Histopathology Flashcards
Which respiratory pathology is defined as persistent dilatation of the bronchial airways?
Bronchiectasis
Which is the most common genetic disease associated with bronchiectasis?
Cystic fibrosis
Which bacterial infections are common in bronchiectasis?
Haemophilus influenzae, pseudomonas aeruginosa, staphylococcus aureus),
What are the characteristic clinical features of bronchiectasis?
- Cough (Productive, mucoid sputum)
- Dyspnoea
- Haemoptysis
- Pleuritic chest pain
- Wheeze
- Bi-basal crepitations
What is the most common infective cause of bronchiectasis in adult patients?
Pertussis
What are the 4 common congenital cause of bronchiectasis?
- Cystic Fibrosis
- Primary Ciliary dyskinesia
- Hypogammaglobulinaemia
4 - Young’s syndrome
What is Young’s syndrome?
Triad of Rhinosinusitis, azoospermia, and bronchiectasis.
What is the diagnostic test for bronchiectasis?
High-resolution CT
What are the findings associated with HRCT?
- Bronchoarterial ratio >1
- Signet Ring sign – Dilated airways
What are the complications associated bronchiectasis?
Recurrent infections, haemoptysis, cor pulmonale and amyloidosis.
What is the inheritance pattern of cystic fibrosis?
Autosomal recessive
What is the pathogenic mutation associated with cystic fibrosis?
Delta F508 of the CFTR gene
Which test is used to diagnose CF in the newborn blood spot test?
Immunoreactive trypsinogen
What is the diagnostic test for confirming CF (include threshold)?
Positive sweat chloride test (>60 mmol/L).
Decreased secretion of which ion underpins the aetiology of CF?
Chloride
Which bacteria is commonly associated with CF respiratory tract infections?
Pseudomonas aeruginosa
Which is the ABx of choice for the management of Pseudomonas aeruginosa in CF patients?
Ciprofloxacin
What is the first line mucolytic in the management of CF?
Dornase alfa
What are the three pathophysiological principles for the aetiology of asthma?
- Mucous hypersecretion
- Smooth muscle contraction
- Inflammatory cell infiltration.
What is the aetiology of the immediate phase of asthma?
Mast cell degranulation resulting in mediator release
Which IL is responsible for eosinophil recruitment?
IL-5
What are the four histological findings associated with asthma?
Hyperaemia
Eosinophils and goblet cell hyperplasia
Hypertrophic constricted muscle
Mucous plugging
What are Curshmann’s spiral in athma?
Spiral-shaped mucous plug
Which type of crystals are found in eosinophils and basophil granules in asthma?
Charcot Leyden Crystal
What are ‘Heart-failure’ cells?
Iron-laded macrophages
How are oxidised LDLs detected?
Scavenger receptors
Macrophage phagocytosis of OxLDLs forms what?
Foam cells
What are the CXR findings for pulmonary oedema?
Alveolar opacification (batwing appearance), Kerley B-lines, cardiomegaly, fluid in horizontal fissure.
What are heart failure cells?
Iron-laded macrophages
Which disease in neonates is characterised by diffuse alveolar damage?
Hyaline membrane disease
What spirometry finding is observed in restrictive lung disease?
- Reduced FEV1 and FVR – normal ratio (FEV1/FVC ratio >70%).
What are the occupational causes of interstitial lung disease?
- Organic dust – Mould spores, aerosolised bird droppings.
- Mineral dust – Silica, asbestos, coal mine dust, beryllium, and hard metal.
- Inhaled gases – Methane, cyanide.
What are the three advanced disease features in Interstitial Lung Disease?
Digital clubbing, pulmonary hypertension (increased P2 sound), Cor pulmonale.
What HRCT changes are observed in Interstitial Lung Disease?
Honeycomb/ground-glass appearance
What changes on light microscopy are observed in minimal change disease?
None
What is the most common cause of nephrotic disease in children?
Minimal change disease
How are OxLDLs detected?
Scavenger receptors
Macrophage phagocytosis of OxLDLs forms what?
Foam cells
Which aortic section is predisposed to atherosclerosis?
Abdominal aorta (due to low shear stress)
What are the three types of angina?
Stable angina
Unstable angina
Prinzmetal angina
What are the histological findings of cardiomyocytes 6-24 hours of myocardial infarction?
Loss of nuclei, homogenous cytoplasm, necrotic cell death.
At what stage does granulation tissue appear due to microfibroblast activity post-myocardial infarction?
1-2 weeks
Most commmon cause of sudden deeath
VF
When does Dressler’s syndrome occur?
~6-8 weeks post-MI
Persistent ST-elevation >4 weeks post-MI, cause?
Ventricular aneurysm
What is the causative organism for rheumatic fever
Lancefield Group A streptococcus
What are the Major Criteria for Rheumatic Fever?
Carditis
Arthritis
Sydenham’s chorea
Erythema marginatum
Subcutaneous nodules
How is rheumatic fever diagnosed?
Jones Criteria
2 Major
OR
1 Major + 2 Minor
What are the minor criteria associated with Rheumatic fever?
Fever
Raised CRP/ESR
Migratory arthralgia
Prolonged PR
Prev. rheumatic fever
Malaise
Tachycardia
Which cardiac valve is predominantly affected in Rheumatic fever?
Mitral valve (70%)
What term describes cell-mediated immunity and antibodies to streptococcal antigens cross-reacting with myocardial antigens?
Antigenic mimicry
What are the three histological findings observed in rheumatic fever?
- Beady fibrous vegetations (verrucae)
- Aschoff bodies (small giant cell granulomas)
- Anitschkov myocytes (regenerating myocytes)
What term describes small giant cell granulomas?
Aschoff bodies
What term describes regenerating myocytes in rheumatic fever?
Anitschkov myocytes
What is the ABx of choice for the management of rheumatic fever?
Benzylpenicillin
What term describes small warty vegetations in rheumatic heart disease?
Verrucae
What is Libman Sacks endocarditis?
Pathogenesis unknown. Associated with SLE and anti-phospholipid syndrome.
Small (up to 2mm) warty vegetations that are sterile and platelet rich
Which organism is implicated in infective endocarditis associated with poor dental hygeine?
Streptococcus viridians
Which infective endocarditis associated organism is associated with colon carcinoma?
Streptococcus bovis
What are the common causative organisms for acute infective endocarditis?
Staphylococcus aureus (30-40%)
Streptococcus pyogenes (Group A)
Which is the common causative organism associated with acute infective endocarditis associated with prosthetic valves?
Coagulase-negative staphylococcus
Which group of organisms are associated with subacute infective endocarditis?
HACEK Organisms:
Haemophilus, Aggregatibacter, Cardiobacterum, Eikenella, and Kingella.
Which two cardiac valves are predisposed to infective endocarditis?
Aortic valve
Mitral valve
Which valve is predisposed to infective endocarditis in the context of IVDU?
Right-sided valves e.g., Tricuspid valve
What are the thromboembolic symptoms associated with infective endocarditis?
- Splinter haemorrhages (thin red-brown lines along fingernails)
- Petechiae
- Janeway lesions (Painless flat macules on the palms and soles)
- Septic abscess in lungs/brains/spleen/kidney
- Micro-emboli
- Splenomegaly
What immune phenomena is associated with infective endocarditis?
- Osler’s nodes (Tender red/purple nodules on the pads of the fingers and toes)
- Roth spots (Retinal haemorrhages)
- Haematuria due to glomerulonephritis
- Finger clubbing
Which diagnostic criteria is used for the diagnosis of infective endocarditis?
Dukes Criteria
What are the two major criteria (Dukes) for the diagnosis of infective endocarditis?
(‘BE’)
Blood cultures - 2 positive cultures >12 hours apart
Echocardiographic evidence of vegetation on TTE or new regurgitant murmur
What are the minor criteria associated with infective endocarditis (TIMER)?
Thromboembolic phenomena
Immune phenomena
- Risk factors (e.g., prosthetic valve, IVDU, congenital valve abnormalities).
- Fever >38
- Positive blood cultures not meeting major criteria.
What is the ABx of choice for subacute infective endocarditis?
Benzylpenicillin + gentamicin or vancomycin for 4 weeks.
What is the ABx of choice for acute infective endocarditis?
- Acute: Flucloxacillin for MSSA, rifampicin + vancomycin + gentamicin for MRSA.
What is preload?
Initial stretch of cardiomyocytes before contraction – due to ventricular filling - increase Increase stroke volume (Frank-Starling Principle).
What is afterload?
- Afterload = Pressure of vessels (Aortic and pulmonary artery pressures) against which the heart must contract to eject blood Increase in afterload will decrease stroke volume (Inverse relationship).
Causes of Heart failure?
- Ischaemic heart disease
- Myocarditis
- Hypertension
- Cardiomyopathy (Dilated)
- Valve disease
- Arrhythmias
Liver pathology associated with right-sided heart failure?
Nutmeg liver
What is the most common cause of right ventricular failure?
Left ventricular failure due to chronic severe pulmonary hypertension
Features of right sided heart failure?
- Manifestations: Peripheral oedema, ascites, facial engorgement.
N.B: Congestion and stasis of venous blood in RHF = Nutmeg liver.
What type of heart failure is associated with dilated cardiomyopathy?
Systolic dysfunction
Hypertrophic and restrictive heart failure is associated with which type of heart failure?
Diastolic heart failure
What are the three most common causes of restrictive cardiomyopathy?
Sarcoidosis, amyloidosis, radiation-induced fibrosis,
What are the histological findings observed in HOCM?
Myocyte disarray
What is the inheritance pattern associated with HOCM?
Autosomal dominant
Which gene is implicated in the pathology of HOCM?
B-myosin gene
What type of hypertropjhy results in outflow tract obstruction in hocm?
Septal hypertrophy
What term describes myocyte loss with fibrofatty replacement affecting the right ventricle?
Arrhythmogenic Right Ventricular Cardiomyopathy
Define Beck’s triad
Muffled heart sounds, raised JVP and hypotension
What is the most common cause of AKI?
Acute tubular necrosis
What is the most common pre-renal cause of acute tubular necrosis?
Ischaemia (sepsis, hypotension)
Which nephrotoxic drugs result in acute tubular necrosis?
Aminoglycosides, amphotericin B, iodinated contrast, sulfa drugs, acyclovir, calcineurin inhibitors, vancomycin.
Which type of casts are associated with acute tubular necrosis?
Brown muddy casts
Eosinophilia and drug-induced allergy is associated with what type of AKI?
Acute tubulo-interstitial nephritis
Which drugs cause AIN?
Beta-lactam antibiotics, penicillin, NSAIDs, PPIs, allopurinol and 5-ASA.
Which infections are associated with AIN?
Legionella, Leptospira, cytomegalovirus, Streptococcus, and mycobacterium tuberculosis.
Which systemic diseases are associated with AIN?
Sarcoidosis, Sjögren’s disease, systemic lupus erythematosus
What are the common post-renal causes associated with AKI?
Obstruction to urinary flow – stones, tumours, (primary & secondary), prostatic hypertrophy, and retroperitoneal fibrosis.
What are the three primary causes of nephrotic syndrome?
- Minimal change disease
- Membranous glomerular disease
- Focal segmental glomerulosclerosis
What are the three major features of nephrotic syndrome?
- Proteinuria (>3g/24h / protein: creatinine ratio >300 mg/mmol) – frothy urine.
- Hypoalbuminaemia (<30 g/L)
- Oedema – Classically = periorbital
What are the secondary causes of nephrotic syndrome (3)?
Diabetes
Amyloidosis
SLE
What is the most common cause of nephrotic syndrome in children?
Minimal change disease
What are the electron microscopy findings in minimal change disease?
Loss of podocyte foot processes
What is the first line management for minimal change disease?
Corticosteroids
Which autoantibody is implicated with membranous disease?
Anti-phospholipase A2 type 2 receptor (Anti-PLA2R)
What are light microscopy findings in membranous glomerular disease?
Diffuse glomerular basement membrane thickening
Spike and Dome appearance is associated with nephrotic syndrome?
Membranous Glomerular Disease
Phosplipae A2 antibodies are associated with which type of nephrotic syndrome?
Membranous glomerular disease
Which type of nephrotic syndrome is most common in Afro-Carribbean people?
Focal Segmental Glomerulosclerosis
Focal Segmental Glomerulosclerosis (FSGS)
Light microscopy findings
Focal and segmental glomerular consolidation and scarring,
Hyalinosis
What histological nodules are associated with diabetic nephropathy?
Kimmelstiel Wilson nodules
Which stain is used in the histological evaluation of amyloidosis?
Congo Red Stain
What is the positive finding following Congo Red staining in amyloidosis?
Apple green birefringence
Kimmelstiel-Wilson lesion are associated with which stage of diabetic nephropathy?
Stage 3
What is stage I of diabetic nephropathy?
Thickened basement membrane
What is stage II of diabetic nephropathy?
Increase in mesangial matrix, without nodules
What is stage 3 of diabetic nephropathy?
nodular lesions/Kimmelstiel-Wilson lesion (KW) – round areas of sclerosis
Advanced glomerulosclerosis is associated with which stage of diabetes nephropathy?
Stage 4
What is azotaemia?
Raised urea and creatinine
What are the manifestations of nephritic syndrome?
Manifestation of glomerular inflammation e.g. glomerulonephritis – syndrome characterised by PHAROH:
* Proteinuria
* Haematuria (coke-coloured urine)
* Azotaemia – raised urea and creatinine.
* Red cell casts – In urine – red cell accumulation and leaks into the tubules.
* Oliguria
* Hypertension
Which nephritic syndrome cause is associated with impetigo or a sore throat?
Acute postinfectious (post-streptococcal) glomerulonephritis
Which organism is implicated in post-infectious glomerulonephritis?
- Lancefield Group A alpha-haemolytic Strep e.g., strep pyogenes
What are the serum investigations for post-streptococcal glomerulnephritis?
Bloods - ASO tire - raised
Complement C3 - Low
What are the electron microscopy findings of post-strep glomerulonephritis?
Subendothelial humps
What is the complication of nephritic syndrome?
End-stage renal failure
When does post-strep glomerulonephritis occur post-strep A infection?
1-3 weeks
Which cell type is implicated in the formation of crescents in rapidly progressive crescenteric glomerulonephritis?
Proliferation of macrophages and parietal cells in the Bowman’s capsule
What is type 1 RPCG?
Anti-BM antibody (Goodpasture’s diseae)
Which auto-antibody is implicated in Goodpasture’s disease?
Anti-GBM
Anti-GBM antibodies are targeted against what?
C-terminal domain of Type IV collagen
What are the extra-renal manifestations of goodpature’s diseae?
Pulmonary haemorrhage
What are the characteristics findings on light microscopy for Goodpasture’s disease?
Crescents
What are type 2 causes of Rapidly Progressive Crescentic GN?
Immune complex mediated e.g., SLE, IgA nephropathy, post-infectious GN, HSP, Alport’s syndrome
What are the fluorescent microscopy findings for anti-GBM disease?
Linear deposition of IgG in GBM
A granular IgG immune complex deposition on GBM is associated with which type of nephritic syndrome?
Immune complex mediated
What is type 3 Rapidly Progressive Crescentic glomerulonephritis?
Pauci-immune
c-ANCA is associated with what renal disease?
Wegener’s granulomatosis
p-ANCA is associated with which renal disease?
Microscopic polyangiitis
What is IgA nephropathy is associated with (aetiology)?
Upper respiratory tract infections or GI illness
What are the characteristic clinical manifestations of IgA nephropathy?
- Macroscopic haematuria - often associated with upper respiratory tract infections or gastrointestinal illness. Haematuria is characteristically recurrent in healthy patients.
- Loin pain
- Proteinuria
What are the renal biopsy findings associated with IgA Nephropathy ?
Mesangial hypercellularity, mesangial matrix expansion
What are the rule of thirds for IgA Nephropathy ?
1/3rd asymptomatic
1/3rd develop CKD
1/3rd develop progressive CKD requiring dialysis
Which classification is used to evaluate IgA Nephropathy ?
Oxford Classification system (MEST-C)
Which monoclonal antibody attenuates the progression of post-streptococcal glomerulonephritis into End-stage renal disease?
Rituximab
What is the inheritance pattern for Alport syndrome?
X-linked dominant
What is the characteristic extra-renal manifestation of Alport Syndrome?
Sensorineural deafness + eye disorders (lens dislocation, cataracts).
What are the clinical manifestations of Alport syndrome?
- Clinical manifestation: Nephritic Syndrome + Sensorineural deafness + eye disorders (lens dislocation, cataracts).
Biopsy finding for Alport syndrome?
Lamellation of the basement membrane.
What is pathogenesis of benign family haematuria?
Diffuse thinning of the GBM (<250 nm thickness) secondary to a mutation in type IV collage alpha
What is the thickness threshold for benign family haematuria?
<250 nm
What are the three common causes of asymptomatic haemturia?
Alport syndrome
Thin basement membrane disease (benign family haematuria)
IgA nephropathy (Berger disease)
What is the cause of haemolytic uraemic syndrome?
Shiga-toxin producing E coli 0157:O7
What is the triad of symptoms associated with HUS?
- Thrombocytopenia
- Microangiopathic haemolytic anaemia
- AKI
Why does thrombotic microangiopathy arise in haemolytic uraemic syndrome?
Due to non-immune erythrocyte mechanical shearing and peripheral blood fragmentation secondary platelet microthrombi
What prodromal illness is associated with HUS?
~5-10-day prodromal illness marked by abdominal pain, vomiting, and diarrhoea (haemorrhagic).
How are STEC infections transmitted?
Following the consumption of contaminated food products e.g., undercooked beef, unpasteurised milk and petting zoos.
Which deficiency should be screened for in haemolytic uraemic syndrome?
ADAMTS13
What are the markers of haemolysis?
Elevated bilirubin
Raised reticulocyte count
Raised LDH
What are the FBC findings for HUS?
Thrombocytopenia (<30)
Anaemia (<8g/dL)
What characteristic RBC cell types are observed on a peripheral blood smear in HUS?
schistocytes and helmet cells
Which agar is used for the confirmatory test for detect shiga-toxin producing E coli?
sorbitol-MacConkey Agar
What are the non-diarrhoea associated causes for thrombotic microangiopathy?
- Defects in the regulation of complement
- ADAMTS13 deficiency
- Drugs (Calcineurin inhibitors)
- Radiation
- Hypertension
- Scleroderma
- Antiphospholipid antibody syndrome (SLE)
What are the pentad of symptoms associated with TTP?
MAHA
Thrombocytopenia
Renal failure
Fever
Neurological symptoms e..g, confusion, seizures
Which genetic deficiency is associated with TTP?
ADAMTS13 deficiency
What is ADAMTS13 deficiency?
Cleaves vWF, deficiency results in the formation of giant vWF multimers - platelet aggregation and fibrin deposition.
What type of hypersensitivity reaction is associated with lupus nephritis?
Type 3 hypersensitivity - marked by the formation of immune-complexes
Which auto-antibody is implicated in the pathogenesis of lupus nephritis?
Anti-dsDNA
Which gender is predominantly affected by lupus nephritis?
Female predominance (9:1)
What is stage 1 of Lupus Nephritis?
Minimal mesangial disease
What stage II of Lupus Nephritis?
Proliferative mesangial
What is stage III of Lupus Nephritis?
Focal
Diffuse changes is associated with which stage of Lupus Nephritis?
Stage 4
Which changes on histology are observed in stage 5 lupus nephritis?
Membranous (Subepithelial immune deposits) - Wire loop capillaries on histology
Stage 6 histology changes for lupus nephritis?
Advanced sclerosis
eGFR parameter for stage 1 CKD?
> 90 mL/min
eGFR parameter for stage 2 CKD?
90-60
eGFR parameter for stage 3a CKD?
60-45
eGFR parameter for stage 3b CKD?
45-30
eGFR parameter for stage 4 CKD?
30-15
eGFR parameter for stage 5 CKD?
<15 (end-stage)
What is the most common cause of CKD?
Diabetes
What is the management for CKD?
Renal replacement therapy
- haemodialysis
-Peritoneal dialysis
-Renal transplant
What are the light microscopy changes observed in hypertensive nephropathy?
Global glomerular collapse and filling of Bowman’s capsule with collagenous material.
What are the multisystem manifestations of adult polycystic kidney disease?
- Multisystem and progressive disease with cyst formation, kidney enlargement and extrarenal organ involvement (e.g., liver, pancreas spleen, and arachnoid membranes).
Which gene is implicated in APKD?
PKD1
What does the PKD1 gene encode?
Polycystin-1
Why is there haematuria in PKD?
Cyst haemorrhage – cyst communicates with the collecting system
Presentation of Adult Polycystic Kidney Disease?
- Hypertension
- Microalbuminuria, proteinuria and haematuria
- Abdominal mass
- Infected cysts
- Stones (Renal in 20% - uric and calcium oxalate).
- Haematuria – Cyst haemorrhage – cyst communicates with the collecting system.
- Aneurysms (Berry)
- Polyuria and nocturia
- Extra-renal cysts e.g., liver, ovaries, pancreas, seminal vesicles.
- Prevalence of hepatic cysts increases with age.
- Systolic murmur – due to mitral valve prolapse.
Why is there a systolic murmur associated with Adult Polycystic Kidney Disease?
Due to mitral valve prolapse
Which classification system is used for Adult Polycystic Kidney Disease?
Mayo Classification system
What is the most common extra-renal manifestation of Adult Polycystic Kidney Disease?
Hepatic cysts
What is the most common cause of urinary calculi?
inadequate hydration and subsequent low urine volume
What is the most common type of urinary calculi?
- Calcium oxalate
What are the common causes implicated in the development of Calcium oxalate stones?
- Hyperparathyroidism, renal calcium leak, hyperoxaluria, hypomagnesemia, and ethylene glycol poisoning.
- Associated with increased gastrointestinal calcium reabsorption.
What are the common causes of uric acid stones?
- (pH <5, high intake of purine foods (e.g., fish, legumes, meat); associated with gout and cancer - rapid cell turnover – TLS.
What are struvite stones composed of?
Magnesium ammonium phosphate stones
Which organism is implicated in the aetiology of struvite stones?
Gram-negative urease positive - proteus sp.
Staghorn calculi are associated with what type of stone?
Struvite stones (Magnesium Ammonium phosphate
What are the most common site for urinary calculi?
pelvic-ureteric junction, pelvic brim, Vesico-ureteric junction.
At which pH does calcium oxalate stones tend to form in?
<7.2
Which types of stones form in alkaline urine?
Calcium phosphate - associated with hyperparathyroidism and renal tubular acidosis
Which dermatome pattern is implicated in renal colic flank pain?
T10 to S4
What is the common microscopic finding associated with renal stones?
Microscopic haematuria
What is the investigation of choice for confirming renal stones?
CT Kub
What is the diameter threshold for a papillary adenoma?
<15 mm
Which syndrome are renal oncocytomas observed in?
Birt–Hogg–Dube Syndrome.
Describe the histology of Renal oncocytoma?
A benign epithelial renal tumour composed of oncocytic cells
Well-circumscribed - circular, associated with a central scar.
Benign mesenchymal renal tumour composed of thick-walled blood vessels, smooth muscle and fat describes which type of renal tumour?
Angiomyolipoma
Tuberous sclerosis is associated with type of benign renal neoplasms?
Angiomyolipoma
What are the macroscopic findings associated with oncocytoma?
Mahogany brown
What are the microscopic findings observed in oncocytoma?
Sheets of oncolytic cells, pink cytoplasm, form nests of cells
What is the commonest form of malignant epithelial renal tumour?
Clear cell renal carcinoma
What are the two types of a malignant epithelial renal tumour?
- Clear Cell Renal Carcinoma
- Papillary renal carcinoma
What is the macroscopic appearance of a clear cell carcinoma?
Golden-yellow tumour with haemorrhagic areas
Which chromosome is implicated in the development of a clear cell renal carcinoma?
Chromosome 3p
What is the diameter threshold for a papillary renal cell carcinoma?
> 15 mm in size
What are the genetic aetiologies implicated in papillary renal cell carcinoma?
Trisomy 7,17 and loss of Y.
A ‘fragile, friable brown tumour’ is associated with what type of renal tumour?
Papillary Renal Cell Carcinoma
What are the microscopic histology findings observed in Papillary Renal Cell Carcinoma ?
Papillary growth-pattern
Papillary Renal Cell Carcinoma is associated with what?
long-term dialysis
What are the two types of papillary renal cell carcinoma?
Type I: Single layer of flatter cells
Type II: More oncolytic cells (worse prognosis)
A well-circumscribed solid brown tumour is associated with what type of malignant renal neoplasm?
Chromophobe Renal Cell Carcinoma
What risk of progression index is implicated for clear-cell renal carcinoma?
Leibovich Risk model
What is the most common renal malignancy in tumour?
NEPHROBLASTOMA/WILM’S TUMOUR
What are the microscopic histological findings observed in nephroblastoma?
Small round blue cells
Which gene is implicated in Nephroblastoma?
WT1 gene
What is WAGR syndrome?
Wilm’s Tumour
Aniridia
Genitourinary anomalies
Mental retardation
What is the histopathology of a Wilm’s tumour?
Well-circumscribed and have a pseudo-capsule.
* Malignant Triphasic Pattern:
What pattern is observed on histology in nephroblastoma?
Malignant triphasic pattern
What is the malignant triphasic pattern observed in a Wilm’s tumour?
- Blastema – Undifferentiated – small, round blue cells with active mitotic activity and overlapping nuclei.
- Epithelial – Rosette-like structures
- Stromal tissues – Mesenchymal cells or loose cellular myxoid areas.
What is the most common type of bladder cancer?
Transitional cell carcinoma
What are the risk factors associated with urothelial carcinoma?
Smoking
Aromatic amines
What is the common presentation of bladder cancer?
Frank haematuria
What are the types of bladder cancer?
Non-invasive papillary urothelial carcinoma
Infiltrating urothelial carcinoma
Flat urothelial carcinoma in situ
Frond-like growths are associated with which type of bladder cancer?
Non-invasive papillary urothelial carcinoma
Which genes are implicated in unstable non-invasive papillary urothelial carcinoma?
RB and TP53 mutations
What are the subtypes of infiltrating urothelial carcinoma?
Micropapillary urothelial carcinoma
Plasmacytoid
Nested
Microcystic
How does a flat urothelial carcinoma appear?
Reddish area
Which bladder carcinoma is associated with a high risk of progression?
Flat urothelial Carcinoma
A reddish area (bladder cancer) is associated with what type?
Flat urothelial Carcinoma in Situ
Endemic urinary schistosomiasis causes what type of bladder cancer?
Squamous cell carcinoma
What promotes BPH?
DHT
How is testosterone converted to DHT?
5-alpha-reductase 2
What are the risk factors associated with BPH?
Alcohol, caffeine, and high-dose supplemental Vitamin C.
Diabetes, insulin
Obesity - high levels of oestrogen
Metabolic syndrome
What are the protective factors for BPH?
beta-carotene, carotenoids, and Vitamin A.
What is the clinical presentation of BPH?
- Frequency, nocturia
- Urgency
- Hesitancy
- Poor flow
- Terminal dribbling
- May present with urinary retention, renal failure and UTI.
What is the histopathology findings for BPH?
- Hyperplastic process with increased cell numbers including both glandular and stromal cellular proliferation in the transition zone.
- Occurs in the periurethral zones – hyperplastic stromal nodules.
- Transition zone – Glandular nodular proliferation.
Which zone is affected in BPH?
Transition zone
What are the two classes of drugs for the management of BPH?
Alpha-blockers
5-alpha reductase inhibitors
Name 2 alpha-blockers implicated in the management of BPH?
alfuzosin
tamsulosin
What class of drug is Finasteride?
5-alpha reductase inhibitors
Mechanism of action of 5-alpha reductase inhibitor?
Inhibit intraprostatic conversion of testosterone to DHT
What is the most common cause of malignancy in men?
Prostatic adenocarcinoma
What is the premalignant condition for prostatic adenocarcinoma?
prostatic intraepithelial neoplasia
What is the prognostic indicator for prostatic adenocarcinoma?
Gleason Score
What marker (threshold) is indicative for prostate cancer?
PSA (>4 ng/mL)
What Gleason score is associated with high-volume tumour?
8-10
What are the risk factors for testicular germ cell?
- Cryptorchidism (undescended testes) – 2-4-fold increase (Associated with right-sided),
- LBW/SGA
- Infections – HPV, EBV, CMV.
What is the common presentation for testicular cancer?
Painless lump
What is the most common histological subtype for testicular germ cell cancer?
Seminoma
What is the histological appearance of a seminoma?
Transformed germ cells, and lymphocytes infiltrate with clear polygonal cells.
What are the biologic cell markers associated with post-pubertal testicular cancer?
AFP, HCG, LDH
What are the 6 histological subtypes associated with testicular germ cell cancer?
Seminoma
Embryonal carcinoma
Post-pubertal
Yolk sac tumour
Choriocarcinoma
Teratoma
Which serum markers are raised in testicular germ cells cancers?
AFP, hCH, LDH
Trans-scrotal ultrasound scan findings for testicular germ cell cancer?
Hypoechoic, solid, vascularised tumour
What is the therapeutic intervention for testicular cancer?
Radical inguinal orchiectomy.
What is the risk associated with a trans-scrotal biopsy?
- Risk of local dissemination
Which type of chemotherapy agents is testicular cancer sensitive to?
Platinum-based chemotherapy agents
What are the three types of non-germ cell testicular cancers?
Lymphoma
Leydig cell tumour
Sertoli cell t umour
What drug therapy is used for the management of testicular cancer (name 3)?
Bleomycin
Etoposide
Cistplatin
What is the most common causative organism for epididymitis?
C. Trachomatis, N. Gonorrhoea
What is the common causative organism for Epididymitis in >39 years of age?
E coli
Which HPV strain causes condylomas?
6 and 11
Which penile disease can predispose to penile carcinoma?
chronic lichen sclerosus
Persistent erythematous plaque on the glans penis is associated with which penile disease?
Zoon’s Balanitis
What are the histological features observed in chronic bronchitis?
Goblet cell hyperplasia
Hypertrophy of mucous glands
What are the causes of upper lobe fibrosis?
C - Cystic fibrosis, coal worker’s pneumococcus
H - Hypersensitivity pneumonitis
A - Ankylosing spondylitis
R - Radiation therapy
T - Tuberculosis
S - Sarcoidosis, silicosis
What is the pathophysiology of cryptogenic fibrosing alveolitis?
Respiratory alveolar epithelial injury Activation of fibroblasts Dysregulated repair of the alveolar epithelium.
Histology:
* Interstitial inflammation
* Honeycomb change beginning at the periphery of the lobule, usually sub-pleural.
- Hyperplasia of type II pneumocytes causing cyst formation, and honeycomb fibrosis.
* Presence of foci of fibroblasts
* Patchy involvement of the lung by fibrosis.
Hyperplasia of which type of pneumocytes is associated with cryptogenic fibrosing alveolitis?
Type II
What are the risk factors for IPF?
Tobacco exposure, metal, wood dust, and GORD.
What types of crackles are observed in IPF?
Velcro crackles
What class of drug is pirfenidone ?
tyrosine kinase inhibitors
What is the main cause of Pneumoconiosis?
An accumulation of fine inhaled particles e.g., silica, asbestos fibres, beryllium, talc and coal dust Inflammatory reaction within the lung.
- has an upper lobe predilection
Pneumoconiosis typically affects which part of the lung zones?
Upper lobe
What is the term for dust-laden macrophages?
Anthrocytes
What is the histology of Pneumoconiosis ?
- Dust-laden macrophages (anthrocytes) with reticulin fibrosis.
- Halo of focal emphysema surrounding the macules.
What lung cancer is associated with Pneumoconiosis?
Mesothelioma
Adenocarcinoma
What is the histology of granulomatous lung disease?
Mature macrophages, histiocytes and multi-nucleate giant cells.
What are the infectious causes of granulomatous lung disease?
TB, schistosomiasis, aspergillus, cryptococcus, coccidioides, mucor, pneumocystis, parasites.
What histological finding is observed in extrinsic allergic alveolitis?
Polypoid plugs
What types of bodies are associated with cryptogenic organising pneumonia?
Masson bodies
What is the cause of Farmer’s lung?
Saccharopolyspora rectivirgula.
What is the cause of humidifier’s lung?
thermactinomyces spp
What is the cause of Malt-Worker’s lung?
Aspergillus
What stage of lobar pneumonia does Red hepatisation occur?
Stage 2
What is Red hepatisation?
Infiltration of RBCs, neutrophils, and fibrin into the alveolar fluid (appear red and firm (similar to the liver)
What follows Red hepatisation in lobar pnuemonia?
Gray hepatisation
What is Gray hepatisation?
RBC. Break down and is associated with fibrosis (red to gray colour transformation).
Which organisms are implicated in lobar pnuemonia?
Streptococcus pneumoniae
What are the common atypical causes of pneumonia?
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
- Legionella pnuemophila
Which ethnicity is a demographic risk factor for sarcoidosis?
Afro-Caribbean ethnicity
What are the dermatologic manifestations associated with sarcoidosis?
Erythema nodosum
Lupus pernio
What are the common sites of erythema nodosum?
Bilateral subcutaneous nodules of the shins
Define lupus pernio
Indurated violaceous lesions on the nose, lips, ears, and cheeks. It is a predictive indicator of a poor prognosis.
Which dermatologic manifestation is a poor prognostic indicator for sarcoidosis?
Lupus pernio
Which pulmonary radiology finding is seen in sarcoidosis?
Hilar lymphadenopathy
What are the cardiac conduction abnormalities associated with sarcoidosis?
Complete heart block, first degree AV block (prolonged PR interval >200 ms)
Define lofgren syndrome (triad)?
Arthritis
Erythema nodosum
Bilateral adenopathy
Which serum marker is raised in sarcoidosis?
Angiotensin-converting enzyme
What electrolyte abnormality is observed in sarcoidosis?
Hypercalcaemia
Why does hypercalcaemia occur in sarcoidosis?
Activated macrophages synthesis ectopic 1,25-dihydroxyvitamin-D3
Which enzyme is secreted by macrophages in sarcoidosis resulting in hypercalcaemia?
1-alpha-hydroxylase
Which scoring system is used to assess and stage sarcoidosis?
Muers scoring system
What is the management for sarcoidosis?
Low-dose oral glucocorticoid therapy (moderate 20 mg OD prednisolone)
What autosomal dominant condition is associated with emphysema?
Alpha-1 anti-trypsin deficiency
What is the most common type of emphysema?
Centrilobular - associated with smoking
Centrilobular emphysema is associated with what risk factor?
Smoking
Panacinar loss in emphysema is associated with which cause?
Alpha-1 antitrypsin deficiency
Which 2 enzymes is inhibited in Alpa-1 AT deficiency?
Neutrophil elastase and trypsinize
Which interleukin factor is released by activated macrophages in emphysema?
IL-8
Which protein is deteriorated in emphysema?
Elastin
What are the two patterns of alveolar parenchyma loss in emphysema?
Centrilobular - loss centred on bronchiole
Panacinar - Diffuse loss of alevolae
Which lung cancer is associated with smokers?
Squamous cell cancer
Small cell lung cancer
Which paraneoplastic syndrome is associated with squamous cell lung carcinoma?
PTHrP - hypercalcaemia of malignancy
Squamous cell lung carcinoma (central or peripheral)?
Central pattern
Which type of lung cancer is associated with non-smokers?
Adenocarcinoma
What are the five types of lung cancer?
Small cell lung cancer
Squamous cel cancer
Adenocarcinoma
Large cell carcinoma
Mesothelioma
Which type of lung cancer is associated with a poor prognosis?
Large cell
What is the major risk factor for small cell lung cancer?
Cigarette smoking
Which two genetic associations are implicated in small-cell lung cancer?
TP53 and RB1
Which histological cell type is observed in small cell lung cancer?
Oat cell carcinoma
Which epithelial cell marker is associated with small cell lung cancer?
Cytokeratin - differentiates from lymphoma
Paraneoplastic syndromes are associated with which type of lung cancer?
Small cell lung cancer
Which neoplastic syndromes are associated with small cell lung cancer?
SIADH
Ectopic Cushing’s syndrome
Lambert–Eaton syndrome
Ectopic Cushing’s syndrome in small cell lung cancer is associated with the production of what?
Ectopic ACTH
Presentation of Lambert–Eaton Myasthenic syndrome?
Weakness of proximal arms and legs
Which hormone is implicated in carcinoid syndrome?
Serotonin
What are the histology findings observed in squamous cell lung carcinoma?
Keratinisation
Intracellular bridges (desmosomes)
Which mutation is associated with squamous cell lung carcinoma?
Myc overexpression
What two features are associated with adenocarcinoma?
Glandular differentiation
Mucin production
What is the precursor lesion for adenocarcinoma?
Atypical adenomatous hyperplasia
Which mutation is implicated in the pathogenesis of adenocarcinoma?
Epidermal growth factor receptor (EGFR)
Which type of treatment does EGFR respond to?
Tyrosine kinase inhibitors
What extra-thoracic manifestations are associated with adenocarcinoma?
Superior vena cava obstruction
Phrenic nerve palsy
Horner syndrome
Pericardial effusion
Compression of the brachial plexus
What is the histology of large cell lung carcinoma?
Large cell, large nuclei, prominent nucleoli
(Undifferentiated neoplasm)
KRAS is associated with which types of lung cancer?
Adenocarcinoma
Squamous cell carcinoma
EGFR mutation is associated with which type of lung cancer?
Adenocarcinoma
Which pulmonary malignancy is associated with affecting the parietal/visceral pleura?
Mesothelioma
What is MAP threshold for pulmonary hypertension?
> 25 mmHg at rest
Class 1 pulmonary hypertension is associated with what cause?
idiopathic, hereditary, drugs/toxins, associated with congenital heart disease
Left heart disease is associated with which class of pulmonary hypertension?
Class II
What is the main cause of class III pulmonary hypertension?
Lung disease (ILD)
What cell type lines the oesophagus?
Squamous stratified epithelium (absent goblet cells)
What cell type is present in acute oesophagitis?
Neutrophils
Neutrophilia
Which classification of severity is used to evaluate reflux oesopahgitis?
Los Angeles Classification of severity
Which layers are affected in an ulcer?
Past muscularis mucosa (into the submucosa)
Which layers are affected in an erosion?
Before muscularis mucosa
Which histological change is observed in Barett’s oesophagus?
Metaplasia of squamous mucosa to columnar epithelium
Which malignant change can arise in Barret’s oesophagus?
Adenocarcinoma
The presence of which cell type is associated with intestinal metaplasia?
Goblet cells
Which type of metaplasia confers an increases malignancy risk?
Intestinal metaplasia (With goblet cells)
Which type is the most common oesophageal cancer?
Oesophageal Adenocarcinoma
What are the risk factors for a squamous cell oesophageal carcinoma
Achalasia of cardia, Plummer-Vinson syndrome, nutritional deficiencies, nitrosamines, HPV
Cause of oesophageal varices?
Portal hypertension
Parietal cells secrete what two factors?
HCl and intrinsic factor
Pepsinogen is produced by which type of gastric cell?
Chief cells
What are the most common causes of acute gastritis?
Aspirin
NSAIDs
Corrosives
Acute H.pylori
Severe stress (burns)
Which immune cell type predominates in acute gastritis?
Neutrophils
Which immune cell type predominates chronic gastritis?
Lymphocytes and plasma cells
H pylori affects which part of the stomach (predominantly)?
Antrum
Autoimmune (atrophic) gastritis is associated with which autoantibody?
Anti-parietal antibodies
H pylori is associated with which type of lymphoma?
Mucosa-associated lymphoid tissue (MALT) lymphoma
Which type of ulcer is relieved by food?
Duodenal ulcer
Which type of ulcer is worse with food?
Gastric ulcer
Incidence of gastric cancer is higher in which demographic?
Japanese
Commonest subtype of gastric cancer?
Adenocarcinoma
Diffuse gastric cancer is associated with what type of carcinoma?
Poorly differentiated signet ring cell carcinoma
What are the two types of gastric cancer?
Intestinal
Diffuse
Which type of gastric cancer is poorly differentiated?
Diffuse
Gastric intestinal metaplasia is associated with which cell type?
Goblet cells
Which enzyme is secreted by h pylori?
Urease
What two toxins are produced by H pylori?
CagA
VacA
Body-predominant atrophic gastritis is associated with which type of dysplasia?
Flat metaplasia-dysplasia
Most common cause of a duodenal ulcer?
H. pylori - antral-predominant strain
What are the histological features associated with Coeliac disease?
Partial villous atrophy
Crypt hyperplasia
Increased intra-epithelial lymphocytes
What is the infective differential diagnosis for coeliac disease?
Tropical sprue
Which antibodies are associated with Coeliac disease?
Anti-endomysial Ab (best sen and spec), anti-tissue transglutaminase (IgA), anti-gliadin
What is the diagnostic investigation for Coeliac disease?
Duodenal/Jejunal biopsy
Pathophysiology of Hirschsprung’s Disease (absence of what type of cell)?
Ganglion cell in the myenteric plexus
Hirschsprung’s Disease is associated with which chromosomal disorder?
Down’s syndrome
What is the diagnostic investigation to confirm Hirschsprung’s Disease?
Full-thickness biopsy
What is the first line management for Hirschsprung’s Disease?
Bowel irrigation
What is the definitive management for Hirschsprung’s Disease?
Resection of constricted segment
Which area of the colon is susceptible to ischaemic colitis?
Splenic flexure
Rectosigmoid
(Watershed areas)
Type of inflammation in Crohn’s disease?
Non-caseating transmural inflammation - full-thickness of the bowel wall (mucosa to the serosa)
Smoking worsens which type of IBD?
Crohn’s diseae
Crohn’s disease affects which bowel segment predominantly?
Terminal ileum
What type of lesions is observed in Crohn’s disease?
Skip lesions
What endoscopic feature is observed in Crohn’s disease?
Cobblestone appearance
What is the first lesion observed in Crohn’s disease?
Aphthous ulcer - deep rose thorn ulcer
Deep rose thorn ulcers forms which type of ulcers in Crohns disease?
Serpentine ulcers
Which hypothesis is implicated in Crohn’s disease?
Hygiene hypothesis – Less food contamination –> Less enteric infection –>Inadequate development of processes that regulate mucosal immune response –> Exaggerated immune response to pathogens.
What extra-intestinal manifestation (ocular) is associated with Crohn’s disease?
Anterior uveitis
What extra-intestinal manifestation (skin) is associated with Crohn’s disease?
Erythema nodosum
Pyoderma gangrenosum
Erythema multiform
Digital clubbing
Complications of Crohn’s disease?
Strictures
Fistulae
Abscess formation
Perforation
Which is the management of mild flares of Crohn’s disease?
Prednisolone
What is the management for severe flares of Crohn’s disease?
IV hydrocortisone, metronidazole
What are the additional therapies for Crohn’s disease?
Azathioprine, methotrexate, Infliximab
Infliximab target (class)
Anti-TNF-Alpha
Ulcerative colitis originates from which part of the colon?
Rectum
Relationship between smoking and UC?
Improves symptoms
What is the histopathology of ulcerative colitis?
Goblet cell depletion, ulcerations, and mucosal crypt arophy
What is a histological marker of active disease in ulcerative colitis?
Crypt abscesses
Which hepatic extraintestinal manifestation is associated with ulcerative colitis?
Primary sclerosing cholangitis
What severe intestinal complication is associated with ulcerative colitis?
Toxic megacolon
What is the risk associated with toxic megacolon?
Adenocarcinoma
What is the first-line management for mild flares of ulcerative colitis?
Prednisolone and mesalazine
What is the remission management for ulcerative colitis?
5-ASA, azathioprine, 6-mercaptopurine
Consider anti-TNF alpha drugs
What types of antibiotics cause a clostridium difficle infection?
Clindamycin, cephalosporins, ciprofloxacin + co-amoxiclav
Colonic complication of C difficile infection?
Pseudomembranous colitis
What are the two toxins produced by c difficile?
Toxin A - Endotoxin
Toxin B - Cytotoxic
What is the antibiotic of choice for C difficle infection?
Vancomycin
Diverticular side predominantly affects which colon?
Left colon/sigmoid colon
What is symptomatic diverticular disease?
Diverticulitis - diverticular bleeding
What are the risk factors associated with diverticular disease?
Low fibre diet
Obesity
Smokers
Drugs -NSAIDs, opiates, steroids
What are the complications associated with diverticular disease?
Fever, peritonism, gross perforation , fistula, obstruction
What is carcinoid syndrome?
Neuroendocrine tumour of the midgut - metastasises of the liver
Cell type of carcinoid syndrome?
Enterochromaffin cells
enterochromaffin cells in carcinoid syndrome produce what?
Serotonin
