

·         Dawson fingers: often seen on FLAIR images - hyperintense lesions penpendicular to the corpus callosum

CSF

·         oligoclonal bands (and not in serum)

·         increased intrathecal synthesis of IgG

Visual evoked potentials

·         delayed, but well preserved waveform

 

 

© Image used on license from Radiopaedia

MRI showing multiple white matter plaques penpendicular to the corpus callosum giving the appearance of Dawson fingers

 

 

© Image used on license from Radiopaedia

MRI from a young patient with multiple sclerosis. Widespread periventricular, juxtacortical, post fossa and upper cervical cord high T2 regions are noted. Note the difference in the lesions with varying degrees of contrast enhancement and restricted diffusion indicating active/recent demyelination. This satisfies the diagnostic criteria in terms of separation in terms of time space.

 

 

© Image used on license from Radiopaedia

MRI FLAIR from the same patient as above. The numerous lesions are more easily identified than in the above T2 image.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Narcolepsy

Overview

·         associated with HLA-DR2

·         it is associated with low levels of orexin (hypocretin), a protein which is responsible for controlling appetite and sleep patterns

·         early onset of REM sleep

Features

·         typical onset in teenage years

·         hypersomnolence

·         cataplexy (sudden loss of muscle tone often triggered by emotion)

·         sleep paralysis

·         vivid hallucinations on going to sleep or waking up

Investigation

·         multiple sleep latency EEG

Management

·         daytime stimulants (e.g. modafinil) and nighttime sodium oxybate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Nutrition - Refeeding syndrome

Refeeding syndrome describes the metabolic abnormalities which occur on feeding a person following a period of starvation. The metabolic consequences include:

·         Hypophosphataemia

·         Hypokalaemia

·         Hypomagnesaemia

·         Abnormal fluid balance

These abnormalities can lead to organ failure.

 

Re-feeding problems

If patient not eaten for > 5 days, aim to re-feed at < 50% energy and protein levels

 

High risk for re-feeding problems

If one or more of the following:

·         BMI < 16 kg/m2

·         Unintentional weight loss >15% over 3-6 months

·         Little nutritional intake > 10 days

·         Hypokalaemia, Hypophosphataemia or hypomagnesaemia prior to feeding (unless high)

If two or more of the following:

·         BMI < 18.5 kg/m2

·         Unintentional weight loss > 10% over 3-6 months

·         Little nutritional intake > 5 days

·         History of: alcohol abuse, drug therapy including insulin, chemotherapy, diuretics and antacids

 

Prescription

·         Start at up to 10 kcal/kg/day increasing to full needs over 4-7 days

·         Start immediately before and during feeding: oral thiamine 200-300mg/day, vitamin B co strong 1 tds and supplements

·         Give K+ (2-4 mmol/kg/day), phosphate (0.3-0.6 mmol/kg/day), magnesium (0.2-0.4 mmol/kg/day)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Paroxysmal hemicrania

Paroxysmal hemicrania (PH) is defined by attacks of severe, unilateral headache, usually in the orbital, supraorbital or temporal region. These attacks are often associated with autonomic features, usually last less than 30 minutes and can occur multiple times a day.

 

PH sits within the group of disorders called trigeminal autonomic cephalgias which also contains cluster headache, a condition which shares many features with PH.

 

Importantly, PH is completely responsive to treatment with indomethacin.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Post-lumbar puncture headache

Headache following lumbar puncture (LP) occurs in approximately one-third of patients. The pathophysiology of is unclear but may relate to a 'leak' of CSF following dural puncture. Post-LP headaches are more common in young females with a low body mass index

 

Typical features

·         usually develops within 24-48 hours following LP but may occur up to one week later

·         may last several days

·         worsens with upright position

·         improves with recumbent position

 

Factors which may contribute to headache

Factors which do not contribute to headache

Increased needle size

Direction of bevel

Not replacing the stylet

Increased number of LP attempts

Increased volume of CSF removed

Bed rest following procedure

Increased fluid intake post procedure

Opening pressure of CSF

Position of patient

Management

·         supportive initially (analgesia, rest)

·         if pain continues for more than 72 hours then specific treatment is indicated, to prevent subdural haematoma

·         treatment options include: blood patch, epidural saline and intravenous caffeine

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Progressive supranuclear palsy

Overview

·         aka Steele-Richardson-Olszewski syndrome

·         a 'Parkinson Plus' syndrome

Features

·         postural instability and falls

o    patients tend to have a stiff, broad-based gait

·         impairment of vertical gaze (down gaze worse than up gaze - patients may complain of difficultly reading or descending stairs)

·         parkinsonism

o    bradykinesia is prominent

·         cognitive impairment

o    primarily frontal lobe dysfunction

Management

·         poor response to L-dopa

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Raised intracranial pressure

As the brain and ventricles are enclosed by a rigid skull, they have a limited ability to accommodate additional volume. Additional volume (e.g. haematoma, tumour, excessive CSF) will therefore lead to a rise in intracranial pressure (ICP).

 

Pathophysiology

·         the normal ICP is 7-15 mmHg in adults in the supine position

·         cerebral perfusion pressure (CPP) is the net pressure gradient causing cerebral blood flow to the brain

·         CPP = mean arterial pressure - ICP

Causes

·         idiopathic intracranial hypertension

·         traumatic head injuries

·         infection

o    meningitis

·         tumours

·         hydrocephalus

Features

·         headache

·         vomiting

·         reduced levels of consciousness

·         papilloedema

·         Cushing's triad

o    widening pulse pressure

o    bradycardia

o    irregular breathing

Investigations and monitoring

·         neuroimaging (CT/MRI) is key to investigate the underlying cause

·         invasive ICP monitoring

o    catheter placed into the lateral ventricles of the brain to monitor the pressure

o    may also be used to take collect CSF samples and also to drain small amounts of CSF to reduce the pressure

o    a cut-off of > 20 mmHg is often used to determine if further treatment is needed to reduce the ICP

Management

·         investigate and treat the underlying cause

·         head elevation to 30º

·         IV mannitol may be used as an osmotic diuretic

·         controlled hyperventilation

o    aim is to reduce pCO2 → vasoconstriction of the cerebral arteries → reduced ICP

o    leads to rapid, temporary lowering of ICP. However, caution needed as may reduce blood flow to already ischaemic parts of the brain

·         removal of CSF, different techniques include:

o    drain from intraventricular monitor (see above)

o    repeated lumbar puncture (e.g. idiopathic intracranial hypertension)

o    ventriculoperitoneal shunt (for hydrocephalus)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Restless legs syndrome

Restless legs syndrome (RLS) is a syndrome of spontaneous, continuous lower limb movements that may be associated with paraesthesia. It is extremely common, affecting between 2-10% of the general population. Males and females are equally affected and a family history may be present

 

Clinical features

·         uncontrollable urge to move legs (akathisia). Symptoms initially occur at night but as condition progresses may occur during the day. Symptoms are worse at rest

·         paraesthesias e.g. 'crawling' or 'throbbing' sensations

·         movements during sleep may be noted by the partner - periodic limb movements of sleeps (PLMS)

Causes and associations

·         there is a positive family history in 50% of patients with idiopathic RLS

·         iron deficiency anaemia

·         uraemia

·         diabetes mellitus

·         pregnancy

The diagnosis is clinical although bloods such as ferritin to exclude iron deficiency anaemia may be appropriate

 

Management

·         simple measures: walking, stretching, massaging affected limbs

·         treat any iron deficiency

·         dopamine agonists are first-line treatment (e.g. Pramipexole, ropinirole)

·         benzodiazepines

·         gabapentin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Seizures: acute management

Most seizures are self-limiting and stop spontaneously but prolonged seizures may be potentially life-threatening.

 

Basics

·         check the airway and apply oxygen if appropriate

·         place the patient in the recovery position

·         if the seizure is prolonged give benzodiazepines

BNF recommend dose for rectal diazepam, repeated once after 10-15 minutes if necessary

 

 

Neonate

1.25 - 2.5 mg

Child 1 month - 1 year

5 mg

Child 2 years - 11 years

5 - 10 mg

Child 12 years - 17 years

10 mg

Adult

10 - 20 mg (max. 30 mg)

Elderly

10 mg (max. 15 mg)

Midazolam oromucosal solution may also be used:

 

 

Neonate

300 mcg/kg (unlicensced)

Child 1 - 2 months

300 mcg/kg (max. 2.5mg, unlicensced)

Child 3 - 11 months

2.5 mg

Child 1 - 4 years

5 mg

Child 5 - 9 years

7.5 mg

Child 10 - 17 years

10 mg

Adult

10 mg (unlicensced)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Spontaneous intracranial hypotension

Spontaneous intracranial hypotension is a very rare cause of headaches that results from a CSF leak. The leak is typically from the thoracic nerve root sleeves.

 

Risk factors include connective tissue disorders such as Marfan's syndrome.

 

Key features

·         strong postural relationship with the headache generally much worse when upright. Patients may, therefore, be bed-bound

Investigations

·         MRI with gadolinium: typically shows pachymeningeal enhancement

Management

·         usually conservative

·         if this fails an epidural blood patch may be tried

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:22

Stroke: a very basic introduction

Strokes represent an important cause of morbidity and mortality. In the UK alone there are over 150,000 strokes per year, with over 1.2 million stroke survivors. Stroke is the fourth largest cause of death in the UK and kills twice as many women than breast cancer each year.

 

The prevention and treatment of strokes has undergone significant changes over the past decade. What was previously considered a devastating but untreatable condition is now viewed more as a 'brain attack', a condition which requires emergency assessment to see if patients may benefit from new treatments such as thrombolysis.

 

 

 

 

© Image used on license from PathoPic

Pathological specimen showing the results of an ischaemic stroke to the occipito-parietal region of the cerebrum. Note there has been some secondary haemorrhage in the affected area.

 

 

What is a stroke?

 

A stroke (also known as cerebrovascular accident,CVA) represents a sudden interruption in the vascular supply of the brain. Remember that neural tissue is completely dependent on aerobic metabolism so any problem with oxygen supply can quickly lead to irreversible damage.

 

There are two main types of strokes:

·         ischaemic: these can be further subdivided between into episodes which last greater than 24 hours (termed an ischaemic stroke) and episodes where symptoms and signs last less than 24 hours (transient ischaemic attacks, TIAs, sometimes termed 'mini-strokes' by patients)

·         haemorrhagic

The table below shows the basic differences:

 

 

 

Ischaemic

Haemorrhagic

Essential problem

'Blockage' in the blood vessel stops blood flow

Blood vessel 'bursts' leading to reduction in blood flow

Proportion of strokes

85%

15%

Subtypes

Thrombotic stroke

·         thrombosis from large vessels e.g. carotid

Embolic stroke

·         usually a blood clot but fat, air or clumps of bacteria may act as an embolus

·         atrial fibrillation is an important cause of emboli forming in the heart

Intracerebral haemorrhage

·         bleeding within the brain

Subarachnoid haemorrhage

·         bleeding on the surface of the brain

Risk factors

General risk factors for cardiovascular disease

·         age

·         hypertension

·         smoking

·         hyperlipidaemia

·         diabetes mellitus

Risk factors for cardioembolism

·         atrial fibrillation

Risk factors

·         age

·         hypertension

·         arteriovenous malformation

·         anticoagulation therapy

 

Symptoms and signs

 

Stroke is defined by the World Health Organization as a clinical syndrome consisting of 'rapidly developing clinical signs of focal (at times global) disturbance of cerebral function, lasting more than 24 hours or leading to death with no apparent cause other than that of vascular origin'. In contrast, with a TIA the symptoms and signs resolve within 24 hours.

 

Features include:

·         motor weakness

·         speech problems (dysphasia)

·         swallowing problems

·         visual field defects (homonymous hemianopia)

·         balance problems

Cerebral hemisphere infarcts may have the following symptoms:

·         contralateral hemiplegia: initially flaccid then spastic

·         contralateral sensory loss

·         homonymous hemianopia

·         dysphasia

Brainstem infarction

·         may result in more severe symptoms including quadriplegia and lock-in-syndrome

Lacunar infarcts

·         small infarcts around the basal ganglia, internal capsule, thalamus and pons

·         this may result in pure motor, pure sensory, mixed motor and sensory signs or ataxia

 

 

 

© Image used on license from PathoPic

An example of a lacunar infarct affecting the internal capsule.

 

 

 

One formal classification system that is sometimes used is the Oxford Stroke Classification (also known as the Bamford Classification), whichclassifies strokes based on the initial symptoms. A summary is as follows:

 

The following criteria should be assessed:

·         1. unilateral hemiparesis and/or hemisensory loss of the face, arm & leg

·         2. homonymous hemianopia

·         3. higher cognitive dysfunction e.g. dysphasia

 

Stroke type

Notes

Total anterior circulation infarcts (TACI, c. 15%)

·         involves middle and anterior cerebral arteries

·         all 3 of the above criteria are present

Partial anterior circulation infarcts (PACI, c. 25%)

·         involves smaller arteries of anterior circulation e.g. upper or lower division of middle cerebral artery

·         2 of the above criteria are present

Lacunar infarcts (LACI, c. 25%)

·         involves perforating arteries around the internal capsule, thalamus and basal ganglia

·         presents with 1 of the following:

·         1. unilateral weakness (and/or sensory deficit) of face and arm, arm and leg or all three.

·         2. pure sensory stroke.

·         3. ataxic hemiparesis

Posterior circulation infarcts (POCI, c. 25%)

·         involves vertebrobasilar arteries

·         presents with 1 of the following:

·         1. cerebellar or brainstem syndromes

·         2. loss of consciousness

·         3. isolated homonymous hemianopia

Whilst symptoms alone cannot be used to differentiate haemorrhagic from ischaemic strokes, patients who've suffered haemorrhages are more likely to have:

·         decrease in the level of consciousness: seen in up to 50% of patients with a haemorrhagic stroke

·         headache is also much more common in haemorrhagic stroke

·         nausea and vomiting is also common

·         seizures occur in up to 25% of patients

 

 

© Image used on license from PathoPic

Pathological specimen showing the consequence of an intracerebral haemorrhage

 

Over recent years there has been a public health campaign to raise awareness of stroke symptoms. The FAST campaign uses the following mnemonic:

·         Face - 'Has their face fallen on one side? Can they smile?'

·         Arms - 'Can they raise both arms and keep them there?'

·         Speech - 'Is their speech slurred?'

·         Ttime - 'Time to call 999 if you see any single one of these signs.'

 

Investigations

 

Patients with suspected stroke need to have emergency neuroimaging. The main cause for urgency is to see whether a patient may be suitable for thrombolytic therapy to treat early ischaemic strokes. The two types of neuroimaging used in this setting are:

·         CT

·         MRI

 

 

Image sourced from Wikipedia

CT scan of the brain showing a right-hemispheric ischemic stroke

 

Management

 

Ischaemic strokes

 

Urgent neuroimaging classifies the stroke as either ischaemic or haemorrhagic. If the stroke is ischaemic, and certain criteria are met, the patient should be offered thrombolysis. Example criteria include:

·         patients present with 4.5 hours of onset of stroke symptoms

·         the patient has not had a previous intracranial haemorrhage, uncontrolled hypertension, pregnant etc

Once haemorrhagic stroke has been excluded patients should be given aspirin 300mg as soon as possible and antiplatelet therapy should be continued.

 

Transient ischaemic attacks

 

Remember with TIAs the, by definition, symptoms last less than 24 hours although in the vast majority of cases the duration is much shorter, typically 1 hour or so. For this reason most patients symptoms will have resolved before they see a doctor.

 

The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE recommend:

 

Immediate antithrombotic therapy:

·         give aspirin 300 mg immediately, unless contraindicated e.g. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)

If the patient has had more than 1 TIA ('crescendo TIA') or has a suspected cardioembolic source or severe carotid stenosis:

·         discuss the need for admission or observation urgently with a stroke specialist

If the patient has had a suspected TIA in the last 7 days:

·         arrange urgent assessment (within 24 hours) by a specialist stroke physician

If the patient has had a suspected TIA which occurred more than a week previously:

·         refer for specialist assessment as soon as possible within 7 days

Haemorrhagic strokes

 

If imaging confirms a haemorrhagic stroke neurosurgical consultation should be considered for advice on further management. The vast majority of patients however are not suitable for surgical intervention. Management is therefore supportive as per haemorrhagic stroke. Anticoagulants (e.g. warfarin) and antithrombotic medications (e.g. clopidogrel) should be stopped to minimise further bleeding. If a patient is anticoagulated this should be reversed as quickly as possible. Trials have shown improved outcomes in patients who have their blood pressure lowered acutely and this is now part of many protocols for haemorrhagic strokes.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

17:23

Multiple sclerosis: management

Treatment in multiple sclerosis is focused at reducing the frequency and duration of relapses. There is no cure.

 

Acute relapse

 

High dose steroids (e.g. oral or IV methylprednisolone) may be given for 5 days to shorten the length of an acute relapse. It should be noted that steroids shorten the duration of a relapse and do not alter the degree of recovery (i.e. whether a patient returns to baseline function)

 

Disease modifying drugs

 

Beta-interferon has been shown to reduce the relapse rate by up to 30%. Certain criteria have to be met before it is used:

·         relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided

·         secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)

·         reduces number of relapses and MRI changes, however doesn't reduce overall disability

Other drugs used in the management of multiple sclerosis include:

·         glatiramer acetate: immunomodulating drug - acts as an 'immune decoy'

·         natalizumab: a recombinant monoclonal antibody that antagonises Alpha-4 Beta-1-integrin found on the surface of leucocytes, thus inhibiting migration of leucocytes across the endothelium across the blood-brain barrier

·         fingolimod: sphingosine 1-phosphate receptor modulator, prevents lymphocytes from leaving lymph nodes. An oral formulation is available

Some specific problems

 

Fatigue

·         once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of amantadine

·         other options include mindfulness training and CBT

Spasticity

·         baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine

·         physiotherapy is important

·         cannabis and botox are undergoing evalulation

Bladder dysfunction

·         may take the form of urgency, incontinence, overflow etc

·         guidelines stress the importance of getting an ultrasound first to assess bladder emptying - anticholinergics may worsen symptoms in some patients

·         if significant residual volume → intermittent self-catheterisation

·         if no significant residual volume → anticholinergics may improve urinary frequency

Oscillopsia (visual fields apper to oscillate)

·         gabapentin is first-line

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

Tuesday, 22 December 2020

18:30

Subacute combined degeneration of spinal cord

Basics

·         due to vitamin B12 deficiency

·         dorsal + lateral columns affected

·         joint position and vibration sense lost first then distal paraesthesia

·         upper motor neuron signs typically develop in the legs, classically extensor plantars, brisk knee reflexes, absent ankle jerks

·         if untreated stiffness and weakness persist

 

 

 

 

21 December 2020

21:52

Stroke: management

The Royal College of Physicians (RCP) published guidelines on the diagnosis and management of patients following a stroke in 2004. NICE updated their stroke guidelines in 2019.

 

Selected points relating to the management of acute stroke include:

·         blood glucose, hydration, oxygen saturation and temperature should be maintained within normal limits

·         blood pressure should not be lowered in the acute phase unless there are complications e.g. Hypertensive encephalopathy*

·         aspirin 300mg orally or rectally should be given as soon as possible if a haemorrhagic stroke has been excluded

·         with regards to atrial fibrillation, the RCP state: 'anticoagulants should not be started until brain imaging has excluded haemorrhage, and usually not until 14 days have passed from the onset of an ischaemic stroke'

·         if the cholesterol is > 3.5 mmol/l patients should be commenced on a statin. Many physicians will delay treatment until after at least 48 hours due to the risk of haemorrhagic transformation

 

Thrombolysis for acute ischaemic stroke

 

Thrombolysis with alteplase should only be given if:

·         it is administered within 4.5 hours of onset of stroke symptoms (unless as part of a clinical trial)

·         haemorrhage has been definitively excluded (i.e. Imaging has been performed)

Contraindications to thrombolysis:

 

 

Absolute

Relative

- Previous intracranial haemorrhage

- Seizure at onset of stroke

- Intracranial neoplasm

- Suspected subarachnoid haemorrhage

- Stroke or traumatic brain injury in preceding 3 months

- Lumbar puncture in preceding 7 days

- Gastrointestinal haemorrhage in preceding 3 weeks

- Active bleeding

- Pregnancy

- Oesophageal varices

- Uncontrolled hypertension >200/120mmHg

- Concurrent anticoagulation (INR >1.7)

- Haemorrhagic diathesis

- Active diabetic haemorrhagic retinopathy

- Suspected intracardiac thrombus

- Major surgery / trauma in the preceding 2 weeks

 

Thrombectomy for acute ischaemic stroke

 

Mechanical thrombectomy is an exciting new treatment option for patients with an acute ischaemic stroke. NICE incorporated recommendations into their 2019 guidelines. It is important to remember the significant resources and senior personnel to provide such a service 24 hours a day. NICE recommend that all decisions about thrombectomy take into account a patient's overall clinical status:

·         NICE recommend a pre-stroke functional status of less than 3 on the modified Rankin scale and a score of more than 5 on the National Institutes of Health Stroke Scale (NIHSS)

Offer thrombectomy as soon as possible and within 6 hours of symptom onset, together with intravenous thrombolysis (if within 4.5 hours), to people who have:

acute ischaemic stroke and

·         confirmed occlusion of the proximal anterior circulation demonstrated by computed tomographic angiography (CTA) or magnetic resonance angiography (MRA)

Offer thrombectomy as soon as possible to people who were last known to be well between 6 hours and 24 hours previously (including wake-up strokes):

·         confirmed occlusion of the proximal anterior circulation demonstrated by CTA or MRA and

·         if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume

Consider thrombectomy together with intravenous thrombolysis (if within 4.5 hours) as soon as possible for people last known to be well up to 24 hours previously (including wake-up strokes):

·         who have acute ischaemic stroke and confirmed occlusion of the proximal posterior circulation (that is, basilar or posterior cerebral artery) demonstrated by CTA or MRA and

·         if there is the potential to salvage brain tissue, as shown by imaging such as CT perfusion or diffusion-weighted MRI sequences showing limited infarct core volume

 

Secondary prevention

 

NICE also published a technology appraisal in 2010 on the use of clopidogrel and dipyridamole

 

Recommendations from NICE include:

·         clopidogrel is now recommended by NICE ahead of combination use of aspirin plus modified-release (MR) dipyridamole in people who have had an ischaemic stroke

·         aspirin plus MR dipyridamole is now recommended after an ischaemic stroke only if clopidogrel is contraindicated or not tolerated, but treatment is no longer limited to 2 years' duration

·         MR dipyridamole alone is recommended after an ischaemic stroke only if aspirin or clopidogrel are contraindicated or not tolerated, again with no limit on duration of treatment

With regards to carotid artery endarterectomy:

·         recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled

·         should only be considered if carotid stenosis > 70% according ECST** criteria or > 50% according to NASCET*** criteria

*the 2009 Controlling hypertension and hypotension immediately post-stroke (CHHIPS) trial may change thinking on this but guidelines have yet to change to reflect this

**European Carotid Surgery Trialists' Collaborative Group

***North American Symptomatic Carotid Endarterectomy Trial

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:52

Visual field defects

The main points for the exam are:

·         left homonymous hemianopia means visual field defect to the left, i.e. Lesion of right optic tract

·         homonymous quadrantanopias: PITS (Parietal-Inferior, Temporal-Superior)

·         incongruous defects = optic tract lesion; congruous defects = optic radiation lesion or occipital cortex

A congruous defect simply means complete or symmetrical visual field loss and conversely an incongruous defect is incomplete or asymmetric. Please see the link for an excellent diagram.

 

Homonymous hemianopia

·         incongruous defects: lesion of optic tract

·         congruous defects: lesion of optic radiation or occipital cortex

·         macula sparing: lesion of occipital cortex

Homonymous quadrantanopias*

·         superior: lesion of the inferior optic radiations in the temporal lobe (Meyer's loop)

·         inferior: lesion of the superior optic radiations in the parietal lobe

·         mnemonic = PITS (Parietal-Inferior, Temporal-Superior)

Bitemporal hemianopia

·         lesion of optic chiasm

·         upper quadrant defect > lower quadrant defect = inferior chiasmal compression, commonly a pituitary tumour

·         lower quadrant defect > upper quadrant defect = superior chiasmal compression, commonly a craniopharyngioma

*this is very much the 'exam answer'. Actual studies suggest that the majority of quadrantanopias are caused by occipital lobe lesions. Please see the link for more details.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

23:04

Tremor

The table below lists the main characteristics of the most important causes of tremor

 

 

Conditions

Notes

Parkinsonism

Resting, 'pill-rolling' tremor

Bradykinesia

Rigidity

Flexed posture, short, shuffling steps

Micrographia

'Mask-like' face

Depression & dementia are common

May be history of anti-psychotic use

Essential tremor

Postural tremor: worse if arms outstretched

Improved by alcohol and rest

Titubation

Often strong family history

Anxiety

History of depression

Thyrotoxicosis

Usual thyroid signs e.g. Weight loss, tachycardia, feeling hot etc

Hepatic encephalopathy

History of chronic liver disease

Carbon dioxide retention

History of chronic obstructive pulmonary disease

Cerebellar disease

Intention tremor

Cerebellar signs e.g. Past-pointing, nystagmus etc

Other causes

·         drug withdrawal: alcohol, opiates

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

16:35

 

Parkinsonism

Causes of Parkinsonism

·         Parkinson's disease

·         drug-induced e.g. antipsychotics, metoclopramide*

·         progressive supranuclear palsy

·         multiple system atrophy

·         Wilson's disease

·         post-encephalitis

·         dementia pugilistica (secondary to chronic head trauma e.g. boxing)

·         toxins: carbon monoxide, MPTP

*Domperidone does not cross the blood-brain barrier and therefore does not cause extra-pyramidal side-effects.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

19:18

Triptans

Triptans are specific 5-HT1B and 5-HT1D agonists used in the acute treatment of migraine. They are generally used first-line in combination therapy with an NSAID or paracetamol.

 

Prescribing points

·         should be taken as soon as possible after the onset of headache, rather than at onset of aura

·         oral, orodispersible, nasal spray and subcutaneous injections are available

Adverse effects

·         'triptan sensations' - tingling, heat, tightness (e.g. throat and chest), heaviness, pressure

Contraindications

·         patients with a history of, or significant risk factors for, ischaemic heart disease or cerebrovascular disease

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

19:20

 

Transient ischaemic attack

The original definition of a transient ischaemic attack (TIA) was time-based: a sudden onset of a focal neurologic symptom and/or sign lasting less than 24 hours, brought on by a transient decrease in blood flow. However, this has now changed as it is recognised that even short periods of ischaemia can result in pathological changes to the brain. Therefore, a new 'tissue-based' definition is now used: a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia, without acute infarction.

 

Patients often use the term 'mini-stroke' for TIAs.

 

Assessment and referral

 

The ABCD2 prognostic score has previously been used to risk stratify patients who present with a suspected TIA. However, data from studies have suggested it performs poorly and it is therefore no longer recommended by NICE Clinical Knowledge Summaries. Instead, NICE recommend:

 

Immediate antithrombotic therapy:

·         give aspirin 300 mg immediately, unless

·         1. the patient has a bleeding disorder or is taking an anticoagulant (needs immediate admission for imaging to exclude a haemorrhage)

·         2. the patient is already taking low-dose aspirin regularly: continue the current dose of aspirin until reviewed by a specialist

·         3. Aspirin is contraindicated: discuss management urgently with the specialist team

If the patient has had more than 1 TIA ('crescendo TIA') or has a suspected cardioembolic source or severe carotid stenosis:

·         discuss the need for admission or observation urgently with a stroke specialist

If the patient has had a suspected TIA in the last 7 days:

·         arrange urgent assessment (within 24 hours) by a specialist stroke physician

If the patient has had a suspected TIA which occurred more than a week previously:

·         refer for specialist assessment as soon as possible within 7 days

Advise the person not to drive until they have been seen by a specialist.

 

 

Further management

 

Antithrombotic therapy

·         clopidogrel is recommended first-line (as for patients who've had a stroke)

·         aspirin + dipyridamole should be given to patients who cannot tolerate clopidogrel

·         these recommendations follow the 2012 Royal College of Physicians National clinical guideline for stroke. Please see the link for more details (section 5.5)

·         these guidelines may change following the CHANCE study (NEJM 2013;369:11). This study looked at giving high-risk TIA patients aspirin + clopidogrel for the first 90 days compared to aspirin alone. 11.7% of aspirin only patients had a stroke over 90 days compared to 8.2% of dual antiplatelet patients

With regards to carotid artery endarterectomy:

·         recommend if patient has suffered stroke or TIA in the carotid territory and are not severely disabled

·         should only be considered if carotid stenosis > 70% according ECST* criteria or > 50% according to NASCET** criteria

*European Carotid Surgery Trialists' Collaborative Group

**North American Symptomatic Carotid Endarterectomy Trial

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

Wednesday, 23 December 2020

00:56

Brain abscess

Brain abscesses may result from a number of causes including, extension of sepsis from middle ear or sinuses, trauma or surgery to the scalp, penetrating head injuries and embolic events from endocarditis

 

The presenting symptoms will depend upon the site of the abscess (those in critical areas e.g. motor cortex) will present earlier. Abscesses have a considerable mass effect in the brain and raised intracranial pressure is common.

·         headache

o    often dull, persistent

·         fever

o    may be absent and usually not the swinging pyrexia seen with abscesses at other sites

·         focal neurology

o    e.g. oculomotor nerve palsy or abducens nerve palsy secondary to raised intracranial pressure

·         other features consistent with raised intracranial pressure

o    nausea

o    papilloedema

o    seizures

Investigations

·         Assessment of the patient includes imaging with CT scanning

Management

·         surgery

o    a craniotomy is performed and the abscess cavity debrided

o    the abscess may reform because the head is closed following abscess drainage.

·         IV antibiotics:  IV 3rd-generation cephalosporin + metronidazole

·         intracranial pressure management: e.g. dexamethasone

 

 

 

 

22 December 2020

19:33

Brain lesions

The following neurological disorders/features may allow localisation of a brain lesion:

 

Gross anatomy

 

Parietal lobe lesions

·         sensory inattention

·         apraxias

·         astereognosis (tactile agnosia)

·         inferior homonymous quadrantanopia

·         Gerstmann's syndrome (lesion of dominant parietal): alexia, acalculia, finger agnosia and right-left disorientation

Occipital lobe lesions

·         homonymous hemianopia (with macula sparing)

·         cortical blindness

·         visual agnosia

Temporal lobe lesion

·         Wernicke's aphasia: this area 'forms' the speech before 'sending it' to Brocas area. Lesions result in word substituion, neologisms but speech remains fluent

·         superior homonymous quadrantanopia

·         auditory agnosia

·         prosopagnosia (difficulty recognising faces)

Frontal lobes lesions

·         expressive (Broca's) aphasia: located on the posterior aspect of the frontal lobe, in the inferior frontal gyrus. Speech is non-fluent, laboured, and halting

·         disinhibition

·         perseveration

·         anosmia

·         inability to generate a list

Cerebellum lesions

·         midline lesions: gait and truncal ataxia

·         hemisphere lesions: intention tremor, past pointing, dysdiadokinesis, nystagmus

More specific areas

 

 

Area

Associated conditions

Medial thalamus and mammillary bodies of the hypothalamus

Wernicke and Korsakoff syndrome

Subthalamic nucleus of the basal ganglia

Hemiballism

Striatum (caudate nucleus) of the basal ganglia

Huntington chorea

Substantia nigra of the basal ganglia

Parkinson's disease

Amygdala

Kluver-Bucy syndrome (hypersexuality, hyperorality, hyperphagia, visual agnosia

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

22 December 2020

19:40

Cranial nerves

The table below lists the major characteristics of the 12 cranial nerves:

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

I (Olfactory)

Smell

 

Cribriform plate

II (Optic)

Sight

 

Optic canal

III (Oculomotor)

Eye movement (MR, IO, SR, IR)

Pupil constriction

Accomodation

Eyelid opening

Palsy results in

·         ptosis

·         'down and out' eye

·         dilated, fixed pupil

Superior orbital fissure (SOF)

IV (Trochlear)

Eye movement (SO)

Palsy results in defective downward gaze → vertical diplopia

SOF

V (Trigeminal)

Facial sensation

Mastication

Lesions may cause:

·         trigeminal neuralgia

·         loss of corneal reflex (afferent)

·         loss of facial sensation

·         paralysis of mastication muscles

·         deviation of jaw to weak side

V1: SOF, V2: Foramen rotundum,

V3: Foramen ovale

VI (Abducens)

Eye movement (LR)

Palsy results in defective abduction → horizontal diplopia

SOF

VII (Facial)

Facial movement

Taste (anterior 2/3rds of tongue)

Lacrimation

Salivation

Lesions may result in:

·         flaccid paralysis of upper + lower face

·         loss of corneal reflex (efferent)

·         loss of taste

·         hyperacusis

Internal auditory meatus

VIII (Vestibulocochlear)

Hearing, balance

Hearing loss

Vertigo, nystagmus

Acoustic neuromas are Schwann cell tumours of the cochlear nerve

Internal auditory meatus

IX (Glossopharyngeal)

Taste (posterior 1/3rd of tongue)

Salivation

Swallowing

Mediates input from carotid body & sinus

Lesions may result in;

·         hypersensitive carotid sinus reflex

·         loss of gag reflex (afferent)

Jugular foramen

X (Vagus)

Phonation

Swallowing

Innervates viscera

Lesions may result in;

·         uvula deviates away from site of lesion

·         loss of gag reflex (efferent)

Jugular foramen

XI (Accessory)

Head and shoulder movement

Lesions may result in;

·         weakness turning head to contralateral side

Jugular foramen

XII (Hypoglossal)

Tongue movement

Tongue deviates towards side of lesion

Hypoglossal canal

Some cranial nerves are motor, some sensory and some are both. The most useful mnemonic is given below.

 

CN I ----------------------------------------------------------------------→XII

 

Some Say Marry Money But My Brother Says Big Brains Matter Most

 

S = Sensory, M = Motor, B = Both

 

 

 

 

Image sourced from Wikipedia

View from the inferior surface of the brain showing the emergence of the cranial nerves

 

 

 

Image sourced from Wikipedia

Diagram showing the nuclei of the cranial nerves in the brainstem

 

 

Cranial nerve reflexes

 

 

Reflex

Afferent limb

Efferent limb

Corneal

Ophthalmic nerve (V1)

Facial nerve (VII)

Jaw jerk

Mandibular nerve (V3)

Mandibular nerve (V3)

Gag

Glossopharyngeal nerve (IX)

Vagal nerve (X)

Carotid sinus

Glossopharyngeal nerve (IX)

Vagal nerve (X)

Pupillary light

Optic nerve (II)

Oculomotor nerve (III)

Lacrimation

Ophthalmic nerve (V1)

Facial nerve (VII)

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

22 December 2020

19:52

Glasgow Coma Scale: adults

 

Modality

Options

Motor response

6. Obeys commands

5. Localises to pain

4. Withdraws from pain

3. Abnormal flexion to pain (decorticate posture)

2. Extending to pain

1. None

Verbal response

5. Orientated

4. Confused

3. Words

2. Sounds

1. None

Eye opening

4. Spontaneous

3. To speech

2. To pain

1. None

Glasgow coma scale (GCS) scores are generally expressed in the following format 'GCS = 13, M5 V4 E4 at 21:30'.

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

22 December 2020

20:16

Bell's palsy

Bell's palsy may be defined as an acute, unilateral, idiopathic, facial nerve paralysis. The aetiology is unknown although the role of the herpes simplex virus has been investigated previously. The peak incidence is 20-40 years and the condition is more common in pregnant women.

 

Features

·         lower motor neuron facial nerve palsy - forehead affected*

·         patients may also notice post-auricular pain (may precede paralysis), altered taste, dry eyes, hyperacusis

Management

·         in the past a variety of treatment options have been proposed including no treatment, prednisolone only and a combination of aciclovir and prednisolone

·         following a National Institute for Health randomised controlled trial it is now recommended that prednisolone 1mg/kg for 10 days should be prescribed for patients within 72 hours of onset of Bell's palsy. Adding in aciclovir gives no additional benefit

·         eye care is important - prescription of artificial tears and eye lubricants should be considered

Prognosis

·         if untreated around 15% of patients have permanent moderate to severe weakness

*upper motor neuron lesion 'spares' upper face

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

21 December 2020

21:51

Guillain-Barre syndrome: features

Guillain-Barre syndrome describes an immune-mediated demyelination of the peripheral nervous system often triggered by an infection (classically Campylobacter jejuni).

 

Initial symptoms

·         around 65% of patients experience back/leg pain in the initial stages of the illness

The characteristic features of Guillain-Barre syndrome is progressive, symmetrical weakness of all the limbs.

·         the weakness is classically ascending i.e. the legs are affected first

·         proximal muscles (e.g. hips/shoulders) are usually affected before than the distal ones (e.g. feet/hands)

·         reflexes are reduced or absent

·         sensory symptoms tend to be mild (e.g. distal paraesthesia) with very few sensory signs

Other features

·         there may be a history of gastroenteritis

·         respiratory muscle weakness

·         cranial nerve involvement

o    diplopia

o    bilateral facial nerve palsy

o    oropharyngeal weakness is common

·         autonomic involvement

o    urinary retention

o    diarrhoea

Less common findings

·         papilloedema: thought to be secondary to reduced CSF resorption

Investigations

·         lumbar puncture

o    rise in protein with a normal white blood cell count (albuminocytologic dissociation) - found in 66%

·         nerve condution studies may be performed

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:51

DVLA: neurological disorders

The guidelines below relate to car/motorcycle use unless specifically stated. For obvious reasons, the rules relating to drivers of heavy goods vehicles tend to be much stricter

 

Epilepsy/seizures - all patient must not drive and must inform the DVLA

·         first unprovoked/isolated seizure: 6 months off if there are no relevant structural abnormalities on brain imaging and no definite epileptiform activity on EEG. If these conditions are not met then this is increased to 12 months

·         for patients with established epilepsy or those with multiple unprovoked seizures:

·         → may qualify for a driving licence if they have been free from any seizure for 12 months

·         → if there have been no seizures for 5 years (with medication if necessary) a ’til 70 licence is usually restored

·         withdrawawl of epilepsy medication: should not drive whilst anti-epilepsy medication is being withdrawn and for 6 months after the last dose

Syncope

·         simple faint: no restriction

·         single episode, explained and treated: 4 weeks off

·         single episode, unexplained: 6 months off

·         two or more episodes: 12 months off

Other conditions

·         stroke or TIA: 1 month off driving, may not need to inform DVLA if no residual neurological deficit

·         multiple TIAs over short period of times: 3 months off driving and inform DVLA

·         craniotomy e.g. For meningioma: 1 year off driving*

·         pituitary tumour: craniotomy: 6 months; trans-sphenoidal surgery 'can drive when there is no debarring residual impairment likely to affect safe driving'

·         narcolepsy/cataplexy: cease driving on diagnosis, can restart once 'satisfactory control of symptoms'

·         chronic neurological disorders e.g. multiple sclerosis, motor neuron disease: DVLA should be informed, complete PK1 form (application for driving licence holders state of health)

 

*if the tumour is a benign meningioma and there is no seizure history, licence can be reconsidered 6 months after surgery if remains seizure free

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:51

Epilepsy: classification

The basic classification of epilepsy has changed in recent years. The new basic seizure classification is based on 3 key features:

·         1. Where seizures begin in the brain

·         2. Level of awareness during a seizure (important as can affect safety during seizure)

·         3. Other features of seizures

Focal seizures

·         previously termed partial seizures

·         these start in a specific area, on one side of the brain

·         the level of awareness can vary in focal seizures. The terms focal aware (previously termed 'simple partial'), focal impaired awareness (previously termed 'complex partial') and awareness unknown are used to further describe focal seizures

·         further to this, focal seizures can be classified as being motor (e.g. Jacksonian march), non-motor (e.g. déjà vu, jamais vu; ) or having other features such as aura

Generalised

·         these engage or involve networks on both sides of the brain at the onset

·         consciousness lost immediately. The level of awareness in the above classification is therefore not needed, as all patients lose consciousness

·         generalised seizures can be further subdivided into motor (e.g. tonic-clonic) and non-motor (e.g. absence)

·         specific types include:

·         → tonic-clonic (grand mal)

·         → tonic

·         → clonic

·         → typical absence (petit mal)

·         → atonic

Unknown onset

·         this termed is reserved for when the origin of the seizure is unknown

Focal to bilateral seizure

·         starts on one side of the brain in a specific area before spreading to both lobes

·         previously termed secondary generalized seizures

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:51

Epilepsy: treatment

Most neurologists now start antiepileptics following a second epileptic seizure. NICE guidelines suggest starting antiepileptics after the first seizure if any of the following are present:

·         the patient has a neurological deficit

·         brain imaging shows a structural abnormality

·         the EEG shows unequivocal epileptic activity

·         the patient or their family or carers consider the risk of having a further seizure unacceptable

It should be remembered that the following are only general guidelines. For example, maternal use of sodium valproate is associated with a significant risk of neurodevelopmental delay in children. Guidance is now clear that sodium valproate should not be used during pregnancy and in women of childbearing age unless clearly necessary.

 

Sodium valproate is considered the first line treatment for patients with generalised seizures with carbamazepine used for focal seizures.

 

Generalised tonic-clonic seizures

·         sodium valproate

·         second line: lamotrigine, carbamazepine

Absence seizures* (Petit mal)

·         sodium valproate or ethosuximide

·         sodium valproate particularly effective if co-existent tonic-clonic seizures in primary generalised epilepsy

Myoclonic seizures**

·         sodium valproate

·         second line: clonazepam, lamotrigine

Focal seizures

·         carbamazepine or lamotrigine

·         second line: levetiracetam, oxcarbazepine or sodium valproate

*carbamazepine may exacerbate absence seizures

 

**carbamazepine may exacerbate myoclonic seizures

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:52

Headache: red flags

Headache is one of the most common presenting complaints seen in clinical practice. The vast majority of these will be caused by common, benign conditions. There are however certain features in a history which should prompt further action. In the 2012 guidelines NICE suggest the following:

·         compromised immunity, caused, for example, by HIV or immunosuppressive drugs

·         age under 20 years and a history of malignancy

·         a history of malignancy known to metastasis to the brain

·         vomiting without other obvious cause

·         worsening headache with fever

·         sudden-onset headache reaching maximum intensity within 5 minutes - 'thunderclap'

·         new-onset neurological deficit

·         new-onset cognitive dysfunction

·         change in personality

·         impaired level of consciousness

·         recent (typically within the past 3 months) head trauma

·         headache triggered by cough, valsalva (trying to breathe out with nose and mouth blocked), sneeze or exercise

·         orthostatic headache (headache that changes with posture)

·         symptoms suggestive of giant cell arteritis or acute narrow-angle glaucoma

·         a substantial change in the characteristics of their headache

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:52

Idiopathic intracranial hypertension

Idiopathic intracranial hypertension (also known as pseudotumour cerebri and formerly benign intracranial hypertension) is a condition classically seen in young, overweight females.

 

Risk factors

·         obesity

·         female sex

·         pregnancy

·         drugs*: oral contraceptive pill, steroids, tetracycline, vitamin A, lithium

Features

·         headache

·         blurred vision

·         papilloedema (usually present)

·         enlarged blind spot

·         sixth nerve palsy may be present

Management

·         weight loss

·         diuretics e.g. acetazolamide

·         topiramate is also used, and has the added benefit of causing weight loss in most patients

·         repeated lumbar puncture

·         surgery: optic nerve sheath decompression and fenestration may be needed to prevent damage to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also be performed to reduce intracranial pressure

*if intracranial hypertension is thought to occur secondary to a known causes (e.g. Medication) then it is of course not idiopathic

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:52

Motor neuron disease: types

Motor neuron disease is a neurological condition of unknown cause which can present with both upper and lower motor neuron signs. It rarely presents before 40 years and various patterns of disease are recognised including amyotrophic lateral sclerosis, primary lateral sclerosis, progressive muscular atrophy and progressive bulbar palsy. In some patients however, there is a combination of clinical patterns

 

Amyotrophic lateral sclerosis (50% of patients)

·         typically LMN signs in arms and UMN signs in legs

·         in familial cases the gene responsible lies on chromosome 21 and codes for superoxide dismutase

Primary lateral sclerosis

·         UMN signs only

Progressive muscular atrophy

·         LMN signs only

·         affects distal muscles before proximal

·         carries best prognosis

Progressive bulbar palsy

·         palsy of the tongue, muscles of chewing/swallowing and facial muscles due to loss of function of brainstem motor nuclei

·         carries worst prognosis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:52

Multiple sclerosis: features

Patient's with multiple sclerosis (MS) may present with non-specific features, for example around 75% of patients have significant lethargy.

 

Diagnosis can be made on the basis of two or more relapses and either objective clinical evidence of two or more lesions or objective clinical evidence of one lesion together with reasonable historical evidence of a previous relapse.

 

Visual

·         optic neuritis: common presenting feature

·         optic atrophy

·         Uhthoff's phenomenon: worsening of vision following rise in body temperature

·         internuclear ophthalmoplegia

Sensory

·         pins/needles

·         numbness

·         trigeminal neuralgia

·         Lhermitte's syndrome: paraesthesiae in limbs on neck flexion

Motor

·         spastic weakness: most commonly seen in the legs

Cerebellar

·         ataxia: more often seen during an acute relapse than as a presenting symptom

·         tremor

Others

·         urinary incontinence

·         sexual dysfunction

·         intellectual deterioration

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

18:15

 

Ataxia

Cerebellar hemisphere lesions cause peripheral ('finger-nose ataxia')

wide-based gait with loss of heel to toe walking,

Cerebellar vermis lesions cause gait ataxia

 

 

 

 

Ataxic gaits are often caused by cerebellar lesions. The mnemonic 'PASTRIES' can be used to remember the causes of an ataxic gait.

 

P - paraneoplastic syndrome

A - abscess/atrophy

S - stroke/sclerosis (multiple sclerosis)

T - trauma

R - raised ICP

I - infection

E - ethanol and poisons

S - spinocerebellar ataxia (progressive degenerative genetic disease)

 

 

 

 

Ataxic gaits typically occur following cerebellar injury, the causes of which can be remembered by the mnemonic 'pastries'

 

P - Posterior fossa tumour

A - Alcohol

S - Multiple sclerosis

T - Trauma

R - Rare causes

I - Inherited (e.g. Friedreich's ataxia)

E - Epilepsy treatments

S - Stroke

 

 

 

 

22 December 2020

19:07

Stroke: assessment

Whilst the diagnosis of stroke may sometimes be obvious in many cases the presenting symptoms may be vague and accurate assessment difficult.

 

The FAST screening tool (Face/Arms/Speech/Time) is widely known by the general public following a publicity campaign. It has a positive predictive value of 78%.

 

A variant of FAST called the ROSIER score is useful for medical professionals. It is validated tool recommended by the Royal College of Physicians.

 

ROSIER score

 

Exclude hypoglycaemia first, then assess the following:

 

 

Assessment

Scoring

Loss of consciousness or syncope

- 1 point

Seizure activity

- 1 point

New, acute onset of:

 

• asymmetric facial weakness

+ 1 point

• asymmetric arm weakness

+ 1 point

• asymmetric leg weakness

+ 1 point

• speech disturbance

+ 1 point

• visual field defect

+ 1 point

A stroke is likely if > 0.

 

Investigations

 

A non-contrast CT head scan is the first line radiological investigation for suspected stroke

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

16:23

Essential tremor

Essential tremor (previously called benign essential tremor) is an autosomal dominant condition which usually affects both upper limbs

 

Features

·         postural tremor: worse if arms outstretched

·         improved by alcohol and rest

·         most common cause of titubation (head tremor)

Management

·         propranolol is first-line

·         primidone is sometimes used

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

Tuesday, 22 December 2020

22:45

Wernicke's encephalopathy

Wernicke's encephalopathy is a neuropsychiatric disorder caused by thiamine deficiency which is most commonly seen in alcoholics. Rarer causes include: persistent vomiting, stomach cancer, dietary deficiency. A classic triad of ophthalmoplegia/nystagmus, ataxia and confusion may occur. In Wernicke's encephalopathy petechial haemorrhages occur in a variety of structures in the brain including the mamillary bodies and ventricle walls.

 

Features

·         nystagmus (the most common ocular sign)

·         ophthalmoplegia

·         ataxia

·         confusion, altered GCS

·         peripheral sensory neuropathy

Investigations

·         decreased red cell transketolase

·         MRI

Treatment is with urgent replacement of thiamine

 

Relationship with Korsakoff syndrome

 

If not treated Korsakoff's syndrome may develop as well. This is termed Wernicke-Korsakoff syndrome and is characterised by the addition of antero- and retrograde amnesia and confabulation in addition to the above symptoms.

 

 

 

A useful mnemonic to remember the features of Wernicke's encephalopathy is CAN OPEN

Confusion

Ataxia

Nystagmus

Ophthamoplegia

PEripheral 

Neuropathy

 

Retrograde amnesia and confabulation are features of Korsakoff's psychosis

 

 

 

 

Wednesday, 23 December 2020

00:53

Cataplexy

Cataplexy describes the sudden and transient loss of muscular tone caused by strong emotion (e.g. laughter, being frightened). Around two-thirds of patients with narcolepsy have cataplexy.

 

Features range from buckling knees to collapse.

 

 

 

 

22 December 2020

20:39

Vestibular schwannoma (acoustic neuroma)

Vestibular schwannomas (sometimes referred to as acoustic neuromas) account for approximately 5% of intracranial tumours and 90% of cerebellopontine angle tumours.

 

The classical history of vestibular schwannoma includes a combination of vertigo, hearing loss, tinnitus and an absent corneal reflex. Features can be predicted by the affected cranial nerves:

·         cranial nerve VIII: vertigo, unilateral sensorineural hearing loss, unilateral tinnitus

·         cranial nerve V: absent corneal reflex

·         cranial nerve VII: facial palsy

Bilateral vestibular schwannomas are seen in neurofibromatosis type 2.

 

Patients with a suspected vestibular schwannoma should be referred urgently to ENT. It should be noted though that the tumours are often slow growing, benign and often observed initially.

 

MRI of the cerebellopontine angle is the investigation of choice. Audiometry is also important as only 5% of patients will have a normal audiogram.

 

Management is with either surgery, radiotherapy or observation.

 

From <https://www.passmedicine.com/question/questions.php?q=0#>

 

 

 

 

 

 

 

 

 

22 December 2020

20:47

Idiopathic intracranial hypertension

Idiopathic intracranial hypertension (also known as pseudotumour cerebri and formerly benign intracranial hypertension) is a condition classically seen in young, overweight females.

 

Risk factors

·         obesity

·         female sex

·         pregnancy

·         drugs*: oral contraceptive pill, steroids, tetracycline, vitamin A, lithium

Features

·         headache

·         blurred vision

·         papilloedema (usually present)

·         enlarged blind spot

·         sixth nerve palsy may be present

Management

·         weight loss

·         diuretics e.g. acetazolamide

·         topiramate is also used, and has the added benefit of causing weight loss in most patients

·         repeated lumbar puncture

·         surgery: optic nerve sheath decompression and fenestration may be needed to prevent damage to the optic nerve. A lumboperitoneal or ventriculoperitoneal shunt may also be performed to reduce intracranial pressure

*if intracranial hypertension is thought to occur secondary to a known causes (e.g. Medication) then it is of course not idiopathic

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Comparing neurology diseases

01 January 2021

18:29

progressive polyneuropathy and hyporeflexia 3 weeks following a gastrointestinal infection - this is very suggestive of Guillain-Barre syndrome.

 

Myasthenia gravis typically presents with muscle fatigue particularly after exercise and ocular manifestations - droop of the upper eyelids is typical with weakness of external ocular muscles producing diplopia. In contrast to Guillain-Barre syndrome, tone is normal, sensation is unimpaired and tendon reflexes are normal in myasthenia gravis.

 

In polymyositis, diffuse weakness in the proximal muscles develops. Distal muscles are spared and weakness may vary from week to week or month to month. This is in contrast to Stephen's progressive distal limb weakness.

 

Acute transverse myelitis presents with an acute episode of weakness or paralysis of both legs, with sensory loss and loss of control of bowels and bladder. Commonly there is associated back or leg pain. This is a differential to consider here, however no bladder or bowel dysfunction is mentioned and there is also no mention of back pain in Stephen's history. Furthermore the history of gastrointestinal infection 3 weeks ago points more towards a diagnosis of Guillain-Barre syndrome.

 

Posterior circulation ischaemic stroke may present with motor or sensory deficits, however symptoms can often also include dizziness, diplopia, dysarthria, dysphagia, disequilibrium, ataxia, or visual field deficits - Stephen does not have any of these symptoms. Furthermore in a posterior circulation stroke, th

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

Hypotension with compensatory tachycardia 4D's

01 January 2021

19:03

Of all the other options, one would expect a compensatory tachycardia on standing. The '4Ds' can be useful in remembering causes of postural hypotension with compensatory tachycardia.

·         Deconditioning.

·         Dysfunctional heart: aortic stenosis.

·         Dehydration: disease (acute illness, adrenal insufficiency), dialysis, drugs (diuretics, narcotics).

·         Drugs: anti-anginals, anti-parkinsonian medications (levodopa), antidepressants, antipsychotics, anti–benign prostatic hyperplasia drugs (tamsulosin).

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

01 January 2021

20:51

Pontine haemorrhage

Is a life-threatening condition. It often occurs as a complication secondary to chronic hypertension. Patients often present with reduces Glasgow coma score, quadriplegia, miosis, and absent horizontal eye movements.

 

 

 

Hyperkinetic movement

05 January 2021

13:23

 

common types of hyperkinetic movements:

 

 

Tremor

An oscillatory, usually rhythmic (to-and-fro) movement of one or more body parts, such as the neck, tongue, chin, or vocal cords or a limb. The rate, location, amplitude, and constancy vary depending on the specific type of tremor.

Dystonia

Both agonist and antagonist muscles of a body region contract simultaneously to produce a twisted posture of the limb, neck, or trunk. In contrast to chorea, dystonic movements repeatedly involve the same group of muscles. They do not necessarily flow or affect different muscle groups randomly.

Myoclonus

Sudden, brief, shock like jerks are caused by muscular contraction (positive myoclonus) or inhibition (negative myoclonus, such as asterixis).

Chorea

Involuntary, irregular, purposeless, nonrhythmic, often abrupt, rapid, and unsustained movements seem to flow randomly from one body part to another; they are unpredictable in timing, direction, and distribution.

Tics

Abnormal, stereotypic, repetitive movements (motor tics) or abnormal sounds (phonic tics) can be suppressed temporarily but may need to be “released” at some point. The release provides internal “relief” to the patient until the next “urge” is felt.

 

 

From <https://mle.ncl.ac.uk/cases/page/17516/>

 

 

Action tremors can occur on different types of movement

·         Postural - occurs when limbs/body specifically postured against gravity (see video at 0:40)

·         Kinetic - occurs on goal-directed movement e.g. lifting a glass to lips

The most common action tremor is essential tremor, sometimes called benign essential tremor. This is a slowly progressive neurological disease that can significantly impact a patient's quality of life. It is often inherited in an autosomal dominant pattern. Patients will often report that their tremor improves with alcohol.

Treatment approach includes

Conservative: relaxation techniques, reduce caffeine

Medical: propanolol, primidone

Surgical: deep brain stimulation (only for very severe/refractory cases)

 

From <https://mle.ncl.ac.uk/cases/page/17513/>

 

 

 

 

 

Physiological tremor

It is normal to sometimes experience a physiological tremor, often an action/postural tremor. Physiological tremor can be exacerbated by stress, anxiety and fatigue. You have probably noticed this in yourself when nervous or after intense exercise. This can also be exacerbated by beta agonists e.g. salbutamol. 

It is worth mentioning that tremors with a lower amplitude (amount of movement), tend to have a high frequency (movements per second).  A normal physiological tremor demonstrates a high frequency (10Hz) but a low amplitude.

 

Functional tremor

Functional tremor is a tremor that is caused by the nervous system not working properly but not due to an underlying neurological disease ( https://www.neurosymptoms.org/functional-tremor/4594357998). Tremors that have a high amplitude AND frequency are more likely to be functional in nature. Features that point towards a functional tremor diagnosis are: abrupt onset, incongruous examination findings, variable, and changes or reduces frequency/amplitude on distraction. These tremors may have a variable frequency and can sometimes be 'entrained' (tremor frequency switches to match exactly the frequency of a voluntary rhythmical movement performed by the unaffected limb.) Functional tremors can be extremely disabling for patients.

 

Intention tremor

Intention tremors are tremors that are worsened during the endpoint of a directed movement towards a target. It has low frequency and a high amplitude. We see this when the cerebellar system is affected because the patient cannot precisely co-ordinate their movement to the target. Notice how the below tremor increases as the person tries to touch their nose.

 

From <https://mle.ncl.ac.uk/cases/page/17513/>

 

 

Type of tremor

Description

Examples

Resting tremor

Occurs when the affected extremity is at complete rest and diminishes with movement

Parkinson’s disease

Postural tremor

 

Occurs when the affected limb is held in position against gravity.

Essential tremor

Medication induced tremor

Physiological tremor

Kinetic tremor

Occurs during voluntary movement.

Essential tremor

Intention tremor

Marked increase in tremor amplitude during the terminal portion of a targeted movement

Cerebellar tremor 

 

From <https://mle.ncl.ac.uk/cases/page/17513/>

 

Dystonias:

 

Dystonia is caused by sustained or intermittent muscle contractions / spasms that often lead the patient to hold abnormal postures or positions. This frequently causes discomfort and pain for the patient. Dystonia can have a genetic cause or be acquired from mechanisms such as trauma, stroke and drug toxicity. We will look at drug induced hyperkinesia later in this tutorial. 

·         Focal: one body part affected

·         Segmental: adjacent body parts affected

·         General: entire body affected

 

From <https://mle.ncl.ac.uk/cases/page/17517/>

 

 

 

Approach to management:

·         Conservative: education, relaxation, massage

·         Medical: A small % of patients respond to dopaminergic medication (e.g. levodopa). Benzodiazepines are also used.

·         Surgical: BoTox injection, especially useful in focal dystonia. Deep brain stimulation may be used in severe cases.

 

 

 

 

Myoclonus:

You will have experienced myoclonus in the form of hypnic jerks when you have been falling asleep. These are the jolty / jerking limb movements that occur at the point of sleep onset. This is a normal nocturnal motor phenomenon but is a form of myoclonus. You can watch the video below to see an example of pathological myoclonus.

When myoclonus is pathological it is more often a feature of an underlying disease than a primary disorder. The characteristics of the myoclonus can help to localise the area of pathology but this is not something you need to know as a medical student.

 

 

Chorea:

 

Chorea is dervied from the Ancient Greek word for dance and describes an involuntary movement that is brief, irregular, nonrhythmic,  non purposeful and flows from one body part to another in a random fashion. The movements typically last longer than myoclonus and are briefer than dystonia (although dystonia may be combined with chorea in some patients).

 

It is usually present at rest and may increase with distracting manoeuvres such as counting  or performing mental arithmetic. The movements may be partially suppressible or incorporated into voluntary movements to make them less conspicuous. They usually disappear in sleep. Chorea can be unilateral or bilateral. It can affect all body parts: face, trunk, and limbs.

 

There are various causes of chorea that include drug-induced, stroke related and genetic causes. We will focus on Huntington's disease as a cause of chorea in the next chapter.

 

Tics:

 

You will likely be familiar with tics as a result of Tourette's syndrome (TS). A tic is an involuntary movement or vocalization that is usually of sudden onset, brief, repetitive, and stereotyped, but nonrhythmic.  They are different to other hyperkinetic movements in that they are suppressible but irresistible.

 

A tic is usually associated with a premonitory “buildup” sensation or feeling of discomfort that is often localized to the affected area. Usually, the individual experiences a sensation of relief once the tic has occurred. Unlike most movement disorders, tics can persist during sleep.

 

They can be classified as motor, phonic or vocal and as simple or complex based on the manifestation. TS is thought to involve abnormalities in corticostriatothalamocortical circuitry. The video below shows some patient experiences with TS.

 

 

 

 

Huntington's disease

05 January 2021

13:38

Machine generated alternative text: Autosomal dominant Unaffected parent Unaffected child Affected child Affected child Affected parent Unaffected child Unaffected • Affected

Huntington's disease (HD) is the most frequent cause of a hereditary neurodegenerative choreic syndrome. It is caused by a faulty gene on chromosome 4, producing a mutant form of a protein called Huntingtin, which is thought to increase the rate of neuronal death in the brain. It is relatively rare disorder and affects about 8,000 people in the UK. HD is an autosomal disorder and therefore each child of an affected parent  has a 50% chance of developing the disease (ref). We will take a deeper look into the genetics after we have learnt a bit more about the disease. 

It is important that you recognise that HD is not only a movement disorder but also has marked cognitive and behavioural effects. In fact, the earliest signs of the disease in a patient are often subtle cognitive or mood related changes. Read the diagram below from https://hopes.stanford.edu/stages-of-huntingtons-disease/#46539 to appreciate the complex nature of the disease. Patients symptoms are highly variable and will present unique difficulties dependent on their particular lifestyle.  

 

 

 

Motor symptoms include chorea, dystonia, and tics.  Characteristically, the first motor symptom exhibited is a chorea (hence HD is also known as Hungtinton's chorea). The examination in the video below is very useful, in terms of being able to see specific signs but also in helping you to develop a general neurological impression of  a patient with established HD.

 

 

 

We learned earlier that Hungtinton's disease has an autosomal dominant inheritance. The huntingtin gene (on the short arm of chromosome 4) codes for the huntingtin protein. The specific pathology of the disease is not completely characterised but mutated huntingtin protein aggregates are found in the basal ganglia, specifically the dorsal striatum (caudate and putamen), and these areas show increased neuronal death rates. There is thought to be a toxic gain-of-function in the mutant huntingtin protein.

FIGURE 8-2 20fnm Caudate atrophy in a patient with Huntington disease documented on T 2-weighted MRI.

 

 

A section of the genetic code for this protein has something called a trinucleotide repeat expansion. This is a repeating sequence of three nucleotides. In the case of huntingtin, this is a CAG repeat (which encodes glutamine and hence is known as a polyglutamine disease).

ΗυΚΙΤΙΝβΤΙΝ (ΗΤΟ Ι— 10-36 6υ-.ΙΤΑΜΙΕΙξ5

 

Patients with 40 or more repeats will develop the disease (100% penetrance) but patients with 36-39 repeats show a reduced penetrance. 27-35 repeats are classified as in the 'intermediate CAG range' and less than this is normal. For example, if a patient has a repeat number of 40, they are certain to develop the disease (assuming they survive until disease onset). A patient with 36 repeats may or may not develop HD and a patient  with fewer repeats than this will not.

 

Number of CAG repeats

Classification

<27

Normal

27-35

Intermediate CAG range

36-39

Reduced penetrance

>39

100% penetrance

 

The intermediate CAG range refers to people who, despite not having the disease, are at risk of passing on mutant alleles due to repeat expansion. This number of trinucleotide repeats causes the sequence to be unstable during DNA replication. There is a small risk that within one generation an error in replication can expand the repeat number into the disease range.  This occurs much more in sperm than ova generation and thus repeat expansion mainly occurs in paternal alleles (ref). Further to this, expansion of repeats already in the disease range leads to an earlier onset and faster progression of symptoms. This phenomenon is known as anticipation. Each successive affected generation has a chance of inheriting a greater number of repeats, again most commonly from the father, and having an earlier disease onset. 

Usually symptomatic onset is between the ages of 30 and 50, although onset  can range from childhood/adolescence to individuals older than 70 years of age.  There is a juvenile form, also known as the Westphal variant HD,  due to a very large repeat count.   

Other trinucleotide repeat disorders you may come across include Friedreich's ataxia,  fragile X syndrome and types of myotonic dystrophy and spinocerebellar ataxia (of these, only spinocerebellar ataxia is a polyglutamine repeat). 

 

 

From <https://mle.ncl.ac.uk/cases/page/17512/>

 

 

No disease modifying therapies are currently available for HD on the NHS. HCurrent treatments include:

 

Conservative: Symptomatic / supportive therapy to alleviate the symptoms

Medicine: Anti-choreic medication – atypical antipsychotics, tetrabenazine

Surgical: Deep brain stimulation for pharmacological resistant chorea with significant disability

Ultimately, there is no cure for HD at present and treatment revolves around supportive care (such as modifications in the patient's house by occupational therapists, physiotherapy, speech and language therapy and additional carers) and symptomatic relief. Tetrabenazine is approved for the treatment of chorea in HD. Antipsychotics can be used to treat psychiatric symptoms, as well as often also helping with chorea

 

 

 

 

Early symptoms

Motor:

Begin in extremities of body, people experience involuntary twitches in their fingers, toes and face. Onlookers generally don't notice these motions, or assume that they are just nerveous twitches.

People in the early years of HD also experience a subtle loss of coordination, and may have more trouble performing complicated motions

 

Cognitive symptoms:

Cognitive symptoms also become noticeable in the early stages of HD, as it become more difficult for people to think through complicated tasks

 

Behavioral:

Can be fairly serious even when motor and cognitive symptoms are quite minor. Depression, irritability, and inhibition are common in the early stages, some patients experience hypersexuality, which can cause problems in relationships

Early-Stage HD Motor Symptoms Motor symptoms usually be*n In the extremities of the body: pec% experience involuntary twitc es in their fingers, toes, and face. On kers generally don't notice these motions, or assume that they are lust nervous twitches. people In the early years of HD also experience a subtle loss coordination, and may have more trmlble performing complicated motions. Cognitive Symptoms Cognitive synptoms also become noticeable In the early stages of HD, as it become difficult for people to think through complicated tasks. Behavioral Symptoms Behavioral symptoms can be fairly serious even when Mor and cognitWe symptoms are quite minor. Depression. irritability and disinhibition ar common in the earty stages. and some patients experience hypersexuality, which can cause problems in relationsh ps.

 

Mid-stage HD

Middle-Stage HD Motor Symptoms Motor symptoms become more serious and chorea - the involuntary dance.llke movements of RD - is usually most severe during the middle stages of HD. People also have Increasing trouble with voluntary tasks, and walking becomes more difficult; patients are more likely to fall or experience problems with balance In this stage. People with middle•stage HD also begin to have trouble swallowing, which leads to the weight loss that begins to become serious In this phase. Cognitive Symptoms Cognitive symptoms become problematic, as patients have more trouble organizing Information and thinkin clearly. Often, patients can't solve problems they normally capaåe Of working through. Behavioral Symptoms Behavioral symptoms are similar to those experienced in the earlier However. some people become increasingly apathetic as the disease continues, losing interest in activities that they used to enjoy. In the mid to late stages of the disease. many people have a desire or ability to have sex.

 

Late-Stage HD Motor Symptoms Motor sympuyns are severe. By this pent, chorea has usual* stopped, although a minority of patients continue to experience severe chorea. Instead. patients generally have the greatest difficulty with voluntary movements. and often experience rigidity, dystonla, and bradyklnesla. Cognitive Symptoms Cognitive symptoms are debilitating, though patients can usually still understand speech and recognize loved ones. Behavioral Symptoms Behavml symptoms tend to Improve slightly in the late stagß of the disease. Depression. in particular. tends to fade in the middle and late stages of HD. Some doctors suggest that this is because tients in the late stages of HD have come to terms with the illness. though some %ieve this is because apathy is a very common symptom in the late stages of HD, and counteracts the effects of depression. Psychosis, a rare problem that causes people to have visual and auditory hallucinations. in 3-11% of patients in late stages of HD.

 

 

 

Drug induced movement disorder

05 January 2021

13:54

 

Drug-induced movement disorders can be caused by a wide variety of drugs, including illicit substances (e.g. cocaine and amphetamines). We will focus on some important examples in this tutorial.

 

 

Tardive dyskinesia

The most common cause of drug-induced movement disorders are dopamine receptor blocking agents. Antipsychotics, metoclopramide and prochlorperazine are prevalent examples that you will undoubtedly prescribe during your career. These medications can cause various movement disorders including tremor, neuroleptic malignant syndrome (covered in the next section), dystonia and parkinsonism.

 

One of these disorders is called tardive dyskinesia. Classically, there are involuntary movements of the mouth, tongue and jaw (oro-buccal-lingual). There are various other 'tardive syndromes' that can affect the trunk and extremities, including causing choreiform movements.  You can see a more classic example in the video below.

 

 

 

The exact pathophysiology of tardive dyskinesia in unclear. A common theory is that there is a dopamine hypersensitivity in the nigrostriatal pathway after chronic pharmacological blockage .

 

Tardive dyskinesia can be diagnosed if:

 

Patient had at least 3 months exposure to a dopamine receptor blocking agent (1 month if patient >60yrs old).

Symptoms present for at least 1 month after medication discontinued

Symptoms can emerge during or up to 4 weeks after stopping the medication - hence the name tardive (late/delayed appearance). You do not need to memorise these criteria but they are useful to appreciate the delayed onset of the disorder .

 

Treatment can be difficult and therefore prevention is crucial. Dopamine receptor blocking medications should be used in the lowest dose for the shortest time possible. Treatment involves withdrawing the offending agent and this may require an analysis of benefit vs. harm (e.g. if the antipsychotic is treating schizophrenia). There is usually a delay before improvement and changes can be irreversible. Tetrabenazine can be effective in some people who have not responded to treatment withdrawal.

 

 

 

 

neuroleptic malignant syndrome (NMS)

Dopamine receptor blocking drugs can cause a severe neurological emergency called neuroleptic malignant syndrome (NMS). This can also be induced by  sudden cessation of dopaminergic medications e.g. levodopa.

NMS is a clinical diagnosis, supported by the diagnostic criteria below. NMS is characterised by high temperatures, rigidity, autonomic dysfunction and altered mental status (often agitated confusion). Patients may demonstrate hyporeflexia.

 

 

Major (need all 3)

Minor (at least 2)

 

 

Exposure to dopamine antagonist

or withdrawal of dopaminergic

Diaphoresis (sweating)

Rigidity

Dysphagia

Hyperthermia 

Tremor

 

 

Incontinence

 

 

Altered levels of consciousness

 

 

Mutism

 

 

Tachycardia

 

 

Elevated or labile BP

 

 

Leukocytosis

 

 

Elevated CK

Adapted from  Diagnostic and Statistical Manual of Mental Disorders, 5th Edition

 

A common scenario for this to occur would be with a patient already on an antipsychotic e.g. haloperidol (highest risk) who is then given a dopamine blocking antiemetic such as metoclopramide. The high temperature and altered mental state would make you think about infection but is important to take note of the patient's medications. Rigidity, a new tremor and a raised CK should make you think about NMS.

The pathophysiology of NMS is thought to be due to the abrupt loss of dopaminergic activity in the nigrostriatal pathway and basal ganglia, with fever thought to be due to dopamine blockade in the hypothalamus (which plays a role in thermoregulation).  

Treatment approach:

·         Stop the dopamine blocking medication

·         Supportive care: IV fluids, correct metabolic abnormalities

·         Medications in severe cases: bromocriptine (a dopamine agonist, to increase dopaminergic activity) and dantrolene (muscle relaxant to reduce rigidity, acts by inhibiting inhibiting calcium release from the sarcoplasmic reticulum in muscle cells.) 

(ref)

 

From <https://mle.ncl.ac.uk/cases/page/17522/>

 

Serotonin syndrome:

Serotonin syndrome is another drug-induced syndrome that causes hyperthermia and neurological changes. In patients with polypharmacy you may need to differentiate this from NMS.

Serotonin syndrome can be caused by prescription of multiple serotonergic drugs or medication overdose. This essentially leads to serotonin toxicity and hyperstimulation in the central nervous system. The video below is a good primer for the topic.

Serotonin syndrome can be caused by multiple classes of drugs that affect signaling in presynaptic and postsynaptic serotonergic neurons (in the raphe nuclei of the brainstem). The picture below demonstrates a serotonin synapse and how medications affect this.

·         MAO inhibitors: reduced breakdown of serotonin

·         Illicit drugs: promote serotonin release into the synaptic cleft or directly stimulate the postsynaptic cleft (amphetamines, ecstasy and cocaine)

·         Tricyclic antidepressants:  reduce serotonin re-uptake into the presynaptic neurone (amitriptyline)

·         SSRIs and SNRIs: reduce serotonin re-uptake into the presynaptic neurone (fluoxetine, sertraline, duloxetine)

·         Synthetic opioids: multiple effects on serotonergic neurons (tramadol, fentanyl) 

  

(ref)

The table below shows the diagnostic criteria for serotonin syndrome. As is characterised by the acute onset of symptoms, commonly after a serotonergic medication change/overdose.

Sternbach's criteria 1. Patient on serotonergic agent Absence of other causes or etiologies No current use of neuroleptic agent . Presence of three of the following: Mental status change (confu- sion, hypomania, restlessness, ataxia) Agitation Myoclonus Hyperreflexia Diaphoresis Shivering Tremor Diarrhea Incoordination Fever Hunter's criteria 1. Patient on serotonergic agent 2. Presence of any of the following: Spontaneous clonus Inducible clonus AND agita- tion OR diaphoresis Ocular clonus AND agitation OR diaphoresis Tremor AND hyperreflexia Hypertonic AND hyperther- mia (>38 QC) AND ocular clonus OR inducible clonus

 

Approach to treatment:

·         Withdraw serotonergic agents

·         Supportive care: IV fluids, cooling

·         Medications in severe cases: Benzodiazepines can be used to reduce agitation and myoclonus. Cyproheptadine (a serotonin antagonist) is sometimes used but the evidence base for this is not strongly established.

 

We can see that a lot of symptoms overlap with NMS. Differentiating between the two conditions clearly begins with checking the patient's medications and any recent changes. If a patient is pharmacologically at risk of both, their neurological symptoms are most helpful in distinguishing between the two.

 

Serotonin Syndrome

Neuroleptic Malignant Syndrome

Timing

More acute (<24hours)

More gradual (days-weeks)

Drugs

Serotonergic

Dopaminergic

Neurological reactivity

Increased: hyperreflexia, clonus, tremor

Decreased: rigidity, hyporeflexia

GI Features

Diarrhoea, increased bowel sounds

Usually normal

 

 

 

 

 

From <https://mle.ncl.ac.uk/cases/page/17514/>

 

 

 

 

 

Future treatments

05 January 2021

14:02

Spinal Muscular Atrophy:

Recent advances in genetic medicine have allowed for the development of new treatments for single gene disorders. This is in the form of a new class of drugs called anti-sense oligonucleotides (ASOs). These compounds bind to specific mRNAs and ultimately affect protein expression in various desired ways, dependent on the disease we are treating. 

For neurological disorders this has led to the development of treatments for Spinal Muscular Atrophy (SMA), and emerging treatments for Huntington's disease and MND (single gene variants). 

 

The SMN protein is particularly important in promoting the survival of alpha motor neurons, which exit through the ventral roots of the spinal cord to directly innervate skeletal muscle and initiate contraction. In SMA the SMN1 gene is mutated or deleted homozygously in a way that ultimately results in insufficient levels of SMN protein. 

The SMN2 gene is a pseudogene copy of SMN1, which means that it is a mutated copy which produces little or no functional protein. In this case very little functional protein is produced. This is because a single nucleotide mutation in exon 7 of SMN2 leads to it being removed in the majority of mRNAs. This resultant protein is non-functional / rapidly degraded. 

Nusinersen is an ASO which binds to a complimentary sequence after exon 7 and causes mRNA processing to include this exon. Thus, functional SMN protein is produced. For many patients this leads to significant motor function and survival benefits.  

 

 

From <https://mle.ncl.ac.uk/cases/page/17569/>

 

Huntington's disease

 

The pathology of Huntington's  disease has been covered in the 'Hyperkinesia' tutorial. You will recall that this is an autosomal dominant condition in which a mutant copy of the huntingtin gene has an expansion of the CAG triplet repeats. This leads to the production of a toxic gain-of-function mutant huntingtin protein.

 

Lowering mutant huntingtin protein levels in the brain has been shown to improve symptoms of the disease. ASOs have therefore been developed to reduce the levels of this protein. In this case, rather than ASO binding resulting in increased levels of a protein, the ASO binding to mutant mRNA targets this mRNA for degradation

 

 

 

Motor neurone disease

 

 

The pathology and types of MND have been covered in the 'Motor Neurone Disease' lecture from this week's content. Amyotrophic lateral sclerosis (ALS) can be classified as either sporadic or familial / inherited (5-10%) . The familial forms of ALS (FALS) have a mutation in one of several genes known to cause ALS. These genes are therefore being researched as targets for ASOs.

 

So far, the most promising research has been undertaken with ASOs in patients with mutant SOD1 genes. Multiple point mutations in this gene have been found to be associated with FALS. However, the mechanism by which these mutations cause ALS is poorly characterised. Despite this results have been promising.

 

At the time of writing there are ongoing clinical trials for SOD1 ASOs. As with Huntington's, the purpose of the ASO is to target mutant mRNA for degradation.

 

 

The SOD1 gene is located on chromosome 21. If mutations in the SOD1  gene cause a gain-of-function,

 

 if there is a gain of function from an allele, it is more likely that only one copy of the gene will be required to cause the disease. Conversely, if there is a loss-of-function in an allele, it is often the case that with wild type (normal) allele will produce enough protein to compensate for this. Thus there is a recessive pattern of inheritance. Again, this is not a hard and fast rule and dominant loss-of-function mutations can also occur. 

 

From <https://mle.ncl.ac.uk/cases/page/17569/>

 

 

 

 

05 January 2021

15:08

Progressive Multifocal Leukoencephalopathy (PML)

This is a rare condition, you don't need to know everything about it.

Just be aware that PML is the big risk that neurologists think about when using DMTs, especially Natalizumab. The strongest DMTs carry the greatest risk.

PML is caused by reactivation of the JC virus in the CNS. Much of the general population has already been exposed to the JC virus and carries it in an inactive form. When the immune system is suppressed by DMTs, this virus can reactivate in the brain and cause significant neurological problems and even death. MS patients will have blood tests to assess the amount of JC virus antibody in their blood. This can guide treatment decisions.

 

From <https://mle.ncl.ac.uk/cases/page/17721/>

 

 

 

 

Differentials diffuse neuropathies

05 January 2021

15:34

·         Motor neurone disease - A mix of UMN and LMN signs. Motor only with absence of sensory involvement. Fasiculation is more prominent in MND.

·         Myasthenia gravis - Neuromuscular junction pathology. Muscle weakness that is fatiguable and varies over the day. Motor only with absence of sensory involvement. Weakness is more proximal. Reflexes are normal. MG may manifest with bulbar involvement, unlike peripheral neuropathy.

·         Spinal cord syndrome - A spinal cord lesion will cause UMN signs. Weakness/sensory loss below the level of the lesion.

·         Cauda Equina syndrome - Cauda Equina syndrome can look like a peripheral neuropathy. Bladder and bowel disturbance can also be present in autonomic neuropathy. Look for Cauda Equina red flag signs e.g. urinary retention, saddle anaesthesia, loss of anal tone etc. Back pain may be present. Have a low threshold for MRI spine if you suspect Cauda Equina syndrome.

·         Myopathies - Motor only with no sensory involvement. Weakness is more proximal than distal (where larger muscle groups are.) Reflexes are normal. Fasiculation is unlikely.

 

 

From <https://mle.ncl.ac.uk/cases/page/17594/>

 

 

 

 

Acute multi-focal neuropathy

05 January 2021

15:36

 

Acute multi-focal neuropathy

An acute multi-focal neuropathy picture of random nerves being "picked off" suddenly is an alarming condition for a neurologist. A hyper-acute rapid onset suggests a vascular cause, fast action and urgent neurology referral is required to save the nerve from irreversible damage. A vasculitic neuropathy is rare, but worth being aware of due to the devastating consequences of delayed treatment.

 

From <https://mle.ncl.ac.uk/cases/page/17650/>

 

 

 

 

 

05 January 2021

15:37

 

Chronic inflammatory demyelinating polyneuropathy (CIDP): 

A demyelinating process, causing predominantly painless motor symptoms. Can be seen on EMG studies. Treated with immune-modifying therapies e.g. steroids/IVIG/plasma exchange. May have future relapses and require further treatment.

 

From <https://mle.ncl.ac.uk/cases/page/17651/>

 

 

 

 

Sub-acute (weeks) are rare causes of a diffuse peripheral neuropathy and will be mostly invested/managed by a neurologist. Be aware of the basic principles.

 

 

 

 

 

 

05 January 2021

15:37

 

Paraneoplastic: 

Cancer can cause a paraneoplastic immune-mediated peripheral neuropathy, especially small cell lung cancer and lymphoma. If suspected, investigations to look for an underlying cancer (e.g. CT chest/abdo/pelvis) may be indicated. Remember, some chemotherapy regimes may also cause a peripheral neuropathy.

 

Sub-acute (weeks) are rare causes of a diffuse peripheral neuropathy and will be mostly invested/managed by a neurologist. Be aware of the basic principles.

 

 

 

 

 

 

24 December 2020

12:23

Pulmonary embolism: investigation

We know from experience that few patients (around 10%) present with the textbook triad of pleuritic chest pain, dyspnoea and haemoptysis. Pulmonary embolism can be difficult to diagnose as it can present with virtually any cardiorespiratory symptom/sign depending on its location and size.

 

So which features make pulmonary embolism more likely?

 

The PIOPED study1 in 2007 looked at the frequency of different symptoms and signs in patients who were diagnosed with pulmonary embolism.

 

The relative frequency of common clinical signs is shown below:

·         Tachypnea (respiratory rate >20/min) - 96%

·         Crackles - 58%

·         Tachycardia (heart rate >100/min) - 44%

·         Fever (temperature >37.8°C) - 43%

It is interesting to note that the Well's criteria for diagnosing a PE use tachycardia rather than tachypnoea.

 

All patients with symptoms or signs suggestive of a PE should have a history taken, examination performed and a chest x-ray to exclude other pathology.

 

 

Pulmonary embolism rule-out criteria (PERC)

 

NICE updated their guidelines on the investigation and management of venous thromboembolism (VTE) in 2020. One of the key changes was the use of the pulmonary embolism rule-out criteria (the PERC rule)

·         a copy of criteria can be found in the image below

·         all the criteria must be absent to have negative PERC result, i.e. rule-out PE

·         this should be done when you think there is a low pre-test probability of PE, but want more reassurance that it isn't the diagnosis

o    this low probability is defined as < 15%, although it is clearly difficult to quantify such judgements

·         a negative PERC reduces the probability of PE to < 2%

·         if your suspicion of PE is greater than this then you should move straight to the 2-level PE Wells score, without doing a PERC

 

2-level PE Wells score

 

If a PE is suspected a 2-level PE Wells score should be performed:

 

 

Clinical feature

Points

Clinical signs and symptoms of DVT (minimum of leg swelling and pain with palpation of the deep veins)

3

An alternative diagnosis is less likely than PE

3

Heart rate > 100 beats per minute

1.5

Immobilisation for more than 3 days or surgery in the previous 4 weeks

1.5

Previous DVT/PE

1.5

Haemoptysis

1

Malignancy (on treatment, treated in the last 6 months, or palliative)

1

Clinical probability simplified scores

·         PE likely - more than 4 points

·         PE unlikely - 4 points or less

If a PE is 'likely' (more than 4 points)

·         arrange an immediate computed tomography pulmonary angiogram (CTPA)

·         If there is a delay in getting the CTPA then interim therapeutic anticoagulation should be given until the scan is performed.

o    interim therapeutic anticoagulation used to mean giving low-molecular-weight heparin

o    NICE updated their guidance in 2020. They now recommend using an anticoagulant that can be continued if the result is positive.

o    this means normally a direct oral anticoagulant (DOAC) such as apixaban or rivaroxaban

- if the CTPA is positive then a PE is diagnosed

·         if the CTPA is negative then consider a proximal leg vein ultrasound scan if DVT is suspected

If a PE is 'unlikely' (4 points or less)

·         arranged a D-dimer test

o    if positive arrange an immediate computed tomography pulmonary angiogram (CTPA). If there is a delay in getting the CTPA then give interim therapeutic anticoagulation until the scan is performed

o    if negative then PE is unlikely - stop anticoagulation and consider an alternative diagnosis

 

 

CTPA or V/Q scan?

 

The consensus view from the British Thoracic Society and NICE guidelines is as follows:

·         CTPA is now the recommended initial lung-imaging modality for non-massive PE. Advantages compared to V/Q scans include speed, easier to perform out-of-hours, a reduced need for further imaging and the possibility of providing an alternative diagnosis if PE is excluded

·         if the CTPA is negative then patients do not need further investigations or treatment for PE

·         V/Q scanning may be used initially if appropriate facilities exist, the chest x-ray is normal, and there is no significant symptomatic concurrent cardiopulmonary disease. V/Q scanning is also the investigation of choice if there is renal impairment (doesn't require the use of contrast unlike CTPA)

 

Some other points

 

D-dimers

·         sensitivity = 95-98%, but poor specificity

·         age-adjusted D-dimer levels should be considered for patients > 50 years

ECG

·         the classic ECG changes seen in PE are a large S wave in lead I, a large Q wave in lead III and an inverted T wave in lead III - 'S1Q3T3'. However, this change is seen in no more than 20% of patients

·         right bundle branch block and right axis deviation are also associated with PE

·         sinus tachycardia may also be seen

Chest x-ray

·         a chest x-ray is recommended for all patients to exclude other pathology

·         however, it is typically normal in PE

·         possible findings include a wedge-shaped opacification

V/Q scan

·         sensitivity of around 75% and specificity of 97%

·         other causes of mismatch in V/Q include old pulmonary embolisms, AV malformations, vasculitis, previous radiotherapy

·         COPD gives matched defects

CTPA

·         peripheral emboli affecting subsegmental arteries may be missed

 

 

 

1. Clinical Characteristics of Patients with Acute Pulmonary Embolism(Data from PIOPED II) Am J Med. Oct 2007; 120(10): 871879.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:23

Angina pectoris: drug management

The management of stable angina comprises lifestyle changes, medication, percutaneous coronary intervention and surgery. NICE produced guidelines in 2011 covering the management of stable angina

 

Medication

·         all patients should receive aspirin and a statin in the absence of any contraindication

·         sublingual glyceryl trinitrate to abort angina attacks

·         NICE recommend using either a beta-blocker or a calcium channel blocker first-line based on 'comorbidities, contraindications and the person's preference'

·         if a calcium channel blocker is used as monotherapy a rate-limiting one such as verapamil or diltiazem should be used. If used in combination with a beta-blocker then use a long-acting dihydropyridine calcium-channel blocker (e.g. modified-release nifedipine). Remember that beta-blockers should not be prescribed concurrently with verapamil (risk of complete heart block)

·         if there is a poor response to initial treatment then medication should be increased to the maximum tolerated dose (e.g. for atenolol 100mg od)

·         if a patient is still symptomatic after monotherapy with a beta-blocker add a calcium channel blocker and vice versa

·         if a patient is on monotherapy and cannot tolerate the addition of a calcium channel blocker or a beta-blocker then consider one of the following drugs: a long-acting nitrate, ivabradine, nicorandil or ranolazine

·         if a patient is taking both a beta-blocker and a calcium-channel blocker then only add a third drug whilst a patient is awaiting assessment for PCI or CABG

Nitrate tolerance

·         many patients who take nitrates develop tolerance and experience reduced efficacy

·         NICE advises that patients who take standard-release isosorbide mononitrate should use an asymmetric dosing interval to maintain a daily nitrate-free time of 10-14 hours to minimise the development of nitrate tolerance

·         this effect is not seen in patients who take once-daily modified-release isosorbide mononitrate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:48

Acute pericarditis

Pericarditis is one of the differentials of any patient presenting with chest pain.

 

Features

·         chest pain: may be pleuritic. Is often relieved by sitting forwards

·         other symptoms include non-productive cough, dyspnoea and flu-like symptoms

·         pericardial rub

·         tachypnoea

·         tachycardia

Causes

·         viral infections (Coxsackie)

·         tuberculosis

·         uraemia (causes 'fibrinous' pericarditis)

·         trauma

·         post-myocardial infarction, Dressler's syndrome

·         connective tissue disease

·         hypothyroidism

·         malignancy

Investigations

·         ECG changes

o    the changes in pericarditis are often global/widespread, as opposed to the 'territories' seen in ischaemic events

o    'saddle-shaped' ST elevation

o    PR depression: most specific ECG marker for pericarditis

·         all patients with suspected acute pericarditis should have transthoracic echocardiography

Management

·         treat the underlying cause

·         a combination of NSAIDs and colchicine is now generally used for first-line for patients with acute idiopathic or viral pericarditis

 

 

© Image used on license from Dr Smith, University of Minnesota

 

ECG showing pericarditis. Note the widespread nature of the ST elevation and the PR depression

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:49

Long QT syndrome

Long QT syndrome (LQTS) is an inherited condition associated with delayed repolarization of the ventricles. It is important to recognise as it may lead to ventricular tachycardia/torsade de pointes and can therefore cause collapse/sudden death. The most common variants of LQTS (LQT1 & LQT2) are caused by defects in the alpha subunit of the slow delayed rectifier potassium channel. A normal corrected QT interval is less than 430 ms in males and 450 ms in females.

 

Causes of a prolonged QT interval:

 

 

Congenital

Drugs*

Other

·         Jervell-Lange-Nielsen syndrome (includes deafness and is due to an abnormal potassium channel)

·         Romano-Ward syndrome (no deafness)

·         amiodarone, sotalol, class 1a antiarrhythmic drugs

·         tricyclic antidepressants, selective serotonin reuptake inhibitors (especially citalopram)

·         methadone

·         chloroquine

·         terfenadine**

·         erythromycin

·         haloperidol

·         ondanestron

·         electrolyte: hypocalcaemia, hypokalaemia, hypomagnesaemia

·         acute myocardial infarction

·         myocarditis

·         hypothermia

·         subarachnoid haemorrhage

Features

·         may be picked up on routine ECG or following family screening

·         Long QT1 - usually associated with exertional syncope, often swimming

·         Long QT2 - often associated with syncope occurring following emotional stress, exercise or auditory stimuli

·         Long QT3 - events often occur at night or at rest

·         sudden cardiac death

Management

·         avoid drugs which prolong the QT interval and other precipitants if appropriate (e.g. Strenuous exercise)

·         beta-blockers***

·         implantable cardioverter defibrillators in high risk cases

*the usual mechanism by which drugs prolong the QT interval is blockage of potassium channels. See the link for more details

 

**a non-sedating antihistamine and classic cause of prolonged QT in a patient, especially if also taking P450 enzyme inhibitor, e.g. Patient with a cold takes terfenadine and erythromycin at the same time

 

***note sotalol may exacerbate long QT syndrome

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:50

Pulmonary embolism: management

NICE updated their guidelines on the management of venous thromboembolism (VTE) in 2020. Some of the key changes include recommending the following:

·         the use of direct oral anticoagulants (DOACs) as first-line treatment for most people with VTE

·         the use of DOACs in patients with active cancer, as opposed to low-molecular weight heparin as was the previous recommendation

·         outpatient treatment in low-risk pulmonary embolism (PE) patients

·         routine cancer screening is no longer recommended following a VTE diagnosis

 

Outpatient treatment in low-risk PE patients

 

Deep vein thrombosis has for a long time been treated on an outpatient condition. In contrast, patients with any form of PE were typically admitted. However, in recent years patients with a new diagnosis of PE who are deemed low-risk are now increasingly managed as outpatients. NICE formally supported this approach in their latest guidance.

·         NICE recommends using a 'validated risk stratification tool' to determine the suitability of outpatient treatment.

o    no guidance is given as to what tool should be used

o    the 2018 British Society guidelines support the use of the Pulmonary Embolism Severity Index (PESI) score

·         key requirements would clearly be haemodynamic stability, lack of comorbidities and support at home

 

Anticogulant therapy

 

The cornerstone of VTE management is anticoagulant therapy. This was historically done with warfarin, often preceded by heparin until the INR was stable. However, the development of DOACs, and an evidence base supporting their efficacy, has changed modern management.

 

Choice of anticoagulant

·         the big change in the 2020 guidelines was the increased use of DOACs

·         apixaban or rivaroxaban (both DOACs) should be offered first-line following the diagnosis of a PE

o    instead of using low-molecular weight heparin (LMWH) until the diagnosis is confirmed, NICE now advocate using a DOAC once a diagnosis is suspected, with this continued if the diagnosis is confirmed

o    if neither apixaban or rivaroxaban are suitable then either LMWH followed by dabigatran or edoxaban OR LMWH followed by a vitamin K antagonist (VKA, i.e. warfarin)

·         if the patient has active cancer

o    previously LMWH was recommended

o    the new guidelines now recommend using a DOAC, unless this is contraindicated

·         if renal impairment is severe (e.g. < 15/min) then LMWH, unfractionated heparin or LMWH followed by a VKA

·         if the patient has antiphospholipid syndrome (specifically 'triple positive' in the guidance) then LMWH followed by a VKA should be used

Length of anticoagulation

·         all patients should have anticoagulation for at least 3 months

·         continuing anticoagulation after this period is partly determined by whether the VTE was provoked or unprovoked

o    a provoked VTE is due to an obvious precipitating event e.g. immobilisation following major surgery. The implication is that this event was transient and the patient is no longer at increased risk

o    an unprovoked VTE occurs in the absence of an obvious precipitating event, i.e. there is a possibility that there are unknown factors (e.g. mild thrombophilia) making the patient more at risk from further clots

·         if the VTE was provoked the treatment is typically stopped after the initial 3 months (3 to 6 months for people with active cancer)

·         if the VTE was unprovoked then treatment is typically continued for up to 3 further months (i.e. 6 months in total)

o    NICE recommend that whether a patient has a total of 3-6 months anticoagulant is based upon balancing a person's risk of VTE recurrence and their risk of bleeding

o    the HAS-BLED score can be used to help assess the risk of bleeding

o    NICE state: 'Explain to people with unprovoked DVT or PE and a low bleeding risk that the benefits of continuing anticoagulation treatment are likely to outweigh the risks. '. The implication of this is that in the absence of a bleeding risk factors, patients are generally better off continuing anticoagulation for a total of 6 months

 

PE with haemodynamic instability

 

Thrombolysis

·         thrombolysis is now recommended as the first-line treatment for massive PE where there is circulatory failure (e.g. hypotension)

·         other invasive approaches should be considered where appropriate facilities exist

Patients who have repeat pulmonary embolisms, despite adequate anticoagulation, may be considered for inferior vena cava (IVC) filters. These work by stopping clots formed in the deep veins of the leg from moving to the pulmonary arteries. IVC filter use is currently supported by NICE but other studies suggest a weak evidence base - please see the link for more details.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:50

Aortic stenosis

Clinical features of symptomatic disease

·         chest pain

·         dyspnoea

·         syncope

·         murmur

o    an ejection systolic murmur (ESM) is classically seen in aortic stenosis

o    classically radiates to the carotids

o    this is decreased following the Valsalva manoeuvre

Features of severe aortic stenosis

·         narrow pulse pressure

·         slow rising pulse

·         delayed ESM

·         soft/absent S2

·         S4

·         thrill

·         duration of murmur

·         left ventricular hypertrophy or failure

Causes of aortic stenosis

·         degenerative calcification (most common cause in older patients > 65 years)

·         bicuspid aortic valve (most common cause in younger patients < 65 years)

·         William's syndrome (supravalvular aortic stenosis)

·         post-rheumatic disease

·         subvalvular: HOCM

Management

·         if asymptomatic then observe the patient is general rule

·         if symptomatic then valve replacement

·         if asymptomatic but valvular gradient > 40 mmHg and with features such as left ventricular systolic dysfunction then consider surgery

·         cardiovascular disease may coexist. For this reason an angiogram is often done prior to surgery so that the procedures can be combined

·         balloon valvuloplasty is limited to patients with critical aortic stenosis who are not fit for valve replacement

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:50

ECG: myocardial ischaemia

One of the main uses of the ECG is to determine whether a patient is having a cardiac event in the context of chest pain. A wide variety of changes can be seen depending on what type of ischaemic event is happening, where it is happening and when it happened.

 

Acute myocardial infarction (MI)

·         hyperacute T waves are often the first sign of MI but often only persists for a few minutes

·         ST elevation may then develop

·         the T waves typically become inverted within the first 24 hours. The inversion of the T waves can last for days to months

·         pathological Q waves develop after several hours to days. This change usually persists indefinitely

Definition of ST elevation myocardial infarction (STEMI)

·         clinical symptoms consistent with ACS (generally of ≥ 20 minutes duration) with persistent (> 20 minutes) ECG features in ≥ 2 contiguous leads of:

o    2.5 mm (i.e ≥ 2.5 small squares) ST elevation in leads V2-3 in men under 40 years, or ≥ 2.0 mm (i.e ≥ 2 small squares) ST elevation in leads V2-3 in men over 40 years

o    1.5 mm ST elevation in V2-3 in women

o    1 mm ST elevation in other leads

o    new LBBB (LBBB should be considered new unless there is evidence otherwise)

A posterior MI causes ST depression not elevation on a 12-lead ECG.

 

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:51

Warfarin

Warfarin is an oral anticoagulant which inhibits epoxide reductase preventing the reduction of vitamin K to its active hydroquinone form, which in turn acts as a cofactor in the carboxylation of clotting factor II, VII, IX and X (mnemonic = 1972) and protein C.

 

Indications

·         venous thromboembolism: target INR = 2.5, if recurrent 3.5

·         atrial fibrillation, target INR = 2.5

·         mechanical heart valves, target INR depends on the valve type and location. Mitral valves generally require a higher INR than aortic valves.

Patients on warfarin are monitored using the INR (international normalised ration), the ratio of the prothrombin time for the patient over the normal prothrombin time. Warfarin has a long half-life and achieving a stable INR may take several days. There a variety of loading regimes and computer software is now often used to alter the dose.

 

Factors that may potentiate warfarin

·         liver disease

·         P450 enzyme inhibitors, e.g.: amiodarone, ciprofloxacin

·         cranberry juice

·         drugs which displace warfarin from plasma albumin, e.g. NSAIDs

·         inhibit platelet function: NSAIDs

Side-effects

·         haemorrhage

·         teratogenic, although can be used in breastfeeding mothers

·         skin necrosis: when warfarin is first started biosynthesis of protein C is reduced. This results in a temporary procoagulant state after initially starting warfarin, normally avoided by concurrent heparin administration. Thrombosis may occur in venules leading to skin necrosis

·         purple toes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:51

Hypercalcaemia: features

Features

·         'bones, stones, groans and psychic moans'

·         corneal calcification

·         shortened QT interval on ECG

·         hypertension

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:51

Thiazide diuretics

Thiazide diuretics work by inhibiting sodium reabsorption at the beginning of the distal convoluted tubule (DCT) by blocking the thiazide-sensitive Na+-Cl− symporter. Potassium is lost as a result of more sodium reaching the collecting ducts. Thiazide diuretics have a role in the treatment of mild heart failure although loop diuretics are better for reducing overload. The main use of bendroflumethiazide was in the management of hypertension but recent NICE guidelines now recommend other thiazide-like diuretics such as indapamide and chlortalidone.

 

Common adverse effects

·         dehydration

·         postural hypotension

·         hyponatraemia, hypokalaemia, hypercalcaemia*

·         gout

·         impaired glucose tolerance

·         impotence

Rare adverse effects

·         thrombocytopaenia

·         agranulocytosis

·         photosensitivity rash

·         pancreatitis

 

 

 

Flow chart showing the management of hypertension as per current NICE guideliness

*the flip side of this is hypocalciuria, which may be useful in reducing the incidence of renal stones

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:52

Aortic dissection: management

Classification

 

Stanford classification

·         type A - ascending aorta, 2/3 of cases

·         type B - descending aorta, distal to left subclavian origin, 1/3 of cases

DeBakey classification

·         type I - originates in ascending aorta, propagates to at least the aortic arch and possibly beyond it distally

·         type II - originates in and is confined to the ascending aorta

·         type III - originates in descending aorta, rarely extends proximally but will extend distally

 

Management

 

Type A

·         surgical management, but blood pressure should be controlled to a target systolic of 100-120 mmHg whilst awaiting intervention

Type B*

·         conservative management

·         bed rest

·         reduce blood pressure IV labetalol to prevent progression

 

Complications

 

Complications of backward tear

·         aortic incompetence/regurgitation

·         MI: inferior pattern often seen due to right coronary involvement

Complications of forward tear

·         unequal arm pulses and BP

·         stroke

·         renal failure

 

 

 

© Image used on license from Radiopaedia

An intraluminal tear has formed a 'flap' that can be clearly seen in the ascending aorta. This is a Stanford type A dissection

 

 

© Image used on license from Radiopaedia

Stanford type B dissection, seen in the descending aorta

*endovascular repair of type B aortic dissection may have a role in the future

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

Medical management consists of decreasing heart rate, blood pressure and the shearing forces  of myocardial contractility in order to decrease the propagation of the dissection.

Oral verapamil is not suitable for precise BP control in the acute setting and IV sodium nitroprusside does not slow down the heart rate.

Stanford type A- ascending aorta  dissection

·         control BP (IV labetalol) + surgery

Stanford type B - descending aortic  dissection

·         control BP (IV labetalol)

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

 

 

 

24 December 2020

12:52

Atrial fibrillation: post-stroke

NICE issued guidelines on atrial fibrillation (AF) in 2006. They included advice on the management of patients with AF who develop a stroke or transient-ischaemic attack (TIA).

 

Recommendations include:

·         following a stroke or TIA, warfarin or a direct thrombin or factor Xa inhibitor should be given as the anticoagulant of choice. Antiplatelets should only be given if needed for the treatment of other comorbidities

·         in acute stroke patients, in the absence of haemorrhage, anticoagulation therapy should be commenced after 2 weeks. If imaging shows a very large cerebral infarction then the initiation of anticoagulation should be delayed

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:52

Chest pain: assessment of patients with suspected cardiac chest pain

NICE updated it's guidelines in 2016 on the 'Assessment and diagnosis of recent onset chest pain or discomfort of suspected cardiac origin'.

 

Below is a brief summary of the key points. Please see the link for more details.

 

Patients presenting with acute chest pain

 

Immediate management of suspected acute coronary syndrome (ACS)

·         glyceryl trinitrate

·         aspirin 300mg. NICE do not recommend giving other antiplatelet agents (i.e. Clopidogrel) outside of hospital

·         do not routinely give oxygen, only give if sats < 94%*

·         perform an ECG as soon as possible but do not delay transfer to hospital. A normal ECG does not exclude ACS

Referral

·         current chest pain or chest pain in the last 12 hours with an abnormal ECG: emergency admission

·         chest pain 12-72 hours ago: refer to hospital the same-day for assessment

·         chest pain > 72 hours ago: perform full assessment with ECG and troponin measurement before deciding upon further action

*NICE suggest the following in terms of oxygen therapy:

·         do not routinely administer oxygen, but monitor oxygen saturation using pulse oximetry as soon as possible, ideally before hospital admission. Only offer supplemental oxygen to:

·         people with oxygen saturation (SpO2) of less than 94% who are not at risk of hypercapnic respiratory failure, aiming for SpO2 of 94-98%

·         people with chronic obstructive pulmonary disease who are at risk of hypercapnic respiratory failure, to achieve a target SpO2 of 88-92% until blood gas analysis is available.

Patients presenting with stable chest pain

 

NICE define anginal pain as the following:

·         1. constricting discomfort in the front of the chest, or in the neck, shoulders, jaw or arms

·         2. precipitated by physical exertion

·         3. relieved by rest or GTN in about 5 minutes

·         patients with all 3 features have typical angina

·         patients with 2 of the above features have atypical angina

·         patients with 1 or none of the above features have non-anginal chest pain

For patients in whom stable angina cannot be excluded by clinical assessment alone NICE recommend the following (e.g. symptoms consistent with typical/atypical angina OR ECG changes):

·         1st line: CT coronary angiography

·         2nd line: non-invasive functional imaging (looking for reversible myocardial ischaemia)

·         3rd line: invasive coronary angiography

Examples of non-invasive functional imaging:

·         myocardial perfusion scintigraphy with single photon emission computed tomography (MPS with SPECT) or

·         stress echocardiography or

·         first-pass contrast-enhanced magnetic resonance (MR) perfusion or

·         MR imaging for stress-induced wall motion abnormalities

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:52

Peri-arrest rhythms: bradycardia

The 2015 Resuscitation Council (UK) guidelines emphasise that the management of bradycardia depends on:

·         1. identifying the presence of signs indicating haemodynamic compromise - 'adverse signs'

·         2. identifying the potential risk of asystole

Adverse signs

 

The following factors indicate haemodynamic compromise and hence the need for treatment:

·         shock: hypotension (systolic blood pressure < 90 mmHg), pallor, sweating, cold, clammy extremities, confusion or impaired consciousness

·         syncope

·         myocardial ischaemia

·         heart failure

Atropine (500mcg IV) is the first line treatment in this situation.

 

If there is an unsatisfactory response the following interventions may be used:

·         atropine, up to maximum of 3mg

·         transcutaneous pacing

·         isoprenaline/adrenaline infusion titrated to response

Specialist help should be sought for consideration of transvenous pacing if there is no response to the above measures.

 

Potential risk of asystole

 

The following are risk factors for asystole. Even if there is a satisfactory response to atropine specialist help is indicated to consider the need for transvenous pacing:

·         complete heart block with broad complex QRS

·         recent asystole

·         Mobitz type II AV block

·         ventricular pause > 3 seconds

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:52

Thrombolysis

Thrombolytic drugs activate plasminogen to form plasmin. This in turn degrades fibrin and help breaks up thrombi. They in primarily used in patients who present with a ST elevation myocardial infarction. Other indications include acute ischaemic stroke and pulmonary embolism, although strict inclusion criteria apply.

 

Examples

·         alteplase

·         tenecteplase

·         streptokinase

Contraindications to thrombolysis

·         active internal bleeding

·         recent haemorrhage, trauma or surgery (including dental extraction)

·         coagulation and bleeding disorders

·         intracranial neoplasm

·         stroke < 3 months

·         aortic dissection

·         recent head injury

·         severe hypertension

Side-effects

·         haemorrhage

·         hypotension - more common with streptokinase

·         allergic reactions may occur with streptokinase

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

24 December 2020

12:53

Torsades de pointes

Torsades de pointes ('twisting of the points') is a form of polymorphic ventricular tachycardia associated with a long QT interval. It may deteriorate into ventricular fibrillation and hence lead to sudden death.

 

Causes of long QT interval

·         congenital: Jervell-Lange-Nielsen syndrome, Romano-Ward syndrome

·         antiarrhythmics: amiodarone, sotalol, class 1a antiarrhythmic drugs

·         tricyclic antidepressants

·         antipsychotics

·         chloroquine

·         terfenadine

·         erythromycin

·         electrolyte: hypocalcaemia, hypokalaemia, hypomagnesaemia

·         myocarditis

·         hypothermia

·         subarachnoid haemorrhage

Management

·         IV magnesium sulphate

 

 

© Image used on license from Dr Smith, University of Minnesota

 

ECG showing torsades de pointes

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

Pacing is contraindicated in patients with torsades de pointes ventricular tachycardia secondary to reversible causes.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

 

24 December 2020

12:53

Atrial fibrillation: a very basic introduction

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. It is very common, being present in around 5% of patients over aged 70-75 years and 10% of patients aged 80-85 years. Whilst uncontrolled atrial fibrillation can result in symptomatic palpitations and inefficient cardiac function probably the most important aspect of managing patients with AF is reducing the increased risk of stroke which is present in these patients.

 

 

Types of atrial fibrillation

 

AF may by classified as either first detected episode, paroxysmal, persistent or permanent.

·         first detected episode (irrespective of whether it is symptomatic or self-terminating)

·         recurrent episodes, when a patient has 2 or more episodes of AF. If episodes of AF terminate spontaneously then the term paroxysmal AF is used. Such episodes last less than 7 days (typically < 24 hours). If the arrhythmia is not self-terminating then the term persistent AF is used. Such episodes usually last greater than 7 days

·         in permanent AF there is continuous atrial fibrillation which cannot be cardioverted or if attempts to do so are deemed inappropriate. Treatment goals are therefore rate control and anticoagulation if appropriate

 

Symptoms and signs

 

Symptoms

·         palpitations

·         dyspnoea

·         chest pain

Signs

·         an irregularly irregular pulse

 

Investigations

 

An ECG is essential to make the diagnosis as other conditions can give an irregular pulse, such as ventricular ectopics or sinus arrhythmia.

 

 

Management

 

There are two key parts of managing patients with AF:

·         1. Rate/rhythm control

·         2. Reducing stroke risk

Rate vs. rhythm control

 

There are two main strategies employed in dealing with the arrhythmia element of atrial fibrillation:

·         rate control: accept that the pulse will be irregular, but slow the rate down to avoid negative effects on cardiac function

·         rhythm control: try to get the patient back into, and maintain, normal sinus rhythm. This is termed cardioversion. Drugs (pharmacological cardioversion) and synchronised DC electrical shocks (electrical cardioversion) may be used for this purpose

For many years the predominant approach was to try and maintain a patient in sinus rhythm. This approach changed in the early 2000's and now the majority of patients are managed with a rate control strategy. NICE advocate using a rate control strategy except in a number of specific situations such as coexistent heart failure, first onset AF or where there is an obvious reversible cause.

 

Rate control

 

A beta-blocker or a rate-limiting calcium channel blocker (e.g. diltiazem) is used first-line to control the rate in AF.

 

If one drug does not control the rate adequately NICE recommend combination therapy with any 2 of the following:

·         a betablocker

·         diltiazem

·         digoxin

Rhythm control

 

As mentioned above there are a subgroup of patients for whom a rhythm control strategy should be tried first. Other patients may have had a rate control strategy initially but switch to rhythm control if symptoms/heart rate fails to settle.

 

When considering cardioversion it is very important to remember that the moment a patient switches from AF to sinus rhythm presents the highest risk for embolism leading to stroke. Imagine the thrombus formed in the fibrillating atrium suddenly being pushed out when sinus rhythm is restored. For this reason patients must either have had a short duration of symptoms (less than 48 hours) or be anticoagulated for a period of time prior to attempting cardioversion.

 

 

Reducing stroke risk

 

Some patients with AF are at a very low risk of stroke whilst others are at a very significant risk. Clinicians use risk stratifying tools such as the CHA2DS2-VASc score to determine the most appropriate anticoagulation strategy.

 

 

 

Risk factor

Points

C

Congestive heart failure

1

H

Hypertension (or treated hypertension)

1

A2

Age >= 75 years

2

 

Age 65-74 years

1

D

Diabetes

1

S2

Prior Stroke or TIA

2

V

Vascular disease (including ischaemic heart disease and peripheral arterial disease)

1

S

Sex (female)

1

The table below shows a suggested anticoagulation strategy based on the score:

 

 

Score

Anticoagulation

0

No treatment

1

Males: Consider anticoagulation

Females: No treatment (this is because their score of 1 is only reached due to their gender)

2 or more

Offer anticoagulation

NICE recommend that we offer patients a choice of anticoagulation, including warfarin and the novel oral anticoagulants (NOACs).

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:53

ECG: hypokalaemia

ECG features of hypokalaemia

·         U waves

·         small or absent T waves (occasionally inversion)

·         prolong PR interval

·         ST depression

·         long QT

The ECG below shows typical U waves. Note also the borderline PR interval.

 

 

 

© Image used on license from Dr Smith, University of Minnesota

 

One registered user suggests the following rhyme

·         In Hypokalaemia, U have no Pot and no T, but a long PR and a long QT

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:53

ECG: normal variants

The following ECG changes are considered normal variants in an athlete:

·         sinus bradycardia

·         junctional rhythm

·         first degree heart block

·         Wenckebach phenomenon

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:53

Loop diuretics

Furosemide and bumetanide are loop diuretics that act by inhibiting the Na-K-Cl cotransporter (NKCC) in the thick ascending limb of the loop of Henle, reducing the absorption of NaCl. There are two variants of NKCC; loop diuretics act on NKCC2, which is more prevalent in the kidneys.

 

Indications

·         heart failure: both acute (usually intravenously) and chronic (usually orally)

·         resistant hypertension, particularly in patients with renal impairment

Adverse effects

·         hypotension

·         hyponatraemia

·         hypokalaemia, hypomagnesaemia

·         hypochloraemic alkalosis

·         ototoxicity

·         hypocalcaemia

·         renal impairment (from dehydration + direct toxic effect)

·         hyperglycaemia (less common than with thiazides)

·         gout

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:54

Myocardial infarction: secondary prevention

NICE produced guidelines on the management of patients following a myocardial infarction (MI) in 2013. Some key points are listed below

 

All patients should be offered the following drugs:

·         dual antiplatelet therapy (aspirin plus a second antiplatelet agent)

·         ACE inhibitor

·         beta-blocker

·         statin

Some selected lifestyle points:

·         diet: advise a Mediterranean style diet, switch butter and cheese for plant oil based products. Do not recommend omega-3 supplements or eating oily fish

·         exercise: advise 20-30 mins a day until patients are 'slightly breathless'

·         sexual activity may resume 4 weeks after an uncomplicated MI. Reassure patients that sex does not increase their likelihood of a further MI. PDE5 inhibitors (e.g, sildenafil) may be used 6 months after a MI. They should however be avoided in patient prescribed either nitrates or nicorandil

Most patients who've had an acute coronary syndrome are now given dual antiplatelet therapy (DAPT). Clopidogrel was previously the second antiplatelet of choice. Now ticagrelor and prasugrel (also ADP-receptor inhibitors) are more widely used. The NICE Clinical Knowledge Summaries now recommend:

·         post acute coronary syndrome (medically managed): add ticagrelor to aspirin, stop ticagrelor after 12 months

·         post percutaneous coronary intervention: add prasugrel or ticagrelor to aspirin, stop the second antiplatelet after 12 months

·         this 12 month period may be altered for people at a high-risk of bleeding or those who at high-risk of further ischaemic events

Aldosterone antagonists

·         patients who have had an acute MI and who have symptoms and/or signs of heart failure and left ventricular systolic dysfunction, treatment with an aldosterone antagonist licensed for post-MI treatment (e.g. eplerenone) should be initiated within 3-14 days of the MI, preferably after ACE inhibitor therapy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:54

Scoring systems

There are now numerous scoring systems used in medicine. The table below lists some of the more common ones:

 

 

Scoring system

Notes

CHA2DS2-VASc

Used to determine the need to anticoagulate a patient in atrial fibrillation

ABCD2

Prognostic score for risk stratifying patients who've had a suspected TIA

NYHA

Heart failure severity scale

DAS28

Measure of disease activity in rheumatoid arthritis

Child-Pugh classification

A scoring system used to assess the severity of liver cirrhosis

Wells score

Helps estimate the risk of a patient having a deep vein thrombosis

MMSE

Mini-mental state examination - used to assess cognitive impairment

HAD

Hospital Anxiety and Depression (HAD) scale - assesses severity of anxiety and depression symptoms

PHQ-9

Patient Health Questionnaire - assesses severity of depression symptoms

GAD-7

Used as a screening tool and severity measure for generalised anxiety disorder

Edinburgh Postnatal Depression Score

Used to screen for postnatal depression

SCOFF

Questionnaire used to detect eating disorders and aid treatment

AUDIT

Alcohol screening tool

CAGE

Alcohol screening tool

FAST*

Alcohol screening tool

CURB-65

Used to assess the prognosis of a patient with pneumonia

Epworth Sleepiness Scale

Used in the assessment of suspected obstructive sleep apnoea

IPSS

International prostate symptom score

Gleason score

Indicates prognosis in prostate cancer

APGAR

Assesses the health of a newborn immediately after birth

Bishop score

Used to help assess the whether induction of labour will be required

Waterlow score

Assesses the risk of a patient developing a pressure sore

FRAX

Risk assessment tool developed by WHO which calculates a patients 10-year risk of developing an osteoporosis related fracture

Ranson criteria

Acute pancreatitis

MUST

Malnutrition

*FAST is also mnemonic to help patients/relatives identify the symptoms of a stroke

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Warfarin: interactions

Interactions of warfarin are important both clinically and in terms of exams.

 

General factors that may potentiate warfarin

·         liver disease

·         P450 enzyme inhibitors (see below)

·         cranberry juice

·         drugs which displace warfarin from plasma albumin, e.g. NSAIDs

·         inhibit platelet function: NSAIDs

Drugs which either inhibit or induce the P450 system may affect the metabolism of warfarin and hence the INR:

 

 

Inducers of the P450 system include - INR will decrease

Inhibitors of the P450 system include - INR will increase

·         antiepileptics: phenytoin, carbamazepine

·         barbiturates: phenobarbitone

·         rifampicin

·         St John's Wort

·         chronic alcohol intake

·         griseofulvin

·         smoking (affects CYP1A2, reason why smokers require more aminophylline)

·         antibiotics: ciprofloxacin, clarithromycine/erythromycin

·         isoniazid

·         cimetidine,omeprazole

·         amiodarone

·         allopurinol

·         imidazoles: ketoconazole, fluconazole

·         SSRIs: fluoxetine, sertraline

·         ritonavir

·         sodium valproate

·         acute alcohol intake

·         quinupristin

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Adenosine

Adenosine is most commonly used to terminate supraventricular tachycardias. The effects of adenosine are enhanced by dipyridamole (antiplatelet agent) and blocked by theophyllines. It should be avoided in asthmatics due to possible bronchospasm.

 

Mechanism of action

·         causes transient heart block in the AV node

·         agonist of the A1 receptor in the atrioventricular node, which inhibits adenylyl cyclase thus reducing cAMP and causing hyperpolarization by increasing outward potassium flux

·         adenosine has a very short half-life of about 8-10 seconds

Adenosine should ideally be infused via a large-calibre cannula due to it's short half-life,

 

Adverse effects

·         chest pain

·         bronchospasm

·         transient flushing

·         can enhance conduction down accessory pathways, resulting in increased ventricular rate (e.g. WPW syndrome)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Amiodarone

Amiodarone is a class III antiarrhythmic agent used in the treatment of atrial, nodal and ventricular tachycardias. The main mechanism of action is by blocking potassium channels which inhibits repolarisation and hence prolongs the action potential. Amiodarone also has other actions such as blocking sodium channels (a class I effect)

 

The use of amiodarone is limited by a number of factors

·         very long half-life (20-100 days). For this reason, loading doses are frequently used

·         should ideally be given into central veins (causes thrombophlebitis)

·         has proarrhythmic effects due to lengthening of the QT interval

·         interacts with drugs commonly used concurrently (p450 inhibitor) e.g. Decreases metabolism of warfarin

·         numerous long-term adverse effects (see below)

Monitoring of patients taking amiodarone

·         TFT, LFT, U&E, CXR prior to treatment

·         TFT, LFT every 6 months

Adverse effects of amiodarone use

·         thyroid dysfunction: both hypothyroidism and hyper-thyroidism

·         corneal deposits

·         pulmonary fibrosis/pneumonitis

·         liver fibrosis/hepatitis

·         peripheral neuropathy, myopathy

·         photosensitivity

·         'slate-grey' appearance

·         thrombophlebitis and injection site reactions

·         bradycardia

·         lengths QT interval

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Aortic regurgitation

Features

·         early diastolic murmur: intensity of the murmur is increased by the handgrip manoeuvre

·         collapsing pulse

·         wide pulse pressure

·         Quincke's sign (nailbed pulsation)

·         De Musset's sign (head bobbing)

·         mid-diastolic Austin-Flint murmur in severe AR - due to partial closure of the anterior mitral valve cusps caused by the regurgitation streams

Causes (due to valve disease)

·         rheumatic fever

·         infective endocarditis

·         connective tissue diseases e.g. RA/SLE

·         bicuspid aortic valve

Causes (due to aortic root disease)

·         aortic dissection

·         spondylarthropathies (e.g. ankylosing spondylitis)

·         hypertension

·         syphilis

·         Marfan's, Ehler-Danlos syndrome

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Chest pain

The table below gives characteristic exam question features for conditions causing chest pain

 

 

Condition

Characteristic exam feature

Myocardial infarction

Cardiac-sounding pain

·         heavy, central chest pain they may radiate to the neck and left arm

·         nausea, sweating

·         elderly patients and diabetics may experience no pain

Risk factors for cardiovascular disease

Pneumothorax

History of asthma, Marfan's etc

Sudden dyspnoea and pleuritic chest pain

Pulmonary embolism

Sudden dyspnoea and pleuritic chest pain

Calf pain/swelling

Current combined pill user, malignancy

Pericarditis

Sharp pain relieved by sitting forwards

May be pleuritic in nature

Dissecting aortic aneurysm

'Tearing' chest pain radiating through to the back

Unequal upper limb blood pressure

Gastro-oesophageal reflux disease

Burning retrosternal pain

Other possible symptoms include regurgitation and dysphagia

Musculoskeletal chest pain

One of the most common diagnoses made in the Emergency Department. The pain is often worse on movement or palpation.

 

May be precipitated by trauma or coughing

Shingles

Pain often precedes the rash

Further notes:

 

Aortic dissection

·         This occurs when there is a flap or filling defect within the aortic intima. Blood tracks into the medial layer and splits the tissues with the subsequent creation of a false lumen. It most commonly occurs in the ascending aorta or just distal to the left subclavian artery (less common). It is most common in Afro-carribean males aged 50-70 years.

·         Patients usually present with a tearing intrascapular pain, which may be similar to the pain of a myocardial infarct.

·         The dissection may spread either proximally or distally with subsequent disruption to the arterial branches that are encountered.

·         In the Stanford classification system the disease is classified into lesions with a proximal origin (Type A) and those that commence distal to the left subclavian (Type B).

·         Diagnosis may be suggested by a chest x-ray showing a widened mediastinum. Confirmation of the diagnosis is usually made by use of CT angiography

·         Proximal (Type A) lesions are usually treated surgically, type B lesions are usually managed non operatively.

Pulmonary embolism

·         Typically sudden onset of chest pain, haemoptysis, hypoxia and small pleural effusions may be present.

·         Most patients will have an underlying deep vein thrombosis

·         Diagnosis may be suggested by various ECG findings including S waves in lead I, Q waves in lead III and inverted T waves in lead III. Confirmation of the diagnosis is usually made through use of CT pulmonary angiography.

·         Treatment is with anticoagulation, in those patients who develop a cardiac arrest or severe compromise from their PE, consideration may be given to thrombolysis.

Myocardial infarction

·         Traditionally described as sudden onset of central, crushing chest pain. It may radiate into the neck and down the left arm. Signs of autonomic dysfunction may be present. The presenting features may be atypical in the elderly and those with diabetes.

·         Diagnosis is made through identification of new and usually dynamic ECG changes (and cardiac enzyme changes). Inferior and anterior infarcts may be distinguished by the presence of specific ECG changes (usually II, III and aVF for inferior, leads V1-V5 for anterior).

·         Treatment is with oral antiplatelet agents, primary coronary angioplasty and/ or thrombolysis.

Perforated peptic ulcer

·         Patients usually develop sudden onset of epigastric abdominal pain, it may be soon followed by generalised abdominal pain.

·         There may be features of antecendant abdominal discomfort, the pain of gastric ulcer is typically worse immediately after eating.

·         Diagnosis may be made by erect chest x-ray which may show a small amount of free intra-abdominal air (very large amounts of air are more typically associated with colonic perforation).

·         Treatment is usually with a laparotomy, small defects may be excised and overlaid with an omental patch, larger defects are best managed with a partial gastrectomy.

Boerhaaves syndrome

·         Spontaneous rupture of the oesophagus that occurs as a result of repeated episodes of vomiting.

·         The rupture is usually distally sited and on the left side.

·         Patients usually give a history of sudden onset of severe chest pain that may complicate severe vomiting.

·         Severe sepsis occurs secondary to mediastinitis.

·         Diagnosis is CT contrast swallow.

·         Treatment is with thoracotomy and lavage, if less than 12 hours after onset then primary repair is usually feasible, surgery delayed beyond 12 hours is best managed by insertion of a T tube to create a controlled fistula between oesophagus and skin.

·         Delays beyond 24 hours are associated with a very high mortality rate.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Complete heart block

Features

·         syncope

·         heart failure

·         regular bradycardia (30-50 bpm)

·         wide pulse pressure

·         JVP: cannon waves in neck

·         variable intensity of S1

Types of heart block

 

First degree heart block

·         PR interval > 0.2 seconds

Second degree heart block

·         type 1 (Mobitz I, Wenckebach): progressive prolongation of the PR interval until a dropped beat occurs

·         type 2 (Mobitz II): PR interval is constant but the P wave is often not followed by a QRS complex

Third degree (complete) heart block

·         there is no association between the P waves and QRS complexes

 

 

© Image used on license from Dr Smith, University of Minnesota

 

ECG showing third degree (complete) heart block

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:55

Constrictive pericarditis

Causes

·         any cause of pericarditis

·         particularly TB

Features

·         dyspnoea

·         right heart failure: elevated JVP, ascites, oedema, hepatomegaly

·         JVP shows prominent x and y descent

·         pericardial knock - loud S3

·         Kussmaul's sign is positive

CXR

·         pericardial calcification

The key differences between constrictive pericarditis and cardiac tamponade are summarized in the table below:

 

 

 

Cardiac tamponade

Constrictive pericarditis

JVP

Absent Y descent

X + Y present

Pulsus paradoxus

Present

Absent

Kussmaul's sign*

Rare

Present

Characteristic features

 

Pericardial calcification on CXR

A commonly used mnemonic to remember the absent Y descent in cardiac tamponade is TAMponade = TAMpaX

 

*a paradoxical rise in JVP during inspiration

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:58

Dabigatran

Dabigatran is an oral anticoagulant that works by being a direct thrombin inhibitor. It is one of the drugs developed over the past 20 years as an alternative to warfarin, with the advantage that it does not require regular monitoring.

 

What is dabigatran used for?

 

Dabigatran is currently used for two main indications.

 

Firstly it is an option in the prophylaxis of venous thromboembolism following hip or knee replacement surgery.

 

Secondly, it is also licensed in the UK for prevention of stroke in patients with non-valvular atrial fibrillation who have one or more of the following risk factors present:

·         previous stroke, transient ischaemic attack or systemic embolism

·         left ventricular ejection fraction below 40%

·         symptomatic heart failure of New York Heart Association (NYHA) class 2 or above

·         age 75 years or older

·         age 65 years or older with one of the following: diabetes mellitus, coronary artery disease or hypertension

What are the known side-effects of dabigatran?

 

Unsurprisingly haemorrhage is the major adverse effect.

 

Doses should be reduced in chronic kidney disease and dabigatran should not be prescribed if the creatinine clearance is < 30 ml/min.

 

Reversing the effects

 

Idarucizumab can be used for rapid reversal of the anticoagulant effects of dabigatran.

 

 

Drug Safety Update 2013

 

The RE-ALIGN study showed significantly higher bleeding and thrombotic events in patients with recent mechanical heart valve replacement using dabigatran compared with warfarin.

 

Previously there had been no guidance to support the use of dabigatran in patients with prosthetic heart valves but the advice has now changed to dabigatran being contraindicated in such patients.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:58

ECG: bi/tri-fascicular block

Bifascicular block

·         combination of RBBB with left anterior or posterior hemiblock

·         e.g. RBBB with left axis deviation

Trifascicular block

·         features of bifascicular block as above + 1st-degree heart block

 

 

 

© Image used on license from Dr Smith, University of Minnesota

 

ECG showing trifascicular block: RBBB + left anterior hemiblock + 1st-degree heart block

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:59

ECG: hypothermia

The following ECG changes may be seen in hypothermia

·         bradycardia

·         'J' wave - small hump at the end of the QRS complex

·         first degree heart block

·         long QT interval

·         atrial and ventricular arrhythmias

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:59

Heart failure: NYHA classification

The New York Heart Association (NYHA) classification is widely used to classify the severity of heart failure:

 

NYHA Class I

·         no symptoms

·         no limitation: ordinary physical exercise does not cause undue fatigue, dyspnoea or palpitations

NYHA Class II

·         mild symptoms

·         slight limitation of physical activity: comfortable at rest but ordinary activity results in fatigue, palpitations or dyspnoea

NYHA Class III

·         moderate symptoms

·         marked limitation of physical activity: comfortable at rest but less than ordinary activity results in symptoms

NYHA Class IV

·         severe symptoms

·         unable to carry out any physical activity without discomfort: symptoms of heart failure are present even at rest with increased discomfort with any physical activity

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:59

Pulses

Pulsus paradoxus

·         greater than the normal (10 mmHg) fall in systolic blood pressure during inspiration → faint or absent pulse in inspiration

·         severe asthma, cardiac tamponade

Slow-rising/plateau

·         aortic stenosis

Collapsing

·         aortic regurgitation

·         patent ductus arteriosus

·         hyperkinetic states (anaemia, thyrotoxic, fever, exercise/pregnancy)

Pulsus alternans

·         regular alternation of the force of the arterial pulse

·         severe LVF

Bisferiens pulse

·         'double pulse' - two systolic peaks

·         mixed aortic valve disease

'Jerky' pulse

·         hypertrophic obstructive cardiomyopathy*

*HOCM may occasionally be associated with a bisferiens pulse

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

Bounding

CO2 retention, liver failure, sepsis

Bisferiens

mixed aortic stenosis and regurgitation

Anacrotic

Aortic stenosis

Collapsing

Aortic regurgitation

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

Jerky- HOCM

 

 

 

 

24 December 2020

12:59

Rheumatic fever

Rheumatic fever develops following an immunological reaction to recent (2-6 weeks ago) Streptococcus pyogenes infection.

 

Pathogenesis

·         Streptococcus pyogenes infection → activation of the innate immune system leading to antigen presentation to T cells

·         B and T cells produce IgG and IgM antibodies and CD4+ T cells are activated

·         there is then a cross-reactive immune response (a form of type II hypersensitivity) thought to be mediated by molecular mimicry

·         the cell wall of Streptococcus pyogenes includes M protein, a virulence factor that is highly antigenic. It is thought that the antibodies against M protein cross-react with myosin and the smooth muscle of arteries

·         this response leads to the clinical features of rheumatic fever

·         Aschoff bodies describes the granulomatous nodules found in rheumatic heart fever

Diagnosis is based on evidence of recent streptococcal infection accompanied by:

·         2 major criteria

·         1 major with 2 minor criteria

Evidence of recent streptococcal infection

·         raised or rising streptococci antibodies,

·         positive throat swab

·         positive rapid group A streptococcal antigen test

Major criteria

·         erythema marginatum

·         Sydenham's chorea: this is often a late feature

·         polyarthritis

·         carditis and valvulitis (eg, pancarditis)*

·         subcutaneous nodules

Minor criteria

·         raised ESR or CRP

·         pyrexia

·         arthralgia (not if arthritis a major criteria)

·         prolonged PR interval

 

 

© Image used on license from DermNet NZ

Erythema marginatum is seen in around 10% of children with rheumatic fever. It is rare in adults

*The latest iteration of the Jones criteria (published in 2015) state that rheumatic carditis cannot be based on pericarditis or myocarditis alone and that there must be evidence of endocarditis (the clinical correlate of which is valvulitis which manifests as a regurgitant murmur).

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:59

Ventricular tachycardia

Ventricular tachycardia (VT) is broad-complex tachycardia originating from a ventricular ectopic focus. It has the potential to precipitate ventricular fibrillation and hence requires urgent treatment.

 

There are two main types of VT:

·         monomorphic VT: most commonly caused by myocardial infarction

·         polymorphic VT: A subtype of polymorphic VT is torsades de pointes which is precipitated by prolongation of the QT interval. The causes of a long QT interval are listed below

Causes of a prolonged QT interval

 

 

Congenital

Drugs

Other

·         Jervell-Lange-Nielsen syndrome (includes deafness and is due to an abnormal potassium channel)

·         Romano-Ward syndrome (no deafness)

·         amiodarone, sotalol, class 1a antiarrhythmic drugs

·         tricyclic antidepressants, fluoxetine

·         chloroquine

·         terfenadine

·         erythromycin

·         electrolyte: hypocalcaemia, hypokalaemia, hypomagnesaemia

·         acute myocardial infarction

·         myocarditis

·         hypothermia

·         subarachnoid haemorrhage

Management

 

If the patient has adverse signs (systolic BP < 90 mmHg, chest pain, heart failure) then immediate cardioversion is indicated. In the absence of such signs antiarrhythmics may be used. If these fail, then electrical cardioversion may be needed with synchronised DC shocks

 

Drug therapy

·         amiodarone: ideally administered through a central line

·         lidocaine: use with caution in severe left ventricular impairment

·         procainamide

Verapamil should NOT be used in VT

 

If drug therapy fails

·         electrophysiological study (EPS)

·         implant able cardioverter-defibrillator (ICD) - this is particularly indicated in patients with significantly impaired LV function

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:59

Acute coronary syndrome: a very basic introduction

Acute coronary syndrome (ACS) is an umbrella term covering a number of acute presentations of ischaemic heart disease.

 

It covers a number of presentations, including

·         ST elevation myocardial infarction (STEMI)

·         non-ST elevation myocardial infarction (NSTEMI)

·         unstable angina

Before we go into more detail into these presentations it's useful to take a step back and consider how such conditions develop.

 

ACS generally develops in patients who have ischaemic heart disease, either known or previously undetected. Ischaemic heart disease is a term synonymous with coronary heart disease and coronary artery disease. It describes the gradually build up of fatty plaques within the walls of the coronary arteries. This leads to two main problems:

·         1. Gradual narrowing, resulting in less blood and therefore oxygen reaching the myocardium at times of increased demand. This results in angina, i.e. chest pain due to insufficient oxygen reaching the myocardium during exertion

·         2. The risk of sudden plaque rupture. The fatty plaques which have built up in the endothelium may rupture leading to sudden occlusion of the artery. This can result in no blood/oxygen reaching the area of myocardium.

Remember that there are a large number of factors which can increase the chance of a patient developing ischaemic heart disease:

 

 

Unmodifiable risk factors

Modifiable risk factors

Increasing age

Male gender

Family history

Smoking

Diabetes mellitus

Hypertension

Hypercholesterolaemia

Obesity

 

Pathophysiology

 

Ischaemic heart disease is a complex process which develops over a number of years. A number of changes can be seen:

·         initial endothelial dysfunction is triggered by a number of factors such as smoking, hypertension and hyperglycaemia

·         this results in a number of changes to the endothelium including pro-inflammatory, pro-oxidant, proliferative and reduced nitric oxide bioavailability

·         fatty infiltration of the subendothelial space by low-density lipoprotein (LDL) particles

·         monocytes migrate from the blood and differentiate into macrophages. These macrophages then phagocytose oxidized LDL, slowly turning into large 'foam cells'. As these macrophages die the result can further propagate the inflammatory process.

·         smooth muscle proliferation and migration from the tunica media into the intima results in formation of a fibrous capsule covering the fatty plaque.

 

 

Image sourced from Wikipedia

Diagram showing the progression of atherosclerosis in the coronary arteries with associated complications on the right.

 

 

 

Image sourced from Wikipedia

Slide showing a markedly narrowed coronary artery secondary to atherosclerosis. Stained with Masson's trichrome.

 

 

Complications of atherosclerosis

 

Once a plaque has formed a number of complications can develop:

·         the plaque forms a physical blockage in the lumen of the coronary artery. This may cause reduced blood flow and hence oxygen to the myocardium, particularly at times of increased demand, resulting clinically in angina

·         the plaque may rupture, potentially causing a complete occlusion of the coronary artery. This may result in a myocardial infarction

 

 

© Image used on license from PathoPic

Ruptured coronary artery plaque resulting in thrombosis and associated myocardial infarction.

 

 

 

© Image used on license from PathoPic

Pathological specimen showing infarction of the anteroseptal and lateral wall of the left ventricle. There is a background of biventricular myocardial hypertrophy.

 

 

Symptoms and signs

 

The classic and most common feature of ACS is chest pain.

·         typically central/left-sided

·         may radiate to the jaw or the left arm

·         often described as 'heavy' or constricting, 'like an elephant on my chest'

·         it should be noted however in real clinical practice patients present with a wide variety of types of chest pain and patients/doctors may confuse ischaemic pain for other causes such as dyspepsia

·         certain patients e.g. diabetics/elderly may not experience any chest pain

Other symptoms in ACS include

·         dyspnoea

·         sweating

·         nausea and vomiting

Patients presenting with ACS often have very few physical signs to ellicit:

·         pulse, blood pressure, temperature and oxygen saturations are often normal or only mildly altered e.g. tachycardia

·         if complications of the ACS have developed e.g. cardiac failure then clearly there may a number of findings

·         the patient may appear pale and clammy

 

Investigations

 

The two most important investigations when assessing a patient with chest pain are:

·         ECG

·         cardiac markers e.g. troponin

 

ECG showing a ST elevation myocardial infarction (STEMI). Note by how looking at which leads are affected (in this case II, III and aVF) we are able to tell which coronary arteries are blocked (the right coronary artery in this case). A blockage of the left anterior descending (LAD) artery would cause elevation of V1-V4, what is often termed an 'anterior' myocardial infarction.

 

 

 

© Image used on license from Dr Smith, University of Minnesota

 

ECG showing a non-ST elevation myocardial infarction (NSTEMI). On the ECG there is deep ST depression in I-III, aVF, and V3-V6. aVR also has ST elevation. Deep and widespread ST depression is associated with very high mortality because it signifies severe ischemia usually of LAD or left main stem.

 

The table below shows a simplified correlation between ECG changes and coronary territories:

 

 

 

ECG changes

Coronary artery

Anterior

V1-V4

Left anterior descending

Inferior

II, III, aVF

Right coronary

Lateral

I, V5-6

Left circumflex

 

 

 

Diagram showing the correlation between ECG changes and coronary territories in acute coronary syndrome

 

 

Management

 

Once a diagnosis of ACS has been made there are a number of elements to treatment:

·         prevent worsening of presentation (i.e. further occlusion of coronary vessel)

·         revascularise (i.e. 'unblock') the vessel if occluded (patients presenting with a STEMI)

·         treat pain

A commonly taught mnemonic for the treatment of ACS is MONA:

·         Morphine

·         Oxygen

·         Nitrates

·         Aspirin

Whilst useful it should be remember that not all patients require oxygen therapy. British Thoracic Society guidelines are now widely adopted and oxygen should only be given if the oxygen saturations are < 94%.

 

For patients who've had a STEMI (i.e. one of the coronary arteries has become occluded) the priority of management is to reopen, or revascularise, the blocked vessel.

·         a second antiplatelet drug should be given in addition to aspirin. Options include clopidogrel, prasugrel and ticagrelor

·         for many years the treatment of choice was thrombolysis. This involved the intravenous administration of a thrombolytic or 'clot-busting' drug to breakdown the thrombus blocking the coronary artery

·         since the early 2000's thrombolysis has been superseded by percutaneous coronary intervention (PCI). In this procedure the blocked arteries are opened up using a balloon (angioplasty) following which a stent may be deployed to prevent the artery occluding again in the future. This is done via a catheter inserted into either the radial or femoral artery

If a patient presents with an NSTEMI then a risk stratification too (such as GRACE) is used to decide upon further management. If a patient is considered high-risk or is clinically unstable then coronary angiography will be performed during the admission. Lower risk patients may have a coronary angiogram at a later date.

 

 

Secondary prevention

 

Patients who've had an ACS require lifelong drug therapy to help reduce the risk of a further event. Standard therapy comprises the following as a minimum:

·         aspirin

·         a second antiplatelet if appropriate (e.g. clopidogrel)

·         a beta-blocker

·         an ACE inhibitor

·         a statin

 

Further images

 

The following images show the progress of coronary artery atherosclerosis:

 

 

 

© Image used on license from PathoPic

Normal coronary artery with blood in the lumen.

 

 

© Image used on license from PathoPic

Slightly stenosed coronary artery

 

 

© Image used on license from PathoPic

Moderately stenosed coronary artery, beetween 50-75%

 

 

© Image used on license from PathoPic

Severely stenosed coronary artery

 

 

© Image used on license from PathoPic

Recanalised old atherothrombotic occlusion of a coronary artery. Numerous small neolumina recanalising the organised occluding thrombus (indicated with arrows)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

12:59

Acute coronary syndrome: prognostic factors

The 2006 Global Registry of Acute Coronary Events (GRACE) study has been used to derive regression models to predict death in hospital and death after discharge in patients with acute coronary syndrome

 

Poor prognostic factors

·         age

·         development (or history) of heart failure

·         peripheral vascular disease

·         reduced systolic blood pressure

·         Killip class*

·         initial serum creatinine concentration

·         elevated initial cardiac markers

·         cardiac arrest on admission

·         ST segment deviation

*Killip class - system used to stratify risk post myocardial infarction

 

 

Killip class

Features

30 day mortality

I

No clinical signs heart failure

6%

II

Lung crackles, S3

17%

III

Frank pulmonary oedema

38%

IV

Cardiogenic shock

81%

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:00

Atrial fibrillation: pharmacological cardioversion

NICE published guidelines on the management of atrial fibrillation (AF) in 2014. The following is also based on the joint American Heart Association (AHA), American College of Cardiology (ACC) and European Society of Cardiology (ESC) 2016 guidelines

 

Agents with proven efficacy in the pharmacological cardioversion of atrial fibrillation

·         amiodarone

·         flecainide (if no structural heart disease)

·         others (less commonly used in UK): quinidine, dofetilide, ibutilide, propafenone

Less effective agents

·         beta-blockers (including sotalol)

·         calcium channel blockers

·         digoxin

·         disopyramide

·         procainamide

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:00

Atrial septal defects

Atrial septal defects (ASDs) are the most likely congenital heart defect to be found in adulthood. They carry a significant mortality, with 50% of patients being dead at 50 years. Two types of ASDs are recognised, ostium secundum and ostium primum. Ostium secundum are the most common

 

Features

·         ejection systolic murmur, fixed splitting of S2

·         embolism may pass from venous system to left side of heart causing a stroke

Ostium secundum (70% of ASDs)

·         associated with Holt-Oram syndrome (tri-phalangeal thumbs)

·         ECG: RBBB with RAD

Ostium primum

·         present earlier than ostium secundum defects

·         associated with abnormal AV valves

·         ECG: RBBB with LAD, prolonged PR interval

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:01

B-type natriuretic peptide

B-type natriuretic peptide (BNP) is a hormone produced mainly by the left ventricular myocardium in response to strain.

 

Whilst heart failure is the most obvious cause of raised BNP levels any cause of left ventricular dysfunction such as myocardial ischaemia or valvular disease may raise levels. Raised levels may also be seen due to reduced excretion in patients with chronic kidney disease. Factors which reduce BNP levels include treatment with ACE inhibitors, angiotensin-2 receptor blockers and diuretics.

 

Effects of BNP

·         vasodilator

·         diuretic and natriuretic

·         suppresses both sympathetic tone and the renin-angiotensin-aldosterone system

Clinical uses of BNP

 

Diagnosing patients with acute dyspnoea

·         a low concentration of BNP(< 100pg/ml) makes a diagnosis of heart failure unlikely, but raised levels should prompt further investigation to confirm the diagnosis

·         NICE currently recommends BNP as a helpful test to rule out a diagnosis of heart failure

Prognosis in patients with chronic heart failure

·         initial evidence suggests BNP is an extremely useful marker of prognosis

Guiding treatment in patients with chronic heart failure

·         effective treatment lowers BNP levels

Screening for cardiac dysfunction

·         not currently recommended for population screening

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:01

Cardiac enzymes and protein markers

Interpretation of the various cardiac enzymes has now largely been superceded by the introduction of troponin T and I. Questions still however commonly appear in exams.

 

Key points for the exam

·         myoglobin is the first to rise

·         CK-MB is useful to look for reinfarction as it returns to normal after 2-3 days (troponin T remains elevated for up to 10 days)

 

 

Begins to rise

Peak value

Returns to normal

Myoglobin

1-2 hours

6-8 hours

1-2 days

CK-MB

2-6 hours

16-20 hours

2-3 days

CK

4-8 hours

16-24 hours

3-4 days

Trop T

4-6 hours

12-24 hours

7-10 days

AST

12-24 hours

36-48 hours

3-4 days

LDH

24-48 hours

72 hours

8-10 days

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:01

Chronic heart failure: diagnosis

NICE issued updated guidelines on diagnosis and management in 2018. Previously the first-line investigation was determined by whether the patient has previously had a myocardial infarction or not this is no longer the case - all patients should have an N-terminal pro-B-type natriuretic peptide (NT‑proBNP) blood test first-line.

 

Interpreting the test

·         if levels are 'high' arrange specialist assessment (including transthoracic echocardiography) within 2 weeks

·         if levels are 'raised' arrange specialist assessment (including transthoracic echocardiography) echocardiogram within 6 weeks

Serum natriuretic peptides

 

B-type natriuretic peptide (BNP) is a hormone produced mainly by the left ventricular myocardium in response to strain. Very high levels are associated with a poor prognosis.

 

 

 

BNP

NTproBNP

High levels

> 400 pg/ml (116 pmol/litre)

> 2000 pg/ml (236 pmol/litre)

Raised levels

100-400 pg/ml (29-116 pmol/litre)

400-2000 pg/ml (47-236 pmol/litre)

Normal levels

< 100 pg/ml (29 pmol/litre)

< 400 pg/ml (47 pmol/litre)

Factors which alter the BNP level:

 

 

Increase BNP levels

Decrease BNP levels

Left ventricular hypertrophy

Ischaemia

Tachycardia

Right ventricular overload

Hypoxaemia (including pulmonary embolism)

GFR < 60 ml/min

Sepsis

COPD

Diabetes

Age > 70

Liver cirrhosis

Obesity

Diuretics

ACE inhibitors

Beta-blockers

Angiotensin 2 receptor blockers

Aldosterone antagonists

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:01

DVLA: cardiovascular disorders

The guidelines below relate to car/motorcycle use unless specifically stated. For obvious reasons, the rules relating to drivers of heavy goods vehicles tend to be much stricter

 

Specific rules

·         hypertension

o    can drive unless treatment causes unacceptable side effects, no need to notify DVLA

o    if Group 2 Entitlement the disqualifies from driving if resting BP consistently 180 mmHg systolic or more and/or 100 mm Hg diastolic or more

·         angioplasty (elective) - 1 week off driving

·         CABG - 4 weeks off driving

·         acute coronary syndrome- 4 weeks off driving

o    1 week if successfully treated by angioplasty

·         angina - driving must cease if symptoms occur at rest/at the wheel

·         pacemaker insertion - 1 week off driving

·         implantable cardioverter-defibrillator (ICD)

o    if implanted for sustained ventricular arrhythmia: cease driving for 6 months

o    if implanted prophylactically then cease driving for 1 month. Having an ICD results in a permanent bar for Group 2 drivers

·         successful catheter ablation for an arrhythmia- 2 days off driving

·         aortic aneurysm of 6cm or more - notify DVLA. Licensing will be permitted subject to annual review.

o    an aortic diameter of 6.5 cm or more disqualifies patients from driving

·         heart transplant: do not drive for 6 weeks, no need to notify DVLA

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:09

Eisenmenger's syndrome

Eisenmenger's syndrome describes the reversal of a left-to-right shunt in a congenital heart defect due to pulmonary hypertension. This occurs when an uncorrected left-to-right leads to remodeling of the pulmonary microvasculature, eventually causing obstruction to pulmonary blood and pulmonary hypertension.

 

Associated with

·         ventricular septal defect

·         atrial septal defect

·         patent ductus arteriosus

Features

·         original murmur may disappear

·         cyanosis

·         clubbing

·         right ventricular failure

·         haemoptysis, embolism

Management

·         heart-lung transplantation is required

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:09

Heart failure: acute management

Management options in acute heart failure include:

·         oxygen

·         IV loop diuretics

·         opiates

·         vasodilators

·         inotropic agents

·         CPAP

·         ultrafiltration

·         mechanical circulatory assistance: e.g. intra-aortic balloon counterpulsation or ventricular assist devices

Consideration should be given to discontinuing beta-blockers in the short-term.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:09

Heart sounds

The first heart sound (S1) is caused by closure of the mitral and tricuspid valves whilst the second heart sound (S2) is due to aortic and pulmonary valve closure

 

S1

·         closure of mitral and tricuspid valves

·         soft if long PR or mitral regurgitation

·         loud in mitral stenosis

S2

·         closure of aortic and pulmonary valves

·         soft in aortic stenosis

·         splitting during inspiration is normal

S3 (third heart sound)

·         caused by diastolic filling of the ventricle

·         considered normal if < 30 years old (may persist in women up to 50 years old)

·         heard in left ventricular failure (e.g. dilated cardiomyopathy), constrictive pericarditis (called a pericardial knock) and mitral regurgitation

S4 (fourth heart sound)

·         may be heard in aortic stenosis, HOCM, hypertension

·         caused by atrial contraction against a stiff ventricle

o    therefore coincides with the P wave on ECG

·         in HOCM a double apical impulse may be felt as a result of a palpable S4

Sites of auscultation

 

 

Valve

Site

Pulmonary valve

Left second intercostal space, at the upper sternal border

Aortic valve

Right second intercostal space, at the upper sternal border

Mitral valve

Left fifth intercostal space, just medial to mid clavicular line

Tricuspid valve

Left fourth intercostal space, at the lower left sternal border

The diagram below demonstrates where the various cardiac valves are best heard.

 

 

Image sourced from Wikipedia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

Left ventricular volume overload causes a third heart sound.

 

 

Regular cannon waves Irregular cannon waves SVT with 1:1 VA conduction AVNRT Complete heart block Multiple random ventricular premature beats VT with AV dissociation with retrograde p waves falling within QT intervals

Cannon waves occur when the atrium contracts against a closing tricuspid valve.

Cannon waves happen only when P waves fall within QT intervals in ECG. P wave represents atrial systolic  contraction and QT represents ventricular systole. When the atrium contracts against a closed tricuspid  valve during a ventricular contraction, a cannon wave projecting into the neck is seen.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

 

 

 

24 December 2020

13:09

Hypothermia

Hypothermia is an unintentional reduction of core body temperature below the normal physiological limits. In initial stages, thermoreceptors in the skin and subcutaneous tissues sense the low temperature and cause a regional vasoconstriction. This causes the hypothalamus to stimulate the release of TSH and ACTH. It also stimulates heat production by promoting shivering.

 

Definitions:

·         Mild hypothermia: 32-35°C

·         Moderate or severe hypothermia: < 32°C

Epidemiology:

·         The incidence of hypothermia varies globally. In the UK, the estimated annual number of hypothermia-related deaths is 300/year, whereas in Canada, it is 8000/year.

·         Hypothermia is most common during the winter, and the elderly are particularly susceptible (see further risk factors below). Many cases of hypothermia also occur indoors, due to poor heating facilities.

Causes can include:

·         Exposure to cold in the environment is the major cause

·         Inadequate insulation in the operating room

·         Cardiopulmonary bypass

·         Newborn babies.

Risk factors:

·         General anaesthesia

·         Substance abuse

·         Hypothyroidism

·         Impaired mental status

·         Homelessness

·         Extremes of age

Signs of hypothermia include:

·         shivering

·         cold and pale skin. Frostbite occurs when the skin and subcutaneous tissue freeze, causing damage to cells.

·         slurred speech

·         tachypnoea, tachycardia and hypertension (if mild)

·         respiratory depression, bradycardia and hypothermia (if moderate)

·         confusion/ impaired mental state

Babies with hypothermia can look healthy. However, they may be limp, unusually quiet and refuse to feed. Heat loss in newborns is extremely common, hence a hat and clothing/ blankets will be applied soon after birth.

 

Investigations:

·         Temperature. Special low-reading rectal thermometers or thermistor probes are preferred for measuring core body temperature. The patient's temperature should be tracked over time, to check for improvement.

·         12 lead ECG. As the core temperature approaches 32°C to 33°C, acute ST-elevation and J waves or Osborn waves may appear

·         FBC, serum electrolytes. Haemoglobin and haematocrit can be elevated (due to haemoconcentration). Platelets and WBCs are low due to sequestration in the spleen. Monitoring potassium is advised as hypothermic patients can be hypokalaemic due to a shift of potassium into the intracellular space.

·         Blood glucose. Stress hormones are increased, and the body can have more peripheral resistance to insulin.

·         Arterial blood gas

·         Coagulation factors

·         Chest X-ray

Initial management includes:

·         Removing the patient from the cold environment and removing any wet/cold clothing,

·         Warming the body with blankets

·         Securing the airway and monitoring breathing,

·         If the patient is not responding well to passive warming, you may consider maintaining circulation using warm IV fluids or applying forced warm air directly to the patient's body

+ rapid re-warming can lead to peripheral vasodilation and shock

·         In severe cases, be prepared to conduct CPR. IV drugs should be avoided if possible, as the patient is more likely to have a drastic response to the drug.

For reference, the NHS also provides advice to the public for what NOT to do when a person has hypothermia (due to the risk of cardiac arrest):

·         Don't put the person into a hot bath.

·         Don't massage their limbs.

·         Don't use heating lamps.

·         Don't give them alcohol to drink.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:09

Infective endocarditis: features

Modified Duke criteria

 

Infective endocarditis diagnosed if

·         pathological criteria positive, or

·         2 major criteria, or

·         1 major and 3 minor criteria, or

·         5 minor criteria

Pathological criteria

 

Positive histology or microbiology of pathological material obtained at autopsy or cardiac surgery (valve tissue, vegetations, embolic fragments or intracardiac abscess content)

 

Major criteria

 

Positive blood cultures

·         two positive blood cultures showing typical organisms consistent with infective endocarditis, such as Streptococcus viridans and the HACEK group, or

·         persistent bacteraemia from two blood cultures taken > 12 hours apart or three or more positive blood cultures where the pathogen is less specific such as Staph aureus and Staph epidermidis, or

·         positive serology for Coxiella burnetii, Bartonella species or Chlamydia psittaci, or

·         positive molecular assays for specific gene targets

Evidence of endocardial involvement

·         positive echocardiogram (oscillating structures, abscess formation, new valvular regurgitation or dehiscence of prosthetic valves), or

·         new valvular regurgitation

Minor criteria

·         predisposing heart condition or intravenous drug use

·         microbiological evidence does not meet major criteria

·         fever > 38ºC

·         vascular phenomena: major emboli, splenomegaly, clubbing, splinter haemorrhages, Janeway lesions, petechiae or purpura

·         immunological phenomena: glomerulonephritis, Osler's nodes, Roth spots

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:10

Infective endocarditis: prophylaxis

The 2008 guidelines from NICE have radically changed the list of procedures for which antibiotic prophylaxis is recommended

 

NICE recommends the following procedures do not require prophylaxis:

·         dental procedures

·         upper and lower gastrointestinal tract procedures

·         genitourinary tract; this includes urological, gynaecological and obstetric procedures and childbirth

·         upper and lower respiratory tract; this includes ear, nose and throat procedures and bronchoscopy

The guidelines do however suggest:

·         any episodes of infection in people at risk of infective endocarditis should be investigated and treated promptly to reduce the risk of endocarditis developing

·         if a person at risk of infective endocarditis is receiving antimicrobial therapy because they are undergoing a gastrointestinal or genitourinary procedure at a site where there is a suspected infection they should be given an antibiotic that covers organisms that cause infective endocarditis

It is important to note that these recommendations are not in keeping with the American Heart Association/European Society of Cardiology guidelines which still advocate antibiotic prophylaxis for high-risk patients who are undergoing dental procedures.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:10

Postural hypotension

Postural hypotension may be defined as a fall of systolic blood pressure > 20 mmHg on standing.

 

Causes

·         hypovolaemia

·         autonomic dysfunction: diabetes, Parkinson's

·         drugs: diuretics, antihypertensives, L-dopa, phenothiazines, antidepressants, sedatives

·         alcohol

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:10

Pulmonary embolism

Potential features of pulmonary embolism include:

·         chest pain

o    typically pleuritic

·         dyspnoea

·         haemoptysis

·         tachycardia

·         tachypnoea

·         respiratory examination

o    classically the chest will be clear

o    however, in real-world clinical practice findings are often found (see below for more details)

We know from experience that few patients (around 10%) present with the medical student textbook triad of pleuritic chest pain, dyspnoea and haemoptysis. Pulmonary embolism can be difficult to diagnose as it can present with virtually any cardiorespiratory symptom/sign depending on it's location and size.

 

So which features make pulmonary embolism more likely?

 

The PIOPED study1 in 2007 looked at the frequency of different symptoms and signs in patients who were diagnosed with pulmonary embolism.

 

The relative frequency of common clinical signs is shown below:

·         Tachypnea (respiratory rate >16/min) - 96%

·         Crackles - 58%

·         Tachycardia (heart rate >100/min) - 44%

·         Fever (temperature >37.8°C) - 43%

It is interesting to note that the Well's criteria for diagnosing a PE use tachycardia rather than tachypnoea.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:10

Takayasu's arteritis

 

pulseless disease of Asian young females

 

Takayasu's arteritis is a large vessel vasculitis. It typically causes occlusion of the aorta and questions commonly refer to an absent limb pulse. It is more common in females and Asian people

 

Features

·         systemic features of a vasculitis e.g. malaise, headache

·         unequal blood pressure in the upper limbs

·         carotid bruit

·         intermittent claudication

·         aortic regurgitation (around 20%)

 

Investigation:

magnetic resonance angiography.

 

 

 

Angiography showing multiple stenoses in the branches of the aorta secondary to Takayasu's arteritis

Associations

·         renal artery stenosis

Management

·         steroids

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

Takayasu arteritis (aka, Pulseless disease) Granulomatous Disease Aorta and its large branches •Thickenina and fibrosis of vessel wall narrows lumen. Nonspecific symtpoms assoc. with Inflammation: Weakness, fatigue, fever, weight loss, arthralgia. Poss. complications: Aneurysm, aortic regurgitation, retinopathy. • Ischemia produces: "Pulselessdisease" Weak/absent pulse. Different pressures in upper extremities. Claudication in limbs, chest pain. Poss. hypertension (renal art. stenosis) Most common in women < 40 y. 0.; esp. Asian ancestry.

 

 

 

 

24 December 2020

13:10

Ventricular septal defect

Ventricular septal defects (VSD) are the most common cause of congenital heart disease. They close spontaneously in around 50% of cases. Congenital VSDs are associated with chromosomal disorders (e.g. Down's syndrome, Edward's syndrome, Patau syndrome) and single gene disorders such as Non-congenital causes include post myocardial infarction

 

Features

·         classically a pan-systolic murmur which is louder in smaller defects

Complications

·         aortic regurgitation*

·         infective endocarditis

·         Eisenmenger's complex

·         right heart failure

·         pulmonary hypertension: pregnancy is contraindicated in women with pulmonary hypertension as it carries a 30-50% risk of mortality

*aortic regurgitation is due to a poorly supported right coronary cusp resulting in cusp prolapse

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:10

Abdominal aorta aneurysm

- Abdominal aortic aneurysms are a common problem in vascular surgery.

·         They may occur as either true or false aneurysm. With the former all 3 layers of the arterial wall are involved, in the latter only a single layer of fibrous tissue forms the aneurysm wall.

·         True abdominal aortic aneurysms have an approximate incidence of 0.06 per 1000 people. They are commonest in elderly men and for this reason the UK is now introducing the aneurysm screening program with the aim of performing an abdominal aortic ultrasound measurement in all men aged 65 years.

Causes

·         Several different groups of patients suffer from aneurysmal disease.

·         The commonest group is those who suffer from standard arterial disease, i.e. Those who are hypertensive, have diabetes and have been or are smokers.

·         Other patients such as those suffering from connective tissue diseases such as Marfan's may also develop aneurysms. In patients with abdominal aortic aneurysms the extracellular matrix becomes disrupted with a change in the balance of collagen and elastic fibres.

Management

·         Most abdominal aortic aneurysms are an incidental finding.

·         Symptoms most often relate to rupture or impending rupture.

·         20% rupture anteriorly into the peritoneal cavity. Very poor prognosis.

·         80% rupture posteriorly into the retroperitoneal space

·         The risk of rupture is related to aneurysm size, only 2% of aneurysms measuring less than 4cm in diameter will rupture over a 5 year period. This contrasts with 75% of aneurysms measuring over 7cm in diameter.

·         This is well explained by Laplaces' law which relates size to transmural pressure.

·         For this reason most vascular surgeons will subject patients with an aneurysm size of 5cm or greater to CT scanning of the chest, abdomen and pelvis with the aim of delineating anatomy and planning treatment. Depending upon co-morbidities, surgery is generally offered once the aneurysm is between 5.5cm and 6cm.

A CT reconstruction showing an infrarenal abdominal aortic aneurysm. The walls of the sac are calcified which may facilitate identification on plain x-rays

 

 

Image sourced from Wikipedia

Indications for surgery

·         Symptomatic aneurysms (80% annual mortality if untreated)

·         Increasing size above 5.5cm if asymptomatic

·         Rupture (100% mortality without surgery)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:10

Acute coronary syndrome: clincial features

Features of acute coronary syndrome (ACS) include:

·         chest pain: classically on the left side of the chest. May radiate to the left arm or neck. This may not be present in elderly or diabetic patients

·         dyspnoea

·         nausea and vomiting

·         sweating

·         palpitations

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:11

Antiplatelets: summary of latest guidance

The table below summarises the most recent guidelines regarding antiplatelets:

 

 

Diagnosis

1st line

2nd line

Acute coronary syndrome (medically treated)

Aspirin (lifelong) & ticagrelor (12 months)

If aspirin contraindicated, clopidogrel (lifelong)

Percutaneous coronary intervention

Aspirin (lifelong) & prasurgrel or ticagrelor (12 months)

If aspirin contraindicated, clopidogrel (lifelong)

TIA

Clopidogrel (lifelong)

Aspirin (lifelong) & dipyridamole (lifelong)

Ischaemic stroke

Clopidogrel (lifelong)

Aspirin (lifelong) & dipyridamole (lifelong)

Peripheral arterial disease

Clopidogrel (lifelong)

Asprin (lifelong)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:11

Atrial myxoma

Atrial myxoma is the most common primary cardiac tumour.

 

Overview

·         75% occur in left atrium, most commonly attached to the fossa ovalis

·         more common in females

Features

·         systemic: dyspnoea, fatigue, weight loss, pyrexia of unknown origin, clubbing

·         emboli

·         atrial fibrillation

·         mid-diastolic murmur, 'tumour plop'

·         echo: pedunculated heterogeneous mass typically attached to the fossa ovalis region of the interatrial septum

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:11

Atrioventricular block

In atrioventricular (AV) block, or heart block, there is impaired electrical conduction between the atria and ventricles. There are three types:

 

First-degree heart block

·         PR interval > 0.2 seconds

·         asymptomatic first-degree heart block is relatively common and does not need treatment

Second-degree heart block

·         type 1 (Mobitz I, Wenckebach): progressive prolongation of the PR interval until a dropped beat occurs

·         type 2 (Mobitz II): PR interval is constant but the P wave is often not followed by a QRS complex

Third-degree (complete) heart block

·         there is no association between the P waves and QRS complexes

 

 

 

ECG showing types of heart block

 

 

 

Type 1 (Wenckebach)

 

 

 

Sinus tachycardia with complete AV block and resulting junctional escape

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:11

Cardiac imaging: non-invasive techniques excluding echocardiography

The ability to image the heart using non-invasive techniques such as MRI, CT and radionuclides has evolved rapidly over recent years.

 

Nuclear imaging

 

These techniques use radiotracers which are extracted by normal myocardium. Examples include:

·         thallium

·         technetium (99mTc) sestamibi: a coordination complex of the radioisotope technetium-99m with the ligand methoxyisobutyl isonitrile (MIBI), used in 'MIBI' or cardiac Single Photon Emission Computed Tomography (SPECT) scans

·         fluorodeoxyglucose (FDG): used in Positron Emission Tomography (PET) scans

The primary role of SPECT is to assess myocardial perfusion and myocardial viability. Two sets of images are usually acquired. First the myocardium at rest followed by images of the myocardium during stress (either exercise or following adenosine / dipyridamole). By comparing the rest with stress images any areas of ischaemia can classified as reversible or fixed (e.g. Following a myocardial infarction). Cardiac PET is predominately a research tool at the current time

 

MUGA

·         Multi Gated Acquisition Scan, also known as radionuclide angiography

·         radionuclide (technetium-99m) is injected intravenously

·         the patient is placed under a gamma camera

·         may be performed as a stress test

·         can accurately measure left ventricular ejection fraction. Typically used before and after cardiotoxic drugs are used

Cardiac Computed Tomography (CT)

 

Cardiac CT is useful for assessing suspected ischaemic heart disease, using two main methods:

·         calcium score: there is known to be a correlation between the amount of atherosclerotic plaque calcium and the risk of future ischaemic events. Cardiac CT can quantify the amount of calcium producing a 'calcium score'

·         contrast enhanced CT: allows visualisation of the coronary artery lumen

If these two techniques are combined cardiac CT has a very high negative predictive value for ischaemic heart disease.

 

Cardiac MRI

 

Cardiac MRI (commonly termed CMR) has become the gold standard for providing structural images of the heart. It is particularly useful when assessing congenital heart disease, determining right and left ventricular mass and differentiating forms of cardiomyopathy. Myocardial perfusion can also be assessed following the administration of gadolinium. Currently CMR provides limited data on the extent of coronary artery disease.

 

Please also see the British Heart Foundation link for an excellent summary.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Choking

Partial or complete airway obstruction is a life-threatening emergency. Episodes often occur whilst eating and patients will often clutch their neck. The first step is to ask the patient 'Are you choking?'

 

Features of airway obstruction (taken from the Resus Council)

 

 

Mild airway obstruction

Severe airway obstruction

Response to question 'Are you choking?'

·         victim speaks and answers yes

Other signs

·         victim is able to speak, cough, and breathe

Response to question 'Are you choking?'

·         victim unable to speak

·         victim may respond by nodding

Other signs

·         victim unable to breathe

·         breathing sounds wheezy

·         attempts at coughing are silent

·         victim may be unconscious

If mild airway obstruction

·         encourage the patient to cough

If severe airway obstruction and is conscious:

·         give up to 5 back-blows

·         if unsuccessful give up to 5 abdominal thrusts

·         if unsuccessful continue the above cycle

If unconscious

·         call for an ambulance

·         start cardiopulmonary resuscitation (CPR)

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Combination antiplatelet and anticoagulant therapy

With the increase in comorbidity, it is now common to find that a patient has an indication for both an antiplatelet (e.g. established cardiovascular disease) and an anticoagulant (e.g. atrial fibrillation, venous thromboembolism or valvular heart disease). However, combination therapy increases the risk of bleeding and may not be needed in all cases. How should this be managed?

 

Whilst there are not guidelines to cover every scenario a recent review in the BMJ offered an expert opinion outlining the approach in common scenarios.

 

Secondary prevention of stable cardiovascular disease with an indication for an anticoagulant

·         normally in this situation, all patients are recommended to be prescribed an antiplatelet

·         if an indication for anticoagulant exists (for example atrial fibrillation) it is indicated that anticoagulant monotherapy is given without the addition of antiplatelets

Post-acute coronary syndrome/percutaneous coronary intervention

·         in these patients, there is a much stronger indication for antiplatelet therapy

·         generally patients are given triple therapy (2 antiplatelets + 1 anticoagulant) for 4 weeks-6 months after the event and dual therapy (1 antiplatelet + 1 anticoagulant) to complete 12 months

·         there is variation from patient to patient however given that the stroke risk in atrial fibrillation varies according to risk factors.

Venous thromboembolism (VTE)

·         if a patient on antiplatelets develops a VTE they are likely to be prescribed anticoagulants for 3-6 months

·         a HAS-BLED score should be calculated. Those with a low risk of bleeding may continue antiplatelets. In patients with an intermediate or high risk of bleeding consideration should be given to stopping the antiplatelets

For more information please see BMJ 2017;358:j3782

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy, accounting for 90% of cases.

 

Causes:

·         idiopathic: the most common cause

·         myocarditis: e.g. Coxsackie B, HIV, diphtheria, Chagas disease

·         ischaemic heart disease

·         peripartum

·         hypertension

·         iatrogenic: e.g. doxorubicin

·         substance abuse: e.g. alcohol, cocaine

·         inherited: either a familial genetic predisposition to DCM or a specific syndrome e.g. Duchenne muscular dystrophy

o    around a third of patients with DCM are thought to have a genetic predisposition

o    a large number of heterogeneous defects have been identified

o    the majority of defects are inherited in an autosomal dominant fashion although other patterns of inheritance are seen

·         infiltrative e.g. haemochromatosis, sarcoidosis

+ these causes may also lead to restrictive cardiomyopathy

·         nutritional e.g. wet beriberi (thiamine deficiency)

Pathophysiology

·         dilated heart leading to predominately systolic dysfunction

·         all 4 chambers are dilated, but the left ventricle more so than right ventricle

·         eccentric hypertrophy (sarcomeres added in series) is seen

Features

·         classic findings of heart failure

·         systolic murmur: stretching of the valves may result in mitral and tricuspid regurgitation

·         S3

·         'balloon' appearance of the heart on the chest x-ray

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

ECG: digoxin

ECG features

·         down-sloping ST depression ('reverse tick', 'scooped out')

·         flattened/inverted T waves

·         short QT interval

·         arrhythmias e.g. AV block, bradycardia

 

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

ECG: right bundle branch block

Right bundle branch block is a common feature seen on ECGs.

 

 

One of the most common ways to remember the difference between LBBB and RBBB is WiLLiaM MaRRoW

·         in LBBB there is a 'W' in V1 and a 'M' in V6

·         in RBBB there is a 'M' in V1 and a 'W' in V6

Causes of RBBB

·         normal variant - more common with increasing age

·         right ventricular hypertrophy

·         chronically increased right ventricular pressure - e.g. cor pulmonale

·         pulmonary embolism

·         myocardial infarction

·         atrial septal defect (ostium secundum)

·         cardiomyopathy or myocarditis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Glycoprotein IIb/IIIa receptor antagonists

Examples include;

·         abciximab

·         eptifibatide

·         tirofiban

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Heart failure (acute): features

Acute heart failure (AHF) is life-threatening emergency. AHF is a term used to describe the sudden onset or worsening of the symptoms of heart failure. Thus it may present with or without a background history of pre-existing heart failure. AHF without a past history of heart failure is called de-novo AHF. Decompensated AHF is more common (66-75%) and presents with a background history of HF.

 

It usually presents after the age of 65-years and is a major cause for unplanned hospital admission in such patients.

 

AHF is usually caused by a reduced cardiac output that results from a functional or structural abnormality.

 

De-novo heart failure is caused by and increased cardiac filling pressures and myocardial dysfunction usually as a result of ischaemia. This causes reduced cardiac output and therefore hypoperfusion. This, in turn can cause pulmonary oedema. Other less common causes of de-novo AHF are:

·         Viral myopathy

·         Toxins

·         Valve dysfunction

Decompensated heart failure accounts for most cases of AHF. The most common precipitating causes of acute AHF are:

·         Acute coronary syndrome

·         Hypertensive crisis

·         Acute arrhythmia

·         Valvular disease

There is generally a history of pre-existing cardiomyopathy. It usually presents with signs of fluid congestion, weight gain, orthopnoea and breathlessness.

 

Patient with heart failure are broadly characterised into 1 of 4 groups based on whether they present:

·         With or without hypoperfusion

·         With or without fluid congestion

Classifying patients into one of these 4 groups is clinically useful as it determines the therapeutic approach.

 

Generally speaking, the signs and symptoms of AHF are as follows:

 

 

Symptoms

Signs

Breathlessness

Cyanosis

Reduced exercise tolerance

Tachycardia

Oedema

Elevated jugular venous pressure

Faitgue

Displaced apex beat

 

Chest signs: classically bibasal crackles but may also cause a wheeze

 

S3-heart sound

Sometimes the presentation will be that of the underlying cause (e.g: chest pain, viral infection)

 

Over 90% of patients with AHF have a normal or increased blood pressure (mmHg).

 

The diagnostic workup for patients with AHF includes:

·         Blood tests – this is to look for any underlying abnormality such as anaemia, abnormal electrolytes or infection.

·         Chest X-ray – findings include pulmonary venous congestion, interstitial oedema and cardiomegaly

·         Echocardiogram – this will identify pericardial effusion and cardiac tamponade

·         B-type natriuretic peptide – raised levels (>100mg/litre) indicate myocardial damage and are supportive of the diagnosis.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Heart failure (chronic): features

Features:

·         dyspnoea

·         cough: may be worse at night and associated with pink/frothy sputum

·         orthopnoea

·         paroxysmal nocturnal dyspnoea

·         wheeze ('cardiac wheeze')

·         weight loss ('cardiac cachexia'): occurs in up to 15% of patients. Remember this may be hidden by weight gained secondary to oedema

·         bibasal crackles on examination

·         signs of right-sided heart failure: raised JVP, ankle oedema and hepatomegaly

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Heart sounds: S2

S2 is caused by the closure of the aortic valve (A2) closely followed by that of the pulmonary valve (P2)

 

 

 

 

Causes of a loud S2

·         hypertension: systemic (loud A2) or pulmonary (loud P2)

·         hyperdynamic states

·         atrial septal defect without pulmonary hypertension

Causes of a soft S2

·         aortic stenosis

Causes of fixed split S2

·         atrial septal defect

Causes of a widely split S2

·         deep inspiration

·         RBBB

·         pulmonary stenosis

·         severe mitral regurgitation

Causes of a reversed (paradoxical) split S2 (P2 occurs before A2)

·         LBBB

·         severe aortic stenosis

·         right ventricular pacing

·         WPW type B (causes early P2)

·         patent ductus arteriosus

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:49

Hyperlipidaemia: xanthomata

Characteristic xanthomata seen in hyperlipidaemia:

 

Palmar xanthoma

·         remnant hyperlipidaemia

·         may less commonly be seen in familial hypercholesterolaemia

Eruptive xanthoma are due to high triglyceride levels and present as multiple red/yellow vesicles on the extensor surfaces (e.g. elbows, knees)

 

Causes of eruptive xanthoma

·         familial hypertriglyceridaemia

·         lipoprotein lipase deficiency

Tendon xanthoma, tuberous xanthoma, xanthelasma

·         familial hypercholesterolaemia

·         remnant hyperlipidaemia

Xanthelasma are also seen without lipid abnormalities

 

Management of xanthelasma, options include:

·         surgical excision

·         topical trichloroacetic acid

·         laser therapy

·         electrodesiccation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Hypertension: a very basic introduction

Hypertension is one of the most common medical conditions encountered in the developed world. Whilst there is a degree of normal variation in blood pressure according to the time of day and whether we are exerting ourselves hypertension describes a chronically raised blood pressure. The main relevance of hypertension lies in the fact that it is an important risk factor for the development of cardiovascular disease such as ischaemic heart disease and stroke. Unless the blood pressure is very high it is unusual for patients to experience any symptoms.

 

What is a 'normal' blood pressure?

 

Normal blood pressure can vary widely according to age, gender and individual physiology. Most healthy people have a blood pressure between 90/60 mmHg and 140/90 mmHg.

 

NICE define hypertension as follows:

·         a clinic reading persistently above >= 140/90 mmHg, or:

·         a 24 hour blood pressure average reading >= 135/85 mmHg

 

Why do some patients have an elevated blood pressure?

 

Patients with hypertension may be divided into two categories. The vast majority (around 90-95%) have primary, or essential, hypertension. This is where there is no single disease causing the rise in blood pressure but rather a series of complex physiological changes which occur as we get older.

 

Secondary hypertension may be caused by a wide variety of endocrine, renal and other causes. The table below lists some of the conditions that may cause secondary hypertension

 

 

Renal disease

Endocrine disorders

Other causes

• Glomerulonephritis

• Chronic pyelonephritis

• Adult polycystic kidney disease

• Renal artery stenosis

• Primary hyperaldosteronism

• Phaeochromocytoma

• Cushing's syndrome

• Liddle's syndrome

• Congenital adrenal hyperplasia (11-beta hydroxylase deficiency)

• Acromegaly

• Glucocorticoids

• NSAIDs

• Pregnancy

• Coarctation of the aorta

• Combined oral contraceptive pill

Symptoms and signs

 

As mentioned earlier, hypertension does not typically cause symptoms unless it is very high, for example > 200/120 mmHg. If very raised patients may experience:

·         headaches

·         visual disturbance

·         seizures

In terms of signs hypertension is obviously usually detected when checking someones blood pressure. For diagnosing longstanding blood pressure there has been a move in recent years to using 24 hour blood pressure monitors. These avoid cases of so called 'white coat' hypertension where a patients blood pressure rises when they are in a clinical setting, for example a GP surgery. Studies have shown that readings from 24 hour blood pressure monitors correlate better with clinical outcomes and hence should be used to guide decisions about treatment.

 

It also also important when assessing a patient with newly diagnosed hypertension to ensure they do not have any end-organ damage:

·         fundoscopy: to check for hypertensive retinopathy

·         urine dipstick: to check for renal disease, either as a cause or consequence of hypertension

·         ECG: to check for left ventricular hypertrophy or ischaemic heart disease

 

Investigations

 

As mentioned previously 24 hour blood pressure is now recommend for the diagnosis of hypertension. If 24 hour blood pressure monitoring is not available then home readings using an automated sphygmomanometer are useful.

 

Following diagnosis patients typically have the following tests:

·         urea and electrolytes: check for renal disease, either as a cause or consequence of hypertension

·         HbA1c: check for co-existing diabetes mellitus, another important risk factor for cardiovascular disease

·         lipids: check for hyperlipidaemia, again another important risk factor for cardiovascular disease

·         ECG

·         urine dipstick

Management

 

The management of patients with hypertension involves several aspects:

·         drug therapy using antihypertensives

·         modification of other risk factors to reduce the overall risk of cardiovascular disease

·         monitoring the patient for the development of complications of hypertension

The table below shows the common drugs used to treat hypertension:

 

 

Drug

Mechanism of action

Common side-effects

Notes

Angiotensin-converting enzyme (ACE) inhibitors

Inhibit the conversion angiotensin I to angiotensin II

Cough

Angioedema

Hyperkalaemia

First-line treatment in younger patients (< 55 years old)

Less effective in Afro-Caribbean patients

Must be avoided in pregnant women

Renal function must be check 2-3 weeks after starting due to the risk of worsening renal function in patients with renovascular disease

Drug names end in '-pril'

Calcium channel blockers

Block voltage-gated calcium channels relaxing vascular smooth muscle and force of myocardial contraction

Flushing

Ankle swelling

Headache

First-line treatment in older patients (>= 55 years old)

Thiazide type diuretics

Inhibit sodium absorption at the beginning of the distal convoluted tubule

Hyponatraemia

Hypokalaemia

Dehydration

Although technically a diuretic, thiazides have a very weak diuretic action

Angiotensin II receptor blockers (A2RB)

Block effects of angiotensin II at the AT1 receptor

Hyperkalaemia

Angiotensin II receptor blockers are generally used in situations where patients have not tolerated an ACE inhibitor, usually due to the development of a cough

Drug names end in '-sartan'

Drug therapy is decided by well established NICE guidelines, which advocate a step-wise approach:

 

 

 

 

Flow chart showing the management of hypertension as per current NICE guideliness

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Hypertension: secondary causes

It is thought that between 5-10% of patients diagnosed with hypertension have primary hyperaldosteronism, including Conn's syndrome. This makes it the single most common cause of secondary hypertension.

 

Renal disease accounts for a large percentage of the other cases of secondary hypertension. Conditions which may increase the blood pressure include:

·         glomerulonephritis

·         pyelonephritis

·         adult polycystic kidney disease

·         renal artery stenosis

Endocrine disorders (other than primary hyperaldosteronism) may also result in increased blood pressure:

·         phaeochromocytoma

·         Cushing's syndrome

·         Liddle's syndrome

·         congenital adrenal hyperplasia (11-beta hydroxylase deficiency)

·         acromegaly

Drug causes:

·         steroids

·         monoamine oxidase inhibitors

·         the combined oral contraceptive pill

·         NSAIDs

·         leflunomide

Other causes include:

·         pregnancy

·         coarctation of the aorta

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Hypertrophic obstructive cardiomyopathy: management

Hypertrophic obstructive cardiomyopathy (HOCM) is an autosomal dominant disorder of muscle tissue caused by defects in the genes encoding contractile proteins. The estimated prevalence is 1 in 500.

 

Management

·         Amiodarone

·         Beta-blockers or verapamil for symptoms

·         Cardioverter defibrillator

·         Dual chamber pacemaker

·         Endocarditis prophylaxis*

 

Maintain fluid at all times

Drugs to avoid

·         nitrates

·         ACE-inhibitors

·         inotropes

*although see the 2008 NICE guidelines on infective endocarditis prophylaxis

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

MR SAM ASH

 

 insertion of an implantable cardioverter defibrillator to lower the risk of sudden cardiac death

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

HOCM is the most common cause of sudden cardiac death in young people.

 

 

Surgery:

Surgical myectomy

Alcohol septal ablation

 

 

 

 

 

 

24 December 2020

13:50

Infective endocarditis: prognosis and management

Poor prognostic factors

·         Staphylococcus aureus infection (see below)

·         prosthetic valve (especially 'early', acquired during surgery)

·         culture negative endocarditis

·         low complement levels

Mortality according to organism

·         staphylococci - 30%

·         bowel organisms - 15%

·         streptococci - 5%

Current antibiotic guidelines (source: British National Formulary)

 

 

Scenario

Suggested antibiotic therapy

Initial blind therapy

Native valve

·         amoxicillin, consider adding low-dose gentamicin

If penicillin allergic, MRSA or severe sepsis

·         vancomycin + low-dose gentamicin

If prosthetic valve

·         vancomycin + rifampicin + low-dose gentamicin

Native valve endocarditis caused by staphylococci

Flucloxacillin

 

If penicillin allergic or MRSA

·         vancomycin + rifampicin

Prosthetic valve endocarditis caused by staphylococci

Flucloxacillin + rifampicin + low-dose gentamicin

 

If penicillin allergic or MRSA

·         vancomycin + rifampicin + low-dose gentamicin

Endocarditis caused by fully-sensitive streptococci (e.g. viridans)

Benzylpenicillin

 

If penicillin allergic

·         vancomycin + low-dose gentamicin

Endocarditis caused by less sensitive streptococci

Benzylpenicillin + low-dose gentamicin

 

If penicillin allergic

·         vancomycin + low-dose gentamicin

Indications for surgery

·         severe valvular incompetence

·         aortic abscess (often indicated by a lengthening PR interval)

·         infections resistant to antibiotics/fungal infections

·         cardiac failure refractory to standard medical treatment

·         recurrent emboli after antibiotic therapy

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Inhaled foreign body

This typically occurs in younger children. Whilst the presentation if often acute it can sometimes go unnoticed, with up to a third of cases being diagnosed after a few days.

 

Features

·         cough

·         stridor

·         dyspnoea

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Investigating palpitations

Palpitations are a common presenting symptom.

 

Possible causes include

·         arrhythmias

·         stress

·         increased awareness of normal heart beat / extrasystoles

First-line investigations include:

·         12-lead ECG: this will only capture the heart rhythm for a few seconds and hence is likely to miss episodic arrhythmias. However, other abnormalities linked to the underlying arrhythmia (for example a prolonged QT interval or PR interval, or changes suggesting recent myocardial ischaemia) may be seen.

·         thyroid function tests: thyrotoxicosis may precipitate atrial fibrillation and other arrhythmias

·         urea and electrolytes: looking for disturbances such as a low potassium

·         full blood count

Capturing episodic arrhythmias

 

First-line investigations are often normal in patients complaining of palpitations. The next step is to exclude an episode arrhythmia.

 

The most common investigation is Holter monitoring

·         portable battery operated device

·         continuously records ECG from 2-3 leads

·         usually done for 24 hours but may be used for longer if symptoms are less than daily

·         patients are asked to keep a diary to record any symptomatic palpitations. This can later be compared to the rhythm strip at the time of the symptoms

·         at the end of the monitoring a report is generated summarising a number of parameters including heart rate, arrhythmias and changes in ECG waveform

If no abnormality is found on the Holter monitor, and symptoms continue, other options include:

·         external loop recorder

·         implantable loop recorder

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Isolated systolic hypertension

Isolated systolic hypertension (ISH) is common in the elderly, affecting around 50% of people older than 70 years old. The Systolic Hypertension in the Elderly Program (SHEP) back in 1991 established that treating ISH reduced both strokes and ischaemic heart disease. Drugs such as thiazides were recommended as first line agents. This approach is contradicated by the 2011 NICE guidelines which recommends treating ISH in the same stepwise fashion as standard hypertension.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Ivabradine

Ivabradine is a class of anti-anginal drug which works by reducing the heart rate. It acts on the If ('funny') ion current which is highly expressed in the sinoatrial node, reducing cardiac pacemaker activity.

 

Adverse effects

·         visual effects, particular luminous phenomena, are common

·         headache

·         bradycardia, heart block

There is no evidence currently of superiority over existing treatments of stable angina.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Mitral regurgitation

Also known as mitral insufficiency, mitral regurgitation (MR) occurs when blood leaks back through the mitral valve on systole. It is the second most common valve disease after aortic stenosis. The mitral valve is located between the left atrium and ventricle, and regurgitation leads to a less efficient heart as less blood is pumped through the body with each contraction. This said, MR is common in otherwise healthy patients to a trivial degree and does not need treatment.

 

As the degree of regurgitation becomes more severe, the body’s oxygen demands may exceed what the heart can supply and as a result, the myocardium can thicken over time. While this may be benign initially, patients may find themselves increasingly fatigued as a thicker myometrium becomes less efficient, and eventually go into irreversible heart failure.

 

Risk factors

·         Female sex

·         Lower body mass

·         Age

·         Renal dysfunction

·         Prior myocardial infarction

·         Prior mitral stenosis or valve prolapse

·         Collagen disorders e.g. Marfan's Syndrome and Ehlers-Danlos syndrome

Causes

·         Following coronary artery disease or post-MI: if the papillary muscles or chordae tendinae are affected by a cardiac insult, mitral valve disease may ensue as a result of damage to its supporting structures.

·         Mitral valve prolapse: Occurs when the leaflets of the mitral valve is deformed so the valve does not close properly and allows for backflow. Most patients with this have a trivial degree of mitral regurgitation.

·         Infective endocarditis: When vegetations from the organisms colonising the heart grow on the mitral valve, it is prevented from closing properly. Patients with abnormal valves are more likely to develop endocarditis as opposed to their peers.

·         Rheumatic fever: While this is uncommon in developed countries, rheumatic fever can cause inflammation of the valves and therefore result in mitral regurgitation.

·         Congenital

Symptoms

·         Most patients with MR are asymptomatic, and patients suffering from mild to moderate MR may stay largely asymptomatic indefinitely. Symptoms tend to be due to failure of the left ventricle, arrhythmias or pulmonary hypertension. This may present as fatigue, shortness of breath and oedema.

Signs

·         The murmur heard on auscultation of the chest is typically a pansystolic murmur described as “blowing”. It is heard best at the apex and radiating into the axilla. S1 may be quiet as a result of incomplete closure of the valve. Severe MR may cause a widely split S2

Investigations

·         ECG may show a broad P wave, indicative of atrial enlargement

·         Cardiomegaly may be seen on chest x-ray, with an enlarged left atrium and ventricle

·         Echocardiography is crucial to diagnosis and to assess severity

Treatment options

·         Medical management in acute cases involves nitrates, diuretics, positive inotropes and an intra-aortic balloon pump to increase cardiac output

·         If patients are in heart failure, ACE inhibitors may be considered along with beta-blockers and spironolactone

·         In acute, severe regurgitation, surgery is indicated

·         The evidence for repair over replacement is strong in degenerative regurgitation, and is demonstrated through lower mortality and higher survival rates

·         When this is not possible, valve replacement with either an artificial valve or a pig valve is considered

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Mitral valve prolapse

Mitral valve prolapse is common, occurring in around 5-10 % of the population. It is usually idiopathic but may be associated with a wide variety of cardiovascular disease and other conditions

 

Associations

·         congenital heart disease: PDA, ASD

·         cardiomyopathy

·         Turner's syndrome

·         Marfan's syndrome, Fragile X

·         osteogenesis imperfecta

·         pseudoxanthoma elasticum

·         Wolff-Parkinson White syndrome

·         long-QT syndrome

·         Ehlers-Danlos Syndrome

·         polycystic kidney disease

Features

·         patients may complain of atypical chest pain or palpitations

·         mid-systolic click (occurs later if patient squatting)

·         late systolic murmur (longer if patient standing)

·         complications: mitral regurgitation, arrhythmias (including long QT), emboli, sudden death

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:50

Myocarditis

Myocarditis describes inflammation of the myocardium. There are a wide range of underlying causes. It should be particularly considered in younger patients who present with chest pain.

 

Causes

·         viral: coxsackie B, HIV

·         bacteria: diphtheria, clostridia

·         spirochaetes: Lyme disease

·         protozoa: Chagas' disease, toxoplasmosis

·         autoimmune

·         drugs: doxorubicin

Presentation

·         usually young patient with an acute history

·         chest pain

·         dyspnoea

·         arrhythmias

Investigations

·         bloods

o    ↑ inflammatory markers in 99%

o    ↑ cardiac enzymes

o    ↑ BNP

·         ECG

o    tachycardia

o    arrhythmias

o    ST/T wave changes including ST-segment elevation and T wave inversion

Management

·         treatment of underlying cause e.g. antibiotics if bacterial cause

·         supportive treatment e.g. of heart failure or arrhythmias

Complications

·         heart failure

·         arrhythmia, possibly leading to sudden death

·         dilated cardiomyopathy: usually a late complication

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

Cyclophosphamide is known to be associated with haemorrhagic myocarditis

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

 

 

 

24 December 2020

13:51

Nitrates

Nitrates are a group of drugs which have vasodilating effects. The main indications for their use is in the management of angina and the acute treatment of heart failure. Sublingual glyceryl trinitrate is the most common drug used in patients with ischaemic heart disease to relieve angina attacks.

 

Mechanism of action

·         nitrates cause the release of nitric oxide in smooth muscle, activating guanylate cyclase which then converts GTP to cGMP, which in turn leads to a fall in intracellular calcium levels

·         in angina they both dilate the coronary arteries and also reduce venous return which in turn reduces left ventricular work, reducing myocardial oxygen demand

Side-effects

·         hypotension

·         tachycardia

·         headaches

·         flushing

Nitrate tolerance

·         many patients who take nitrates develop tolerance and experience reduced efficacy

·         the BNF advises that patients who develop tolerance should take the second dose of isosorbide mononitrate after 8 hours, rather than after 12 hours. This allows blood-nitrate levels to fall for 4 hours and maintains effectiveness

·         this effect is not seen in patients who take modified release isosorbide mononitrate

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Orthostatic hypotension

Orthostatic hypotension is more common in older people and patients who have neurodegenerative disease (e.g. Parkinson's) diabetes, or hypertension

 

Iatrogenic causes include alpha-blockers (e.g. for benign prostatic hyperplasia).

 

Features

·         a drop in BP (usually >20/10 mm Hg) within three minutes of standing

·         presyncope

·         syncope

Management

·         treatment options include midodrine and fludrocortisone

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Parenteral anticoagulation

Parenteral anticoagulants are used for the prevention of venous thromboembolism and in the management of acute coronary syndrome.

 

Unfractionated heparin and low molecular weight heparin are discussed in detail so this note will focus on fondaparinux and direct thrombin inhibitors.

 

Fondaparinux

 

Activates antithrombin III, which in turn potentiates the inhibition of coagulation factors Xa. It is given subcutaneously.

 

Direct thrombin inhibitors

 

Examples include bivalirudin. These are generally given intravenously.

 

Dabigatran is a type of direct thrombin inhibitor that is taken orally. It is often grouped alongside the direct oral anticoagulants (DOACs).

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Pulmonary artery occlusion pressure monitoring

The pulmonary artery occlusion pressure is an indirect measure of left atrial pressure, and thus filling pressure of the left heart. The low resistance within the pulmonary venous system allows this useful measurement to be made. The most accurate trace is made by inflating the balloon at the catheter tip and 'floating' it so that it occludes the vessel. If it is not possible to occlude the vessel in this way then the measurement gained will be the pulmonary artery end diastolic pressure.

 

Interpretation of PAOP

 

PAOP

mmHg

Scenario

Normal

8-12

 

Low

<5

Hypovolaemia

Low with pulmonary oedema

<5

ARDS

High

>18

Overload

When combined with measurements of systemic vascular resistance and cardiac output it is possible to accurately classify patients.

 

Systemic vascular resistance

Derived from aortic pressure, right atrial pressure and cardiac output.

 

SVR=80(mean aortic pressure-mean right atrial pressure)/cardiac output

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Saphenous vein

Long saphenous vein

 

This vein may be harvested for bypass surgery, or removed as treatment for varicose veins with saphenofemoral junction incompetence.

·         Originates at the 1st digit where the dorsal vein merges with the dorsal venous arch of the foot

·         Passes anterior to the medial malleolus and runs up the medial side of the leg

·         At the knee, it runs over the posterior border of the medial epicondyle of the femur bone

·         Then passes laterally to lie on the anterior surface of the thigh before entering an opening in the fascia lata called the saphenous opening

·         It joins with the femoral vein in the region of the femoral triangle at the saphenofemoral junction

Tributaries

·         Medial marginal

·         Superficial epigastric

·         Superficial iliac circumflex

·         Superficial external pudendal veins

 

Short saphenous vein

·         Originates at the 5th digit where the dorsal vein merges with the dorsal venous arch of the foot, which attaches to the great saphenous vein.

·         It passes around the lateral aspect of the foot (inferior and posterior to the lateral malleolus) and runs along the posterior aspect of the leg (with the sural nerve)

·         Passes between the heads of the gastrocnemius muscle, and drains into the popliteal vein, approximately at or above the level of the knee joint.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Subclavian artery

Path

·         The left subclavian comes directly off the arch of aorta

·         The right subclavian arises from the brachiocephalic artery (trunk) when it bifurcates into the subclavian and the right common carotid artery.

·         From its origin, the subclavian artery travels laterally, passing between anterior and middle scalene muscles, deep to scalenus anterior and anterior to scalenus medius. As the subclavian artery crosses the lateral border of the first rib, it becomes the axillary artery. At this point it is superficial and within the subclavian triangle.

 

 

Image sourced from Wikipedia

Branches

·         Vertebral artery

·         Internal thoracic artery

·         Thyrocervical trunk

·         Costocervical trunk

·         Dorsal scapular artery

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Takotsubo cardiomyopathy

Takotsubo cardiomyopathy is a type of non-ischaemic cardiomyopathy associated with a transient, apical ballooning of the myocardium. It may be triggered by stress.

 

Pathophysiology

·         Takotsubo is a Japanese word that describes an octopus trap

·         the apical ballooning appearance occurs due to severe hypokinesis of the mid and apical segments with preservation of activity of the basal segments. In simple terms, the bottom of the heart (the apex) does not contract and therefore appears to balloon out. However, the area closer to the top (the base) continues to contract (creating the neck of the octopus trap)

Features

·         chest pain

·         features of heart failure

·         ECG: ST-elevation

·         normal coronary angiogram

Treatment is supportive.

 

Prognosis

·         the majority of patients improve with supportive treatment

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

24 December 2020

13:51

Travel-related thrombosis

It is not uncommon for us to be asked by patients whether they should take aspirin prior to a long haul flight. So called 'economy class syndrome' as a concept has increased in the public's mind over the past 10 years or so. It is certainly true that long-haul air travel is associated with an increased risk of VTE. A 2001 study in the New England Journal of Medicine1 showed the following risk of pulmonary embolism:

·         0.01 cases per million for travel under 5,000 km

·         1.5 cases per million for travel between 5,000 - 10,000 km

·         4.8 cases per million for travel over 10,000 km

The Civil Aviation Authority do not give specific guidance relating to venous thromboembolism. The British Committee for Standards in Haematology did however produce guidelines in 2005 as did SIGN in 2010 and Clinical Knowledge Summaries (CKS) in 2013. Unfortunately, there is no universal agreement on what to advise patients.

 

The most recent CKS guidelines advise that we take a risk based approach. For example, a patient with no major risk factors for VTE (i.e. the average person) then no special measures are needed.

 

Patients with major risk factors should consider wearing anti-embolism stockings. These can either be bought by the patient or prescribed (class I). Clearly if the risk is very high (e.g. a long-haul flight following recent major surgery) then consideration should be given to delaying the flight or specialist advice sought regarding the use of low-molecular weight heparin.

 

All guidelines agree there is no role for aspirin in low, medium or high risk patients.

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

16:11

Hypertension: management

NICE published updated guidelines for the management of hypertension in 2019. Some of the key changes include:

·         lowering the threshold for treating stage 1 hypertension in patients < 80 years from 20% to 10%

·         angiotensin receptor blockers can be used instead of ACE-inhibitors where indicated

·         if a patient is already taking an ACE-inhibitor or angiotensin receptor blocker, then a calcium channel blocker OR a thiazide-like diuretic can be used. Previously only a calcium channel blocker was recommended

Blood pressure classification

 

This becomes relevant later in some of the management decisions that NICE advocate.

 

 

Stage

Criteria

Stage 1 hypertension

Clinic BP >= 140/90 mmHg and subsequent ABPM daytime average or HBPM average BP >= 135/85 mmHg

Stage 2 hypertension

Clinic BP >= 160/100 mmHg and subsequent ABPM daytime average or HBPM average BP >= 150/95 mmHg

Severe hypertension

Clinic systolic BP >= 180 mmHg, or clinic diastolic BP >= 110 mmHg

 

 

 

Flow chart showing simplified schematic for diagnosis hypertension following NICE guidelines

Managing hypertension

 

Lifestyle advice should not be forgotten and is frequently tested in exams:

·         a low salt diet is recommended, aiming for less than 6g/day, ideally 3g/day. The average adult in the UK consumes around 8-12g/day of salt. A recent BMJ paper* showed that lowering salt intake can have a significant effect on blood pressure. For example, reducing salt intake by 6g/day can lower systolic blood pressure by 10mmHg

·         caffeine intake should be reduced

·         the other general bits of advice remain: stop smoking, drink less alcohol, eat a balanced diet rich in fruit and vegetables, exercise more, lose weight

ABPM/HBPM >= 135/85 mmHg (i.e. stage 1 hypertension)

·         treat if < 80 years of age AND any of the following apply; target organ damage, established cardiovascular disease, renal disease, diabetes or a 10-year cardiovascular risk equivalent to 10% or greater

·         in 2019, NICE made a further recommendation, suggesting that we should 'consider antihypertensive drug treatment in addition to lifestyle advice for adults aged under 60 with stage 1 hypertension and an estimated 10-year risk below 10%. '. This seems to be due to evidence that QRISK may underestimate the lifetime probability of developing cardiovascular disease

ABPM/HBPM >= 150/95 mmHg (i.e. stage 2 hypertension)

·         offer drug treatment regardless of age

For patients < 40 years consider specialist referral to exclude secondary causes.

 

 

 

 

 

 

Flow chart showing the management of hypertension as per current NICE guideliness

 

Step 1 treatment

·         patients < 55-years-old or a background of type 2 diabetes mellitus: ACE inhibitor or a Angiotensin receptor blocker (ACE-i or ARB): (A)

o    angiotensin receptor blockers should be used where ACE inhibitors are not tolerated (e.g. due to a cough)

·         patients >= 55-years-old or of black African or African–Caribbean origin: Calcium channel blocker (C)

o    ACE inhibitors have reduced efficacy in patients of black African or African–Caribbean origin are therefore not used first-line

Step 2 treatment

·         if already taking an ACE-i or ARB add a Calcium channel blocker or a thiazide-like Diuretic

·         if already taking a Calcium channel blocker add an ACE-i or ARB

o    for patients of black African or African–Caribbean origin taking a calcium channel blocker for hypertension, if they require a second agent consider an angiotensin receptor blocker in preference to an ACE inhibitor

·         (A + C) or (A + D)

Step 3 treatment

·         add a third drug to make, i.e.:

o    if already taking an (A + C) then add a D

o    if already (A + D) then add a C

·         (A + C + D)

Step 4 treatment

·         NICE define step 4 as resistant hypertension and suggest either adding a 4th drug (as below) or seeking specialist advice

·         first, check for:

o    confirm elevated clinic BP with ABPM or HBPM

o    assess for postural hypotension.

o    discuss adherence

·         if potassium < 4.5 mmol/l add low-dose spironolactone

·         if potassium > 4.5 mmol/l add an alpha- or beta-blocker

Patients who fail to respond to step 4 measures should be referred to a specialist. NICE recommend:

 

If blood pressure remains uncontrolled with the optimal or maximum tolerated doses of four drugs, seek expert advice if it has not yet been obtained.

 

Blood pressure targets

 

 

 

Clinic BP

ABPM / HBPM

Age < 80 years

140/90 mmHg

135/85 mmHg

Age > 80 years

150/90 mmHg

145/85 mmHg

New drugs

 

Direct renin inhibitors

·         e.g. Aliskiren (branded as Rasilez)

·         by inhibiting renin blocks the conversion of angiotensinogen to angiotensin I

·         no trials have looked at mortality data yet. Trials have only investigated fall in blood pressure. Initial trials suggest aliskiren reduces blood pressure to a similar extent as angiotensin converting enzyme (ACE) inhibitors or angiotensin-II receptor antagonists

·         adverse effects were uncommon in trials although diarrhoea was occasionally seen

·         only current role would seem to be in patients who are intolerant of more established antihypertensive drugs

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:47

Heart failure: drug management

NICE issued updated guidelines on management in 2018, key points are summarised here

 

Whilst loop diuretics play an important role in managing fluid overload it should be remembered that no long-term reduction in mortality has been demonstrated for loop diuretics such as furosemide.

 

The first-line treatment for all patients is both an ACE-inhibitor and a beta-blocker

·         generally, one drug should be started at a time. NICE advise that clinical judgement is used when determining which one to start first

·         beta-blockers licensed to treat heart failure in the UK include bisoprolol, carvedilol, and nebivolol.

·         ACE-inhibitors and beta-blockers have no effect on mortality in heart failure with preserved ejection fraction

Second-line treatment is an aldosterone antagonist

·         these are sometimes referred to as mineralocorticoid receptor antagonists. Examples include spironolactone and eplerenone

·         it should be remember that both ACE inhibitors (which the patient is likely to already be on) and aldosterone antagonists both cause hyperkalaemia - therefore potassium should be monitored

Third-line treatment should be initiated by a specialist. Options include ivabradine, sacubitril-valsartan, hydralazine in combination with nitrate, digoxin and cardiac resynchronisation therapy

·         ivabradine

o    criteria: sinus rhythm > 75/min and a left ventricular fraction < 35%

·         sacubitril-valsartan

o    criteria: left ventricular fraction < 35%

o    is considered in heart failure with reduced ejection fraction who are symptomatic on ACE inhibitors or ARBs

o    should be initiated following ACEi or ARB wash-out period

·         digoxin

o    digoxin has also not been proven to reduce mortality in patients with heart failure. It may however improve symptoms due to its inotropic properties

o    it is strongly indicated if there is coexistent atrial fibrillation

·         hydralazine in combination with nitrate

o    this may be particularly indicated in Afro-Caribbean patients

·         cardiac resynchronisation therapy

o    indications include a widened QRS (e.g. left bundle branch block) complex on ECG

Other treatments

·         offer annual influenza vaccine

·         offer one-off pneumococcal vaccine

o    adults usually require just one dose but those with asplenia, splenic dysfunction or chronic kidney disease need a booster every 5 years

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

In acute decompensated heart failure, the negative inotropic effects  of beta blockers can worsen stroke volume and therefore aggravate  heart failure.

Chronic beta-blocker use in stable heart failure is associated with  significantly improved survival in patients but should be deferred  until patient is no longer congested after treatment with appropriate  diuresis and post-load reduction.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

Haemodynamic profile is that of wet decompensated heart failure. Intravenous loop diuretic is more effective than oral diuretic in clearing the congestion.

Beta-blocker is not advisable in patients with acute decompensated heart  failure.

 

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

N-type pro B-type natriuretic peptide

·         >2000ng/L refer for specialist assessment urgently, transthoracic echo within 2 weeks

·         400-2000ng/L refer for specialist assessment within 6 weeks

·         <400ng/L, diagnosis of heart failure less likely

Reduced levels in obese, African-Caribbean, patients on diuretics, ACEi, beta-blockers

Need to rule out other causes (>70 years old, LVH, ischaemia, pulmonary embolism) in patients with high natriuretic peptide levels 

 

From <https://mle.ncl.ac.uk/cases/page/17993/>

 

 

 

 

 

 

21 December 2020

22:11

Statins

Statins inhibit the action of HMG-CoA reductase, the rate-limiting enzyme in hepatic cholesterol synthesis.

 

Adverse effects

·         myopathy: includes myalgia, myositis, rhabdomyolysis and asymptomatic raised creatine kinase. Risks factors for myopathy include advanced age, female sex, low body mass index and presence of multisystem disease such as diabetes mellitus. Myopathy is more common in lipophilic statins (simvastatin, atorvastatin) than relatively hydrophilic statins (rosuvastatin, pravastatin, fluvastatin)

·         liver impairment: the 2014 NICE guidelines recommend checking LFTs at baseline, 3 months and 12 months. Treatment should be discontinued if serum transaminase concentrations rise to and persist at 3 times the upper limit of the reference range

·         there is some evidence that statins may increase the risk of intracerebral haemorrhage in patients who've previously had a stroke. This effect is not seen in primary prevention. For this reason the Royal College of Physicians recommend avoiding statins in patients with a history of intracerebral haemorrhage

Contraindications

·         macrolides (e.g. erythromycin, clarithromycin) are an important interaction. Statins should be stopped until patients complete the course

·         pregnancy

Who should receive a statin?

·         all people with established cardiovascular disease (stroke, TIA, ischaemic heart disease, peripheral arterial disease)

·         following the 2014 update, NICE recommend anyone with a 10-year cardiovascular risk >= 10%

·         patients with type 2 diabetes mellitus should now be assessed using QRISK2 like other patients are, to determine whether they should be started on statins

·         patients with type 1 diabetes mellitus who were diagnosed more than 10 years ago OR are aged over 40 OR have established nephropathy

Statins should be taken at night as this is when the majority of cholesterol synthesis takes place. This is especially true for simvastatin which has a shorter half-life than other statins.

 

NICE currently recommends the following for the prevention of cardiovascular disease::

·         atorvastatin 20mg for primary prevention

o    increase the dose if non-HDL has not reduced for >= 40%

·         atorvastatin 80mg for secondary prevention

 

 

 

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:54

Warfarin: management of high INR

The following is based on the BNF guidelines, which in turn take into account the British Committee for Standards in Haematology (BCSH) guidelines.

 

 

Situation

Management

Major bleeding

Stop warfarin

Give intravenous vitamin K 5mg

Prothrombin complex concentrate - if not available then FFP*

INR > 8.0

Minor bleeding

Stop warfarin

Give intravenous vitamin K 1-3mg

Repeat dose of vitamin K if INR still too high after 24 hours

Restart warfarin when INR < 5.0

INR > 8.0

No bleeding

Stop warfarin

Give vitamin K 1-5mg by mouth, using the intravenous preparation orally

Repeat dose of vitamin K if INR still too high after 24 hours

Restart when INR < 5.0

INR 5.0-8.0

Minor bleeding

Stop warfarin

Give intravenous vitamin K 1-3mg

Restart when INR < 5.0

INR 5.0-8.0

No bleeding

Withhold 1 or 2 doses of warfarin

Reduce subsequent maintenance dose

*as FFP can take time to defrost prothrombin complex concentrate should be considered in cases of intracranial haemorrhage

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

17:56

ECG: coronary territories

The table below shows the correlation between ECG changes and coronary territories:

 

 

 

ECG changes

Coronary artery

Anteroseptal

V1-V4

Left anterior descending

Inferior

II, III, aVF

Right coronary

Anterolateral

V4-6, I, aVL

Left anterior descending or left circumflex

Lateral

I, aVL +/- V5-6

Left circumflex

Posterior

Tall R waves V1-2

Usually left circumflex, also right coronary

It should be remembered that a new left bundle branch block (LBBB) may point towards a diagnosis of acute coronary syndrome.

 

 

 

 

Diagram showing the correlation between ECG changes and coronary territories in acute coronary syndrome

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21 December 2020

21:54

Atrial fibrillation: rate control and maintenance of sinus rhythm

The Royal College of Physicians and NICE published guidelines on the management of atrial fibrillation (AF) in 2006. The following is also based on the joint American Heart Association (AHA), American College of Cardiology (ACC) and European Society of Cardiology (ESC) 2012 guidelines

 

 

Medication

 

Agents used to control rate in patients with atrial fibrillation

·         beta-blockers

o    a common contraindication for beta-blockers is asthma

·         calcium channel blockers

·         digoxin

o    not considered first-line anymore as they are less effective at controlling the heart rate during exercise

o    however, they are the preferred choice if the patient has coexistent heart failure

Agents used to maintain sinus rhythm in patients with a history of atrial fibrillation

·         sotalol

·         amiodarone

·         flecainide

·         others (less commonly used in UK): disopyramide, dofetilide, procainamide, propafenone, quinidine

The table below indicates some of the factors which may be considered when considering either a rate control or rhythm control strategy

 

 

Factors favouring rate control

Factors favouring rhythm control

Older than 65 years

History of ischaemic heart disease

Younger than 65 years

Symptomatic

First presentation

Lone AF or AF secondary to a corrected precipitant (e.g. Alcohol)

Congestive heart failure

 

Catheter ablation

 

NICE recommends the use of catheter ablation for those with AF who have not responded to or wish to avoid, antiarrhythmic medication.

 

Technical aspects

·         the aim is to ablate the faulty electrical pathways that are resulting in atrial fibrillation. This is typically due to aberrant electrical activity between the pulmonary veins and left atrium

·         the procedure is performed percutaneously, typically via the groin

·         both radiofrequency (uses heat generated from medium frequency alternating current) and cryotherapy can be used to ablate the tissue

Anticoagulation

·         should be used 4 weeks before and during the procedure

·         it should be remember that catheter ablation controls the rhythm but does not reduce the stroke risk, even if patients remain in sinus rhythm. Therefore, patients still require anticoagulation as per there CHA2DS2-VASc score

o    if score = 0: 2 months anticoagulation recommended

o    if score > 1: longterm anticoagulation recommended

Outcome

·         notable complications include

o    cardiac tamponade

o    stroke

o    pulmonary valve stenosis

·         success rate

o    around 50% of patients experience an early recurrence (within 3 months) of AF that often resolves spontaneously

o    longer term, after 3 years, around 55% of patients who've had a single procedure remain in sinus rhythm. Of patient who've undergone multiple procedures around 80% are in sinus rhythm

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

Wednesday, 23 December 2020

01:07

ACE inhibitors

Angiotensin-converting enzyme (ACE) inhibitors are now the established first-line treatment in younger patients with hypertension and are also extensively used to treat heart failure. They are known to be less effective in treating hypertensive Afro-Caribbean patients. ACE inhibitors are also used to treat diabetic nephropathy and have a role in the secondary prevention of ischaemic heart disease.

 

Mechanism of action:

·         inhibit the conversion angiotensin I to angiotensin II

·         ACE inhibitors are activated by phase 1 metabolism in the liver 

Side-effects:

·         cough

o    occurs in around 15% of patients and may occur up to a year after starting treatment

o    thought to be due to increased bradykinin levels

·         angioedema: may occur up to a year after starting treatment

·         hyperkalaemia

·         first-dose hypotension: more common in patients taking diuretics

Cautions and contraindications

·         pregnancy and breastfeeding - avoid

·         renovascular disease - may result in renal impairment

·         aortic stenosis - may result in hypotension

·         hereditary of idiopathic angioedema

·         specialist advice should be sought before starting ACE inhibitors in patients with a potassium >= 5.0 mmol/L

Interactions

·         patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day)

o    significantly increases the risk of hypotension

Monitoring

·         urea and electrolytes should be checked before treatment is initiated and after increasing the dose

o    a rise in the creatinine and potassium may be expected after starting ACE inhibitors

o    acceptable changes are an increase in serum creatinine, up to 30% from baseline and an increase in potassium up to 5.5 mmol/l.

o    significant renal impairment may occur in patients who have undiagnosed bilateral renal artery stenosis

 

 

 

Flow chart showing the management of hypertension as per current NICE guideliness

 

 

 

 

22 December 2020

16:57

Hypertension: diagnosis

NICE published updated guidelines for the management of hypertension in 2019. This builds on the significant guidelines released in 2011 that recommended:

·         classifying hypertension into stages

·         recommending the use of ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM)

 

 

 

 

Flow chart showing simplified schematic for diagnosis hypertension following NICE guidelines

 

Why were these guidelines needed?

 

It has long been recognised by doctors that there is a subgroup of patients whose blood pressure climbs 20 mmHg whenever they enter a clinical setting, so called 'white coat hypertension'. If we just rely on clinic readings then such patients may be diagnosed as having hypertension when, the vast majority of the time, their blood pressure is normal.

 

This has led to the use of both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) to confirm the diagnosis of hypertension. These techniques allow a more accurate assessment of a patients' overall blood pressure. Not only does this help prevent overdiagnosis of hypertension - ABPM has been shown to be a more accurate predictor of cardiovascular events than clinic readings.

 

Blood pressure classification

 

This becomes relevant later in some of the management decisions that NICE advocate.

 

 

Stage

Criteria

Stage 1 hypertension

Clinic BP >= 140/90 mmHg and subsequent ABPM daytime average or HBPM average BP >= 135/85 mmHg

Stage 2 hypertension

Clinic BP >= 160/100 mmHg and subsequent ABPM daytime average or HBPM average BP >= 150/95 mmHg

Severe hypertension

Clinic systolic BP >= 180 mmHg, or clinic diastolic BP >= 120 mmHg

Diagnosing hypertension

 

Firstly, NICE recommend measuring blood pressure in both arms when considering a diagnosis of hypertension.

 

If the difference in readings between arms is more than 20 mmHg then the measurements should be repeated. If the difference remains > 20 mmHg then subsequent blood pressures should be recorded from the arm with the higher reading.

 

It should of course be remember that there are pathological causes of unequal blood pressure readings from the arms, such as supravalvular aortic stenosis. It is therefore prudent to listen to the heart sounds if a difference exists and further investigation if a very large difference is noted.

 

NICE also recommend taking a second reading during the consultation, if the first reading is > 140/90 mmHg. The lower reading of the two should determine further management.

 

NICE suggest offering ABPM or HBPM to any patient with a blood pressure >= 140/90 mmHg.

 

If the blood pressure is >= 180/120 mmHg:

·         admit for specialist assessment if:

o    signs of retinal haemorrhage or papilloedema (accelerated hypertension) or

o    life-threatening symptoms such as new-onset confusion, chest pain, signs of heart failure, or acute kidney injury

·         NICE also recommend referral if a phaeochromocytoma is suspected (labile or postural hypotension, headache, palpitations, pallor and diaphoresis)

·         if none of the above then arrange urgent investigations for end-organ damage (e.g. bloods, urine ACR, ECG)

o    if target organ damage is identified, consider starting antihypertensive drug treatment immediately, without waiting for the results of ABPM or HBPM.

o    if no target organ damage is identified, repeat clinic blood pressure measurement within 7 days

Ambulatory blood pressure monitoring (ABPM)

·         at least 2 measurements per hour during the person's usual waking hours (for example, between 08:00 and 22:00)

·         use the average value of at least 14 measurements

If ABPM is not tolerated or declined HBPM should be offered.

 

Home blood pressure monitoring (HBPM)

·         for each BP recording, two consecutive measurements need to be taken, at least 1 minute apart and with the person seated

·         BP should be recorded twice daily, ideally in the morning and evening

·         BP should be recorded for at least 4 days, ideally for 7 days

·         discard the measurements taken on the first day and use the average value of all the remaining measurements

Interpreting the results

 

ABPM/HBPM >= 135/85 mmHg (i.e. stage 1 hypertension)

·         treat if < 80 years of age AND any of the following apply; target organ damage, established cardiovascular disease, renal disease, diabetes or a 10-year cardiovascular risk equivalent to 10% or greater

·         in 2019, NICE made a further recommendation, suggesting that we should 'consider antihypertensive drug treatment in addition to lifestyle advice for adults aged under 60 with stage 1 hypertension and an estimated 10-year risk below 10%. '. This seems to be due to evidence that QRISK may underestimate the lifetime probability of developing cardiovascular disease

ABPM/HBPM >= 150/95 mmHg (i.e. stage 2 hypertension)

·         offer drug treatment regardless of age

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:47

Beta-blockers

Beta-blockers are an important class of drug used mainly in the management of cardiovascular disorders.

 

Indications

·         angina

·         post-myocardial infarction

·         heart failure: beta-blockers were previously avoided in heart failure but there is now strong evidence that certain beta-blockers improve both symptoms and mortality

·         arrhythmias: beta-blockers have now replaced digoxin as the rate-control drug of choice in atrial fibrillation

·         hypertension: the role of beta-blockers has diminished in recent years due to a lack of evidence in terms of reducing stroke and myocardial infarction.

·         thyrotoxicosis

·         migraine prophylaxis

·         anxiety

Examples

·         atenolol

·         propranolol: one of the first beta-blockers to be developed. Lipid soluble therefore crosses the blood-brain barrier

Side-effects

·         bronchospasm

·         cold peripheries

·         fatigue

·         sleep disturbances, including nightmares

·         erectile dysfunction

Contraindications

·         uncontrolled heart failure

·         asthma

·         sick sinus syndrome

·         concurrent verapamil use: may precipitate severe bradycardia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:48

Peri-arrest rhythms: tachycardia

The 2015 Resuscitation Council (UK) guidelines have simplified the advice given for the management of peri-arrest tachycardias. Separate algorithms for the management of broad-complex tachycardia, narrow complex tachycardia and atrial fibrillation have been replaced by one unified treatment algorithm

 

Following basic ABC assessment, patients are classified as being stable or unstable according to the presence of any adverse signs:

·         shock: hypotension (systolic blood pressure < 90 mmHg), pallor, sweating, cold, clammy extremities, confusion or impaired consciousness

·         syncope

·         myocardial ischaemia

·         heart failure

If any of the above adverse signs are present then synchronised DC shocks should be given

 

Treatment following this is given according to whether the QRS complex is narrow or broad and whether the rhythm is regular or irregular. The full treatment algorithm can be found at the Resuscitation Council website, below is a very limited summary:

 

Broad-complex tachycardia

 

Regular

·         assume ventricular tachycardia (unless previously confirmed SVT with bundle branch block)

·         loading dose of amiodarone followed by 24 hour infusion

Irregular

·         1. AF with bundle branch block - treat as for narrow complex tachycardia

·         2. Polymorphic VT (e.g. Torsade de pointes) - IV magnesium

Narrow-complex tachycardia

 

Regular

·         vagal manoeuvres followed by IV adenosine

·         if above unsuccessful consider diagnosis of atrial flutter and control rate (e.g. Beta-blockers)

Irregular

·         probable atrial fibrillation

·         if onset < 48 hr consider electrical or chemical cardioversion

·         rate control (e.g. Beta-blocker or digoxin) and anticoagulation

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

22:38

Acute coronary syndrome: initial management

Acute coronary syndrome (ACS) is a very common and important presentation in medicine. The management of ACS has evolved over recent years, with the development of new drugs and procedures such as primary coronary intervention (PCI).

 

Emergency departments often have their own protocols based around local factors such as availability of PCI and hospital drug formularies. The following is based around the 2020 update to the NICE ACS guidelines.

 

Acute coronary syndrome can be classified as follows:

·         ST-elevation myocardial infarction (STEMI): ST-segment elevation + elevated biomarkers of myocardial damage

·         non ST-elevation myocardial infarction (NSTEMI): ECG changes but no ST-segment elevation + elevated biomarkers of myocardial damage

·         unstable angina

The management of ACS depends on the particular subtype. NICE management guidance groups the patients into two groups:

·         1. STEMI

·         2. NSTEM/unstable angina

Common management of all patients with ACS

·         aspirin 300mg

·         oxygen should only be given if the patient has oxygen saturations < 94% in keeping with British Thoracic Society oxygen therapy guidelines

·         morphine should only be given for patients with severe pain

o    previously IV morphine was given routinely

o    evidence, however, suggests that this may be associated with adverse outcomes

·         nitrates

o    can be given either sublingually or intravenously

o    useful if the patient has ongoing chest or hypertension

o    should be used in caution if patient hypotensive

The next step in managing a patient with suspected ACS is to determine whether they meet the ECG criteria for STEMI. It is, of course, important to recognise that these should be interpreted in the context of the clinical history.

 

STEMI criteria

·         clinical symptoms consistent with ACS (generally of ≥ 20 minutes duration) with persistent (> 20 minutes) ECG features in ≥ 2 contiguous leads of:

o    2.5 mm (i.e ≥ 2.5 small squares) ST elevation in leads V2-3 in men under 40 years, or ≥ 2.0 mm (i.e ≥ 2 small squares) ST elevation in leads V2-3 in men over 40 years

o    1.5 mm ST elevation in V2-3 in women

o    1 mm ST elevation in other leads

o    new LBBB (LBBB should be considered new unless there is evidence otherwise)

Management of STEMI

 

Once a STEMI has been confirmed the first step is to immediately assess eligibility for coronary reperfusion therapy. There are two types of coronary reperfusion therapy:

·         primary coronary intervention

o    should be offered if the presentation is within 12 hours of onset of symptoms AND PCI can be delivered within 120 minutes of the time when thrombolysis could have been given (i.e. consider thrombolysis if there is a significant delay in being able to provide PCI)

o    if patients present after 12 hours and still have evidence of ongoing ischaemia then PCI should still be considered

o    drug-eluting stents are now used. Previously 'bare-metal' stents were sometimes used but have higher rates of restenosis

o    radial access is preferred to femoral access

·         thrombolysis

o    should be offered within 12 hours of onset of symptoms if primary PCI cannot be delivered within 120 minutes of the time when thrombolysis could have been given

o    a practical example may be a patient who presents with a STEMI to a small district general hospital (DGH) which does not have facilities for PCI. If they cannot be transferred to a larger hospital for PCI within 120 minutes then thrombolysis should be given. If the patient's ECG taken 90 minutes after thrombolysis failed to show resolution of the ST elevation then they would then require transfer for PCI

If patients are eligible this should be offered as soon as possible.

 

Primary coronary intervention for patients with STEMI

 

Further antiplatelet prior to PCI

·         this is termed 'dual antiplatelet therapy', i.e. aspirin + another drug

·         if the patient is not taking an oral anticoagulant: prasugrel

·         if taking an oral anticoagulant: clopidogrel

Drug therapy during PCI

·         patients undergoing PCI with radial access:

o    unfractionated heparin with bailout glycoprotein IIb/IIIa inhibitor (GPI) - this is the action of using a GPI during the procedure when it was not intended from the outset, e.g. because of worsening or persistent thrombus

·         patients undergoing PCI with femoral access:

o    bivalirudin with bailout GPI

Other procedures during PCI

·         thrombus aspiration, but not mechanical thrombus extraction, should be considered

·         complete revascularisation should be considered for patients with multivessel coronary artery disease without cardiogenic shock

 

Thrombolysis for patients with STEMI

 

Thrombolysis used to be the only form of coronary reperfusion therapy available. However, it is used much less commonly now given the widespread availability of PCI.

 

The contraindications to thrombolysis and other factors are described in other notes.

 

Patients undergoing thrombolysis should also be given an antithrombin drug.

 

If patients have persistent myocardial ischaemia following thrombolysis then PCI should be considered.

 

 

Management of NSTEMI/unstable

 

The management of NSTEMI/unstable is complicated and depends on individual patient factors and a risk assessment. The summary below provides an overview but the full NICE guidelines should be reviewed for further details.

 

Further drug therapy

·         antithrombin treatment

o    fondaparinux should be offered to patients who are not at a high risk of bleeding and who are not having angiography immediately

o    if immediate angiography is planned or a patients creatinine is > 265 µmol/L then unfractionated heparin should be given

Risk assessment

 

The Global Registry of Acute Coronary Events (GRACE) is the most widely used tool for risk assessment. It can be calculated using online tools and takes into account the following factors:

·         age

·         heart rate, blood pressure

·         cardiac (Killip class) and renal function (serum creatinine)

·         cardiac arrest on presentation

·         ECG findings

·         troponin levels

This results in the patient being risk stratified as follows:

 

 

Predicted 6‑month mortality

Risk of future adverse cardiovascular events

1.5% or below

Lowest

> 1.5% to 3.0%

Low

> 3.0% to 6.0%

Intermediate

> 6.0% to 9.0%

High

over 9.0%

Highest

Based on this risk assessment key decisions are made regarding whether a patient has coronary angiography (with follow-on PCI if necessary) or has conservative management. The detailed pros/cons of this descision are covered in other notes.

 

Which patients with NSTEMI/unstable angina should have a coronary angiography (with follow-on PCI if necessary)?

·         immediate: patient who are clinically unstable (e.g. hypotensive)

·         within 72 hours: patients with a GRACE score > 3% i.e. those at immediate, high or highest risk

·         coronary angiography should also be considered for patients is ischaemia is subsequently experienced after admission

Primary coronary intervention for patients with NSTEMI/unstable angina

 

Further drug therapy

·         unfractionated heparin should be given regardless of whether the patient has had fondaparinux or not

·         further antiplatelet ('dual antiplatelet therapy', i.e. aspirin + another drug) prior to PCI

o    if the patient is not taking an oral anticoagulant: prasugrel or ticagrelor

o    if taking an oral anticoagulant: clopidogrel

Conservative management for patients with NSTEMI/unstable angina

 

Further drug therapy

·         further antiplatelet ('dual antiplatelet therapy', i.e. aspirin + another drug)

o    if the patient is not at a high-risk of bleeding: ticagrelor

o    if the patient is at a high-risk of bleeding: clopidogrel

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

17:22

 

Coarctation of the aorta

Coarctation of the aorta describes a congenital narrowing of the descending aorta.

 

Overview

·         more common in males (despite association with Turner's syndrome)

Features

·         infancy: heart failure

·         adult: hypertension

·         radio-femoral delay

·         mid systolic murmur, maximal over back

·         apical click from the aortic valve

·         notching of the inferior border of the ribs (due to collateral vessels) is not seen in young children

Associations

·         Turner's syndrome

·         bicuspid aortic valve

·         berry aneurysms

·         neurofibromatosis

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

22:49

Atrial fibrillation: anticoagulation

NICE updated their guidelines on the management of atrial fibrillation (AF) in 2014. They suggest using the CHA2DS2-VASc score to determine the most appropriate anticoagulation strategy. This scoring system superceded the CHADS2 score.

 

 

 

Risk factor

Points

C

Congestive heart failure

1

H

Hypertension (or treated hypertension)

1

A2

Age >= 75 years

2

 

Age 65-74 years

1

D

Diabetes

1

S2

Prior Stroke or TIA

2

V

Vascular disease (including ischaemic heart disease and peripheral arterial disease)

1

S

Sex (female)

1

The table below shows a suggested anticoagulation strategy based on the score:

 

 

Score

Anticoagulation

0

No treatment

1

Males: Consider anticoagulation

Females: No treatment (this is because their score of 1 is only reached due to their gender)

2 or more

Offer anticoagulation

Remember that if a CHA2DS2-VASc score suggests no need for anticoagulation it is important to ensure a transthoracic echocardiogram has been done to exclude valvular heart disease, which in combination with AF is an absolute indication for anticoagulation.

 

NICE recommend that we offer patients a choice of anticoagulation, including warfarin and the novel oral anticoagulants (NOACs). There are complicated rules surrounding which NOAC is licensed for which risk factor - these can be found in the NICE guidelines. Aspirin is no longer recommended for reducing stroke risk in patients with AF

 

Doctors have always thought carefully about the risk/benefit profile of starting someone on warfarin. A history of falls, old age, alcohol excess and a history of previous bleeding are common things that make us consider whether warfarinisation is in the best interests of the patient. NICE now recommend we formalise this risk assessment using the HASBLED scoring system.

 

 

 

Risk factor

Points

H

Hypertension, uncontrolled, systolic BP > 160 mmHg

1

A

Abnormal renal function (dialysis or creatinine > 200)

Or

Abnormal liver function (cirrhosis, bilirubin > 2 times normal, ALT/AST/ALP > 3 times normal

1 for any renal abnormalities

 

1 for any liver abnormalities

S

Stroke, history of

1

B

Bleeding, history of bleeding or tendency to bleed

1

L

Labile INRs (unstable/high INRs, time in therapeutic range < 60%)

1

E

Elderly (> 65 years)

1

D

Drugs Predisposing to Bleeding (Antiplatelet agents, NSAIDs)

Or

Alcohol Use (>8 drinks/week)

1 for drugs

 

1 for alcohol

There are no formal rules on how we act on the HAS-BLED score although a score of >= 3 indicates a 'high risk' of bleeding, defined as intracranial haemorrhage, hospitalisation, haemoglobin decrease >2 g/L, and/or transfusion.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

For anyone struggling with remember CHA2DS2-VASc, I find SADCHAVS easier to remember. The top two in the list are the 2 point scores, and the rest 1.

 

Stroke 2

Age >75 2

Diabetes 1

Congestive Heart Failure 1

HTN 1

Age >65 1

Vascular Hx 1

Sex Female 1

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

22 December 2020

18:06

Infective endocarditis

The strongest risk factor for developing infective endocarditis is a previous episode of endocarditis. The following types of patients are affected:

·         previously normal valves (50%, typically acute presentation)

o    the mitral valve is most commonly affected

·         rheumatic valve disease (30%)

·         prosthetic valves

·         congenital heart defects

·         intravenous drug users (IVDUs, e.g. typically causing tricuspid lesion)

·         others: recent piercings

Causes

·         historically Streptococcus viridans was the most common cause of infective endocarditis. This is no longer the case, except in developing countries. Staphylococcus aureus is now the most common cause of infective endocarditis. Staphylococcus aureus is also particularly common in acute presentation and IVDUs

·         coagulase-negative Staphylococci such as Staphylococcus epidermidis commonly colonize indwelling lines and are the most cause of endocarditis in patients following prosthetic valve surgery, usually the result of perioperative contamination. After 2 months the spectrum of organisms which cause endocarditis return to normal (i.e. Staphylococcus aureus is the most common cause)

·         Streptococcus viridans still accounts for around 20% of cases. Technically Streptococcus viridans is a pseudotaxonomic term, referring to viridans streptococci, rather than a particular organism. The two most notable viridans streptococci are Streptococcus mitis and Streptococcus sanguinis. They are both commonly found in the mouth and in particular dental plaque so endocarditis caused by these organisms is linked with poor dental hygiene or following a dental procedure

·         Streptococcus bovis is associated with colorectal cancer

o    the subtype Streptococcus gallolyticus is most linked with colorectal cancer

·         non-infective: systemic lupus erythematosus (Libman-Sacks), malignancy: marantic endocarditis

Culture negative causes

·         prior antibiotic therapy

·         Coxiella burnetii

·         Bartonella

·         Brucella

·         HACEK: Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella)

*Lancet 2016; 387: 882-93 Infective Endocarditis

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:47

Murmurs

Ejection systolic

·         louder on expiration

o    aortic stenosis

o    hypertrophic obstructive cardiomyopathy

·         louder on inspiration

o    pulmonary stenosis

o    atrial septal defect

·         also: tetralogy of Fallot

Holosystolic (pansystolic)

·         mitral/tricuspid regurgitation (high-pitched and 'blowing' in character)

o    tricuspid regurgitation becomes louder during inspiration, unlike mitral stenosis

o    during inspiration, the venous blood flow into the right atrium and ventricle are increased → increases the stroke volume of the right ventricle during systole

·         ventricular septal defect ('harsh' in character)

Late systolic

·         mitral valve prolapse

·         coarctation of aorta

Early diastolic

·         aortic regurgitation (high-pitched and 'blowing' in character)

·         Graham-Steel murmur (pulmonary regurgitation, again high-pitched and 'blowing' in character)

Mid-late diastolic

·         mitral stenosis ('rumbling' in character)

·         Austin-Flint murmur (severe aortic regurgitation, again is 'rumbling' in character)

Continuous machine-like murmur

·         patent ductus arteriosus

 

 

Image sourced from Wikipedia

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

17:38

 

Supraventricular tachycardia

Whilst strictly speaking the term supraventricular tachycardia (SVT) refers to any tachycardia that is not ventricular in origin the term is generally used in the context of paroxysmal SVT. Episodes are characterised by the sudden onset of a narrow complex tachycardia, typically an atrioventricular nodal re-entry tachycardia (AVNRT). Other causes include atrioventricular re-entry tachycardias (AVRT) and junctional tachycardias.

 

Acute management

·         vagal manoeuvres: e.g. Valsalva manoeuvre, carotid sinus massage

·         intravenous adenosine 6mg → 12mg → 12mg: contraindicated in asthmatics - verapamil is a preferable option

·         electrical cardioversion

Prevention of episodes

·         beta-blockers

·         radio-frequency ablation

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

22:04

Syncope

Syncope may be defined as a transient loss of consciousness due to global cerebral hypoperfusion with rapid onset, short duration and spontaneous complete recovery. Note how this definition excludes other causes of collapse such as epilepsy.

 

The European Society of Cardiology published guidelines in 2009 on the investigation and management of syncope. They suggested the following classification:

 

Reflex syncope (neurally mediated)

·         vasovagal: triggered by emotion, pain or stress. Often referred to as 'fainting'

·         situational: cough, micturition, gastrointestinal

·         carotid sinus syncope

Orthostatic syncope

·         primary autonomic failure: Parkinson's disease, Lewy body dementia

·         secondary autonomic failure: e.g. Diabetic neuropathy, amyloidosis, uraemia

·         drug-induced: diuretics, alcohol, vasodilators

·         volume depletion: haemorrhage, diarrhoea

Cardiac syncope

·         arrhythmias: bradycardias (sinus node dysfunction, AV conduction disorders) or tachycardias (supraventricular, ventricular)

·         structural: valvular, myocardial infarction, hypertrophic obstructive cardiomyopathy

·         others: pulmonary embolism

Reflex syncope is the most common cause in all age groups although orthostatic and cardiac causes become progressively more common in older patients.

 

Evaluation

·         cardiovascular examination

·         postural blood pressure readings: a symptomatic fall in systolic BP > 20 mmHg or diastolic BP > 10 mmHg or decrease in systolic BP < 90 mmHg is considered diagnostic

·         ECG

·         carotid sinus massage

·         tilt table test

·         24 hour ECG

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

16:25

 

Atrial fibrillation: cardioversion

There are two scenarios where cardioversion may be used in atrial fibrillation:

·         electrical cardioversion as an emergency if the patient is haemodynamically unstable

·         electrical or pharmacological cardioversion as an elective procedure where a rhythm control strategy is preferred.

The notes below refer to cardioversion being used in the elective scenario for rhythm control. The wording of the 2014 NICE guidelines is as follows:

 

 

offer rate or rhythm control if the onset of the arrhythmia is less than 48 hours, and start rate control if it is more than 48 hours or is uncertain

 

 

Onset < 48 hours

 

If the atrial fibrillation (AF) is definitely of less than 48 hours onset patients should be heparinised. Patients who have risk factors for ischaemic stroke should be put on lifelong oral anticoagulation. Otherwise, patients may be cardioverted using either:

·         electrical - 'DC cardioversion'

·         pharmacology - amiodarone if structural heart disease, flecainide or amiodarone in those without structural heart disease

Following electrical cardioversion if AF is confirmed as being less than 48 hours duration then further anticoagulation is unnecessary

 

Onset > 48 hours

 

If the patient has been in AF for more than 48 hours then anticoagulation should be given for at least 3 weeks prior to cardioversion. An alternative strategy is to perform a transoesophageal echo (TOE) to exclude a left atrial appendage (LAA) thrombus. If excluded patients may be heparinised and cardioverted immediately.

 

NICE recommend electrical cardioversion in this scenario, rather than pharmacological.

 

If there is a high risk of cardioversion failure (e.g. Previous failure or AF recurrence) then it is recommend to have at least 4 weeks amiodarone or sotalol prior to electrical cardioversion

 

Following electrical cardioversion patients should be anticoagulated for at least 4 weeks. After this time decisions about anticoagulation should be taken on an individual basis depending on the risk of recurrence

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

16:20

 

Cardiac tamponade

Cardiac tamponade is characterized by the accumulation of pericardial fluid under pressure.

 

Classical features - Beck's triad:

·         hypotension

·         raised JVP

·         muffled heart sounds

Other features:

·         dyspnoea

·         tachycardia

·         an absent Y descent on the JVP - this is due to the limited right ventricular filling

·         pulsus paradoxus - an abnormally large drop in BP during inspiration

·         Kussmaul's sign - much debate about this

·         ECG: electrical alternans

The key differences between constrictive pericarditis and cardiac tamponade are summarised in the table below:

 

 

 

Cardiac tamponade

Constrictive pericarditis

JVP

Absent Y descent

X + Y present

Pulsus paradoxus

Present

Absent

Kussmaul's sign

Rare

Present

Characteristic features

 

Pericardial calcification on CXR

A commonly used mnemonic to remember the absent Y descent in cardiac tamponade is TAMponade = TAMpaX

 

Management

·         urgent pericardiocentesis

 

 

© Image used on license from Dr Smith, University of Minnesota

 

An ECG demonstrating electrical alternans. Note the alternation of QRS complex amplitude between beats.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

22:46

Diabetes mellitus: hypertension management

Patient diabetes mellitus have traditionally had their blood pressure controlled more aggressively to help reduce their overall cardiovascular risk. However, a 2013 Cochrane review casted doubt on the wisdom of lower blood pressure targets for patients with diabetes. It compared patients who had tight blood pressure control (targets < 130/85 mmHg) with more relaxed control (< 140-160/90-100 mmHg). Patients who were more tightly controlled had a slightly reduced rate of stroke but otherwise outcomes were not significantly different.

 

In light of this, NICE recommends a blood pressure target of < 140/90 mmHg for type 2 diabetics, the same as for patients without diabetes.

 

For patients with type 1 diabetes, NICE recommends:

 

 

Intervention levels for recommending blood pressure management should be 135/85 mmHg unless the adult with type 1 diabetes has albuminuria or 2 or more features of metabolic syndrome, in which case it should be 130/80 mmHg

 

 

Because ACE-inhibitors have a renoprotective effect in diabetes they are the first-line antihypertensives recommended for NICE. Patients of African or Caribbean family origin should be offered an ACE-inhibitor plus either a thiazide diuretic or calcium channel blocker. Further management then reverts to that of non-diabetic patients, as discussed earlier in the module.

 

Remember than autonomic neuropathy may result in more postural symptoms in patients taking antihypertensive therapy.

 

The routine use of beta-blockers in uncomplicated hypertension should be avoided, particularly when given in combination with thiazides, as they may cause insulin resistance, impair insulin secretion and alter the autonomic response to hypoglycaemia.

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

21:47

Myocardial infarction: STEMI management

A number of studies over the past 10 years have provided an evidence for the management of ST-elevation myocardial infarction (STEMI)

 

In the absence of contraindications, all patients should be given

·         aspirin

·         P2Y12-receptor antagonist. Clopidogrel was the first P2Y12-receptor antagonist to be widely used but now ticagrelor is often favoured as studies have shown improved outcomes compared to clopidogrel, but at the expense of slightly higher rates of bleeding. This approached is supported in SIGN's 2016 guidelines. They also recommend that prasugrel (another P2Y12-receptor antagonist) could be considered if the patient is going to have a percutaneous coronary intervention

·         unfractionated heparin is usually given for patients who're are going to have a PCI. Alternatives include low-molecular weight heparin

NICE suggest the following in terms of oxygen therapy:

·         do not routinely administer oxygen, but monitor oxygen saturation using pulse oximetry as soon as possible, ideally before hospital admission. Only offer supplemental oxygen to:

·         people with oxygen saturation (SpO2) of less than 94% who are not at risk of hypercapnic respiratory failure, aiming for SpO2 of 94-98%

·         people with chronic obstructive pulmonary disease who are at risk of hypercapnic respiratory failure, to achieve a target SpO2 of 88-92% until blood gas analysis is available.

Primary percutaneous coronary intervention (PCI) has emerged as the gold-standard treatment for STEMI but is not available in all centres. Thrombolysis should be performed in patients without access to primary PCI

 

With regards to thrombolysis:

·         tissue plasminogen activator (tPA) has been shown to offer clear mortality benefits over streptokinase

·         tenecteplase is easier to administer and has been shown to have non-inferior efficacy to alteplase with a similar adverse effect profile

An ECG should be performed 90 minutes following thrombolysis to assess whether there has been a greater than 50% resolution in the ST elevation

·         if there has not been adequate resolution then rescue PCI is superior to repeat thrombolysis

·         for patients successfully treated with thrombolysis PCI has been shown to be beneficial. The optimal timing of this is still under investigation

Glycaemic control in patients with diabetes mellitus

·         in 2011 NICE issued guidance on the management of hyperglycaemia in acute coronary syndromes

·         it recommends using a dose-adjusted insulin infusion with regular monitoring of blood glucose levels to glucose below 11.0 mmol/l

·         intensive insulin therapy (an intravenous infusion of insulin and glucose with or without potassium, sometimes referred to as 'DIGAMI') regimes are not recommended routinely

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

21 December 2020

21:47

Aortic dissection

Aortic dissection is a rare but serious cause of chest pain.

 

Pathophysiology

·         tear in the tunica intima of the wall of the aorta

Associations

·         hypertension: the most important risk factor

·         trauma

·         bicuspid aortic valve

·         collagens: Marfan's syndrome, Ehlers-Danlos syndrome

·         Turner's and Noonan's syndrome

·         pregnancy

·         syphilis

Features:

·         chest pain: typically severe, radiates through to the back and 'tearing' in nature

·         aortic regurgitation

·         hypertension

·         other features may result from the involvement of specific arteries. For example coronary arteries → angina, spinal arteries → paraplegia, distal aorta → limb ischaemia

·         the majority of patients have no or non-specific ECG changes. In a minority of patients, ST-segment elevation may be seen in the inferior leads

Classification

 

Stanford classification

·         type A - ascending aorta, 2/3 of cases

·         type B - descending aorta, distal to left subclavian origin, 1/3 of cases

DeBakey classification

·         type I - originates in ascending aorta, propagates to at least the aortic arch and possibly beyond it distally

·         type II - originates in and is confined to the ascending aorta

·         type III - originates in descending aorta, rarely extends proximally but will extend distally

 

 

© Image used on license from Radiopaedia

Stanford type A / DeBakey type I

 

 

© Image used on license from Radiopaedia

Stanford type A / DeBakey type II

 

 

© Image used on license from Radiopaedia

Stanford type B / DeBakey type III

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

17:03

Atrial flutter

Atrial flutter is a form of supraventricular tachycardia characterised by a succession of rapid atrial depolarisation waves.

 

ECG findings

·         'sawtooth' appearance

·         as the underlying atrial rate is often around 300/min the ventricular or heart rate is dependent on the degree of AV block. For example if there is 2:1 block the ventricular rate will be 150/min

·         flutter waves may be visible following carotid sinus massage or adenosine

Management

·         is similar to that of atrial fibrillation although medication may be less effective

·         atrial flutter is more sensitive to cardioversion however so lower energy levels may be used

·         radiofrequency ablation of the tricuspid valve isthmus is curative for most patients

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From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

22:54

 

Mitral stenosis

It is said that the causes of mitral stenosis are rheumatic fever, rheumatic fever and rheumatic fever. Rarer causes that may be seen in the exam include mucopolysaccharidoses, carcinoid and endocardial fibroelastosis

 

Features

·         mid-late diastolic murmur (best heard in expiration)

·         loud S1, opening snap

·         low volume pulse

·         malar flush

·         atrial fibrillation

Features of severe MS

·         length of murmur increases

·         opening snap becomes closer to S2

Chest x-ray

·         left atrial enlargement may be seen

Echocardiography

·         the normal cross sectional area of the mitral valve is 4-6 sq cm. A 'tight' mitral stenosis implies a cross sectional area of < 1 sq cm

 

 

© Image used on license from Radiopaedia

Chest x-ray from a patient with mitral stenosis. This patient has had a sternotomy and a prosthetic mitral valve. There is splaying of the carina with elevation of the left main bronchus, a double right heart border and cardiomegaly. The features are those of left atrial enlargement. Although the entire heart is enlarged, a double contour is seen through the right side of the heart. The more medial line is the enlarged left atrium (white dotted line) and the heart heart border is more lateral (blue dotted line).

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

16:31

 

Cardiomyopathies: key points

The old classification of dilated, restricted and hypertrophic cardiomyopathy has been largely abandoned due to the high degree of overlap. The latest classification of cardiomyopathy by the WHO and American Heart Association reflect this.

 

The tables below shows a very limited set of exam related facts for the various cardiomyopathies:

 

Primary cardiomyopathies - predominately involving the heart

 

Genetic - both conditions listed below are autosomal dominant. An implantable cardioverter-defibrillator is often inserted to reduce the incidence of sudden cardiac death.

 

 

Type of cardiomyopathy

Selected points

Hypertrophic obstructive cardiomyopathy

Leading cause of sudden cardiac death in young athletes

Usually due to a mutation in the gene encoding β-myosin heavy chain protein

Common cause of sudden death

Echo findings include MR, systolic anterior motion (SAM) of the anterior mitral valve and asymmetric septal hypertrophy

Arrhythmogenic right ventricular dysplasia

Right ventricular myocardium is replaced by fatty and fibrofatty tissue

Around 50% of patients have a mutation of one of the several genes which encode components of desmosome

ECG abnormalities in V1-3, typically T wave inversion. An epsilon wave is found in about 50% of those with ARV - this is best described as a terminal notch in the QRS complex

Mixed - rather confusingly most of the causes of dilated and restrictive cardiomyopathy are now listed separately in the 'secondary' causes. This category servers as a reminder that many patients will have a genetic predisposition to cardiomyopathy which is then triggered by the secondary process, hence the 'mixed' category

 

 

Type of cardiomyopathy

Selected causes/points

Dilated cardiomyopathy

Classic causes include

·         alcohol

·         Coxsackie B virus

·         wet beri beri

·         doxorubicin

Restrictive cardiomyopathy

Classic causes include

·         amyloidosis

·         post-radiotherapy

·         Loeffler's endocarditis

Familial restrictive cardiomyopathy demonstrates autosomal dominant inheritance in the majority of cases.

 

 

Acquired

 

 

Type of cardiomyopathy

Selected points

Peripartum cardiomyopathy

Typical develops between last month of pregnancy and 5 months post-partum

More common in older women, greater parity and multiple gestations

Takotsubo cardiomyopathy

'Stress'-induced cardiomyopathy e.g. patient just found out family member dies then develops chest pain and features of heart failure

Transient, apical ballooning of the myocardium

Treatment is supportive

 

Secondary cardiomyopathies- pathological myocardial involvement as part of a generalized systemic disorder

 

 

Type of cardiomyopathy

Selected causes/points

Infective

Coxsackie B virus

Chagas disease

Infiltrative

Amyloidosis

Storage

Haemochromatosis

Toxicity

Doxorubicin

Alcoholic cardiomyopathy

Inflammatory (granulomatous)

Sarcoidosis

Endocrine

Diabetes mellitus

Thyrotoxicosis

Acromegaly

Neuromuscular

Friedreich's ataxia

Duchenne-Becker muscular dystrophy

Myotonic dystrophy

Nutritional deficiencies

Beriberi (thiamine)

Autoimmune

Systemic lupus erythematosis

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

Arrhythmogenic right ventricular cardiomyopathy is characterised by right ventricular  myocardium replacement by fatty and fibrofatty tissue.

Arrhythmogenic right ventricular cardiomyopathy in late stages may cause dilation of the ventricles but not initially.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

Progressive deterioration of AV block risk is high in myotonic muscular dystrophy.

Permanent pacemaker for AV block first degree

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

Reversible cardiomyopathies: (not exhaustive)

 

Viral myocarditis

PVC-induced cardiomyopathy

Tachycardia cardiomyopathy

Alcohol cardiomyopathy

 

 

 

 

 

 

 

24 December 2020

13:09

ECG: ST elevation

Causes of ST elevation

·         myocardial infarction

·         pericarditis/myocarditis

·         normal variant - 'high take-off'

·         left ventricular aneurysm

·         Prinzmetal's angina (coronary artery spasm)

·         Takotsubo cardiomyopathy

·         rare: subarachnoid haemorrhage

 

From <https://www.passmedicine.com/review/textbook.php?s=#>

 

 

 

 

 

22 December 2020

17:25

ECG: P wave changes

Increased P wave amplitude

·         cor pulmonale

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

21 December 2020

22:35

ECG: T wave changes

Peaked T waves

·         hyperkalaemia

·         myocardial ischaemia

Inverted T waves

·         myocardial ischaemia

·         digoxin toxicity

·         subarachnoid haemorrhage

·         arrhythmogenic right ventricular cardiomyopathy

·         pulmonary embolism ('S1Q3T3')

·         Brugada syndrome

 

From <https://www.passmedicine.com/question/questions.php?q=0>

 

 

 

 

 

22 December 2020

17:13




 

 

 

Endothelin receptor antagonists

28 December 2020

22:03

Endothelin receptor antagonists decrease pulmonary vascular resistance. The aim of endothelin  receptor antagonist therapy is to reduce pulmonary vascular resistance and hence reduce the  strain on the right-sided cardiac chambers. Right ventricular failure is the commonest cause of  death in primary pulmonary hypertension.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

Catecholaminergic polymorphic  ventricular

28 December 2020

22:02

HOCM is the most common cause of sudden cardiac death in young people.

 

Catecholaminergic polymorphic  ventricular

Inherited cardiac disease associated with sudden cardiac death  autosomal dominant with prevalence of  1:10,000.

 

Brugada

More common in South East Asia. Sodium channelopathy.

Arrhythmogenic right ventricular  dysplasia

 

Fibro fatty infiltration of right ventricle.  Cause of sudden death

Long QT

Inherited and acquired. Family history  with inherited form. Usually preceded by  history of recurrent syncopes. Severe  forms may cause sudden deaths.

 

 

 

Prostacyclins

28 December 2020

22:05

 

Prostacyclins are used in the treatment of primary pulmonary hypertension.

Hydrochlorothiazide is not used to treat PAH but may be used for heart failure and systemic  hypertension.

Aspirin does not affect PAH.

Lisinopril and carvedilol are first line drugs for heart failure treatment.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

occupational asthma

28 December 2020

22:14

Industrial chemicals like isocyanates are the most common cause of occupational asthma.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

 

ICD implantation

28 December 2020

23:05

Indications for an Implantable Cardioverter-Defibrillator Left ventricular ejection fraction 35% due to prior myocardial infarction who are 40-days post infarction and are in NYHA Functional Class Il or Ill Left ventricular dysfunction due to prior myocardial infarction who are 40 days post-infarction, have a left ventricular ejection fraction 30% and are in NYHA Functional Class I Nonischemic dilated cardiomyopathy with a left ventricular ejection fraction s 35% and are in NYHA Functional Class Il or Ill Non-sustained ventricular tachycardia due to prior myocardial infarction with left ventricular ejection fraction < 40% and inducible ventricular fibrillation or sustained ventricular tachycardia at electrophysiological study Structural heart disease (valvular, ischemic, hypertrophic, dilated, or infiltrative cardiomyopathies) and spontaneous sustained ventricular tachycardia, whether hemodynamically stable or unstable Syncope of undetermined origin with clinically relevant, hemodynamically significant sustained ventricular tachycardia or ventricular fibrillation induced at electrophysiological study

 

 

 

Obesity venous insufficiency

28 December 2020

23:08

 Exertional dyspnoea walking up an incline is  likely due to morbid obesity.

 

 diurnal variation to his ankle swelling, worse at night  compared to morning plus venous varicosities, probably secondary to obesity.

 

From <https://mle.ncl.ac.uk/cases/page/18128/>

 

 

 

Mitochrondrial cardiomyopathy

28 December 2020

23:13

Retinitis pigmentosa may be present

 

Maternal inheritance

 

Nuclear genes coding mitochondrial proteins may be mutated

 

Neuromuscular manifestations are often apparent

 

 

 

Diastolic dysfunction in hypertrophic cardiomyopathy

28 December 2020

23:14

Cause:

 

Increased LV stiffness

Impairment of ventricular relaxation

Compromised myocardial energy metabolism

Impairment of coronary blood flow

 

 

 

Sudden cardiac death with HCM

28 December 2020

23:15

Associations:

 

·         Unexplained syncope

 

·         History of premature SCD in a first-degree relative with hypertrophic cardiomyopathy

 

·         Non-sustained ventricular tachycardia on Holter

 

·         Previous history of cardiac arrest

 

 

 

Pulmonary hypertension Classification

28 December 2020

15:57

Defined as mean pulmonary artery pressure (mPAP) ≥ 20mmHg at rest (measured by right heart catheterisation)

 

Considered severe when:

·         mPAP ≥35 mmHg

·         mPAP ≥20 mmHg + elevated right atrial pressure

        +/- cardiac index <2L/min/m2

 

Cardiac index-

·         More accurate picture of heart function relative to individual body size

·         Cardiac index (L/min/m2)

·        

·         Normal range 2.5-4.0 L/min/m2

·         Minimum cardiac index of 2.0 L/ min/ m2 required to maintain life without mechanical support

 

Risk factors-

·         Family history of pulmonary arterial hypertension

·         Congenital heart disease

·         Connective tissue disease (systemic sclerosis, SLE)

·         Drugs and toxins

·         Aminorex, Methamphetamine, Fenfluramine

o    Aminorex =a type of SSRI, stimulates weight loss

o    Fenfluramine= appetite suppressant

·         Human Immunodeficiency Virus (HIV)

·         Mechanism not known

·         Portal hypertension

 

 

Clinical classifications-

 

 

Group 1: Pulmonary Arterial Hypertension (PAH) with Pulmonary Artery Occlusion Pressure <15mmHg

·         Idiopathic PAH

·         Hereditary PAH

·         Drug and toxin-induced PAH

 

PAH associated with

·         Connective tissue disease

·         HIV infection

·         Portal hypertension

·         Congenital Heart Disease

·         Schistosomiasis

 

Group 2: Pulmonary Hypertension due to left heart disease

·         Heart failure with preserved ejection fraction

·         Heart failure with reduced ejection fraction

·         Valvular heart diseases

 

 

Group 3: Pulmonary Hypertension due to lung diseases/ hypoxia

·         Obstructive lung disease

·         Restrictive lung disease

·         Other lung disease with mixed restrictive/ obstructive pattern

·         Developmental lung disorders

 

Group 4: Pulmonary Hypertension due to pulmonary artery obstructions

·         Chronic thromboembolic pulmonary hypertension (CTEPH)

·         Other pulmonary artery obstructions

 

Group 5: Pulmonary Hypertension with unclear/ multifactorial mechanism

·         Systemic and metabolic disorders

·         Others

·         Complex congenital heart diseases

 

 

Investigation:

Gold standard:  cardiac catheterisation.

Right heart pressure measurements are required via cardiac catheterisation.

 

 

 

 

Management:

 

Pulmonary arterial hypertension patients with negative response to vasodilator testing may be treated with prostacyclin analogues, endothelin receptor antagonists or phosphodiesterase  inhibitors. Combination therapy is often necessary.

 

Pulmonary arterial hypertension patients with positive response to vasodilator testing are  treated with calcium channel blockers e.g.  nifedipine, felodipine.

 

Prostacyclin analogues

Iloprost, epoprostenol

 

Endothelin receptor antagonists  (sentans)

Bosentan, ambrisentan

 

Phosphodiesterase inhibitor (afils)

Sildenafil, tadalafil, vardenafil

 

 

 

 

Pulmonary Arterial Hypertension (PAH)

29 December 2020

00:05

Problem comes from pulmonary artery

BMPR2 gene

Can be genetically passed on

Female sex important factor

 

Risk factors-

Collagen vascular disease

Congenital heart disease

Portal hypertension

HIV infection

Drugs and toxins

Pregnancy

 

Susceptibility- Abnormal BMPR2 gene + other genetic factors

 

Vascular injury-

Endothelial dysfunction- reduced nitric oxide synthase, reduced prostacyclin production, increased thromboxane production, increased endothelin 1 production

Vascular smooth muscle dysfunction- impaired voltage-gated potassium channel

 

Disease progression- loss of response to short acting vasodilator trial

 

Genetics and Genomics of PAH The most common genetic mutations in familial PAH and IPAH are in BMPR2 and its sequence variants (SMADI, SMAD4, SMAD9) Highly expressed in pulmonary vascular endothelium and forms complexes with ALKI or ALK2 receptors Female sex is an important factor in penetrance of BMPR2 mutations Nearly 25% to 30% of patients diagnosed with IPAH should be re- classified as having HPAH Genetic testing can explain etiology and stratify risk for family members and future children HPAH Genes Identified Through Whole Genome Sequencing Higher level BMPR2; EIF2AK4; TBX4; ATP13A3; GDF2; SOX17; Of evidence (with causal AQPI,• ACVRLI; SMAD9,• ENG; KCNK3; CAVI role in disease) Lower level SMAD4; SMADI; KLF2; BMPRIB; KCNA5 of evidence Morrell NW, et al. Eur RespirJ. 2018. [Epub ahead of print].

 

• Risk Factors and Associated Conditions Collagen vascular disease Congenital heart disease Portal hypertension HIV infect.on Drugs and toxins Pregnancy Susceptibility 2. Vascular injury Endothelial dysfunction Nitric oxide synthase Prostacyclin production Thromboxane production •t Endothelin I production Vascular smooth muscle dysfunction Impaired voltage-gated potassium channel (Kvs_s) 3. Disease progression Loss of response to short- acting vasodilator trial • Abnormal BMPR2 gene • Other genetic factors Srn 00th Advent it; a hYPertfOPhY intimøl

 

Endothelium Intima Media & SMC Adventitia Intimal fibrosis Endothelial proliferation Medial thickening: SMC hypertrophy & hyperplasia

 

 

 

Idiopathic Pulmonary Arterial Hypertension

29 December 2020

12:18

·         Most common among group 1 PAH

·         Female : Male = >3:1

·         No known triggering factor

·         Not associated with family history of PAH

·         Pathology mainly in distal arteries

·         Hypertrophy of tunica media

·         Proliferation and fibrotic changes in tunica intima

·         Thickened tunica adventitia with perivascular infiltrates, as well as complex and thrombotic lesions

·         Pulmonary veins unaffected

 

 

 

Hereditary Pulmonary Arterial Hypertension

29 December 2020

12:18

·         6-10% patients with PH

·         Female > Male

 

·         Autosomal dominance inheritance with incomplete penetrance

·         20% carriers will develop disease

 

·         BMPR2

·         1st PAH-predisposing gene

·         Regulates growth, differentiation and apoptosis of pulmonary artery endothelial and smooth muscle cells

·         Associated with KCNK3 channelopathy

 

 

 

BMPR2 gene

·         Most commonly associated genetic mutation in hereditary PAH

·         Highly expressed in pulmonary vascular endothelium

·         Forms complexes with ALK1/ ALK2 receptors

·         Female sex important factor in penetrance of BMPR2 mutations

 

 

 

 

Pulmonary Hypertension due to left heart diseases

29 December 2020

12:27

Problems come from left side of the heart

 

 

Group 2 = PH by Left Sided Heart Diseases • Most common cause of PH overall • Passive backward transmission of elevated LA pressure to the TRANS PULMONARY GRADIENT mPAP—PAWP <12mmHg • Enlarged & thickened pulmonary veins pulmonary pulmonary vasculature P VH capillary dilation interstitial • PAWP >15mmHG • PVR Wood unit (initially) Primary or pathognomic vascular changes in arterial wall may be absent oedema -5 alveolar haemorrhage -5 lymphatic & lymph node enlargement • Distal arteries may be affected by medial hypertrophy & intimal fibrosis

 

Most common cause of Pulmonary hypertension

Backward transmission of Left Arterial pressure to the pulmonary vasculature leads to pulmonary vascular resistance (PVH)

 

Enlarged and thickened pulmonary veins, pulmonary capillary dilation

Alveolar hemorrhage, lymphatic and lymph node enlargement

Distal arteries may be affected by medial hypertrophy and intimal fibrosis

 

Trans pulmonary gradient mPAP-PAWP= <12mmHg

 

Primary or pathognomic vascular changes in arterial wall may be present

 

 

 

Pulmonary Hypertension due to lung disorders

29 December 2020

15:34

Problems come from the lungs

 

Chronic inflammation causing alveolar hypoxic + loss of capillaries d/t due to emphysema

Mechanical injury due to hyperinflation

Muscularization of small resistance vessels

 

Group 3 = PH d/t Lung disorders • Chronic inflammation, alveolar hypoxia, loss of capillaries d/t emphysema, mechanical injury d/y hyperinflation • Muscularisation of small resistance vessels EC Loss Neo intima Hypoxia Endothelial Cells Perturbatim. Cava Dysfunction t proliferative Wsc. Remo&ling PH • RVH EC damage, cava. vWF Source

 

 

 

Chronic Thromboembolic Pulmonary hypertension CTEPH

29 December 2020

15:55

PH d/t Chronic Thromboembolic Pulmonary Hypertension CTEPH • Definition is based on findings described after 3 months of effective anti-coagulation. (to discriminate from acute) • Pre-capillary PH and at least one segmental perfusion defect detected by V/Q scan, MDCT Angio, Pulmonary Angio • D/t obstruction of major PA by PE which can be symptomatic or asymptomatic, acute or chronic Infection. ilarnmation genetic disposion Pulmonary embolism res""• organzaton 01 trontus In-st u thrrnbosis ocüsion/sten%is Of majc« vessels Shear stress in non-obstucted vessels smal vessels •alteri»athy' hcrease puhmary arterial yessure (gwlmmary vascular resista nee and capacitance) CTEPH

 

Definition is based on findings described after 3 months of effective anti-coagulation to discriminate from acute

Pre-capillary PH and at least one segmental perfusion defect detected by V/Q scan, MDCT angiography, or Pulmonary angiography

 

Due to obstruction of major Pulmonary Artery by Pulmonary embolism which can be symptomatic or asymptomatic, acute or chronic

 

 

 

Pulmonary Arterial hypertension due to Multifactorial causes

29 December 2020

15:58

Unclear Multi-factorial Mechanism • Chronic Haemolytic anaemia CELL-FREE • Myeloproliferative disorders ANEW aEurEo VO "COWRY TO VASCI.UA • Splenectomy • Sarcoidosis • Pulmonary LCH • Lymphangioleiomyomatosis • NFI • Gaucher's disease • Tumoral obstruction of PA • CRF t PLATELET STRESS 'PLATELETS PSEXPOSL*E t RAS" ÆWGLOe% AmwAur1Es

 

 

Chronic Haemolytic anaemia

Myeloproliferative disorders

Splenectomy

Sarcoidosis

Pulmonary LCH Langerhans cell histiocytosis

NF1

Gaucher's disease

Tumoral obstruction of Pulmonary Artery

CRF chronic renal failure?

 

 

 

PAH a/w CTDs • Maximum in scleroderma patients • Long duration of disease >8yrs • Limited scleroderma > diffuse scleroderma • 8-12% prevalence • Poor prognosis • Patients with limited scleroderma have the risk of developing progressive blood vessel narrowing in the lungs frequently in the absence ot lung scarring and inflammation • Low DLCO <55% predicted • FVC%/DLCO% >1.6 • Anti-centromere • Anti-nucleolar pattern on ANA Resolution CT Findings in Scleroderma and the lings (ILO) This is seen both "fruse and united The lings have no tot tip are dilated. This IS typical hypertensün (PAYO Which is rnanty •n

 

Pulmonary Arterial Hypertension with Connective Tissue Disease

Maximum in Scleroderma patients

Long duration of disease > 8 years

Limited scleroderma> diffuse scleroderma

8-12% prevalence

Poor prognosis

 

Patient with limited scleroderma have the risk of developing progressive blood vessel narrowing in the lungs frequently in the absence of lung scarring and inflammation

 

Low DLCO<55% predicted - Diffusing Capacity for Carbon Monoxide


Forced Vital Capacity FVC%/ DLCO% >1.6

Anti-centromere

Antinuclear pattern on ANA

 

High resolution CT findings in scleroderma

Scarring and inflammation of lungs (ILD)- both diffuse and limited scleroderma

 

Lungs have no scar but larger blood vessels are dilated, typical of pulmonary arterial hypertension which is seen mainly in limited scleroderma

 

 

 

Pulmonary Arterial Hypertension - Portal hypertension

29 December 2020

16:08

PAH a/w Portal Hypertension • 6% of patients with portal hypertension develop PAH • Problem for liver transplantation as PAH particularly >35mmhg increases the mortality during and after the surgery • Poor pro nosis as 3yr survival is only 40 • Females, autoimmune he atitis have increase risk while hag decrease risk • independent of the cause of the portal hypertension -• severity of the underlying liver disease does not correlate with the severity of PAH • Hyperdvnamic circulation and high CO lead to - on the pulmonary circulation. • The histological abnormalities are similar to IPAH • Portosystemic shunts m allow the shunting of ET-I, 5HT, TXA2, ILI & escape metabolism

 

 

6% of patients with Portal hypertension develop Pulmonary Arterial Hypertension

Problem for liver transplantation as PAH increases mortality during and after surgery

Poor prognosis as 3 year survival is only 40%

 

Females, autoimmune hepatitis have increased risk while HCV (Hep C virus) has decreased risk

 

Independent of the cause of the portal hypertension

Severity of underlying liver disease does not correlate with the severity of PAH

 

Hyperdynamic circulation and high CO lead to increased shear stress on Pulmonary Circulation

 

The histological abnormalities are similar to Idiopathic PAH

 

Portosystemic shunts may allow the shunting of ET-1, VIP, 5HT, TXA2, IL1 and escape metabolism

 

 

 

 

 

Pulmonary arterial hypertension associated with Congenital heart disease

29 December 2020

16:13




 

 

 

Pulmonary Veno-Occlusive Disease

29 December 2020

17:00

Most devastating form of PH

Median survival 84 fays

71% dead in 6 months

10% of PHs are PVOD

Luminal narrowing and occlusion of pulmonary veins

Difficult to distinguish from PH

-profound hypoxia at rest

-CT chest: septal thickening and ground glass

Vasodilators NOT used due to pulmonary oedema risk

LUNG TRANSPLANTATION management

 

Rare disease

Characterized pathologically by evidence of repeated pulmonary venous thrombosis

The characteristic histologic feature of pulmonary veno-occlusive disease is obstruction of pulmonary venules and veins by intima fibrosis; intravascular fibrous septa are nearly always present

Etiology of disease is unknown

 

Drugs given in IPAH is contraindicated here

Pulmonary oedema after giving PAH therapy is 1st clue

Pulmonary Veno-occlusive IDs PVOD PVOD Pulmonary Very) •Occlusive Disease Most devastating form Of PH Median survival after 84 days • 71% dead in 6 months Probably of PH is in fact PVOD Histology: luminal narrowing and occlusion of pulmonary veins Difficult to distinguish from PH • profound hypoxia at rest • CT Chest: septal thickening and ground glass Vasodilators not used due to risk of pulmonary oedema LUNG TRANSPLANTATION Pulmonary Veno-OccIusive Disease • Rare disease • Characterized pathologically by evidence Of repeated pulmonary venous thrombosis. • The characteristic histologic feature of pulmonary veno-occlusive disease is obstruction Of pulmonary venules and veins by intimal fibrosis; intravascular fibrous septa are nearly always present. • The etiology Of this disease is unknown. Rapid development of pulmonary oedema after giving PAH specific therapy is sometimes the 1ST clue for diagnosis and can be life threatening. Hence the drugs given in IPAH are here.

 

 

 

Pulmonary Hypertension symptoms

29 December 2020

17:12

Shortness of breath

Chest pain

Dizziness

Syncope

Fatigue

Oedema

Dry cough

Raynaud’s phenomenon (associated with CTDs) (connective tissue diseases)

 

 

Skin- Telangiectasias, Raynaud’s phenomena, Sclerodactyly (when associated with CTD)

Increased jugular venous pressure (JVP)

Hepatojugular reflux

Peripheral oedema +/- ascites

Heart sounds:

Accentuated split S2

Third heart sound present

Tricuspid regurgitation- heard best at left lower sternal border

 

 

 

 

University WHO Functional Classification of PAH Class Clinical M*ing Definition No limitation of physical activities Patients comfortable at rest, but ordinary physical activities will cause dyspnoea, fatigue, chest pain or near svncope Marked limitation of physical activity Less than ordinary activity' causes dyspnoea, fatigue, chest pain or near syncope Manifest signs of right-sided heart failure Dyspnoea+/ fatigue presentat rest Discomfort increase with exertion Complexity in AA

 

 

 

Pulmonary Arterial Hypertension Screening, Investigation, Diagnosis and Assessment

29 December 2020

17:43

Screening and diagnosis in PAH Awareness + Screening High risk populations Key to early diagnosis Schematic ECHOCARDIOGRAPHY RV enlargement Decreased LV cavity size Abnormal septal configuration consistent with RV overload Marked dependence on atrial systole for ventricular filling Normal PAH Right Heart Catheterisation Mandatory to confirm and characterise disease

 

 

ECG screening- electrocardiogram not recommended

RV strain may show

Prognostic information

Right heart disease

May show right axis deviation

Insufficiently sensitive as a screening tool

 

Echocardiography screening- RV enlargement, decreased LV capacity size, abnormal septal configuration consistent with RV overload, marked dependence on atrial systole for ventricular filling

 

Right heart catheterization is MANDATORY to confirm and characterize disease

PAH is defined by

 

·         mPAP >25mmHg at rest

 

·         mPAP >30mmHg with exercise

 

·         PCWP <15mmHg (Pulmonary Capillary Wedge Pressure= indirectly measure left atrial pressure)

 

·         PVR >3 units (Pulmonary vascular resistance)

o    Cardiac output is required to calculate PVR

 

 

Screening with CX-ray

Large central pulmonary arteries

Peripheral pruning

Enlarged right heart

Asymptomatic patients may have normal chest xray

May reveal underlying cause of PH

 

Ventilation perfusion lung scan- check perfusion defects

 

CTEPH- pulmonary angiography

Chronic thromboembolic pulmonary hypertension

Assess thrombus accessibility

Confirm diagnosis

Angiographic patterns- Web narrowing, post stenotic dilatation, proximal occlusion, pouch defects

 

cMRI-

Access RV morphology and function

RV systolic and diastolic dysfunction- poor prognostic indicator

cMRl Assess RV morphology and function RV systolic & diastolic dysfunction--- poor prognostic indicator • - RV SV 25ml/m2 - RV-EDV 84ml/m2 - LV-EDV</= 40ml/m2 ,predictors of mortality and Rx failurel - RV:LV mass index> 0.6 -PH - Delayed contrast enhancement—function of PH severity3

 

Ventilation Perfusion Lung Scan Perf Perf PAH Vent CTEPH Vent

 

CTEPH: Pulmonary Angiography Confirms diagnosis of CTEPH in • patients with PH Assess thrombus accessibility • • Distinct angiographic patterns "Web" narrowing — Poststenotic dilatation — Proximal occlusion — "Pouch" defects

 

NICE PAH Diagnostic Algorithm Symptoms, signs, history suggestive of PAH Echocardiography compatible with PH? Consider most common causes of PH i.e., left heart disease, lung disease istory, signs, risk factors, ECG, -ray, PFT incl. D consider BGA HR-CT o s gns of severe functio Treat nderl n disea Diagnosis or heart disease or lun disease confirmed? HIR VIQ scintigraphV Unmatched rfusion defects? PH unlikely nsider other causes or recheck igns o severe H functio Refer to PH ex center DLco = diffusing capacity for carbon monoxide. Hoeper MM, et al. J Am suppo:D42-50.

 

NICE PAH Diagnostic Algorithm VIQ scintigraphy Unmatched perfusion defects? CTEPH likely CT angiography, RHC plus PA (PEA expert center) RHC 225 mmHg, PAWP S15 mmHg, PVR WU Toxins HIV PAH likely Consider other causes Specific diagnostic tests CHO Group 1 PAH 5 Family history; consider Idiopathic or Heritable genetic studies (expert centers only) Hpgpe! MM, et al. J Am Coll Cardiol. 2013;62(25 SuppD:D42-50.

 

 

 

 

Management of Pulmonary Hypertension

29 December 2020

17:54

Machine generated alternative text: naive patient era Treatment of PAH enera measure confirmed by expert center PPO Ive era vasoreactivity test D-PAH onl Low/int Risk Therapy Monothera Inadequate response High Risk including IV PC Inadequate response Lung Transplant Double/triple sequential therapy Galie N, ESC/ERS 2015 Guidelines

 

 

Acute Vasoreactivity test- idiopathic, Hereditary, Drug induced

Vasoactive- CCB therapy, Calcium channel blocker

 

Non vasoactive

Low risk- oral monotherapy/ combo therapy

 

High risk- combo therapy including IV PC

 

Inadequate response= double/triple sequential therapy

Lung transplant

 

 

Therapy for PAH

Low level graded aerobic exercise- not heavy exertion, may provoke syncope

Oxygen supplementation

Sodium restricted diet

Routine immunization- influenza and pneumococcal pneumonia

 

Nitric oxide-

Inhaled form

Acts as direct smooth muscle relaxant via activation of guanylate cyclase system

Short therapeutic half-life

Ameliorates hypoxemia and lowers PVR by direct pulmonary vasodilatation

 

Specific measure for Idiopathic PAH-

Long term anticoagulation with warfarin 1.5.2.5 inr

Pulmonary vasodilators- calcium channel blockers, prostacyclin, nitric oxide pathway (PD5 inhib, ER antagonists)

 

Prostacyclin analogues

Iloprost, epoprostenol

 

Endothelin receptor antagonists  (sentans)

Bosentan, ambrisentan

 

Phosphodiesterase inhibitor (afils)

Sildenafil, tadalafil, vardenafil

Therapeutic Options for PAH FDA approved PAH therapies Prostanoids Epoprostenol (flolan/veletri) Treprostinil (IV/SQ/lnhaled) Inhaled Iloprost (Ventavis) Oral treprostinil (Orenitram) Selexipag (Uptravi) ERA's Bosentan (Trecleer) Ambrisentan (Letairs) Macitentan (Opsumit) PDE-5 Inhibitors Sildenafil (Revatio) Tadalafil (Adcirca) Soluable Guanylate Cyclase Stimulator Riociguat (Adempas) (Only medication currently approved for the use in CTEPH)

 

Machine generated alternative text: Rx of Pulmonary Hypertension Stage A High risk with no symptoms Stage B PAH with + VOC Stage C PAH with - VOC Low Risk Stage C PAH with - VOC High Risk Stage D Refractory symptoms requiring special intervention Hospice Transplantation Inotropes, atrial septostomy Consider multidisciplinary team Combination therapy IV meds (Flolan or Trepostonil) Aldactone and digoxin Dietary sodium restriction, diuretics Bosentan +1• Sildenafil +/• Ventavis Calcium Channel Blockers Risk factor reduction, patient and family education Sleep apnea. Obesity. Uncontrolled hypertension and/or depress LVEF. drug abuse

 

Non-vasoreactive patients-

Depends on WHO functional class

Class I

PAH specific agent e.g. PDE5I

Class II or III

Dual therapy e.g. endothelin receptor antagonist plus a PDE5I

Class IV

Combination therapy to include a parenteral prostainoid e.g. iv                 epoprostenol (alternatives: iv, sub-cut or inhaled treprostinil,                 inhaled iloprost)                        

 

 

 

Lung transplant indications-

New York Heart Association (NYHA) functional class       III

or IV

Mean right atrial pressure >10mmHg

Mean pulmonary  arterial pressure >50 mmHg

Failure to improve functionally despite  medical therapy

Rapidly progressive disease

 

Transplants >surgical interventions — considered only in extreme cases >treatment for severe secondary PH if treatment of the underlying disorder fails >surgically replace damage organs with healthy donated organs Aung and/or heart transplantation >most common : single-lung transplant, fewer complications than double-lung or heart-lung transplant Aung transplant - improvement in structure and functioning of right ventricle >major risks : rejection of transplanted organ, serious infection >take immunosuppressant drugs for life — help reduce chance of rejection >survival rate is about 60% per year and 37% per 5 years

 

 

 

Cardiomyopathy Causes

29 December 2020

18:08

Morphologically and functionally abnormal myocardium

·         In absence of any other diseases sufficient to explain the observed phenotype

Divided into Primary and Secondary Cardiomyopathy

 

Primary-

·         Pathology predominantly involves the heart

·         Examples:

·         Dilated cardiomyopathy

·         Hypertrophic cardiomyopathy

·         Restrictive cardiomyopathy

·         Arrhythmogenic right ventricular cardiomyopathy

·         Obliterative cardiomyopathy

 

Secondary-

Secondary Causes of Cardiomyopathy University Autol mmune/ Inflammatory Dermatomyositis Rheumatoid arthritis Scl erod erma Systemic lupus erythematosus Polyarteritis nodosa Clinical M*ing Infections Chagas disease • HIV Hepatitis C • Rickettsia • Viral (adenovirus, Coxsackie, Epstein- Barr, parvovirus) Endo crine • Acromegaly • Diabetes mellitus Hyperthyroidism Hypothyroidism Hyperparathyroidism Complexity in AA

 

Newcastle Secondary Causes of Cardiomyopathy University Toxms • Alcohol • Anabolic steroids Chlomquine • Heavy metals (arsenic, cobalt, lead) Haemochromatosis • Stimulants (cocaine) Clinical M*ing Infiltrative disorders Amyloidosis • Gaucher disease • Hunter Syndrome Nutri ti d eficiencies • Kvnshiorkor • Niacin deficiency Neuromuscular and stora& disea± Glycogen storage disorders • Neurofibromatosis • Muscular dystrophy (Becker's, Duchenne, myotonic) Complexity in AA

 

 

 

Dilated Cardiomyopathy

29 December 2020

18:19

systolic dysfunction + ventricular dilation

 

 

Autosomal Dominant inheritance

1:2500 prevalence

 

Presentation:

Heart failure

Cardiac arrythmia

Thromboembolism

Sudden death- family history obtained

Conduction defects

 

 

Investigations:

Bedside ECG

-nonspecific ST segment and T wave changes

-Sinus tachycardia

-Arrhythmias

·         Atrial Fibrillation, Ventricular tachycardia

 

Imaging

CXR- generalized cardiac enlargement

 

Echocardiogram

-LV +/- RV dilation

Decreased ventricular wall motility

Tricuspid and mitral valve insufficiency (Doppler)

Poor global function

 

 

Cardiac MRI

Coronary angiography- to exclude coronary artery disease

 

Endomyocardial Biopsy indications-

Acute dilated cardiomyopathy + refractory heart failure symptoms

Dilated cardiomyopathy in presence of systemic diseases- SLE Polymyositis, sarcoidosis

Rapidly progressive ventricular dysfunction

-in unexplained, recent onset cardiomyopathy

New onset cardiomyopathy + recurrent VT/high grade heart block

Heart failure in setting of fever, rash, and peripheral eosinophilia

 

 

 

 

 

 

Management

Manage symptoms of cardiac failure

Implantable Cardioverter Defibrillator (ICD)

Cardiac transplant

 

 

 

 

Hypertrophic Cardiomyopathy

29 December 2020

19:00



Prolonged ventricular relaxation Leads to diastolic dysfunction Increased myocardial wall stress Increased bodily oxygen demand Decreased cardiac output Mitral Regurgitation Result from systolic anterior motion of mitral valve Severity directly proportional to outflow obstruction Patients complain of dyspnoea and orthopnoea Diastolic Dysfunction Impaired ventricular relaxation High systolic contraction load Contraction/ relaxation of ventricles not uniform Exertional dyspnoea symptoms Abnormal diastolic filling Increased pulmonary venous pressure Myocardial Ischemia Often occurs without atherosclerotic coronary artery disease Postulated mechanism: Abnormally small +/- partially obliterated intramural coronary arteries Due to hypertrophy Inadequate number of capillaries for the degree of mass Symptoms* some asymptomatic Chest pain Dyspnoea Syncope with exertion Pulmonary oedema Cardiac arrhythmias e.g. atrial fibrillation Sudden death Signs- Palpation of pulses Double apical pulsation Forceful atrial contraction Jerky carotid pulse Short upstroke, prolonged systolic ejection Jugular venous pulse Prominent a wave: decreased ventricular compliance Signs- Auscultation Fourth heart sound (S4) Cardiac hypertrophy Ejection systolic murmur Along left lower sternal border Intensity increase with decreased preload (Valsalva manoeuvre), vice versa (during squatting) Mitral regurgitation





Myocardial Infiltration Fabry" s Disease Lysosoma Storage Diseases Hemochromatosis -Dyspnea -Angina -Syncope -Palpitations -Holosystolic murmur at apex T Valsalva, standing -Pulsus bisferiens HYPERTROPHIC CARDIOMYOPATHY 1. Wall thickness 215 mm (TTE/CT/MRI) 2. Absence of Secondary Cause of LVH (Supportive: genetic testing, LGE on MRI) LV Obstruction stress CM Val-ular Aortic Stenosisl Subvaivular Echo Findin LVOT Assessment LVOT Gradients Gradient nunHg at Rest Gradient 50 mmHg at Rest Valsalva > 50 mmHg Amyl nitrate mmHg Stress testing mmHg Obstruction Prevent Symptoms Medical Therapy: 8B, CCB Disopyramide AVOID: Diuretics, Vasodilators, Dgoxin Drug Refractory: Surgical Myectomy Alcohol Septal Ablation Heart Transplant cath mmHg Prevent Stroke Atrial tachyarrhythmias Anticoagulation (regardless of CHADSVASC) -Asymmetric septal thickness -MR: posterior jet -Diastolic dysfunction -Pulmonary Hypertension I HCM: aneu -LVH -Repolarization abnormalities (TWI, horizontal/downsloping ST) -Apical HCM: >10mm AL TWI -Low intensity aerobic exercise (avoid isometric) alcohol, stimulants, temp extremes, de prevent SCD in Family Screening All 12 relatives Genetic testing Serial echocardiography 4 P's of Prevention Family Hx SCD ('la). Prevent SCD Septum > 3cm (lla) hx unexplained syncope (lla) NSVT/abnormal BP response LGE on CMR, wall thickness approaching 3 cm, remote FHSCD, HCM mutation, syncope yrs) (lla) NSVT, abnormal BP response exercise (11b) Risk Scores, CMR

 

• bcerfional syncope • Dyspnea on exertion • Young patient • Autosomal dominant • mid-sysfogc crescendo- decrescendo murmur • Befa-blockers & calcium channel blockers decrease obstruction • Avoid positive inotropes & nitrates septal Q waves (worsens obstruction) t Murmur Valsalva Standing up Murmur Squatting Trendelenberg

 

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