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Define cerebral infarction.  What % of strokes does this comprise?

An area of tissue death due to lack of oxygen - 70-80% of strokes


What are the common causes of cerebral infarction?

  • Cerebral atherosclerosis is the most common
  • Also embolism from intra/extracranial plaques is another common cause


How common is stroke and TIA?

100,000 new strokes/year in the UK

0.4/1000 per year TIA - 15% of first strokes are preceded by a TIA


What are the risk factors for stroke and TIA?

Same as for atheroma

  • Smoking
  • DM
  • HTN
  • FH
  • Past TIAs
  • OCP
  • PVD
  • Alcohol
  • Hyperviscosity e.g. sickle cell, polycythaemia vera


What are the symptoms of stroke?

  • Sudden onset
  • FAST
  • Numbness
  • Loss of vision
  • Dysphagia
  • (depends on territory)


What are the symptoms of TIA?

  • Last <24 hours (often much less)
  • Amaurosis fugax
  • Carotid bruit


Which vascular territories are commonly affected in stroke?

Anterior vs posterior

Commonest is MCA


Which vascular territories are commonly affected in TIA?

Any but characteristically embolic atherogenic debris from the carotid artery travel to the ophthalmic branch of the internal carotid


What investigations should you do in stroke and TIA?

  • Stroke - CT/MRI to look for infarct vs haemorrhage
  • TIA - carotid USS
  • Investigations for vascular risk: BP, FBP, ESR, U+E, glucose, lipids, CXR, ECG, carotid doppler


How do you manage a stroke?

  • Aspirin +/- dipyridamole
  • Thrombolytics (if <3h fro the event) +/- carotid endarterectomy
  • Long term: treat hypertension, decrease lipids, anticoagulants


How do you manage a TIA?

  • Aspirin +/- dipyridamole +/- carotid endarterectomy
  • Long term: treat hypertension, decrease lipids, anticoagulants


Which kinds of cerebral haemorrhage tend to be traumatic and which tend to be non-traumatic?

  • Traumatic: extradural, subdural, traumatic parenchymal injury
  • Non traumatic: intraparenchymal, subarachnoid


What are the features of intraparenchymal haemorrhage?

  • 50% due to hypertension
  • Onset is abrupt
  • Can cause Charcot-bouchard microaneurysms (likely to rupture)
  • Common site = basal ganglia


What are the features of subarachnoid haemorrhage?

  • 85% from ruptured berry aneurysms
  • Most internal cortid bifurcation
  • F>M, usually <50 years, increased in PKD, Ehler's Danlos and aortic coarctation
  • Thunderclap headacche, vomiting, loss of consciousness
  • Associated with vascular abnormalities including AV malformations, capillary telangiectasias, venous and cavernous angiomas, Ehlers Danlos


What are the features of extradural haemorrhage?

  • Skull fracture, ruptured middle meningeal artery
  • Rapid arterial bleed, lucid interval, then LOC


What are the features of subdural haemorrhage?

  • Previous history of minor trauma -> damaged bridging veins with slow venous bleed
  • Often elderly, alcoholic
  • Associated wtih brain atrophy and fluctuating consciousness


What are the different kinds of traumatic parenchymal injury?

  • Concussion: transient LOC and paralysis, recovery in hours or days
  • Diffuse axonal injury: vegetative state, post traumatic dementia
  • Contusions: when brain contacts skull +/- fracture
  • Coup = where impact occurs, contracoup = opposite to region of impact
  • Traumatic intracerebral haemorrhage


What are the 6 types of increased ICP?

  • Uncal
  • Central (transtentorial)
  • Cingulate (subfalcine)
  • Transcalvarial
  • Upward
  • Tonsillar


What are the signs of bacterial meningitis and what should you do?

  • Marked systemic symptoms: unwell, rash, drowsy, coma, septic shock
  • If suspected give immediate IV antibiotics then confirm diagnosis from LP and blood culture


What are the features of viral meningitis?

Mild systemic symptoms, not unwell, rash unusual


What would you see in CSF in pyogenic meningitis?

  • Appearance
  • Predominant cell
  • Cell count
  • Glucose
  • Protein
  • Bacteria


What would you see in CSF in pyogenic meningitis?


  • Appearance - often turbid
  • Predominant cell - polymorphs e.g. neutrophils
  • Cell count - 90-1000+
  • Glucose - decreased (<40)
  • Protein - increased (often >250)
  • Bacteria - in smear and culture


What would you see in CSF in TB meningitis?

  • Appearance
  • Predominant cell
  • Cell count
  • Glucose
  • Protein
  • Bacteria

What would you see in CSF in TB meningitis?

  • Appearance - often fibrin web
  • Predominant cell - mononuclear - lymphocytes
  • Cell count - 10-1000
  • Glucose - decreased (<40)
  • Protein - increased (50-500)
  • Bacteria - often none in smear


What would you see in CSF in viral meningitis?

  • Appearance
  • Predominant cell
  • Cell count
  • Glucose
  • Protein
  • Bacteria

What would you see in CSF in viral meningitis?

  • Appearance - usually clear
  • Predominant cell - mononuclear - lymphocytes
  • Cell count - 50-1000
  • Glucose - normal (>40)
  • Protein - normal or increased (<100)
  • Bacteria - none seen or cultured


What are the following normal CSF ranges?

  • Glucose
  • Protein

What are the following normal CSF ranges?

  • Glucose - 40-90 mg/dl
  • Protein - 15-45 g/L


What are the causative organisms in neonatal meningitis?

Bacterial: GBS, E coli, listeria

Viral: echovirus, Coxsackie, mumps, HIV


What are the causative organisms in meningitis in children aged 1 month-6 years?

Strep pnumoniae (Haemophilus influenzae)


What are the causative organisms in meningitis in young adults and adolescents?

Neisseria meningitidis, sterp penumoniae


What are the causative organisms in meningitis in the elderly?

Strep pneumoniae, gram negative bacilli (e.g. E coli)


What locations might be involved in viral encephalitis?

Can be localised (e.g. temporal/frontal lobes) or general.  If it involves the meninges it's meningoenephalitis


What are some causes of viral encephalitis?

Herpes simplex 1, rabies


What are the symptoms of viral encephalitis?

  • Drowsiness
  • Sezirues
  • Behavioural changes
  • Headaches
  • Fever


What kind of tumours cause metastatic lesions in the brain most commonly?

Lung, breast, malignant melanoma


How do metastatic brain lesiosn tend to appear?

Well demarcated, solitary or multiple with surrounding oedema


What is the commonest form of adult brain tumour?



What are the features of primary brain tumours?

Originate in the brain, spinal cord or meninges and rarely metastasise outside the CNS


What's the commonest kind of primary brain tumour?

Astrocytoma - range from pilocytic astrocytoma to glioblastoma multiforme


What kind of brain tumour is associated with neurofibromatosis type II?



What kind of brain tumour is a ventricular tumour with hydrocephalus??



What kind of brain tumour is indolent and occurs in childhood?

Pilocytic astrocytoma


What kind of brain tumour is soft, gelatinous, and calcified??



What is the common pathogenic mechanism in neurodegenerative disease?

Accumulation of misfolded proteins which may be intra- or extra-cellular


Define dementia

A global impairment of cognitive function and personality without impairment of consciousness.  This impairment goes beyond what might be expected of normal ageing.  Includes memory ipairment and at least one of the following cognitive disturbances - aphasia, apraxia, agnosia, or a disturbane in executive functioning


What is aphasia?

Language disorder - can be receptive or expressive


What is apraxia?

Loss of ability to carry out learned purposeful tasks


What is agnosia?

Loss of ability to recognise objects, people etc


What is the pathological protein in Alzheimer's disease?

Tau, beta-amyloid


What is the pathological protein in dementia with Lewy bodies?

Alpha synuclein, ubiquitin


What is the pathological protein in corticobasal degeneration??



What is the pathological protein in frontotemporal dementia linked to Chr17?



What is the pathological protein in pick's disease?



What is the commonest cause of dementia?



When does Alzheimer's usually begin?

<50 years


What is the pathology in Alzheimer's disease?

Generalised atrophy of the brain, widened sulci, narrowed gyri and enlarged ventricles (most marked in tepmoral and frontal lobes with loss of cholinergic neurons)


How is Alzheimer's diagnosed?

Clinically, but a PET and MRI may help showing senile plaques of beta amyloid proteina and neurofibrillary tangles of tau protein


How is Alzheimer's treated?

Syptomatically - 

  • Anticholinesterases
  • nAchR agonists
  • Glutamate antagonists


What are teh features of dementia with lewy bodies?

  • Psychological disturbancecs occur early
  • Day-to-day fluctuations in cognitive performance, visual hallucinations, spontaneous motor signs of Parkinsonism
  • Recurrent falls and syncope
  • Pathologically indistinguishable from PD


What causes Parkinson's disease?

Decreased stimulation of the motor cortex by the basal ganglia, caused by death of dopaminergic neurones in the substantia nigra


What are the features of Parkinson's disease?

  • TRAP:
    • Tremor
    • Rigidity
    • Akinesia
    • Postural instability
  • Some develop psychiatric features later in the disease e.g. Parkinson's disease dementia, hallucinations, anxiety
  • Lewy bodies present in affected neurons:
    • Alpha synuclein protein is main component
    • Mutations reported in familial PD


What is MS and what's the pathology?

Autoimmune demyelinating disease.  MS plaques seen showing sharp margins of myelin loss.  EMQ markers: myelin basic protein, proteo-lipid protein


What's myelin?

  • Produced by oligodendrocytes
  • Wraps around axons
  • Important for axon conduction


What are the features of MS and how is it classified?

20-40 years, focal symptoms usually: optic neuritis, poor coordination.



  • Primary progressive
    • 10%
    • Gets continually worse
  • Relapsing remitting
    • Better between episodes
    • Progresses over years


What is multiple system atrophy and what are the different types?

Degenerative neurological disorder, which can present in a similar way to Parkinson's but shows a poor response to Parkinson's medication.

  • Shy Drager - autonomic dysfunction
  • Striatonigral - difficulty with movement
  • Olivopontocerebellar - difficulty with balance and coordination


What is the aetiology and risk factors for osteoporosis?

Aetiology: age related (post menopause in females) or secondary to systemic disease/drugs.

Risk factors: age, female, poor diet, smoking, low BMI


What is the aetiology and risk factors for osteomalacia/rickets?

Aetiology: low dietary vitamin D, low sunlight, malabsorption of Vit D (GI acuses) and genetic causes)

Risk factors: poor diet, malabsorption, CLD, CKD, lack of sun


What is the aetiology and risk factors for hyperparathyroidism (primary)?

Aetiology: excess PTH production causes increased Ca reabsorption and increased PO4 excretion.  Causes includ eparathyroid adenoma, hyperplasia, carcinoma, MEN. 

Risk factors: secondary hyperPTH, CRF, low vitamin D, malabsorption


What is the aetiology and risk factors for Paget's disease?

Aetiology: disorder of bone turnover

Risk fators: >50 years old, M=F, Caucasian


What is the aetiology for renal osteodystrophy?

Aetiology: all skeletal changes associated with CKD:

  • Osteitis fibrosa cystica (secondary hyperPTH)
  • Osteomalacia
  • Osteosclerosis
  • Adynamic bone disease
  • Osteoporosis



What are the features and symptoms of osteoporosis?

  • Decreased bone mass
  • DEXA: T score <2.5SD below normal (1-2.5 = osteopenia)
  • Low impact #: NOF, vertebrae, Colles
  • Pain (back)


What are the features and symptoms of osteomalacia/rickets?

  • Decreased bone mineralisation
  • Adults: bone pain, tenderness, proximal muscle weakness
  • Children: bone pain, bowing tibia, rachitic rosary, frontal bossing, pidgeon chest, delayed walking


What are the features and symptoms of hyperparathyroidism (primary)?

  • Bone changes of osteitis fibrosa cystica
  • Hypercalcaemia: mans, stones, bones, groans
    • Depression/confusion
    • Renal stones
    • Bone pain
    • Fractures
    • Constipation
  • Pancreatitis
  • Polyuria 
  • Polydipsia


What are the features and symptoms of Paget's disease?

  • Both lytic and sclerotic lesions
  • Bone pain
  • Microfractures
  • Nerve compressoin
  • Skull changes - increased head size
  • Deafness
  • High output cardiac failure


What are the features and symptoms of renal osteodystophy?

Depends on the form o f bone disease


What are the X-ray features and histology in osteoporosis?

  • Usually no X ray features
  • Histology: loss of cancellous bone


What are the X-ray features and histology in osteomalcia?

  • X-ray: Looser's zones (pseudofractures), splaying of metaphysis
  • Histology: excess of unmineralised bone (osteoid)


What are the X-ray features and histology in hyperparathyroidism (primary)?

  • X-ray: Brown's tumours, salt and pepper skull, subperiosteal bone resporption in phalanges
  • Histology: osteitis fibrosa cystica (marrow fibrosis and cysts) aka Brown tumour


What are the X-ray features and histology in Paget's disease?

  • X-ray: mixed lytic and sclerotic
    • Skull: osteoporosis, circumscripta, cotton wool
    • Vertebrae: picture frame, ivory vertebra
    • PElvis: sclerosis and luceny
  • Histology: huge osteoclasts with >100 nuclei, mosaic pattern of lamellar bone (like jigsaw puzzle)


What are the biochemical features of osteoporosis?

  • Normal calcium
  • Normal phosphate
  • Normal ALP


What are the biochemical features of osteomalacia/rickets?

  • Normal or low calcium
  • Low phosphate
  • Increased ALP


What are the biochemical features of hyperparathyroidism (primary)?

  • High calcium
  • Normal or low phosphate
  • Normal or high ALP


What are the biochemical features of Paget's disease?

  • Normal calcium
  • Normal phosphate
  • Very high ALP


What are the biochemical features of renal osteodystrophy?

  • Low calcium
  • High phosphate
  • Secondary hyperPTH, metabolic acidosis


What is the epidemiology and aetiology of gout?

  • Male, middle aged
  • Increased dietary purine intake
  • ETOH
  • Diuretics
  • Inherited metabolic abnormalities


What's the epidemiology and aetiology of pseudogout?

  • >50 years
  • Idiopathic
  • HyperPTH
  • DM
  • Hyperthyroid
  • Wilsons


Which joints are affected in gout vs pseudogout?

  • Gout: great toe MTP (podagra), lower extremities e.g. knee
  • Pseudogout: knee and shoulder


What are the clinical features of gout vs pseudogout?

  • Gout:
    • Hot, swollen, red, exquisitely painful joint
    • Tophus (=depostis of waste) is the pathognomonic lesion e.g. on pinna and hands
  • Pseudogout
    • Hot, swollen joint with effusion


What is the crystal type in gout vs pseudogout?

  • Gout: urate crystals, needle shaped, negatively birefringent
  • Pseudogout: calcium pyrophosphate crystals, rhomboid shaped, positively birefringent


What is the management of gout vs pseudogout?

  • Gout:
    • Acute attack: colchicine
    • Long term: allopurinol 
    • Conservative: low ETOH an dpurine intake e.g. sardines, liver
  • Pseudogout: NSAIDs or intra articular steroids


What are the stages in fracture repair?

  1. Organisation of haematoma (pro callus)
  2. Formation of fibrocartilagenous callus
  3. Mineralisation fo fibrocartilagenous callus
  4. Remodelling of bone along weight bearing lines


What factors affect how a fractur eheals?

Fracture type, neoplasm, metabolic disorder, drugs, vitamin deficiency and infection


What are the causative organisms in osteomyelitis?

  • Adults: staph aureus
    • Vertebrae, jaw (secondary to dental abcess), toes (secondary to diabetic ulcer)
  • Children: haemophilus influenza, group B strep)
    • Long bones


How does osteomyelitis present and what are the X ray changes?

  • Pain, swelling, tenderness
  • General features of malaise, fever, chills, leukocytosis
  • X ray changes: ~10 days post onset; lytic destruction of bone



What are some rare but important causes of osteomyelitis?

TB (immunocmopromised), syphilis (congenital/acquired)


What are the features of osteoarthritis?

  • Degenerative joint disease mainly affecting vertebrae, hips and knees
  • May see Heberden's nodes (DIPJ), Bouchard's nodes (PIPJ)


What are the features of rheumatoid arthritis?

  • Usually slowly progressing
  • Symmetrical, small joints of hands and feed (sparing DIPJ), wrists, elbows, ankles, knees
  • Characteristic deformities:
    • Radial deviation of wrist and ulnar deviation of fingers
    • Swan neck and Boutonniere deformity of fingers
    • Z shaped thumb


What is sarcoidosis and what is the histology?

Multisystem disease of unkown cause, commonly affecting young adults.  Characterised by non-caseating granulomas in many tissues and Chaumann and asteroid bodies


What is the epidemiology of sarcoidosis?

More severe disease in Afro Caribbeans; F>M


What are the pulmonary features of sarcoidosis?

  • Lungs are most commonly involved and often detected at routine CXR
  • Bilateral hilar lymphadenopathy (ddx TB, lymphoma, bronchial Ca)
  • Also see pulmonary infiltrates -> fine nodular shadowing in mid zones


What are the presenting complaints in sarcoidosis?

Insidious shortness of breath, cough, chest pain, and night sweats


What are the extrapulmonary manifestations of sarcoidosis?

  • Skin: erythema nodosum,lupus pernio, skin nodules
  • LNs: lymphadenopathy, painless and rubbery
  • Joints: arthritis, bone cysts
  • Eyes: anterior uveitis -> misting of vision and painful red eye, posterior uveitis -> progressive visual loss
    • Uveoparotid fever: bilateral uveitis, parotid enlargement +/- facial nerve palsy
  • Hepatosplenomegaly
  • Leukopaenia/anaemia
  • Hypercalcaemia/hypercalciuria -> renal calculi + nephrocalcinosis
  • Myocardial involvement -> dysrhythmias, cardiomyopathy, conduction defects
  • CNS involvement
  • Keratoconjunctivitis sicca + lacrimal grand involvement


How is sarcoidosis diagnosed?

  • Increased Ca2+
  • Increased ESR
  • Increased ACE
  • Transbronchial biopsy: Kveim test - intradermal injection of sarcoid splenic tissue -> granuloma formation


What is amyloidosis?

A multisystem disorder caused by abnormal folding of proteins that are depostied as amyloid fibrils in tissues, disrupting their normal function.  Can be primary or secondary


What are the features of primary (AL) amyloidosis?

  • Most common
  • Associated with plasma cell dyscrasias and paraproteins e.g. multiple myeloma (although most don't have multiple myeloma)
  • Most have monoclonal Ig, free light chains in serum and urine (Bence Jones), and increased bone marrow plasma cells


What are the features of secondary (AA) amyloidosis and what is it associated with?

  • Amyloid formed from serum amyloid A = acute phase protein, therefore secondary to chronic infections/inflammation
    • Autoimmune disease: RA, ank spond, IBD
    • Chronic infection: TB osteomyelitis, IVDU (skin infection)
    • Non immune: renal cell carcinoma, Hodgkin's


What is the pathology in haemodialysis associated amyloidosis?

Deposition of beta2 microglobulin


What is the most common kind of familial amyloidosis?

Familial Mediterranean Fever 


What is the pathophysiology/aetiology behind Familial Mediterranean Fever?

  • +++ production of IL-1 -> attacks of fever and inflammation of serosal surfaces (pleura, peritoneum, synobium)
  • Associated gene encodes pyrin
  • AA amyloid, predominant renal deposition


What causes the clinical features of amyloidosis and what are they?

Caused by amyloid deposits in various organs:

  • Kidney: nephrotic syndrome (most common)
  • Heart: conduction defects, heart failure
  • Liver/spleen: hepatosplenomegaly
  • Tongue: macroglossia in 10%
  • Neuropathies including carpal tunnel


How do you stain for amyloidosis and how does it appear?

  • Apple green birefringence with Congo red stain under polarised light (otherwise pink/red) caused by beta pleated sheet configuration
  • Misfolded proteins unstable and self associated to form the fibrils


What are some examples of large, medium, and small vessel vasculitides?

  • Large:
    • Takayasu's arteritis
    • Temporal arteritis
  • Medium:
    • Polyarteritis nodosa
    • Kawasaki's disease
    • Buerger's disease (thromboangitis obliterans)
  • Small:
    • Wegener's granulomatosis
    • Churg Strauss
    • Microscopic polyangiitis
    • Henoch Schonlein purpura


What are the key features of Takayasu's arteritis?

  • Pulseless disease
  • Japanese women
  • Vascular symptoms: absent pulse, bruits, claudication


What are the key features of Temporal arteritis?

  • Elderly, scalp tenderness, temporal headache
  • Jaw claudication, blurred vision
  • High ESR
  • Overlap with polymyalgia rheumatica
  • Histo: granulomatous transmural inflammaiton + giant cells + skip lesions


What are the key features of polyarteritis nodosa?

  • Renal involvement is the main feature
  • Can have other organs involved but spares the lungs
  • 30% have underlying Hep B
  • Microaneurysms on angiography


What are the key features of Kawasaki's disease?

  • Children <5
  • Fever >5 days + rash - red palsma and soles with later desquamation, conjunctivitis
  • Inflammation of lips, mouth, or tongue (strawberry tongue)
  • Cervical LNs
  • Coronary arteries may be involved with aneurysm formation


What are the key features of Buerger's disease (thromboangitis obliterans)?

  • Heavy smokers, usually men <35 years
  • Inflammation of arteries of extremities - usually tibial and radial
  • Pain, ulceration of toes, feet, fingers
  • Angiogram - corkscrew appearance from segmental occlusive lesions


What are the key features of Wegener's granulomatosis?

  • Triad:
    • Upper resp tract: sinusitis, epistaxis, saddle nose
    • Lower resp tract: cavitation, pulmonary haemorrhage
    • Kidneys: crescenteric glomerulonephritis
  • cANCA (anti-PR3) positive



What are the key features of Churg strauss?

  • Asthma, allergic rhinitis
  • Eosinophilia
  • Later systemic involvement
  • pANCA (anti-MPO) positive


What are the key features of microscopic polyangiitis?

  • Pulmonary renal syndrome:
    • Pulmonary haemorrhage
    • Glomerulonephritis
  • pANCA (anti-MPO) positive


What are the key features of Henoch Schonlein purpura?

  • IgA mediated vasculitis
  • In children <10 years
  • Preceding URTI
  • Palpable purpuric rash (lower limbs extensors, buttocks)
  • Colicky abdo pain
  • Glomerulonephritis
  • Arthritis
  • Orchitis


What is SLE and what causes it?  Which HLA is it associated with?

  • Autoimmune multi system disorder
  • Type III hypersensitivity reaction
  • Increased in classical complement deficiencies
  • Can be drug induced
  • More common in Afro Caribbeans and F>M
  • HLA DR3 (or 2)


What is CREST/diffuse scleroderma and what causes it?  Which HLA is it associated with?

  • Autoimmune multi system disorders
  • Scleroderma = hard skin - main clinical feature is skin fibrosis
  • HLA DR5 + DRw8


What is polymyositis/dermatomyositis?  What is it associated with?

  • Autoimmune inflammatory disorder of the muscle +/- skin
  • Associated with underlying malignancy


Which autoantibodies are associated wtih SLE?

  • ANA (95%)
    • Anti dsDNA
    • Anti-Sm
  • Drug induced
  • Anti-histone


Which autoantibodies are associated with limited scleroderma (CREST)?

  • Anti centromere


Which autoantibodies are associated with diffuse scleroderma?

  • Anti-Scl-70
  • Fibrillarin
  • RNA pol I, II, III
  • PM-Scl


Which autoantibodies are associated with polymyositis/dermatomyositis?

  • Anti-Jo-1 (= tRNA synthetase)


What histology is seen in SLE?

  • LE bodies
  • Renal involvement
  • CNS: small vessel angiopathy
  • Spleen: onion skin lesions
  • Heart: Libman-Sack endocarditis


What histology is seen in limited scleroderma?

  • Increased collagen in skin and organs
  • Onion skin thickening of arterioles


What histology is seen in diffuse scleroderma?

  • Inflammation within or around muscle fibres


What histology is seen in polymyositis/dermatomyositis?

  • Endomysial inflammatory infiltrate
  • 'Drop out' of capillaries and myofibre damage


What are the signs and symptoms of SLE?

4 of 11 ACR criteria - SOAP BRAIN MD

  • Serositis
  • Oral ulcers
  • Arthritis
  • Photosensitivity
  • Blood siorders (AIHA, ITP, leucopenia)
  • Renal involvement
  • ANA positive
  • Immune phenomena (dsDNA, anti SM, anti phosphlipid Ab)
  • Neuro symptoms
  • Malar rash
  • Discoid rash


What are the signs and symptoms of limited scleroderma?

  • Skin cahnges on face and distal to elbows and knees
  • CREST:
    • Calcinosis
    • Raynaud's
    • Esophageal dysmotility
    • Sclerodactyly
    • Telangiectasia
  • Associated with pulmonary hypertension


What are the signs and symptoms of diffuse scleroderma?

  • Skin changes can ocur anywhere
  • Widespread organ involvement
  • Associated wtih pulmonary fibrosis


What are the signs and symptoms of polymyositis/dermatomyositis?

  • Proximal muscle weakness
  • Increased CK
  • Abnormal EMG
  • DM has cutaneous features:
    • Heliotrope rash
    • Gottron papules
  • Associated wtih pulmonary fibrosis


What are the features of pityriasis rosea?

  • Salmon pink rash
  • Herald patch first followed by oral macules in Christmas tree distribution
  • Appears after viral illness
  • Remits spontaneously


What are the features of SJS + Toxic Epidermal Necrolysis?

  • Dermatological emergency
  • Sheets of skin detachment:
    • <10% body surface in SJS
    • >30% in TEN
  • Nikolsky sign positive
  • Mucosal involvement prominent
  • Commonly caused by drugs (sulfonamide antibiotics, anticonvulsants)


What are the 3 kinds of melanocytic naevi?

Junctional, compound, intradermal


What histopathology is seen in malignant melanoma?

  • Atypical melanocytes
  • Initially grow horizontally in epidermis (radial growth phase)
  • Then grow vertically into the dermis (vertical growth phase)
  • Vertical growth produces 'buckshot appearance' (Pagetoid cells)


What is the most important prognostic factor in malignant melanoma?

Breslow thickness


What are the subtypes of malignant melanoma?

  • Lentigo maligna melanoma: occurs on sun exposed areas in elderly Caucasians; flat, slowly growing black lesions
  • Superficial spreading malignant melanoma: irregular borders with variation in colour
  • Nodular malignant melanoma: can occur on all sites more common in younger age group
  • Acral lentiginous melanoma: occurs on the palms, soles, subungual areas


What are the characteristics of seborrhoeic keratosis?

  • Rough plaques, waxy, "stuck on"
  • Appear in middle age/the elderly


What are the 3 types of premalignant epidermal cutaneous neoplasms?

  • Actinic (solar/senile) keratosis
  • Keratoacanthoma
  • Bowen's disease


What are the 3 types of malignant epidermal cutaneous neoplasms?

  • Squamous cell arcinoma
  • Basal cell carcinoma


What are the characteristics of actinic keratosis?

  • Rough, sandpaper like, scaly lesions
  • On sun exposed areas


What are the histological features of actinic keratosis?

  • SPAIN:
    • Solar elastosis
    • Parakeratosis
    • Atypia/dysplasia
    • Inflammation
    • Not full thickness


What are the characteristics of keratoacanthoma?

  • Rapidly growing dome shaped nodule which may develop a necrotic, crusted centre
  • Grows over 2-3 weeks and clears spontaneously


What are the histological features of keratoacanthoma?

Similar to SCC and hard to differentiate


What are the characteristics of Bowen's disease?

  • Intra epidermal squamous cell carcinoma in situ
  • Flat, red, scaly patches over sun exposed areas


What are the histological features of Bowen's disease?

  • Full thickness atypia/dysplasia
  • Basement membrane intact - ie not invading the dermis


What are the characteristics of squamous cell carcinoma?

  • When Bowen's has spread to involve the dermis
  • Similar clinical features to Bowen's but may ulcerate


What are the histological features of squamous cell carcinoma?

Atypia/dysplasia throughout the epidermis, nuclear crowding and spreading through the basement membrane into the dermis


What are the characteristics of basal cell carcinoma?

  • AKA rodent ulcer
  • Slow growing tumour
  • Rarely metastatic but locally destructive 
  • Pearly surface, often with telangiectasia


What are the histological features of basal cell carcinoma?

  • Mass of basal cells pushing down into the dermis
  • Palisading (nuclei align in outermost layer)


Dermatitis herpetiformis

  • Pathophysiology
  • Clinical features
  • Histology

Dermatitis herpetiformis

  • Pathophysiology - associated with coeliac, IgA antibodies bind to the basement membrane -> subepidermal bulla
  • Clinical features - itchy vesicles on extensor surfaces of elbows, buttocks
  • Histology - microabscesses with coalesce to form subepidermal bullae; neutrophil and IgA deposits at tips of dermal papillae



  • Pathophysiology
  • Clinical features
  • Histology


  • Pathophysiology - IgG antibodies bind to hemidesmosomes of basement membrane -> subepidermal bulla; pemphigoiD - bullea are Deep
  • Clinical features - large, tense bullae on erythematous base; often on forearms, groin and axillae, elderly, bullae don't rupture as easily as pemphigus
  • Histology - subepidermal bulla with eosinophils, linear deposition of IgG along basement membrane



  • Pathophysiology
  • Clinical features
  • Histology


  • Pathophysiology - IgG antibodies bind to desmosomal proteins -> intraepidermal bulla; pemphiguS - bullae are Superficial
  • Clinical features - bullae are easily ruptured, found on skin and mucosal membranes
  • Histology - intraepidermal bulla; netlike pattern of intercellular IgG deposits; acantholysis


What are the clinical features of erythema multiforme?

  • Classically: annular target lesions most commonly on hands and feet
  • Pleomorphic lesions
  • Combination of macules, papules, urticarial wheals, vesicles, bullae, petechiae


What are the causes of erythema multiforme?

  • Infections e.g. herpes simplex, mycoplasma
  • Drug reactions e.g. penicillin, salicylates, anti malarials


What is seen histologically in erythema multiforme?

Subepidermal bullae


What other disordres is erythema multiforme thought to be on a spectrum with?

Stevens Johnsons syndrome and toxic epidermal necrolysis


What are the features of lichen planus, and what is seen histologically?  What causes it?

  • Lesions:
    • Pruritic
    • Purple
    • Polygonal
    • Papules
    • Plaques
  • Mother of pearl sheen
  • Wickham's striae: fine white network on surface of lesions
  • Usually on inner surfaces of wrists but can also affect oral mucous membrane (with lacy apperance)
  • Aetiology unknown
  • Histopathology: hyperkeratosis with saw-toothing of rete ridges and basal cell degeneration


What is psoriasis and what is the commonest form of it?

Common chronic inflammatory dermatosis with well demarcated red scaly plaques.

Commonest form is chfronic plaque psoriasis:

  • Salmon pink plaques
  • Silver scale
  • Affects extensor aspects of knees, elbows and scalp


What is the Auspitz sign and the Koebner phenomenon in psoriasis?

Auspitz sign: rubbing them causes pinpoint bleeding

Koebner phenomenon: lesions form at sites of trauma


What are the histopathologyical features of psoriasis?

  • Cells in the psoriatic plaque have increased proliferation rate
  • Parakeratosis
  • Loss of granular layer
  • Clubbing of rete ridges giving 'test tubes in a rack' apperance
  • Munro's miroabscesses


What are some forms of psoriasis other than chronic plaque?

  • Flexural: seen in later life, usually groin, natal cleft and sub-mammary areas
  • Guttate: 'rain drop' plaque distribution, often in children, usually seen 2 weeks post strep throat
  • Erythrodermic/pustular psoriasis: severe widespread disease, often systemic symptoms, can be limited to hands and feet (= palmo-plantar psoriasis)


What is psoriasis associated with?

  • Nail changes: POSH
    • Pitting
    • Onycholysis
    • Subungual Hyperkeratosis
  • Arthritis (5-10%)


What is the histology seen in dermatitis/eczema?

  • Acute:
    • Spongiosis
    • Inflammatory infiltrate in dermis
    • Dilated dermal capillaries
  • Chronic:
    • Acanthosis
    • Crusting, scaling


What are the features of atopic dermatitis?

  • Infants: face, scalp
  • Older: flexural surfaces
  • If chronic: lichenification
  • Persists into adulthood in those with FHx of atopy


What are the features of contact dermatitis?

  • Type IV hypersensitivity - e.g. to nickel, rubber
  • Erythema, swelling, pruritus
  • Commonly affects:
    • Ear lobes and neck (from jewellry)
    • Wrist (leather wrist straps)
    • Feet (from shoes)


What are the features of seborrhoeic dermatitis?

  • Inflammatory reaction to a yeast: Malassezia
  • Infants: cradle cap (large yellow scales on scalp)
  • Young adults: mild erythema, fine scaling, mildly pruritic - affects face, eyebrow, eyelid, anterior chest, external ear


What are the layers and features within each layer of the skin?

  • Epidermis:
    • Stratum corneum - non-nucleated, contains keratin
    • Stratum granulosum - nuclei disintegrate
    • Stratum spinosum (prickle layer) - cells linked by desmosomes
    • Stratum basale - mitosis: cells bound to BM by hemidesmosomes
  • Dermis
  • Subcutis (fat)


What does hyperkeratosis mean?

Increase in stratum corneum/increased keratin


What does parakeratosis mean?

Nulei in the stratum corneum


What does acanthosis mean?

Increase in stratum spinosum


What does acantholysis mean?

Decreased cohesions between keratinocytes


What does spongiosus mean?

Intercellular oedema


What does lentiginous mean?

Linear pattern of melanocyte proliferation within epidermal basal cell layer (reactive or neoplastic)


Benign bone tumours - osteoid osteoma

  • Age
  • Bone
  • Special features
  • Histology
  • X ray features

Benign bone tumours - osteoid osteoma

  • Age - adolescent
  • Bone - tibia/femur
  • Special features - small benign bone forming lesion, night pain relieved by aspirin
  • Histology - normal bone
  • X ray features - radiolucent nidus with sclerotic rim


Benign bone tumours - osteoma

  • Age
  • Bone
  • Special features
  • Histology

Benign bone tumours - osteoma

  • Age - middle age
  • Bone - head and neck
  • Special features - bone outgrowths attached to normal bone
    • Gardner syndrome: GI polyps and multiple osteomas and epidermoid cysts
  • Histology - normal bone


Benign bone tumours - Enchondroma

  • Age
  • Bone 
  • Special features
  • Histology
  • X ray

Benign bone tumours - Enchondroma

  • Age - middle age
  • Bone - hands 43%
  • Special features - benign tumours of cartilage
    • Ollier's syndrome: multiple enchondromas
    • Maffuci's syndrome: multiple enchondromas and haemangiomas
  • Histology - normal cartilage
  • X ray - lytic lesion, cotton wool calcification, expansile, O ring sign


Benign bone tumours - Osteochondroma (=exostosis)

  • Age
  • Bone 
  • Special features
  • Histology
  • X ray

Benign bone tumours - Osteochondroma (=exostosis)

  • Age - adolescent
  • Bone - long bones
  • Special features - cartilage capped bony outgrowth
    • Diaphyseal aclasis/hereditary multiple exostoses: multiple exostoses and short stature and bone deformities
  • Histology - cartilage capped bony outgrowth
  • X ray - well defined bone protuberance from bone


Benign bone tumours - fibrous dysplasia

  • Age
  • Bone 
  • Special features
  • Histology
  • X ray

Benign bone tumours - fibrous dysplasia

  • Age - middle age, F>M
  • Bone - femur
  • Special features - a bit of bone is replaced by fibrous tissue
    • Albright syndrome: polyostotic dysplasia + cafe au lait spots + precocious puberty
  • Histology - Chinese letters (misshapen bony trabeculae)
  • X ray - soap bubble osteolysis, shepherd's crook deformity


What bone is a simple bone cyst most common in and what does it appear as on X-ray?

Fluid filled, unilocular cyst usually in the humerus or femur.  On X-ray: lytic, well defined


What are the features of an osteoblastoma and what does it look like on X-ray?

Similar to osteoid osteoma in features.

X-ray: speckled mineralisation


Malignant bone tumours - osteosarcoma

  • Age
  • Bone
  • Histology
  • X-ray appearance

Malignant bone tumours - osteosarcoma

  • Age - adolescence
  • Bone - knee (60%)
  • Histology - malignant mesenchymal cells, ALP positive
  • X-ray appearance - elevated periosteum (Codman's triangle), sunburst appearance


Malignant bone tumours - chondrosarcoma

  • Age
  • Bone
  • Histology
  • X-ray appearance

Malignant bone tumours - chondrosarcoma

  • Age - >40 years
  • Bone - axial skeleton, femur/tibia/pelvis
  • Histology - malignant chondrocytes
  • X-ray appearance - lytic lesion wtih fluffy calcification, axial skeleton


Malignant bone tumours - Ewing's sarcoma

  • Age
  • Bone
  • Histology
  • X-ray appearance

Malignant bone tumours - Ewing's sarcoma

  • Age - <20 years
  • Bone - long bones, pelvis
  • Histology - sheets of small round cells, CD99 positive, T11:22 translocation
  • X-ray appearance - onion skinning of the periosteum


Malignant bone tumours - giant cell (borderline malignancy)

  • Age
  • Bone
  • Histology
  • X-ray appearance

Malignant bone tumours - giant cell (borderline malignancy)

  • Age - 20-40 years, F>M
  • Bone - knee - epiphysis
  • Histology - osteoclast-type multinucleate giant cells on background of spindle/ovoid cells
  • X-ray appearance - lytic/lucent lesions right up to articular surface


What are the principal features of invasive breast carcinoma?

Malignant epithelial tumours which infiltrate within the breast and have the capacity to spread to distant sites


What are the types of invasive breast carcinoma and what are their main features?

  • Invasive ductal - carcinoma that can't be subclassified into another group, most common
  • Invasive lobular - cells aligned in single file chains/strands
  • Tubular carcinomas - well formed tubules with low grade nuclei, rarely palpable as <1cm
  • Mucinous carcinoma cells - produce abundant quantities of extracellular mucin which dissects into surrounding stroma


What is breast carcinoma in situ and what are the two main types?

Neoplastic epithelial proliferation limited by basement membrane.  Can be ductal or lobular.


What are the features of lobular carcinoma in situ?

  • Always incidental finding on biopsy as no microcalcifications
  • Also no stromal reactions
  • 20-40% bilateral
  • Cells lack adhesion protein E-cadherin
  • Risk factor for subsequent invasive breast carcinoma


What are the features of ductal carcinoma in situ?

  • Incidence increased dramatically since development of mammography
  • Appears as areas of microcalcification
  • 10% present with clinical symptoms
  • Much increased risk of progressing to invasive breast Ca
  • High, intermediate and low grade


How common is breast carcinoma?  In which groups is it more common?

Most common cancer in women.  1:8 lifetime risk (99% in women).  Age 75-80 years, younger in Afro-Caribbeans


What are the risk factors for breast carcinoma?

  • Susceptibility genes (12%)
    • BRCA1/BRCA2, which also increase risk of ovarian, prostate and pancreatic malignancy,
    • BRCA mtuations -> lifetime risk of invasive breast carcinoma of up to 85%)
  • Hormone exposure: early menarche, late menopause, late 1st live birth (pregnancy -> terminal differentiation of milk producing luminal cells, removing these from the pool of potential cancer precursors), OCP/HRT
  • Advancing age
  • Family history
  • Race (Caucasian > Afro-Caribbean > Asian > Hispanic)
  • Obesity
  • Tobacco
  • Alcohol


How does breast carcinoma present?

  • Hard, fixed lump
  • Paget's disease
  • Peau d'orange
  • Nipple retraction


How is breast carcinoma screened for?

47-73 year old women invited every 3 years for mammography (looks for abnormal areas of calcification or a mass wihtin the breast)


What are the 3 types of malignant neoplastic breast disease?

Breast carcinoma

Basal-like carcinoma

Phyllodes tumour


What are the 2 types of breast carcinoma?

Carcinoma in situ

Invasive breast carcinoma (mor common)


What are the features of basal like carcinoma?

  • Sheets of atypical cells with lymphocytic infiltrate
  • Stain positive for Ck5/6/14


What are the features of Phyllodes tumour and what is done to manage it?

  • ARises from interlobular stroma (like fibroadenomas and can arise from within existing fibroadenomas) with increased cellularity and mitoses
  • Presents >50 years as a palpable mass
  • Low grade or high grade lesions
  • Mostly relatively benign but can be aggressive so excised with wide local excision/mastectomy to limit local recurrence
  • Mets very rare


How are neoplastic breast conditions diagnosed?

Triple assessment: examination, radiological (mammography/USS/MRI), FNA, cytology


How are breast neoplasms graded and subtyped histologically?

  • Core needle biopsy
  • Assess nuclear pleomorphism, tubule formation and mitotic activity
  • Each gets a score /3, meaning the total score is /9
  • 3-5/9 - grade I, well differentiated
  • 6-7/9 - grade 2/moderately differentiated
  • 8-9/9 - grade 3/poorly differentiated


Other than histologically grading, how are malignant breast lesions assessed?

All neoplastic lesions are assessed for oestrogen receptor, progesterone receptor and HER2 receptor status:

  • ER/PR receptor positive = good prognosis (predicts response to tamoxifen)
  • HER2 receptor positive = bad prognosis


What is tamoxifen?

Mixed agonist/antagonist of oestrogen at its receptor


What are herceptin and trastuzumab and what do they do?

Monoclonal Ig to HER2 - direct toxic effect on myocardium, must monitor LVEF


What are the features of fibroadenoma of the breast - what causes it and how is it treated?

  • Most common benign tumour, from stroma, often mlutiple and bilateral
  • Occurring at ang age within the reproductive period, usually at 20-30 years
  • Epithelium responsive to hormones: increases in size during pregnancy and calcifies after menopause
  • Spherical, freely mobile, variable size, and rubbery
  • Overgrowth of collagenous mesenchyme
  • 'shelling out' is curative


What are the features of duct papilloma and how is it diagnosed?

  • Bening papillary tumour arising within the duct system of the breast
  • It can be within small terminal ductules (peripheral papilloma) or larger lactiferous ducts (central papilloma)
  • Causes bloody discharge
  • No lump
  • Not seen on mammogram
  • Ix - galactogram


What are the features of a radial scar (breast) and how is it seen?

  • Benign sclerosing lesion
  • Central scarring surrounded by proliferating glandular tissue in stellate pattern
  • Resembles carcinoma on mammogram


What are the features of fibrocystic disease/fibroadenosis of the breast?

  • Very common - breast lumpiness
  • Group of changes caused by exaggerted normal response to hormones
  • Cystic change: small cysts form by dilatation of lobules, contain fluid, often calcified
  • Fibrosis: inflamamtion and fibrosis secondary to cyst rupture
  • Adenosis: increased number of acini per lobule (normally seen in pregnancy)


What are the clinical and histological features of gynaecomastica?  What does it indicate?

  • Unilateral or bilateral enlargement of the male breast
  • Histology: epithelial hyperplasia, finger-like projections into ducts
  • Indicates hyperoestrinism: alcohol, age, liver cirrhosis, functioning testicular tumour


What are the features of acute mastitis and how is it treated?

  • Painful red breast and fever
  • Almost all occur during lactation and breast feeding as a result of staphylococcal infection via cracks in the nipple
  • Involved breast tissue is necrotic and infiltrated by neutrophils
  • Treatment: continued expression of milk and antibiotics +/- surgical drainage


What are the features of periductal mastitis?

  • Mostly in smokers an dnot associated with lactation
  • Histologically, keratinising squamous epithelium extends deep into nipple dut orifices


What are the features of mammary duct ectasia and what causes it?

  • Occurs mainly in multiparous, 40-60 year old women
  • Poorly defined palpable periareolar mass with thick, white nipple secretions
  • Caused by granulomatous inflammation and dilatation of large breast ducts
  • Mimics mammographic appearance of cancer
  • Cytology - proeinaceous material, inflammatory cells


what are the features of fat necrosis of the breast and what causes it?

  • Inflammatory reaction to damaged adipose tissue
  • Presents as painless breast mass/skin thickening/mammographic lesion
  • Causes: trauma, radiotherapy, surgery


What are the forms of cervical carcinoma?

  • Most commonly squamous cell carcinoma (70-80%)
  • ~20% are other forms: adenocarcinomas, adenosquamous carcinomas and others


What marks the change from CIN to carcinoma?

Invasion through the basement membrane


What are the clinical features of cervical carcinoma?

  • Post coital bleeding
  • Intermenstrual bleeding
  • Postmenopausal bleeding
  • Discharge
  • Pain


How is cervical carcinoma staged?

FIGO system


Describe the normal histology of the cervix

  • Outer cervix covered by squamous epithelium 
  • Endocervical canal lined by columnar glandular epithelium
  • Squamocolumnar junction (SCJ) separates them
  • Transformation zone = the area where columnar epithelium transforms into squamous cells
    • Normal physiologica lprocess
    • Susceptible to malignant change


What is CIN and what are the forms of CIN?

Dysplasia at the TZ as a result of infection by HPV 16 + 18.

  • CIN1 - dysplasia confined to lower 1/3 of epithelium
  • CIN 2 - lower 2/3
  • CIN 3 - full thickness but basement membrane intact


What is the prognosis for CIN?

  • 60-90% of CIN reverts to normal over 10-23 months
  • 30% risk of CIN3 progressing to cervical cancer over 10 years


What are the risk factors for CIN?

  • Early age at first intercourse
  • Multiple partners
  • Multiparity
  • Smoking
  • HIV
  • Immunosuppression


What is CGIN?

Less common that CIN and difficult to diagnose on cytology - treatment requires excision of entire endocervix which can compromise fertility


What are the 3 main kinds of ovarian carcinoma and how common is each?

  • Epithelial - 70%
    • Dervied from surface epithelium which covers ovary; can be benign, borderline, or malignant serous
  • Germ cell (20%)
    • Derived from germ cells, usually benign in adults and malignant in children
  • Sex cord/stroma (10%)
    • From sex cord or stroma of gonad
    • Can differentiate toward femal granulosa and theca cells or male (Sertoli and Leydig cells) structures


What are the 4 subtypes of epithelial ovarian carcinomas?




Clear cell


What are the characteristics of serous ovarian carcinomas?

  • Most common type
  • Mimics tubal epithelium i.e. columnar epithelium
  • Psammoma bodies common


What are the characteristics of mucinous ovarian carcinomas?

  • Mucin secreting cells, similar to those of endocervical mucosa
  • OR intestinal type - metastatic from appendix in some cases -> pseudomyxoma peritonei
  • No psammoma bodies


What are the characteristics of endometrioid ovarian carcinomas?

Mimics endometrium - i.e. form tubular glands


What are the characteristics of clear cell ovarian carcinomas?

  • Abundant clear cytoplasm - intracellular glycogen
  • Hobnail appearance


What is a dysgerminoma ovarian cancer?

Female equivalent of testicular seminoma


What are the characteristics of teratoma?

  • Shows differentiation toward somatic structures
  • Mature teratomas (dermoid cyst): benign, usually cystic
    • Differentiation of germ cells into mature tissues e.g. skin, hair, teeth, bone ,cartilage
  • Immature teratomas:
    • Malignant, usually solid
    • Contains immature, embryonal tissues


What do ovarian choriocarcinomas do?

Secrete HCG


What are the characteristics of fibroma (sex cord/stroma) ovarian carcinomas?

  • From cells of ovarian stroma
  • No hormone production
  • 50% associated with Meig's syndrome (ascites and pleural effusion)


What are the characteristics of granulosa ovarian carcinomas?

  • Thecal cell tumour
  • Produce E2
  • Look for oestrogenic effects - irregular menstrual cycles, breast enlargement, endometrial/breast cancer


What are the characteristics of Sertoli-Leydic cell ovarian carcinomas?

  • Secrete androgens
  • Defeminisation (Breast atrophy)
  • Virilisation (hirsutism, deepened voice, enlarged clitoris)


What kind of epithelium is on the vulva?



What is VIN?

  • Similar to CIN
  • Dysplasia of the epithelium 
  • Associated with HPV
  • Graded as VIN I, II and III
  • Progression to invasive disease is lower than for CIN (~5%)


What kind of carcinoma is vulval carcinoma and where can it arise from?

  • Mainly squamous cell carcinoma
  • Can arise from VIN or other skin abnormalities e.g. Paget's of the vulva


How commonly is endometrial cancer the cause of postmenopausal bleeding?

10% of PMB is endometrial cancer


How is endometrial carcinoma staged?

FIGO system


What are the two types of endometrial carcinoma?

Endometrioid - 80%

Non-endometrioid - 20%


What are the features of endometrioid endometrial carcinoma, and what are the risk factors for it?

  • Looks similar to endometrial galnds
  • Related to oestrogen excess, usually in peri-menopausal women
  • Mainly adenocarcinomas (85%) but may show squamous differentiation
  • Risk factors:
    • E2 excess: obesity, anovulatory amenorrhoea (e.g. PCOS), nulliparity, early menarche, late menopause, tamoxifen
    • DM
    • HTN


What are the kinds of non-endometrioid endometrial carcinoma and what is the pathophysiology?

  • Papillary, serous, clear cell
  • More aggressive
  • Unrelated to oestrogen excess; usually in elderly women with endometrial atrophy


What is a leiomyoma and how common is it?

Benign tumour of smooth muscle origin - a fibroid

Most common tumour of female genital tract, occurring in 20% of women >35


What are the 3 kinds of leiomyoma?

Intramural, submucosal, subserosal


What stimulates leiomyomas?

Oestrogen - they enlarge during pregnancy and regress post menopause


What are the macroscopic and microscopic features of leiomyoma?

  • Macroscopically: sharply circumscribed, discrete, round, firm, gray-white, size variable
  • Microscopically: bundles of smooth muscle cells


What are the clinical features of leiomyoma?

  • Heavy menstrual bleeding
  • Dysmenorrhoea
  • Pressure effects (urinary frequency, tenesmus)
  • Subfertility
  • In pregnancy: red degeneration of fibroids


Can leiomyomas become malignant?

  • Benign to malignant transformation (to a leiomyosarcoma) is rare
  • Leiomyosarcomas likely arise de novo, usually occurring in post menopausal women


What is adenomyosis and what are its clinical features?

  • Similar to endometriosis
  • Presence of ectopic endometrial tissue deep within the myometrium
  • Clinically:
    • Heavy menstrual bleeding
    • Dysmenorrhoea
    • Deep dyspareunia
    • Globular uterus


What is endometriosis and where does it occur?

  • Presence of endometrial glands or stroma in abnormal locations outside the uterus 
  • Locations: ovaries, uterine ligaments, rectovaginal septum, pouch of Douglas, pelvic peritoneum
  • Ectopic tissue is functional, undergoing cyclical bleeding -> pain, scarring and infertility


What are the 3 main theories behind endometriosis?

  • Regurgitant/implantation
  • Metaplastic
  • Vascular or lymphatic dissemination


What are the clinical features of endometriosis?

  • Pelvic pain
  • Dysmenorrhoea
  • Deep dyspareunia
  • Decreased fertility
  • Nodules/tenderness in vagina, posterior fornix or uterus
  • Immobile uterus which is retroverted in advanced disease


What are the macroscopic and microscopic features of endometriosis?

  • Macroscopic: red-blue to brown nodules ('powder burns') and 'chocolate cysts' in ovaries (endometriomas)
  • Microscopic: endometrial glands and stroma


What is pelvic inflammatory disease?

Infection ascending from the vagina and cervix up to the uterus and tubes, leading to inflammation (endometritis, salpingitis) and the formation of adhesions


What are the causative organisms of PID?

Chlamydia trachomatis

Neisseria gonorrhoea (These 2 are the most common in the UK)


Schistosomiasis (these 2 are common elsewhere)


What are the clinical features of PID?

  • Lower abdo pain
  • Dyspareunia
  • Vaginal bleeding/discharge
  • Fever
  • Adnexal tenderness
  • Cervical excitation


What are the complications of PID?

  • Fitz Hugh Curtis syndrome: RUQ pain from peri-hepatitis and violin string peri-hepatitic adhesions
  • Infertility
  • Increased risk of ectopic pregnancy
  • Inestinal obstruction -> bacteraemia
  • Tubo-ovarian abscess
  • Chronic pelvic pain
  • Peritonitis
  • Plical fusion


What are the possible clinical presentations of lupus nephritis and what determines these?

The site and intensity of immune complex deposition. Can include:

  • Isolated urinary abnormalities
  • Acute renal failure
  • Nephrotic syndrome
  • Progressive chronic renal failure


What are the categories of lupus nephritis?

  • Class I - minimal mesangial lupus nephritis
    • Immune complexes but no structural alteration
  • Class II - mesangial proliferative lupus nephritis
    • Immune complexes and mild/moderate increase in mesangial matrix and cellularity
  • Class III - focal lupus nephritis
    • Active swelling + proliferation in less than half the glomeruli
  • Class IV - diffuse lupus nephritis
    • Involvement of more than half of the glomeruli
  • Class V - membranous lupus nephritis
    • Subepithelial immune complex deposition
  • Class VI - complete sclerosis of >90% of the glomeruli


What are the causes of aduly polycystic kidney disease?

  • Autosomal dominant
  • 85% due to mutations in PKD1 on chromosome 16 (encoding polycystin-1)
  • Remainder are due to mutations in PDK2 on chromosome 4 (encoding polycystin 2)


How much of CKD is caused by adult polycystic kidney disease?



What are the pathological features of adult polycystic kidney disease?

  • Large multicystic kidneys with destroyed renal parenchyma
  • Liver cysts (in PKD1)
  • Berry aneurysms


What are the clinical features of adult polycystic kidney disease?

  • Haematuria
  • Flank pain
  • UTI
  • Clinical features often caused by cyst complications e.g. cyst rupture, cyst infection, cyst haemorrhage


What is chronic renal failure?

Progressive, irreversible loss of renal function characterised by prolonged symptoms and signs of uraemia (fatigue, itching, anorexia, and if severe eventually confusion)


What are the commonest causes of chronic renal failure in the UK?

  • Diabetes: 19.5%
  • Glomerulonephritis 15.3%
  • Hypertension and vascular disease 15%
  • Reflux nephropathy (chronic pyelonephritis) 9.5%
  • Polycystic kidney disease 9.4%


What are the 5 stages of chronic renal failure?

  1. Kidney damage with normal renal function (often proteinuria), GFR >90
  2. Mildly impaired, GFR 60-89
  3. Moderately impaired, GFR 30-59
  4. Severely impaired, GFR 15-29
  5. Renal failure (Generally requires replacement therapy), GFR <15, or if being treated with renal replacement therapy


What is acute renal failure and what characterises it?

Rapid loss of renal function, manifested as increased serum creatinine and urea


What are the complications of acute renal failure?

  • Metabolic acidosis
  • Hyperkalaemia
  • Fluid overload
  • Hypertension
  • Low Ca2+
  • Uraemia


How can you classify the causes of acute renal failure?

  • Pre renal
    • Most common
    • Renal hypoperfusion e.g. hypovolaemia, sepsis, burns, acute pancreatitis, renal artery stenosis
  • Renal
    • Acute tubular necrosis (ATN) is commonest renal cause
    • Acute glomerulonephritis
    • Thrombotic microangiopathy
  • Post renal
    • OBstrucrtion to urine flow e.g. stones, tumours (primary or secondary), prostatic hypertrophy and retroperitoneal fibrosis


What are the 2 main kinds of thrombotic microangiopathies?

Haemolytic uraemic syndrome (HUS)

Thrombotic thrombocytopenic purpura (TTP)


What characterises the thrombotic microangiopathies?

  • Thrombosis (generally renal in HUS and widespread in TTP)
  • Triad of:
    • Microangiopathic haemolytic anaemia (MAHA)
    • Thrombocytopenia
    • Sometimes renal failure (generally in HUS)


What is the pathophysiology of the thrombotic microangiopathies?

  • Widespread fibrin deposition in vessels
  • Formation of platelet-fibrin thrombi which damage passing platelets and RBCs
  • Platelet and RBC destruction i.e. thrombocytopenia and MAHA)


What is the difference in epidemiology between HUS and TTP?

HUS is usually children, TTP usually adults


What is the pathophysiology of HUS?

  • Usually associated with idarrhoea caused by E Coli 0157:H7 with outbreaks caused by children visiting petting zoos
  • Can be 'non diarrhoea associated' due to abnormal proteins in complement pathway/endothelium - can be familial
  • Thrombi confiend to the kidneys


What is the pathophysiology of TTP?

Thrombi occur throughout circulation especially in CNS


What are the signs/symptoms of HUS and TTP?

Low platelets and bleeding (petechiae, haematemesis, melaena)

MAHA = pallor and jaundice


What is the difference in symptoms between HUS and TTP?

HUS: usually involves renal failure

TTP: usually no renal failure and involves neuro symptoms: headache, altered consciousness, seizures, coma


How do you diagnose HUS and TTP?

  • Low Hb, low platelets
  • Signs of haemolysis: high bilirubin, high reticulocytes, high LDH
  • Fragmented RBCs on blood smear
  • Coombs test negative (as not AIHA)


What are the features of acute pyelonephritis?

  • Bacterial infection of the kidney, usually due to ascending infection, most commonly E coli
  • Presents with fever, chills, sweats, flank pain, renal angle tenderness, leukocytosis +/- frequency, dysuria and haematuria
  • Leukocytic casts are seen in urine


What is chronic pyelonephritis and what causes it?

  • Chronic inflammation and scarring of the parenchyma caused by recurrent and persistent bacterial infection
  • Causes:
    • Chronic obstruction - posterior urethral valves, renal calculi
    • Reflux nephropathy - caused by urine reflux


What is acute interstitial nephritis and how does it present?

  • A hypersensitivity reaction, usually to a drug (Abx, NSAIDs, diuretics)
  • Usually begins days after drug exposure
  • Presents with: fever, skin rash, haematuria, proteinuria, eosinophilia


When is chronic interstitial nephritis/analgesic nephropathy seen and what are the symptoms?

  • Seen in elderly with long term analgesic consumption (NSAIDs/paracetamol)
  • Symptoms only occur late in disease: HTN, anaemia, proteinuria, haematuria


What is the process of acute tubular injury/necrosis?

  1. Damage ot tubular epithelial cells
  2. Blockage of tubules by casts
  3. Reduced flow and haemodynamic change
  4. Acute renal failure


What is the most common cause of acute renal failure?

Acute tubular injury/necrosis


What are the causes of acute tubular injury/necrosis?

  • Ischaemia: burns, septicaemia
  • Nephrotoxins: drugs (gentamicin, NSAIDs), radiographic contrast agents, myoglobin, heavy metals


What are the differentials for asymptomatic haematuria?

  • Thin basement membrane disease (benign familial haematuria)
  • IgA nephropathy (Berger disease)
  • Alport syndrome


What is IgA nephropathy likely to cause (if no histological findings given in the question)?

  • Frank haematuria
  • Change in renal function/raised creatinine
  • Slightly more common in Asian population
  • Also, IgA And thin BM disease are more common causes of asymptomatic haematuria than of nephritic syndrome


What is rapidly progressive/crescenteric GN?

Most aggressive glomerulonephritis that can cause ESRF within weeks.  Presents as nephritic syndrome but oliguria and reanl failure are more pronounced.  All types have crescents in the glomeruli.


What are the classifications of rapidly progressive/crescenteric GN?

  • Type 1: anti-GBM antibody
  • type 2: immune complex
  • Type 3: pauci-immune/ANCA associated


Type 1 Rapidly Progressive/Crescenteric GN:

  • Pathogenesis
  • Causes
  • Light microscopy
  • Fluorescence microscopy
  • Additional organ involvement

Type 1 Rapidly Progressive/Crescenteric GN:

  • Pathogenesis - anti-GBM Ab against Col4-A3 (collagen type IV)
  • Causes - Goodpastures syndrome, HLA-DRB1 association
  • Light microscopy - crescents
  • Fluorescence microscopy - linear deposition of IgG in GBM
  • Additional organ involvement - lungs - pulmonary haemorrhage


Type 2 Rapidly Progressive/Crescenteric GN:

  • Pathogenesis
  • Causes
  • Light microscopy
  • Fluorescence microscopy
  • Additional organ involvement

Type 2 Rapidly Progressive/Crescenteric GN:

  • Pathogenesis - immune complex mediated
  • Causes - SLE, IgA nephropathy, post infectious GN
  • Light microscopy - crescents
  • Fluorescence microscopy - Granular (lumpy, bumpy) IgG immune complex deposition on GBM/mesangium
  • Additional organ involvement - often limited, except in SLE


Type 3 Rapidly Progressive/Crescenteric GN:

  • Pathogenesis
  • Causes
  • Light microscopy
  • Fluorescence microscopy
  • Additional organ involvement

Type 3 Rapidly Progressive/Crescenteric GN:

  • Pathogenesis - pauci immune i.e. lack of anti-GBM or immune complex
  • Causes - cANCA (Wegener's granulomatosis), pANCA (microscopic polyangiitis)
  • Light microscopy - crescents
  • Fluorescence microscopy - lack of/scanty significant immune complex deposition
  • Additional organ involvement - vasculitis - particularly presenting as skin rashes or pulmonary haemorrhage


What are the causes of nephritic syndrome?

  • Acute post-infectious (post-streptococcal) GN
  • IgA nephropathy (Berger disease)
  • Rapidly progressive (crescenteric) GN
  • Hereditary nephritis (Alport's syndrome)
  • Thin basement membrane disease (benign familial haematuria)


What are the features of acute post-infectious GN?

  • 1-3 weeks after streptococcal throat infection (usually group A alpha haemolytic - strep pyogenes) or impetigo
  • Glomerular damage from immune complex deposition
  • Haematuria (red cell casts), proteinuria, oedema, HTN
  • Bloods: ASOT titre increased, low C3
  • Biopsy:
    • Light microscopy: increased cellularity of glomeruli
    • Fluorescence microsopy: granular deposits of IgG and C3 in GBM
    • Electron microscopy: subendothelial humps


What are the features of IgA nephropathy (Berger's disease)?

  • Commonest GN worldwide
  • Deposition of IgA complexes in glomeruli
  • PResents 1-2 days after a URTI with frank haematuria
  • Main symptoms: persistent or recurrent frank haematuria, or asymptomatic microscopic haematuria
  • OTher symptoms of nephritic syndrome not prominent
  • Can progress to ESRF
  • Biopsy - fluorescence microscopy: granular deposition of IgA and complement in mesangium


What are the features of hereditary nephritis (Alport's syndrome)?

  • Hereditary glomerular disease caused by a mutation in type IV collagen alpha 5 chain
  • X linked
  • Nephritic syndrome + sensorineural deafness + eye disorders (lens dislocation, cataracts)
  • Presents at 5-20 years with nephritic syndrome progressing to ESRF


What are the features of thin basement membrane disease (benign familial haematuria)?

  • Very rarely a cause of nephritic syndrome (normally exclusively asymptomatic haematuria)
  • Diffuse thinning of GBM caused by mutation in type IV collagen alpha 4 chain
  • Autosomal dominant
  • Quite common: prevalence ~5%
  • Usually asymptomatic - incidentally diagnosed with microscopic haematuria
  • Renal function usually normal


What characterises nephritic syndrome?

  • Glomerular inflammation
  • Haematuria (coca-cola urine)
  • Dysmorphic RBCs and red cell casts in urine


Other features:

  • Oliguria
  • Increased urea and creatining
  • Hypertension
  • Proteinuria (but not nephrotic range)


What are the characteristic features of nephrotic syndrome?

  • Characteristically:
    • Proteinuria (>3g/24h)
    • Hypoalbuminaemia
    • Oedema
    • (+ hyperlipidaemia)
  • EMQ features:
    • Swelling (characteristically facial in kids and peripheral in adults)
    • Frothy urine


What are the primary and secondary causes of nephrotic syndrome?

  • Primary: minimal change disease, membranous glomerular disease, focal segmental glomerulosclerosis (FSGS)
  • Secondary: diabetes, amyloidosis


Minimal change disease:

  • Epidemiology
  • Light microscopy
  • Electron microscopy
  • Immunofluorescence
  • Response to steroids
  • Prognosis

Minimal change disease:

  • Epidemiology - most common in children (75% cases) with another peak in the elderly
  • Light microscopy - no changes
  • Electron microscopy - loss of podocyte foot processes
  • Immunofluorescence - no immune deposits
  • Response to steroids - 90% respond
  • Prognosis - <5% ESRF


Membranous glomerular disease:

  • Epidemiology
  • Light microscopy
  • Electron microscopy
  • Immunofluorescence
  • Response to steroids
  • Prognosis
  • Misc

Membranous glomerular disease:

  • Epidemiology - common in adults (~30%)
  • Light microscopy - diffuse glomerular basement membrane thickening
  • Electron microscopy - loss of podocyte foot processes, subepithelial deposits = spiky
  • Immunofluorescence - Ig and complement in granular deposits along entire GBM
  • Response to steroids - poor
  • Prognosis - 40% ESRF after 2-20 years
  • Misc - can be primary or secondary to SLE, infection, drugs and malignancy


Focal segmental glomerulosclerosis (FSGS):

  • Epidemiology
  • Light microscopy
  • Electron microscopy
  • Immunofluorescence
  • Response to steroids
  • Prognosis
  • Misc

Focal segmental glomerulosclerosis (FSGS):

  • Epidemiology - common in adults (~30%); most so in Afro-Caribbeans
  • Light microscopy - focal and segmental glomerular consolidation and scarring, hyalinosis
  • Electron microscopy - loss of podocyte foot processes
  • Immunofluorescence - Ig and complement in scarred areas
  • Response to steroids - 50% respond
  • Prognosis - 50% ESRF in 10 years
  • Misc - primary, but can be secondary to obesity and HIV nephropathy


For diabetic nephrotic syndrome, what would be the histological features and what are the hints in the question?

  • Diffuse GBM thickening 
  • Mesangial matrix nodules aka Kimmelstiel Wilson nodules
  • Hints: Asian


What are the histological features of amyloidosis nephrotic syndrome and what would be hints to this in the question?

  • Histology: apple green birefringence with Congo red stain
  • May have chronic inflammation: rheumatoid arthritis, chronic infections e.g. TB causing AA protein deposition
  • May have immunoglobulin light chain deposition, most commonly from multiple myeloma, -> AL protein deposition
  • Clinical clues of amyloidosis: macroglossia, hepatomegaly, heart failure


Which kidney diseases affect the glomerulus?

  • Nephrotic syndrome: breakdown of selectivity of the glomerular filtration barrier
  • Nephritic syndrome


Which kidney diseases affect the tubules and interstitium?

  • Acute tubular necrosis
  • Tubulointerstitial nephritis:
    • Acute pyelonephritis
    • Chronic pyelonephritis + reflux nephropathy
    • Interstitial nephritis


Which kidney diseases affect the blood vessels?

  • Thrombotic microangiopathies:
    • Haemolytic uraemic syndrome
    • Thrombotic thrombocytopenic purpura


What kind of epithelium is in the oesophagus?

  • Proximal 2/3: squamous epithelium
  • Distal 1/3: columnar epithelium
  • Joined by squamo columnar junction (Z line)


What are the characteristics of reflux oesophagitis?

  • Commonest cause of oesophagitis
  • Complications: ulceration, haemorrhage causing haematemesis/melaena, Barrett'soesophagus, stricture, perforation
  • Los Angeles classification
  • Treatment: lifestyle changes (stop smoking, weight loss), PPI/H2 receptor antagonists


What are the characteristics of Barrett's oesophagus?

  • Metaplasia of squamous mucosa -> columnar epithelium (have goblet cells) following chronic GORD -> upwards migration of the SCJ
  • Seen in 10% of those with symptomatic GORD
  • Can lead to adenocarcinoma: metaplasia -> dysplasia -> Ca


What are the characteristics of oesophageal adenocarcinoma?

  • Associatd with Barrett's oesophagus so usually seen in the distal 1/3
  • Other risk factors: smoking, obesity, prior radiation therapy
  • Most common in Caucasians, M>>F


What are the characteristics of squamous cell oesophageal carcinoma?

  • Associated with ETOH and smoking
  • Other risk factors: achalasia of cardia, Plummer Vinson, nutritional deficiencies, nitrosamines, HPV (in high prevalence areas)
  • 6x more common in Afro Caribbeans, M>F
  • Usually found in middle 1/3 (50%); upper 1/3 20%, lower 1/3 30%
  • Presentation: progressive dysphagia (solids then fluids), odynophagia (pain), anorexia, severe weight loss
  • Rapid growth and early spread to lymph nodes, liver, and directly to proximal structures -> palliative care


What are the characteristics of oesophageal varices?

  • Engorged dilated veins, usually due to portal hypertension (back pressure)
  • Pt vomits units of blood
  • Emergency endoscopy -> sclerotherapy/banding


What are the causes of acute, chronic & 'special types' gastritis and what cells would you find?

  • Acute
    • Neutrophils
    • Aspirin, NSAIDs, corrosives (bleach), acute H pylori, severe stress (eg burns)
  • Chronic
    • Lymphocytes and plasma cells
    • H pylori (tends to be antral), autoimmune e.g. pernicious anaemia, ETOH, smoking
  • Special types: chemical (foveolar hyperplasia, chronic infalmmation), infection (HSV, CMV, strongyloides), IBD


What are the complications of gastritis?

If chronic can lead to gastric ulcer formation.

Can also result in metaplasia -> dysplasia -> cancer


What is a gastric ulcer?

A breach through the muscularis mucosa into the usbmucosa


What are the symptoms of gastric ulcer?

Epigastric pain +/- weight loss.  Worse with food (contrast to duodenal), and relieved by antacids


What are the risk factors for a gastric ulcer?

H pylori




Delayed gastric emptying

Occurs mainly in the elderly


What investigations should you do if you suspect a gastric ulcer?

  • Biopsy for H pylori histology status
  • Punched out lesion with rolled margins (endoscopy)


What are the possible complications of a gastric ulcer?

Anaemia (IDA) and perofration (do an erect CXR), also malignancy


What causes gastric lymphoma and how do you treat it?

  • Caused by H pylori - chronic antigen stimulation
  • Treatment:
    • Remove cause with triple therapy:
      • PPI
      • Clarithromycin
      • Plus amoxicillin or metronidazole


What lines the stomach?

Gastric mucosa, columnar epithelium (mucin secreting) and glands


What are the features of, risk factors for, and complications of duodenal ulcer?

  • 4x more common than gastric ulcer
  • Epigastric pain worse at night
  • Relieved by food and milk
  • Occurs in younger adults
  • Risk factors: H pylori, drugs, aspirin, NSAIDs, steroids, smoking, increased acid secretion
  • Complications: anaemia (IDA) and perforation (seen on erect CXR)


What is coeliac disease?

A T cell mediated autoimmune disease associated with DQ2, DQ8 HLA status.  Gluten intolerance results in villous atrophy and malabsorption


What are the features of coeliac disease?

  • Young children and Irish women
  • Symptoms of malabsorption:
    • Steatorrhoea
    • Abdo pain
    • Bloating
    • Nausea and vomiting
    • Weight loss
    • Fatigue
    • IDA
    • Failure to thrive
    • Rash (dermatitis herpetiformis)


What tests should you do in coeliac disease?

  • Serological tests:
    • Anti endomysial antibodies (best sensitivity and specificity)
    • Anti tissue transglutaminase (IgA)
    • Anti-gliadin (poor marker of disase control)
  • Gold standard:
    • Upper GI endoscopy
    • Duodenal biopsy showing: villous atrophy, crypt hyperplasia, lymphocyte infiltrate


How common is T cell lymphoma in coeliac sufferers?

~10% will progress to T cell lymphoma if not treated adequately


What are the different kinds of congenital lower GI disease?

  • Atresia
  • Stenosis
  • Duplication
  • Imperforate anus
  • Hirschsprung's disease


What is Hirschsprung's disease, what are its features and how is it treated?

  • Congenital absence of ganglion cells in the myenteric plexus (80% males)
  • PResents with symptoms and signs of obstruction in young babies
  • Associated with Down's (2%)
  • Genetics: RET proto oncogene Cr10+
  • Biopsy - hypertrophied nerve fibres, no ganglia
  • Treatment: resection of affected (restricted) segment


What are the causes of lower GI obstruction?

  • Constipation
  • Diverticular disease (common)
  • Adhesions
  • Herniation
  • External mass e.g. foetus, aneurysm, foreign body
  • Volvulus: complete twisting of bowel loop at mesenteric base or vascular pedicle, small bowel (infants), sigmoid>caecal (elderly)
  • Intussusception


What are the causes of acute and chronic colitis?

  • Acute:
    • Infection (bacterial, viral, protozoal) -> diarrhoea very common
    • Drug/toxin (especially antibiotics)
    • Chemo/radiotherapy
  • Chronic:
    • IBD: Crohn's and UC
    • TB


What are the causes of ischaemic colitis and where does it occur?

Causes: arterial of venous occlusion, small vessel disease, low flow states, obstruction.

Common in 'watershed areas' - splenic flexure (SMA Transition to IMA), rectosigmoid (IMA transition to internal iliac)


What causes C diff, how should you investigate suspected C diff and what's the treatment?

Antibiotics (cipro, cephalosporins) kill off commensal bacteria allowing C diff to flourish.  Its exotoxins cause pseudomembranous colitis.


Investigations: stool culture


Treatment: metronidazole (covers anaerobic), or vancomycin (effective but 2nd line)


Other than C diff, which bacteria commonly cause lower GI infection?

  • Campylobacter
  • Salmonella
  • Shigella spp


What causes diverticular disease, what are the features and what's a possible complication?

  • High incidence in West, probably linked to low fibre diet
  • High intraluminal pressure results in outpuchings of weak points of bowel wall
  • Seen in barium enema CT or endoscopy
  • 90% occur in left colon
  • Often asymptomatic but can have PR bleed
  • Complication: diverticulitis - fever and peritonism, gross perofration, fistula, obstruction (due to fibrosis)


What's the difference in epidemiology between UC and Crohn's?

  • Crohn's:
    • Western, white 2-5x non white
    • Peak onset 20s
    • F>M
    • Smoking worsens Sx
  • UC:
    • Slightly more common that Crohn's
    • Whites > non whites
    • Peak age 20-25


What's the aetiology of IBD?

Nort really known.  Greater MZ twin concordance in Crohn's than in UC.

Hygiene hypothesis: less food contamination -> less enteric infection -> inadquate development of processes that regulate mucosal immune response -> exaggerated immune esponse to pathogens that would cause self limiting disease


What is the pathophysiology/histology in Crohn's disease?

  • Affects whole GI tract from mouth to anus, most common in terminal ileum and caecum
  • Patchy distribution -> skip lesions
  • Areas of healthy mucosa lie above disease mucosa -> 'cobblestone' appearance
  • First lesion = aphthous ulcer; these are deep 'rosethron ulcers' that can join together to form serpentine ulcers
  • Non caseating granulomas
  • Transmural inflammation
  • Fistula/fissure formation common


What is the pathophysiology/histology in UC?

  • Extends proximally from rectum
  • Continuous involvement of mucosa
  • Small bowel not affected unless very severe pancolitis causes 'backwash ileitis'
  • Extensive superficial borad ulcers
  • Inflammation superficial, confined to mucosa
  • No granulomas/fissures/fistulae/strictures
  • Islands of regenerating mucosa bulge into lumen -> pseudopolyps (can fuse to form mucosal bridges)


What are the clinical features of Crohn's and UC?

  • Crohn's: usually intermittent diarrhoea, pain and fever
  • UC: bloody diarrhoea, mucus, crampy abdo pain relieved by defecation


What are the extra-GI  manifestations of Crohn's and UC?

  • Malabsorption and Fe deficiency anaemia -> stomatitis
  • Eyes: uveitis (iris and ciliary body) -> conjunctivitis
  • Skin: erythema nodosum, pyoderma gangrenosum, erythema multiforme, clubbing
  • Joints: migratory asymmetrical polyarthropathy of large joints (15%), sacroiliitis, myositis, ankylosing spondylitis
  • Liver: pericholangitis, primary sclerosing cholangitis (UC>CD), steatosis


What are the complications of Crohn's?

  • Strictures (requiring bowel resection, often recurrent)
  • Fistulae
  • Abscess formation
  • Perforation


What are the complications of UC?

  • Severe haemorrhage
  • Toxic megacolon -> perforation (damage to muscularis propria with disruption of neuromuscular function -> colonic dilatation)
  • 30% require colectomy within 3 years for uncontrollable symptoms
  • 20-30x risk of adenocarcinoma


What investigations should you do in Crohn's/UC?

  • Systemic markers of inflammation e..g ESR, CRP
  • Barium contrast
  • Endoscopy
  • Rectal biopsy
  • Flexi sig/colonoscopy
  • AXR
  • Stool cultre


How is Crohn's disease managed?

  • Mild attack: prednisolone
  • Severe attack: IV hydrocortisone + metronidazole
  • Additional therapes: azathioprine, methotrexate, infliximab


How is UC managed?

  • Mild: prednisolone and mesalazine (5-ASA)
  • Moderate: prednisolone + 5 ASA + steroid enema bd
  • Severe: admit, nil by mouth, IV fluids and IV hydrocortisone, rectal steroids
  • For remission: 5-ASA (1st line), azathioprine (2nd line)



What are carcinoud tumours and where do they occur?

Diverse group of tumours of enterochromaffin cell origin which are usually slow growing and produce 5-HT (serotonin.  Commonly found in the bowel but also in the lung, ovaries, testes.


What are the features of carcinoid syndrome?

  • Bronchoconstriction
  • Flushing
  • Diarrhoea


What are the features of carcinoid disease?

  • Life threatening
  • Vasodilation
  • Hypotension
  • Tachycardia
  • Bronchoconstriction
  • Hyperglycaemia


What investigations and treatment should you do for carcinoid tumours?

Investigate: 24hr urine 5-HIAA (main metabolite of serotonin)

Treat: octreotide (somatostatin analogue)


What are adenomas/polyps of the colon and rectum and what are their features?

  • Benign dysplastic lesions that are precursors to adenocarcinomas (Though most stay benign)
  • 50% of those >50 in the Western world have them; mostly asymptomatic so they need regular surveillance if >3.4cm (45% malignant change)
  • Tubular, tubulovillous, or villous
  • Large size is most important risk factor for malignancy in addition to degree of dysplasia and increased villous component


What is a risk of having a villous adenoma in the colon/rectum (other than cancer)?

Hypoproteinaemic hypokalaemia as they leak large amounts of protein and potassium


Describe the adenoma carcinoma progression in the colon and rectum

  • Classical chromosomal instability sequence
  • Colon -> at risk mucosa after 'first  hit' mutation in 1st copy of APC gene (those with FAP are born with a mutation)
  • At risk -> adenoma after 'second hit' mutation to remaining APC gene
  • Progression to carcinoma follows activation of KRAS, LOF, mutations of p53


What are the features of hamartomatous colonic/rectal polyps?

  • Found sporadically in some genetic/acquired syndromes
  • Juvenile polyps are focal malformation of mucosa + lamina propria, vast majority in those <5 years old, mostly in rectum -> bleeding
  • Usually solitary, but up to 100 found in juvenile polyposis (AD) that may require colectomy to stop haemorrhage


In what syndrome are hamartomatous colonic/rectal polyps found (other than juvenile polyposis) and what are the other features?

Peutz Jeghers syndrome:

  • AD - LKB1
  • Multiple polyps, mucocutaneous hyperpigmentation, freckles around mouth, palms and soles
  • Increased risk of intussusception and of malignancy
  • Need regular surveillance of GI tract, pelvis and gonads


When are hyperplastic colonic polyps seen and what is thought to be the cause of them?

50-60 yeas; thought to be caused by shedding of epithelium -> cell buildup


What is the cause of pseudo polyps?

Inflammatory processes e.g. IBD


What is the epidemiology of colorectal cancer?

  • 2nd commonest cause of cancer deaths in the UK
  • Age 60-79 years; if <50 consider familial syndrome
  • Commoner in Western populations
  • 98% adenocarcinoma, 45% in rectum


What are the aetiological factors in colorectal cancer?

  • Diet (low fibre, high fat)
  • Lack of exercise
  • Obesity
  • Familial syndromes
  • Chronic IBD
  • NSAIDs are protective (COX2 is over expressed in 90%)


What are the clinical features of colorectal cancer?

  • Right sided: IDA, weight loss
  • Left sided: change in bowel habit, LLQ crampy pain


What investigations should you do for suspected colorectal cancer?

  • Proctoscopy
  • Sigmoidoscopy
  • Colnoscopy
  • Barium enema
  • Bloods e.g. FBC
  • CT/MRI
  • CEA (carcinoembryonic antigen) to monitor disease


How are colorectal cancers classified?

Duke's staging:

  • A - confined to muicosa (5 year survival >95%)
  • B1 - extending into muscularis propria (5 year survival 67%)
  • B2 - transmural invasion, no lymph nodes involved (5 year survival 54%)
  • C1 - extending into muscularis propria, with LN metastases (5 year survival 43%)
  • C2 - transmural invasion with lymph node metastases (5 year surivival 23%)
  • D - distant metastases (5 year survival <10%)


How is colorectal cancer managed?

  • Surgery
    • Rectal/low sigmoid:
      • <1-2 cm above anal sphincter (lower 1/3 of rectum) - abdomino-perineal resection
      • >1-2cm above anal sphincter - anterior resection
    • Sigmoid: sigmoid colectomy
    • Descending colon and distal transverse - left hemicolectomy
    • Caecum, ascending colon and proximal transverse - right hemicolectomy
    • Transverse - extended right hemicolectyom
  • Radiotherapy post op to decrease local recurrence
  • Chemotherapy in palliation - 5-FU (fluorouracil)


What is familial adenomatous polyposis and what are teh risks?

  • 70% AD mutation in APC gene (C5q1), 30% AR mutation in DNA mismatch repair genes
  • Presents at 10-15 years with >100 adenomatous polyps requierd for diagnosis but usually 100s-1000s seen
  • At birth, hypertrophy of retinal pigment epithelium
  • All will become adenocarcinoma if left untreated by 30 years, so most hav ea prophylactic colectomy
  • Increased risk of neoplasia elsewhere e.g. ampulla of Vater and stomach


What is Gardner's syndrome?

Like FAP but with extraintestinal features e.g. osteomas, dental caries


What is HNPCC/Lynch syndrome?

  • AD mutations in DNA mismatch repair genes
  • Carcinomas usually in right colon, few polyps but fast progression to malignancy therefore present usually <50 years
  • Associated with endometrial, ovarian, small bowel, transitional cell and stomach cancer


How much bicarbonate rich fluid does the pancreas produce per day and what stimulates this?

About 2L - stimulated by secretin and CCK


Where is secretin produced and what's it for?

S-cells of the duodenum, controls gastric acid secretion and buffering with HCO3-


Where is CCK produced and what's it for?

I cells in the duodenum.  Responsible for stimulating digestion of fat and proteins, causes release of digestive enzymes


What is the exocrine function of the pancreas?

Digestive - proteases, lipase, and amyloase secreted into ducts


Which cells of the pancreas are involved in its endocrine function and what do they make?

  • Alpha cells - glucagon which increases blood glucose
  • Beta cells - insulin which decreases blood glucose
  • Delta cells - somatostatin which regulates the above cells
  • Also:
    • D1 = vasocative peptide which stimulates the secretion of H20 into the pancreatic system
    • PP = pancreatic polypeptide, which self regulates secretion activities


What are the features of metabolic syndrome?

  • Fasting hyperglycaemia >6 mmol/L
  • BP >140/90
  • Central obesity (>94cm in M, >80cm in F)
  • Dyslipidaemia: decreased HDL cholesterol <1mmol/L and increased triglycerides >2mmol/L
  • Microalbuminaemia


What comprises a diagnosis of diabetes mellitus?

Fasting plasma glucose >7 mmol/L or random plasma glucose >11.1 mmol/L


What is the pathophysiology of T1DM?

Autoimmune destruction of pancreatic beta cells by CD4+ and CD8+ T lymphocytes.  May present with DKA and is insulin dependent


What is the pathophysiology of T2DM?

Strongly linked to obestiy and insulin RESISTANCE


What are the presenting features of diabetes and what are the potential complications?

  • Polyuria and polydipsia (osmotic diuresis and raised plasma osmolality)
  • Hyperglycaemia predisposes to recurrent infections
  • Macrovascular complications
    • Cardiac: MI
    • Renal: glomerulonephritis
    • Cerebral: CVA
  • Microvascular:
    • Ocular: diabetic retinopathy
    • PVS: claudication, change in colour/temp, poor healing and ulcers


What are the causes of acute pancreatitis?









Scorpion venom



Drugs e.g. thiazides


What are the presenting features/histology in acute pancreatitis?

  • Severe epigastric (or central) pain radiating tot he back, relieved by sitting forwards
  • Vomiting prominent
  • Amylase only transiently increased - serum lipase is more sensitive
  • Can result in formation of a pseudocyst (pathological collection of fluid), associated with alcoholic pancreatitis
  • Histology: coagulative necrosis


What are the causes of chronic pancreatitis?

  • Alcoholism
  • Cystic fibrosis
  • Hereditary
  • Pancreatic duct obstruction e.g. stones/tumour
  • Autoimmune e.g. IgG 4 sclerosing


What are the presenting features + histology of chronic pancreatitis?

  • Epigastric pain radiatin to back
  • Malabsorption (weight loss and steatorrhoea) due to lack of enzymes
  • Secondary DM
  • Histology:
    • Very similar to carcinoma of the pancreas
    • Fibrosis and loss of exocrine tissue
    • Duct dilatation with thick secretions
    • Calcification


Acinar cell carcinoma

  • Presentation
  • Histology
  • Prognosis

Acinar cell carcinoma

  • Presentation
    • Rare, older adults
    • Non specific symptoms - abdo pain, weight loss, nausea and diarrhoea
    • ~10% get multifocal fat necrosis and polyarthralgia due to lipase secretion
  • Histology
    • Neoplastic epithelial cells with eosinophilic granular cytoplasm
    • Positive immunoreactivity for lipase, trypsin and chymotrypsin
  • Prognosis
    • Median survival is 18 months from diagnosis
    • 5 year survival <10%


Ductal adenocarcinoma of the pancreas

  • Epidemiology
  • Site
  • Risk factors

Ductal adenocarcinoma of the pancreas

  • Epidemiology
    • 85% of all pancreatic malignancies
    • Avg age 60 years M>F
  • Site - normally head of pancreas
  • Risk factors
    • Smoking
    • Diet
    • Genetic e.g. FAP, HNPCC


What are the clinical features of ductal adenocarcinoma of the pancreas?

  • Weight loss (cachexia) and anorexia
  • Upper abdo and back pain (chronic, persistent and severe)
  • Jaundice (painless), pruritus, steatorrhoea
  • DM
  • Trousseau's syndrome (25%) - recurrent superficial thrombophlebitis
  • Ascites
  • Abdominal mass
  • Virchow's node
  • Courvoisier's sign


What would be the investigation findings in ductal adenocarcinoma of the pancreas?

  • Bloods: low Hb, high bilirubin, high Ca2+
  • Ca19.9 >70IU/mL


How is ductal adenocarcinoma of the pancreas managed & what's the prognosis?

  • Chemotherapy is palliative with 5-FU
  • Surgery (15%) of cases) - Whipple's procedure - surgical resection
  • Prognosis is very poor - 5 year survival is <5%


Where are neuroendocrine islet cell tumours found and what do they look like?

Normally body or tail of pancreas.  Circumscribed, 1-5cm; cells arranged in nests or trabeculae with granular cytoplasm.


What syndrome are neuroendocrine islet cell tumours associated with?

MEN1 - may be multiple


What are the kinds of neuroendocrine islet cell tumours and what distinguishes them?

  • Functional - present with symptoms related to hormone excess
    • Insulinoma - hypoglycaemia
    • Gastrinoma - Zollinger Ellison syndrome (high acid output - recurrent ulceration)
    • OThers: VIPoma - diarrhoea
    • Glucagonoma - necrolytic migrating erythema
  • Non-functional - picked up on imaging or when they get big enough to produce symptoms of local disease/metastasis


How do you investigate and manage neuroendocrine islet cell tumours?


Management: surgery


What is multiple endocrine neoplasia and what are the types?

Group of genetic syndromes where there are functioning hormone producing tumours in multiple organs.

  • MEN1 = PPP
    • Parathyroid hyperplasia/adenoma
    • Pancreatic endocrine tumour (often phaeo)
    • Pituitary adenoma
  • MEN2A: parathyroid, thyroid, phaeo
  • MEN2B: Medullary thyroid, phaeo, neuroma; Marfanoid phenotype


What are the 3 main kinds of pancreatic malformations?

  • Ectopic pancreas - especially stomach, small intestine
  • Pancreas divisum - failure of fusion of dorsal and ventral buds, increased risk of pancreatitis
  • Annular pancreas - can present with duodenal obstruction approx 1 year old


What is the basic structural unit of the liver and what's within it?

Hepatic lobule - a 1-2mm hexagon

  • Centre - terminal branches of the hepatic vein (= centrilobular vein)
  • Angles are formed by the portal tracts that contain 3 structures:
    • Branches of the bile ducts
    • Hepatic artery and
    • Portal vein


What's the difference between centrilobular (perivenular) hepatocytes and periportal hepatocytes?

  • Centrilobular (perivenular) hepatocytes - near the terminal hepatic vein (zone 3) - more metabolically active
  • Periportal hepatocytes - near the portal tract (zone 1) - receive blood rich in nutrients and O2


What are the functions of the liver?

  • Metabolism: glycolysis, glycogen storage, glucose, AA, fatty acid syndthesis, lipoportein and drug metabolism
  • Protein synthesis: makes all circulating proteins except gammaglobulins, incluidng albumin, fibrinogin and clotting factors
  • Storage: glycogen, vits A, D, B12 in large amounts, small amounts of vit K, folate, iron, copper
  • Hormone metabolism: activates vitamin D, conjugation and exfcretion of steroid hormones (oestrogen/glucocorticoids), peptide hormone metabolism (insulin, GH, PTH)
  • Bile synthesis: 600-1000ml daily
  • Immune function: antigens from gut reach the liver via portal circulation and are phagocytosed by Kupffer cells


What are the benign and malignant kinds of liver tumours?

  • Benign: hepatic adenoma, haemangioma
  • Malignant:
    • Hepatocellular carcinoma
    • Angiosarcoma
    • Hepatoblastoma
    • Cholangiocarcinoma
    • Metastases from other primary tumours


What are the features of hepatic adenoma?

  • Associated with OCP
  • Presents with abdo pain/intraperitoneal bleeding
  • Resection if symptomatic, >5cm or no shrinkage when stopping OCP


What are the features of haemangioma?

  • Most common benign lesion of liver
  • No treatment needed


What are the causes of/investigations for hepatocellular carcioma?

  • Causes: hepatitis B + C, alcoholic cirrhosis, haemochromatosis, NAFLO, aflatoxin, androgenic steroids
  • Investigations: alpha fetoprotein, USS


What are the features & causes of cholangiocarcinoma?

  • =adenocarcinomas arising from bile ducts
  • 10% of liver tumours
  • Can be intra or extra hepatic
  • Poor prognosis
  • Causes:
    • Primary sclerosing cholangitis
    • Parasitic liver disease
    • Chronic liver disease
    • Congenital liver abnormalities
    • Lynch syndrome type II


Where do metastatic liver lesions usually come from?

  • GI tract, breast, or bronchus
  • Most common malignant liver lesion and usually multiple


Define 'cirrhosis'

Diffuse abnormality of liver architecture that interferes with blood flow and liver function


What is the process leading to cirrhosis?

  1. Hepatocyte necrosis
  2. Fibrosis
  3. Nodules of regenerating hepatocytes
  4. Disruption of liver architecture -> increased resistance to blood flow through liver -> portal hypertension


What are the causes of cirrhosis?

  • Alcoholic liver disease
  • Non-alcoholic fatty liver disease
  • Chronic viral hepatitis (hep B/D, C)
  • Autoimmune hepatitis
  • Biliary causes: primary biliary cirrhosis, primary sclerosing cholangitis
  • Genetic causes
    • Haemochromatosis - HFE gene Chr6
    • Wilson's disease - ATP7B gene Chr13
    • Alpha 1 antitrypsin deficiency - A1At
    • Galactosaemia
    • Glycogen storage disease
  • Drugs e.g. methotrexate


How is cirrhosis classified?

By the size of the regenerating nodules:

  • Micronodular (nodules <3mm) - uniform liver involvement, caused by alcoholic hepatitis and biliary tract disease
  • Macronodular (nodules >3mm) - variable nodule size, caused by viral hepatitis, Wilson's disease, alpha 1 antitrypsin deficiency


What are the histological changes/pathophysiology in cirrhosis?

  • Chronic inflammation activates stellate cells (usually quiescent in the Space of Disse)
  • They become myofibroblasts that initiate fibrosis by deposition of collagen in the space of Disse
  • Myofibroblasts contract, constricting sinusoids and increasing vascular resistance
  • Undamaged hepatocytes regenerate in nodules between fibrous septa


What is the Modified Child's Pugh Score?

Used to indicate prognosis in cirrhosis.

  • Ascites: none (1), mild (2), moderate/severe (3)
  • Encephalopathy: none (1), mild (2), marked (3)
  • Bilirubin: <34 = 1, 34-50 = 2, >50 = 3
  • Albumin >35 = 1, 28-35 = 2, <28 = 3
  • Prothrombin time (seconds above normal): <4 = 1, 4-6 = 2, >6 = 3


  • Score <7 = Child's Pugh A (45% 5 year survival)
  • Score 7-9 = B (20% 5 year survival)
  • Score 10+ = C (<20% 5 year survival)


What are some mechanisms by which portal pressure can increase?

  • Increased vascular resistance in liver
  • Hyperdynamic circulation
  • Sodium retention and plasma volume expansion


What happens when portal pressure is >10-12 mmHg?

The venous system dilates and collateral vessels form at:

  • Gastro oesophageal junction
  • Rectum
  • L renal vein
  • Diaphragm
  • Retroperitoneum
  • Anterior abdominal wall - umbilical vein


What are the causes of portal hypertension?

  • Prehepatic: portal vein thrombosis (e.g. factor V leiden)
  • Hepatic:
    • Pre sinusoidal - schistosomiasis, primary biliary cirrhosis, sarcoidosis
    • Sinusoidal - cirrhosis
    • Post-sinusoidal - veno-occlusive disease
  • Post hepatic: Budd Chiari syndrome (= occlusion of hepatic vein)


What are the causes of Budd-Chiari syndrome and how is it treated?

  • Occlusion of hepatic vein
  • 30% idiopathic
  • Otherwise: thrombophilia, OCP, leukaemias, compression by renal tumours, HCC, radiotherapy
  • Treatment: thrombolytic, treat underlying cause, TIPS (transjugular intrahepatic portosystemic shunt)


What are the macroscopic and microscopic features of hepatic steatosis?

  • Macroscopic: large, pale, yellow, greasy liver
  • Microscopic:
    • Accumulation of fat droplets in hepatocytes (=steatosis)
    • Chronic exposure -> fibrosis (late stage)
    • Fully reversible if alcohol avoided


What are the macroscopic and microscopic features of alcoholic hepatitis?

  • Macroscopic: large, fibrotic liver
  • Microscopic: 
    • Hepatocyte ballooning and necrosis due to accumulation of fat, water and proteins
    • Mallory bodies
    • Fibrosis
    • Seen acutely after a night of heavy drinking and ranges form asymptomatic to fulminant liver failure
    • Each episode has a 10-20% mortality


What are the macroscopic and microscopic features of alcoholic cirrhosis??

  • Macroscopic: yellow-tan, fatty, enlarged, which transforms into a shrunken, non-fatty, brown organ
  • Microscopic:
    • Micronodular cirrhosis - i.e. small nodules and bands of fibrous tissue


Who gets non-alcoholic fatty liver disease?

= Hepatic steatosis in non alcoholics - most common cause of chronic liver disease in the West.

Mainly obese individuals with hyperlipidaemia/metabolic syndrome (diabetes also a risk factor)


Which 2 conditions come under the umbrella of non-alcoholic fatty liver disease?

  • Simple steatosis: fatty infiltration, relatively benign
  • Non-alcoholic steatohepatitis (NASH): steatosis and hepatitis (fatty infiltration and inflammation), can progress to cirrhosis


Who gets autoimmune hepatitis/what's it associated with?

  • Common with other autoimmune diseases
  • 78% female - young and postmenopausal
  • Associated with HLA-DR3


What are the 2 types of autoimmune hepatitis and what Ig are they associated with?

  • Type 1:
    • ANA (antinuclear Ig)
    • Anti-Sm (anti smooth muscle) Ig
    • Anti-actin Ig
    • Anti soluble liver antigen Ig
  • Type 2:
    • Anti LKM (liver-kidney microsomal) Ig


How is autoimmune hepatitis treated and what's the prognosis?

Immune suppression until transplant, but returns in up to 40%



What is primary biliary cirrhosis?

Autoimmune inflammatory destruction of medium sized intrahepatic bile ducts -> cholestasis -> SLOW development of cirrhosis over many years


Who gets primary biliary cirrhosis?

F>M 10:1, peak incidence at 40-50 years


What are the features of primary biliary cirrhosis (lab, histology, symptoms)?

  • High: serum ALP, cholesterol, IgM, bilirubin (late); anti-mitochondrial antibodies in >90%
  • USS: no bile duct dilatation
  • Histology: bile duct loss with granulomas
  • Presenting features: fatigue, pruritus, abdo discomfort
  • Secondary symptoms: skin pigmentation, xanthelasma, steatorrhoea, vit D malabsorption, inflammatory arthropathy


How is primary biliary cirrhosis treated?

Ursodeoxycholic acid in early phase - induces remission in 25%


What is primary sclerosing cholangitis?

Inflammation and obliterative fibrosis of extrahepatic and intrahepatic bile ducts -> multifocal stricture formation with dilatation of preserved segments


Who gets primary sclerosing cholangitis?

M>F; peak incidence 40-50 years; associated with IBD,  especially UC


What are the features of primary sclerosing cholangitis and what's the risk?

  • High serum ALP
  • Several associated auto-Ig, particularly p-ANCA
  • US: bile duct dilatation
  • ERCP: beading of the bile ducts due to multifocal strictures
  • Increased incidence of cholangiocarcinoma


What's the incidence and age for haemochromatosis?

Homozygotes: 1 in 400

Heterozygotes: 1 in 10 (carriers - Caucasians)

Age: 40-50 years


What's the pathophysiology and histology in haemochromatosis?

  • Autosomal recessive
  • Mutated HFE gene on 6p21.3 causes increased iron gut absorption which deposits in liver, heart, pancreas, adrenals, pituitary, joints, and skin causing fibrosis
  • Histology: iron deposits in liver, whch stains with Prussian blue stain


What are the investigation findings and treatment for haemochromatosis?

  • Investigations:
    • High Fe, high ferritin
    • Transferrin saturation >45%
    • Low TIBC
  • Treatment
    • Venesection
    • Desferrioxamine
    • 30% with cirrhosis will get HCC


What's the incidence and age for Wilson's disease?

1 in 30,000 (very rare)

11-14 years


What's the pathophysiology and histology of Wilson's disease?

  • Autosomal recessive
  • Mutated gene ATP7B (Chr13)
  • Gene encodes copper transporting ATPase expressed on canalicular membrane, therefore decreased biliary Cu excretion and deposition in liver, CNS, and iris
  • Histology:
    • Cu stains with Rhodanine stain
    • Mallory bodies and fibrosis on miscroscopy


What are the signs/symptoms of haemochromatosis?

  • Skin bronzing (melanin deposition)
  • Diabetes
  • Hepatomegaly with micronodular cirrhosis
  • Cardiomyopathy
  • Hypogonadism
  • Pseudogout


What are the signs/symptoms of Wilson's disease?

  • Liver disease: acute hepatitis, fulminant liver failure, or cirrhosis
  • Neuro disease: Parkinsonism, psychosis, dementia (basal ganglia involvement)
  • Kayser-Fleischer rings: copper deposits in Descemet's membrane in cornea


What are the investigation findings and treatment for Wilson's disease?

  • Investigations:
    • Low serum caeruloplasmin
    • Low serum copper
    • High urinary copper
  • Treatment
    • Lifelong penicillamine
    • Good prognosis with early treatment but any neuro damage is permanent
    • May need liver transplant


What is the pathophysiology and histology in alpha-1-anti-trypsin deficiency?

  • Autosomal dominant
  • A1AT accumulates in hepatocytes -> intra cytoplasmic inclusoins -> hepatitis
  • Lack of A1AT in lungs -> emphysema
  • Histology:
    • Intracytoplasmic inclusions of A1AT which stan with periodic acid Schiff


What are the signs and symptoms of alpha-1-anti-trypsin deficiency?

  • Kids: neonatal jaundice
  • Adults: emphysema and chronic liver disease


What are the investigation findings in alpha-1-anti-trypsin deficiency?

  • Low A1At
  • Absent alpha globulin band on electrophoresis


What are the causative organisms for cystitis?

  • 85% gram negative bacilli that normally reside in the intestine
  • E coli commonest
  • Also: Proteus, Klebsiella, Enterobacter, Strep faecalis


What are the predisposing factors to cystitis?

  • Female
  • Bladder calculi
  • Urinary obstruction
  • DM
  • Sexually active
  • Instrumentation
  • Cyclophosphamide associated with haemorrhagic cystitis


What are the clinical features of cystitis?

Suprapubic pain, low grade fever, dysuria, frequency


What are teh possible complications of cystitis and how do you treat it?

Ascending infection can cause pyelonephritis

Treat with trimethoprim/nitrofurantoin


What are the 3 main kinds of bladder tumour?

Transitional cell (urothelial) - 90%

Squamous cell carcinoma



Who gets Transitional cell (urothelial) tumours?

  • M:F = 3:1
  • 80% occur between 50-80 years
  • Contributing factors: cigarette smoking, industrial exposure to aromatic amines


What are the features of Transitional cell (urothelial) tumours and how are they diagnosed?

  • PAinlesss haematuria
  • Frequency, urgency
  • Pyelonephritis or hydronephrosis if ureteral orifice involved
  • Tendence to develop new tumours after excision with recurrences showing higher grade
  • Diagnose with cystoscopy and biopsy


What are the causes of bladder squamous cell carcinomas and adenocarcinomas?

  • Squamous - schistosomiasis
  • Adeno - rare, arises from extensive intestinal metaplasia or from urachal remnants


What is benign prostatic hyperplasia?

Dihydrotestosterone-mediated hyperplasia of prostatic stromal and epithelial cells, resulting in formation of large nodules


What are the symptoms of benign prostatic hyperplasia?

  • Difficulty urinating
  • Retention
  • Frequency
  • Nocturia
  • Overflow dribbling


How is benign prostatic hyperplasia treated?

TURP, 5alpha reductase inhibitors


What is the most common form of protstate cancer in men over 50?



Prostatic adenocarcinoma:

  • Risk factors
  • Location
  • Spread
  • Grading
  • Diagnosis

Prostatic adenocarcinoma:

  • Risk factors - age, race, family history, hormonal and environmental influences
  • Location - classically arises in peripheral zone
  • Spread - local spread to the bladder, haematogenous sperad to bone
  • Grading - Gleason system - deree of differentiation and glandular patterns
  • Diagnosis - history, examination, PSA (over 4ng/ml)


What are the 3 kinds of prostatitis?

  • Acute bacterial
    • E coli, gram negatives, enterococci
  • Chronic bacterial
    • History of recurrent UTI
  • Chronic abacetrial prostatis
    • No history of recurrent UTI


What are the 2 kinds of testicular tumours and which is more common?

Germ cell - 95%

Sex cord stromal - 5%


What are the types of germ cell testicular tumours?

  • Seminoma
  • Spermatocytic seminoma
  • Embryonal carcioma
  • Yolk sac
  • Choriocarcinoma
  • Teratoma


What are the types of sex cord stromal testicular tumour?

  • Leydig cell tumour (derived from stroma)
  • Sertoli cell tumour (derived from sex cord)


What are the predisposing factors to a germ cell testicular tumour?

  • Cryptorchidism
  • Testicular dysgenesis
  • Genetic factors e.g. Klinefelter's, testicular feminisation


What are the characteristics of testicular seminoma?

  • Most common germinal tumour
  • Peak age 30s
  • Radiosensitive


What are the characteristics of testicular teratoma?

  • Any age from infancy to adult life
  • Malignant when it occurs in the post pubertal male
  • Chemosensitive
  • Biologic markers for germ cell tumours: AFP, HCG, LDH
  • Clinical features - painless enlargement


How common is maldescent of testes?

1% of males - 90-95% in the inguinal canal


What are the types of renal cell carcinoma and what distinguishes them?

  • Clear cell - well differentiated
  • Papillary - commonset in dialysis associated cystic disease
  • Chromophobe - pale, eosinophilic cells


What are the risk factors for renal cell carcinoma?

  • Smoking
  • Obesity
  • HTN
  • Unopposed oestrogen
  • Heavy metals
  • CKD


What are the clinical features of renal cell carcinoma?

  • Costovertebral pain
  • Palpable mass
  • Haematuria
  • Possible paraneoplastic syndrome:
    • Polycythaemia
    • Hypercalcaemia
    • HTN
    • Cushing's syndrome
    • Amyloidosis


What is pulmonary oedema, what causes it and what is seen on histology?

  • Intra alveolar fluid accumulation leading to poor gas exchange
  • Mainly from left heart failure
  • Histology:
    • Intra alveolar fluid
    • Iron laden macropahges ("heart failure cells")


What are the features of diffuse alveolar disease, its causes, and what is seen on histology?

  • ARDS in adults e.g. infection, aspiration, trauma
  • Hyaline membrane disease in neonates e.g. insufficient surfactant production in prems
  • Histology
    • Lung expanded
    • Firm
    • Plum coloured
    • Airless


How many PEs are from DVTs?



What are the risk factors for PE?

  • Female
  • Immobility
  • Cardiac disease
  • Cancer
  • Primary and secondary hypercoagulable states (Virchow's: blood stasis, damage to endothelium, increased coagulation)


What are the consequences of large and small pulmonary emboli?

  • Large: impact in main pulmonary arteries causing acute cor pulmonale, cardiogenic shock and death if >60% pulmonary bed occluded
    • If occluding pulmonary trunk = saddle embolus
  • Small: can be silent or cause peripheral wedge infarctions; repeated infarctions can cause pulmonary hypertension


What are some sources of non-thrombotic pulmonary emboli?

  • Bone marrow
  • Amniotic fluid
  • Tumour
  • Air
  • Foreign body


What is the definition of pulmonary hypertension?

Mean pulmonary arterial pressure of >25mmHg at rest


What are the causes of pulmonary hypertension?

  • Primary - most common in young women aged 20-40
  • Secondary:
    • Pre-capillary - chronic hypoxia/embolus
    • Capillary - pulmonary fibrosis
    • Post-capillary - left heart disease, veno-occlusive disease
    • Pulmonary vasoconstriction of arterioles - intimal fibrosis, thickened walls


What are the consequences of pulmonary hypertension?

  • RHF
  • Venous congestion of organs (nutmeg liver)
  • Peripheral oedema


Where does mesothelioma arise from and what's it associated with?

  • Arises from parietal or visceral pleura
  • Caused by asbestos exposure but long latent period of 25-45 years
  • Spreads widely within pleural space
  • Associated symptoms:
    • Extensive pleural effusion
    • Chest pain
    • Dyspnoea


What are some molecular markers in lung cancer and what do they mean?

  • ERCC1 - NSCLC - poorer response to cisplatin
  • EGFR - adeno (usually) - target for anti-EGFR (usually tyrosine kinase inhibitor) therapy
  • Kras - adeno/squamous - poor prognosis, non response to TKI
  • EML4-ALK - adeno (usually) - no benefit from TKI


What are the features of lung large cell carcinoma?

  • 10-15% of lung tumours
  • Poorly differentiated malignant epithelial tumour: large cells, large nuclei, prominent nuclei
  • Histology: no evidence of glandular or squamous differentiation
  • Poor prognosis
  • Paraneoplastic syndromes: ADH, ACTH, PTH, PTHrP, calcitonin, serotonin, bradykinin


What are the features of/associations with small cell carcinoma of the lung?

  • 20-25% lung tumours
  • Usually occurs centrally, proximal bronchi
  • Arises from neuroendocrine cells
  • Associated with:
    • Ectopic ACTH
    • Lambert Eaton
    • Cerebellar degeneration
  • Highly malignant, metastasise early, usually be diagnosis, commonly to bone, adrenal, liver, and brain
  • Poor prognosis despite being very chemosensitive as metastasises so early
  • Strong relationship to smoking
  • Associated with p53 and RB1 mutations


What are the features of lung adenocarcinoma?  How does it progress?

  • 20-30% lung tumours
  • Most common in women and non-smokers
  • Mailgnant epithelial tumour with glandular differentiation or mucin production
  • Occurs peripherally and metastasises early
  • Histology: glandular differentiation (gland formation and mucin production)
  • Cytology: cells containing vacuoles
  • Molecular: EGFR mutations
  • Progression:
    • Atypical adenomatous hyperplasia ->
    • Non mucinous BAC ->
    • Mixed pattern adenocarcinoma


What are the features of lung squamous cell carcinoma?  What's it associated with and how does it progress?

  • 30-50% lung cancers
  • Risk factors: M>F, closely correlated with smoking
  • Highest rate of p53/c-myc mutations
  • Usually proximal bronchi, local spread with late metastasis
  • Less responsive to chemo
  • Histopathology: keratinisation, intercellular prickles (desmosomes)
  • Cytology - squamous cells
  • Variety of subtypes e.g. papillary, basaloid
  • Associated with cavitation and hypercalcaemia
  • Progression:
    • Epithelium -> hyperplasia -> squamous metaplasia -> angiosquamous dysplasia -> carcinoma in situ -> invasive carcinoma


What is a granuloma?

A collection of histiocytes, macrophages, +/- multinucleate giant cells


What are some infectious and non infectious granulomatous lung diseases?

  • Infections: TB, fungal (histoplasma, Cryptococcus coccidioides, aspergillus, mucor), pneumocystis, parasites
  • Non infectious: sarcoid, foreign body (aspiration or IVDU), drugs or occupational lung disease


What is the histology of extrinsic allergic alveolitis (& the similar conditions)?

Polypoid plugs of loose connective tissue within alveoli/bronchioles - granuloma formation and organising pneumonia


What is the acute presentation of  extrinsic allergic alveolitis?

Inhalation of antigenic dust in sensitised individual -> systemic symptoms (fever, chills, chest pain, SOB, cough) within hours of exposure, usually settle by following day and progresses to chronic EAA


What is the chronic presentation of EAA (etc)?

Progressive persistent productive cough + SOB, finger clubbing + severe weight loss


What are the different varieties of extrinsic allergic alveolitis?

  • Farmer's lung - mouldy hay/grain/silage - Saccharopolyspora rectivirgula
  • Pigeon fancier's lung - proteins in excreta/feathers
  • Humidifier's lung - heated water reservoirs - thermactinomyces spp
  • Malt workers lung - germinating barley - Aspergillus clavatus/fumigatus
  • Cheese washer's lung - mouldy cheese - Aspergillus clavatus/penicillum casei


What causes cryptogenic fibrosing alveolitis/idiopathic ppulmonary fibrosis?

Uknown but it's more common in men


What's the histology in cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?

  • Needed for diagnosis is the histological pattern of fibrosis, Usual Interstitial Pneumonia, also seen in connective tissue disease, asbestosis and EAA
    • Progressive patchy interstitial fibrosis with loss of normal lung architecture and honeycomb change, beginning at the periphery of the lobule, usually sub pleural
    • Hyperplasia of type II pneumocytes causing cyst formation - honeycomb fibrosis


What is the clinical presentation of cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?

  • Increasing exertional dyspnoea and non productive cough
  • 40-70 years old at perentation
  • Hypoxaemia -> cyanosis and pulmonary hypertension +/- cor pulmonale and clubbing


What's the treatment for cryptogenic fibrosing alveolitis/idiopathic pulmonary fibrosis?

Steroids, cyclophosphamide, azathioprine, but little impact on survival


What are the features of pneumoconiosis?

  • Typically occupational
  • Non neoplastic lung reacton to inhalaton of mineral dusts or inorganic particles
  • The majority affect the upper lobe e.g. coal worker's pneumoconiosis, silicosis
  • Asbestosis can cause benign pleural lesions (plaques, fibrosis) and also malignant lesions (adenocarcinoma, mesothelioma)


What characterises interstitial lung disease?

  • Inflammation and fibrosis of the pulmonary connective tissue, particularly the most peripheral and delicate interstitium of the alveolar wall
  • Features of restrictive lung disease on spirometry:
    • Decreased CO diffusion capacity
    • Decreased lung volume
    • Decreased compliance
  • Presents with:
    • SOB
    • End inspiratory crackles
    • Cyanosis, pulmonary HTN and cor pulmonale
  • When end stage they all have honeycomb lung


What are the categories of interstitial lung disease?

  • Fibrosing
    • Idiopathic pulmonary fibrosis
    • Pneumoconiosis
    • Cryptogenic organising pneumonia
    • Associated with connective tissue disease
    • Drug induced
    • Radiation pneumonitis
  • Granulomatous
    • Sarcoid
    • Extrinsic allergic alveolitis
    • Associated wtih vasculitides e.g. Wegener's, Churg-Strauss, microscopic polyangiitis
  • Eosinophilic
  • Smoking related


Chronic bronchitis

  • Site
  • Pathology
  • Aetiology
  • Clinical features
  • Histological features
  • Complications

Chronic bronchitis

  • Site - bronchus
  • Pathology - dilatation of airways and excess mucus
  • Aetiology - tobacco smoke, air pollution
  • Clinical features - cough and sputum on most days for 3 months over 2 years
  • Histological features - dilatation of the airways, goblet cell hyperplasia, and hypertrophy and mucous glands
  • Complications - recurrent infections, chronic hypoxia, pulmonary HTN



  • Site
  • Pathology
  • Clinical features
  • Histological features
  • Complications


  • Site - bronchus
  • Pathology - airway dilatation and scarring
  • Clinical features - cough, purulent sputum, fever
  • Histological features - permanent dilatation of bronchi
  • Complications - recurrent infections, haemoptysis, pulmonary hypertension, amyloidosis



  • Site
  • Pathology
  • Aetiology
  • Clinical features
  • Histological features
  • Complications


  • Site - bronchus
  • Pathology - SM cell hyperplasia, excess mucus, inflammation
  • Aetiology - immunologic: allergens, drugs, cold, exercise
  • Clinical features - episodic coughing, wheezing, dyspnoea
  • Histological features - whorls of shed epithelium (Curschmann spirals), eosinophils, Charcot-Leyden crystals
  • Complications - chronic asthma, death



  • Site
  • Pathology
  • Aetiology
  • Clinical features
  • Histological features
  • Complications


  • Site - acinus
  • Pathology - air space enlargement, wall destruction
  • Aetiology - tobacco smoke, alpha1 antitrypsin deficiency
  • Clinical features - dyspnoea, cough
  • Histological features - loss of the alveolar parenchyma distal to the terminal bronchiole
  • Complications - pneumothorax, respiratory failure, pulmonary HTN


Small airway disease/bronchiolitis

  • Site
  • Pathology
  • Aetiology
  • Clinical features

Small airway disease/bronchiolitis

  • Site - bronchiole
  • Pathology - inflammatory scarring/obliteration
  • Aetiology - tobacco smoke, air pollutants
  • Clinical features - dyspnoea, cough


What are the causes of bronchiectasis?


  • Post infectious (especially children)
  • Abnormal host defence (primary or secondary)
  • Ciliary dyskinesia (primary e.g. Kartagener's or secondary)
  • Obstruction: extrinsic/intrinsic/middle lobe syndrome
  • Post inflammatory (aspiration)
  • Secondary to bronchiolar disease and interstitial fibrosis
  • Systemic disease (connective tissue)
  • Asthma



  • Cystic fibrosis
  • Primary ciliary dyskinesia
  • Hypogammaglobulinaemia


What are the types/causes of pericarditis?

  • Fibrinous - MI, uraemia
  • Purulent - staphylococcus
  • Granulomatous - TB
  • Haemorrhagic - tumour, TB, uraemia
  • Fibrous aka constrictive - arises from any of the above


What is pericardial effusion and what causes it?

  • Serous fluid in pericardial sac
  • Usually due to chornic heart failure
  • Exudative fluid can be secondary to inflammatory, infectious, malignant or autoimmune processes within the pericardium


What's haemopericardium?

Myocardial rupture from myocardial infarction or trauma


What are the features of rheumatic valve disease?

  • Predominantly lef sided and most commonly mitral
  • Mitral > aortic > tricuspid > pulmonic
  • Thickening of the valve leaflet especially along lines of closure, and fusion of commissures
  • Also thickening, shortening and fusion of chordae tendinae


What are the characteristics of mitral valve prolapse?

Clinically appears in middle aged women short of breath with chest pans.

Signs: mid systolic click and late systolic murmur


What causes aortic stenosis?

Calcification - can be accelerated by bicuspid valve


What are teh causes of aortic regurgitation?

  • Rigidity: rheumatic, degeneration
  • Destruction: endocarditis
  • Dilatation: valve insufficient to cover increased area:
    • Cystic medial degeneration
    • Marfan's
    • Dissecting aneurysm (medial degeneration or hypertension)
    • Syphilitic aortitis
    • Ankylosing spondylitis


What are some causes of infective endocarditis?

  • Poor dental hygiene
  • Soft tissue infection
  • Cannulae/lines
  • IVDU
  • Dental treatments
  • Cardiac surgery/pacemakers


What are some predisposing factors to infective endocarditis?

  • Rheumatic heart disease
  • Calcified valves
  • Prosthetic valves
  • Mitral valve prolapse
  • Bicuspid aortic valve
  • Congenital defects


What are the causative organisms for acute and subacute endocarditis?

  • Acute: staph aureus, strep pyogenes
  • Subacute: strep viridans, staph epidermis, HACEK (culture negative), coxiella, candida, mycoplasma


Acute vs subacute endocarditis:

  • Virulence
  • Vegetation morphology
  • Spread

  • Acute
    • Virulence - high
    • Vegetation - larger and more localised
    • Spread - aorta
  • Subacute
    • Virulence - low
    • Vegetation - friable, soft thrombi a few mm in size
    • Spread - chordae


What are the clinical features of infective endocarditis?

  • Fever
  • Anaemia
  • Splenomegaly
  • Malaise
  • Rigors
  • New murmurs
  • Roth spots
  • Janeway lesions
  • Splinter haemorrhages
  • Osler's nodes
  • Usually mitral/aortic valve unless IVDU in which case right sided valves are involved


What are the criteria for infective endocarditis diagosis and what's the treatment?

Dukes criteria

Benpen + gent


What are the causes of vegetative endocarditis?

  • Rheumatic heart disease
  • Infective endocarditis
  • Non-bacterial thrombotic endocarditis (marantic)
  • Libman-Sacks endocarditis


What is the pathology in rheumatic endocarditis, including the characteristics of the vegetations?

  • Antigenic mimicry - cross reaction of anti streptococcal antibodies with heart tissue
  • Small, warty vegetations found along the lines of closure of valve leaflet - verrucae


What is the pathology in infective endocarditis, including the characteristics of the vegetations?

  • Colonisation or invasion of heart valves or mural endocardium by microbe
  • Large, irregular masses on valve cusps, extending into the chordae


What is the pathology in non-bacterial thrombotic endocarditis, including the characteristics of the vegetations?

  • DIC/hypercoagulable states
  • Small, bland genetations attached tot he lines of closure formed of thrombi


What is the pathology in Libman-Sacks endocarditis, including the characteristics of the vegetations?

  • Pathogenesis unknown
  • Associated with SLE, and anti-phospholipid syndrome
  • Small (up to 2mm) warty vegetations that are sterile and platelet-rich


When is the peak for acute rheumatic fever, what's the main pathogen and what is the main pathology?

  • Peaks at 5-15 years
  • Lancefield group A strep is main pathogen
  • Antigenic mimicry - cell mediated immunity and antibodies to streptococcal antigen cross react with myocardial antigens


Which systems are affected in acute rheumatic fever?

  • Heart: pancarditis i.e. endocarditis, myocarditis, pericarditis
  • Joints: arthritis and synovitis
  • Skin: erythema marginatum, subcutaneous nodules
  • Neuro: encephalopathy, Sydenham's chorea


What are the clinical features of acute rheumatic fever?

  • Develops 2-4 weeks after strep throat infection
  • Often minor symptoms: fever, tachycardia, malaise, migrating polyarthralgia
  • Commonly affects mitral valve only (70%) but also mitral and aortic (25%)


What is the histology in acute rheumatic fever?

  • Beady fibrous vegetations (verrucae)
  • Aschoff bodies (small giant-cell granulomas)
  • Anitschkor myocytes - regenerating myocytes


How is acute rheumatic fever diagnosed?

  • Jones criteria with
  • Lab tests showing raised ESR and ASOT titres


What is the treatment for acute rheumatic fever?

Benpen, or erythromycin if penicillin allergic


Dilated cardiomyopathy:

  • Mechanism of heart failure
  • Causes
  • Indirect myocardial dysfunction

Dilated cardiomyopathy:

  • Mechanism of heart failure - systolic dysfunction
  • Causes - idiopathic, alcohol, peripartum, genetic, sarcoidosis, haemochromatosis, myocarditis
  • Indirect myocardial dysfunction - IHD, valvular disease, hypertension, congenital heart disease


Hypertrophic cardiomyopathy:

  • Mechanism of heart failure
  • Causes
  • Indirect myocardial dysfunction

Hypertrophic cardiomyopathy:

  • Mechanism of heart failure - diastolic dysfunction
  • Causes - genetic, storage diseases
  • Indirect myocardial dysfunction - hypertension, AS


Restrictive cardiomyopathy:

  • Mechanism of heart failure
  • Causes
  • Indirect myocardial dysfunction

Restrictive cardiomyopathy:

  • Mechanism of heart failure - diastolic dysfunction
  • Causes - sarcoidosis, amyloidosis, radiation induced fibrosis
  • Indirect myocardial dysfunction - pericardial constriction


What is arrhythmogenic right ventricular cardiomyopathy?

Myocyte loss with fibrofatty replacement


What are the features of hypertrophic cardiomyopathy?

  • Heart typically thick walled, heavy and hyper contrating
  • Common phenotype is myocardial hypertrophy (especially within septum an dleft ventricle) without ventricular dilatation
  • Histologically - myocyte disarray (which is arrhythmogenic)
  • AD inheritance - mutation in genes encoding sarcomeric proteins (in betaMHC most common - 403 Arg-Gln)
    • MYBP-C and trop-T also common 0 together account for 70-80% of cases
  • Different mutations result in different amount of hypertrophy and affects incidence of arrhythmias
  • May cause sudden cardiac death in young people; trop T mutations higher risk
  • Hypertrophic obstructive cardiomyopathy = septal hypertrophy resulting in outflow tract obstruction
  • 15-20% go on to develop DCM phenotype


What are the common causes of heart failure?

  • IHD
  • Hypertension
  • Valve disease
  • Dilated cardiomyopathy
  • Myocarditis
  • Arrhythmias


What are the complications of heart failure?

  • Sudden death
  • Systemic emboli
  • Hepatic cirrhosis (nutmeg liver)
  • Pulmonary oedema with superimposed infection
  • Arrhythmias
  • DVT + PE


What is the process leading to heart failure?

  • Insult results in decreased cardiac output
  • Compensatory mechanisms kick in which are beneficial in the short term but bad long term
    • Reduced CO activates renin-angiotensin system causing salt and water retention; maintains perfuson but eventually leads to fluid overload
    • Decrease in stroke volume activates the sympathetic nervous system via baroreceptors; prolonged activation increases TPR -> increased afterload -> ventricular hypertrophy
    • Increased afterload -> increased end diastolic volume -> dilatation of ventricle -> worsening contractile function


How does the heart appear macroscopically in heart failure?

LV hypertrophied and dilated with myocardial fibrosis


What are the features of LV failure?

  • Damming of blood within pulmonary circulation causes:
    • Dyspnoea
    • Orthopnoea
    • PND
    • Wheeze
    • Fatigue
  • Eventually leads to decreased peripheral blood pressure and flow


What are the features of RV failure?

  • Often secondary to LVF but can be caused by chronic, severe pulmonary hypertension
  • Minimal pulmonary congestion but engorgement of systemic and portal venous systems, clinically seen as:
    • Peripheral oedema
    • Ascites
    • Facial engorgement



What investigations should you do in heart failure?

BNP, CXR, echo, ECG


What is the pathogenesis in MI?

  • Dynamic interaction between coronary atherosclerosis, plaque rupture, superimposed platelet activation, thrombosis and vasospasm ->
  • Occlusive intracoronary thrombus overlying a disrupted plaque
  • Results in necrosis secondary to ischaemia
  • Severe ischaemia lasting >20-40 mins causes irreversible injury and myocyte death


What are the complications of MI?

  • Mechanical
    • contractile dysfunction -> cardiogenic shock
    • Congestive cardiac failure
    • LV infarct - papillary muscle dysfunction/necrosis/rupture -> mitral regurg
    • Cardiac rupture of ventricular wall (haemopericardium), septum (left to right shunt), papillary muscle (mitral regurg)
    • Ventricular aneurysm usually develops >4 weeks post MI
  • Arrhythmias
    • VF - usually occurs in first 24h and is a common cause of sudden death
    • 90% of patients develop an arrhythmia following an MI
  • Pericardial problems
    • Early/peri infarct pericarditis (dusky haemorrhagic tissue)
    • Pericardial effusion +/- tamponade
    • Dressler's syndrome: chest pain, fevers and effusion weeks-months after MI
    • Fibrinous pericarditis - occurs if infarct extends to epicardium
  • Mural thrombus -> embolisation (often develop in ventricular aneurysms)


What are the histological findings in the hours, weeks and months post MI?

  • <6h: normal by histology (CK-MB also normal)
  • 6-24h: loss of nuclei, homogenous cytoplasm, necrotic cell death
  • 1-4 days: infiltration of polymorphs then macrophages
  • 5-10 days: removal of debris
  • 1-2 weeks: granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
  • Weeks-months: strengthening, decellularising scar tissue


What are the steps in atherogenesis?

  1. Endothelial injury
  2. LDL enters intima and is trapped in sub intimal space
  3. LDL is converted into modified and oxidised LDL causing inflammation
  4. Macrophages take up ox/modLDL via scavenger receptors and become foam cells
  5. Apoptosis of foam cells causes inflammationa and cholesterol core of plaque
  6. Increase in adhesion molecules on endothelium results in more macrophages and T cells entering the plaque
  7. Vascular smooth muscle cells form the fibrous cap


What is in an atherogenic plaque?

  • Cells - SMC, macrophages, other leukocytes
  • ECM including collagen
  • Intracellular and extracellular fluid


Where in the body is atherosclerosis most common?

  • Abominal aorta >thoracic aorta
  • More prominent around origins (ostia) of major branches - turbulent blood flow has low oscillatory/shear stress whih is atherogenic
  • High laminar flow is protective


What are the risk factors for atherosclerosis?

  • Modifiable: T2DM, hypertension, hypercholesterolaemia, smoking
  • Non modifiable: gender (males > females), increasing age, FH