Case 8 notes
Epidermis
Integument= skin (cutaneous membrane) and its accessory structures
Function- water barrier, thermo-regulator, protection, innate immune system, sensory functions, endocrine role
Skin- physical barrier to air movement, epithelial organisation of tight junctions and desomosomes, fatty avid and anti-bacterial peptides, commensal bacteria microbiology
Epidermis- stratified squamous epithelium (keratinised)
Dermis variety of connective tissues
-Papillary layer- dermal papillae
-Reticular layer
Hypo dermis/ subcutaneous layer
Accessory structures- nails, exocrine glands, hair
2 types of epidermis
Thin skin, 4 layers
Thick skin, 5 layers (contain stratum lucidum)
All layers made of keratinocytes, produces keratin- fibrous protein
Avascular- oxygen and nutrients diffuse from dermis
Specialised cell types in epidermis
Melanocytes- produce pigment
Langerhans cells (dendritic cells), phagocyte to lymph nodes when activated
Merkel cells- touch, pressure
Stratum corneum
Stratum lucidum (only thick)
Stratum granulosum
Stratum Spinosum
Stratum basale
Basal Lamina
Then dermis + dermal papillae
Cells move from stratum basale to surface
Differentiation and programmed cell death as cells move upwards
Papillary layer- loose connective tissue, collagen, contains blood vessels, nerves supply, lymphatic capillaries, meissner corpuscles, fibroblasts, adipocytes, phagocytes
Reticular layer- much thicker collagen and elastin, rich sensory and sympathetic nerve supply
Hypodermis, connect skin to underlying fascia, fibrous tissue of bones and muscles
Not part of the skin
Well vascularized, loose, areolar connective tissue and adipose tissue. Insulation and cushioning
2
Glaborous / thick skin
Protection against abrasion and fine sensation, for grip
Hairy/ non glaborous, protection and sensation
Sensation
Meissners corpuscles- delicate touch, dermis
Pacinian corpuscles- vibration pressure, dermis
Merkel cells- light touch, stratum basale
Ruffini corpuscles- skin stretch
Hairy skins possess lower density of these receptors
In epidermis
Hair shaft
Pore
In dermis
Sebaceous gland
Hair root
Eccrine sweat gland
Apocrine sweat gland
Eccrine (merocrine)
Empties to skin
All over body, palms soles have high abundance +forehead
Clear secretion that is 99% water, NaCL and trace of others
Involved in thermo-regulation of body
Contains myoepithelial cells, dark cells and clear cells
Simple coiled structure
Secretory cells cuboidal light staining
Lower reticular layer+ hypodermis
Ducts 2 cell thick and stain darker
Apocrine
Empty on hair follicle
High density in armpits and pubes
Viscous secretion, cloudy and smells
Begins during puberty
Apocrine coiled structure
Larger than eccrine
Large lumen
Secretory products stored at apex of cell in secretory regions
Hypodermis
Eccrine
Ach stimulate secretion, sympathetic post ganglionic fibre innervation
Coil cells in secretory component
Isotonic to plasma, NCL/ Lactate/ Water
Nacl is reabsorbed, water low permeability in Absorptive component
Final secretion hypotonic to plasma
In CF, salty sweat as Cl not reabsorbed
Pilo sebacous unit
Sebaceous glands- oil to hair
Apocrine sweat glands
Arrector Pili muscles
Sebaceous glands
Holocrine gland
Cell moves from periphery of secretory lobule producing sebum
Apoptosis and release contents into canal lumen
Sebum- lipid and oil rich, waterproofs and lubricates skin
Arrector Pili muscle
Smooth muscle innervated by sympathetic nervous system
Raises hair, flight response and cold
Hair follicle- hair bulb, cells that produce hair
Dermal papilla- loose connective tissue
Matrix cells- produce keratinocytes that differentiate into hair producing cells and the internal root sheath
Medulla, central core, large vacuolated cells in thick hair
Cortex compressed cuboidal cells
Cuticle flattened squamous cells
Internal root sheath
Acne- inflammatory disease of pilo sebaceous unit
Hyperseborrhoea
Abnormal follicular keratinization
Bacterial proliferation in the pilosebaceous unit
Sepsis- life threatening organ dysfunction caused by a dysregulated host response to infection
Septic shock subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities are associated with greater risk of mortality than with sepsis alone
SIRS- Systemic Inflammatory Response Syndrome
Infection- inflammatory response to microorganisms or invasion of normally sterile tissues
Bacteraemia- presence of bacteria in blood
People are risk- <1 year="">75 year, pregnant, immunocompromised, people with device, line in situ or recent surgery.
SOFA- Sequential (sepsis related) Organ Failure Assessment, more than 2 points mortality geater than 10 %
qSOFA (quick SOFA) bedside prompt, low BP <100mmhg high="" rate="" respiratory="">22 bpm, Glasgow coma scale <15 o:p="">
Sepsis = infection + SIRS
Septic shock = Sepsis + persistent hypotension/ perfusion, lactate >4
SIRS criteria- 2 of the following
Temperature >38.3 <36 o:p="">
Temperature >37.5 recent chemotherapy
Respiratory rate >20bpm
Heart >90 bpm
Acute confusion/ reduced conscious level
Glucose >7.7 unless DM
WBC <4 or="">12x10^9/ L
SIRS causes
Infection
Trauma + burns
Pancreatitis
Ischemia
Hemorrhage
Adrenal Insufficiency
Cardiac tamponade
Anaphylaxis
Drugs
Surgery
Aortic Aneurysm
Management
3in 3 out
Oxygen
Fluid
Antibiotics
Urine
Lactate
Culture
Sepsis
Bacteria cause an immune response. The cytokines and other factors directly cause endothelial damage, vasodilation leads to leaky vessels and hypoxia, both of these lead to tissue damage and organ dysfunction.
Diseases of the skin
Rash
Viral-
Maculopapular rash- both macules and papules
Macules flat discolored area of skin
Papule small raised bump
Vesicular rash- presence of one or more vesicles/ blisters
Maculopapular rash examples, measles, rubella, parvovirus B19, HHV6 and 7, Enteroviruses
Vesicular rash include- HSV herpes simplex virus, VZV varicella Zoster Virus, Enteroviruses, Pox viruses i.e. smallpox
Rash usually immune response rather than viral replication
Vasuculitis
Inflammation of the blood vessels i.e. Kawazaki disease, microscopic polyangiitis
Cause variety of rashes like palpable purpura
Diabetes- high frequency of skin infections like styes, boils, folliculitis, carbuncules, nail infections
Diabetic dermopathy- light brown scaly patches that are oval on the front of both legs, harmless
Acanthosis nigricans, tan or brown raised areas appear on the sides of the neck, armpits or groin, sign of underlying malignancy
Diabetic blisters, rare eruption of blisters in diabetics, painless no inflammation, self healing- treat, bring blood sugar levels under control
Eruptive xanthomatoisis, firm yellow, pea like enlargements, red halo and may itch, uncontrolled type 1 diabetes, treat- diabetes control
SLE systemic lupus erythematosus, heterogenous, inflammatory multi-system autoimmune disease
Antinuclear antibodies damage skin + connective tissue, unknown cause
Impetigo, superficial skin infection- S.aureus + some by S. pyogenes, crusty lesion, dried serum, blood, bacteria and cellular debris, treat- fusidic acid, flucloxacillin
Follicultis/ furuncle/ carbuncle, superficial infection of hair follicles causing papules and pustules.
Furuncles(boils) deeper infections of hair follicle, inflammatory nodules with pustular drinage
Carbuncles are coalesced furuncles (come together to form one mass), S. aureus, treat- fluoxacillin or vancomycin if MRSA, surgical drainage
Cellulitis/ Erysipelas, spreading infection of the skin
Cellulitis, deep subcutaneous tissue, Erysipelas, superficial form of cellulitis dermis and upper subcutaneous tissue (uniform appearance defined edges)
Caused by Streptococcus pyogenes (erysipelas) and staphlococcus aureus (cellulitis)
Common in lower limb, risk factors- immunosuppression, wounds, leg ulcers, minor skin injury
Can have fever, malaise or rigors particularly erysipelas
Treat- fluoxacillin (staph) or benzylpenicillin (strep)
Necrotising faciitis, rapidly spreading infection of deep fascia
Group A haemolytic streptococcus
Risk- abd surgery, diabetes, malignancy
Symptoms- severe pain, erythematous, blistering and necrotic skin, fever, tachycardia, crepitus, xray soft tissue gas
Treat- extensive surgical debridement
IV antibiotics
76% mortality
Staphs + streps
Staph- grapes, streps chains
S. aureus can cause toxic mediated disease including scalded skin syndrome, food poisoning, toxix shock.
Suppurative (production of pus) infections:
Impetigo, folliculitis, epyema, endocarditis, septic arthritis, osteomyelitis, pneumonia, carbuncle, furuncles
Also UTIs Cellulitis, wound infections, catheter infections, prosthetic devices infections+ SEPSIS\
Present in 90% of hospital workers
Pathogenicity of S. aureus
Capsule- prevents phagocytosis
Protein A
Binds to IgG exerting anti-opsonisation effect
Fibronectin binding protein- aids binding to host cell
Cytolytic exotoxins- haemolysins that destroy red blood cells
Panton-valentine leukocidin- lyses polymorphonuclear lymphocytes (immune cells)
Superantigens exotoxins- cause damage over time by overstimulating immune system
Entereotoxins (A, B, C, D, E, G)
Toxic shock syndrome toxin( TSST-1)
Exfoilatin toxin
MRSA (Methicillin Resistant S. aureus)
Fluoxacillin will not work
Glycopeptides e.g. vancomycin
Tetracycline, 3rd generation penicillin
Streptococci- haemolytic properties and serological properties
Growth on blood agar allow determination of haemolytic type
a-haemolytic streptococci causes haemoglobin to change colour (looks green)
B-haemolytic streptococci lyse red blood cells (clear, complete haemolysis)
y- haemolytic cause no change
Classification- serological grouping
B-haemolytic streptococci based on cell wall polysaccharide
Clinically most important is B-haemolytic + are group A and B (pyogenes and agalactiae)
Group A
Streptococcus pyogenes, normal flora, opportunistic pathogen in compromised individuals
Cause, pharyngitis- rheumatic fever, impetigo, scarlet fever, erysipelas, cellulitis, necrotising faciitis, puerperal sepsis, invasive group A streptococcal disease, streptococcal toxic shock syndrome, sepsis
Skin/ nasopharynx reservoir, spread by droplet/ direct contact then colonisation,
Binds to pharyngeal mucosa through
Protein Fm
Lipotechoic acid
M antigen
Pathogencity
Avoid opsonisation, phagocytosis, adhere to cells, toxin production and enzymes
Secretion of toxins
Streptolysin O and S, lysis of eukaryotic cells
Hyaluronidase, breaks down connective tissues
Pyogenic toxins, superantigens responsible for many of the clinical manifestations
Streptodornases, breakdown DNA in lysed tissues
Streptokinase, lysis of clots, facilitates spread of organisms
C5A peptidase, inactive complement
Pharyngitis, Streptococcal pharyngitis cause sore throat and severe pain when swallowing.
Correct diagnosis important for strep throat so rheumatic fever and rheumatic heart disease are to be avoided
FEVERPAIN index
Rapid antigen test
FEVERPAIN
>38 temp
Purulence
Attend rapidly 3 days or less
Severely inflamed tonsils
No cough or coryza
Treat- penicillin, amoxicillin, no vaccine
Post strep pharyngitis, complications: acute rheumatic fever, autoimmune reaction, symptoms, 1-5 weeks after- fever, rash, arthritis, CNS manifestations
1/3 acute RF develops Rheumatic heart disease- permanent damage to cardiac valve tissues, chest pain, heart failure, shortness of breathe, tiredness
S. pneumoniae, Gram + diplococci,
Present in nasopharynx of healthy people
a- Haemolyic
Pneumococcal disease
Exogenous infection, by droplet
Bacterial pneumonia- CAP- community acquired pneumonia
Otitis media
Pneumococcal- bacteremia, sepsis, meningitis
Pathogenicity factors,
Capsule, pili, choline binding protein, autolysins, pneumolyisn
Pneumoccal meningitis- treat penicillin
B lactam resistant strain now emerging
Cephalosporins, vancomysin
S.pneumoniae vaccine
Clinical reasoning
Melanoma, major features- change in size, irregular shape, irregular colour (2 pts)
Minor features- large diameter 7mm or more, inflammation, oozing, change in sensation. (1 pt)
7 pt checklist, score of 3 or more, 2 weeks appointment, suspected cancer pathway referal
UV directly damages DNA- Thymidine Dimer
UV indirectly Damages DNA, free radicals mediate, oxidative DNA damage.
Benign moles, congenital or acquired
More common in sun exposed areas, massive concentration of melanocytes
ABCDE – skin cancer presentation
Asymmetry, Boarder, Colour, Diameter, Evolving
Risk factors, fair skin, many/ atypical moles, family history
50% from existing moles, rest from normal skin
I.e. Superficial spreading melanoma (most common), lentigo maligna melanoma, nail melanoma, amelanotic melanoma (growth vertically)
Typical melanoma Mimics, dysplastic melanocytic nevus, solar lentigo, seborrheic keratosis, dermatofibroma
Non-invasive melanoma, surgical excision, 98% curative prognosis.
Invasive melanoma, pharmacological intervention, 18% 5 year survival
B-RAF turned on and off by GF, mutated B-RAF always on- hyper proliferation
Actinic keratosis, Squamous cell carcinoma and basal cell carcinoma are not melanoma
PREVENTION better than cure
Broad spectrum SPF 30 or more water resistant sunscreen
Eczema, acute skin rash
Typically, on flexor surfaces and exposed skin
Hypersensitivity disorder, excess or inappropriate immune response
Eczema pathophysiology
Allergen triggers antigen presenting cells
Helper T cell – B cells – antibodies
Mast Cells + basophils – degranulation ( histamines and leukotrienes)
Dilate and become leaky brining in more immune cells
Inflammation makes skin leaky
More of the allergen
More water escape
DRY And ITCHY
Damaged skin
Cycle
Psoriasis
Psoriatic plaque formation
Promotes kerotinocyte cell growth, antigen presenting cell, cytokines, helper T cells
Dilate and become leaky, brining in more immune cells, H20 goes to skin
Recurrent infection
Actinic Keratosis, precursor lesion to squamous cell carcinoma
Chronic sun exposure risk factor,
Imiquimod- treatment 99% curative prognosis
0.5% per year progress to squamous cell carcinoma if untreateed
Squamous cell Carcinoma
2nd most common type of skin cancer
Risk- long term sun exposure and immunocomprimised
Non invasion SSC 98% curative prognosis in surgical excision
Untreated -0.5% per year progress to invade and spread
Invasion SSC- Chemotherapy- poor 15% 5 year survival prognosis
Basal Cell Carcinoma
Most common type of Skin Cancer
Surgical Excision 99% curative prognosis
Nodular BCC and Superficial BCC
Invasion is extremely rare
Infiltrative BCC
Sonic Hedgehog inhibitor
Antibiotic Susceptibility Testing
Sample Taken
Appropriate cultures
Organism ID
Susceptibility Testing
Broth dilution test- minimum inhibitory concentration
Antimicrobial gradient method- strip growth scale
Disk diffusion test- radius
Intrinsic resistance- natural, chromosomally encoded, old
Acquired resistance, mutation in the DNA, acquisition of new DNA carrying resistance
Mechanism
Intrinsic mechanisms- reduced bacterial permeability of bacteria to antibiotics, antibiotic efflux
Acquired mechanisms
Change in antibiotic targets by mutation, modification of targets, direct modification of the antibiotic