Pathology
MBBS Pathology — high-yield long questions and short notes from Robbins & Cotran and Harsh Mohan, covering general pathology (cell injury, inflammation, haemodynamics, immunopathology, neoplasia), haematology, and systemic pathology of the cardiovascular, respiratory, GI, hepatobiliary, renal, endocrine and other systems, written to the marks with definitions, mechanisms, morphology, classification, clinical correlation and pearls.
12chapters144questions99High-Yield
Definition
Glomerulonephritis is a group of disorders with immune-mediated inflammation of the glomeruli, presenting with proteinuria, haematuria or renal failure.
Mechanisms
- Circulating immune complex deposition — granular immunofluorescence (post-streptococcal, SLE)
- In-situ antibody against GBM — linear pattern (Goodpasture)
- Pauci-immune — ANCA-associated vasculitis; scanty deposits
- Complement activation → neutrophil influx → capillary wall injury
Important Types
- Post-streptococcal (acute proliferative) — subepithelial humps, low C3, follows sore throat by 1–3 weeks
- Rapidly progressive (crescentic) — crescents in Bowman space; renal failure in weeks
- Membranous — spike and dome, subepithelial deposits; commonest nephrotic cause in adults
- Minimal change — normal light microscopy, foot process effacement; children
- IgA nephropathy (Berger) — mesangial IgA; haematuria with infection
Immune deposits initiate the inflammation that damages the filter. Type Pattern Deposit Post-streptococcal Granular Subepithelial humps Goodpasture Linear Anti-GBM IgA nephropathy Mesangial IgA Applied
- Renal biopsy with light, immunofluorescence and electron microscopy is essential
- Crescentic glomerulonephritis is a nephrological emergency
🔑KEY POINTS TO REMEMBER- Glomerulonephritis is immune-mediated: granular (complexes), linear (anti-GBM) or pauci-immune.
- Post-streptococcal shows subepithelial humps with low C3.
- Crescents indicate rapidly progressive disease.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Nephrotic syndrome results from severe glomerular protein leak, while nephritic syndrome results from glomerular inflammation with haematuria.
Nephrotic Syndrome
- Proteinuria >3.5 g/day
- Hypoalbuminaemia (<3 g/dL), generalised oedema
- Hyperlipidaemia and lipiduria (oval fat bodies, fatty casts)
- Causes: minimal change (children), membranous (adults), focal segmental glomerulosclerosis, diabetes, amyloidosis
- Complications: infection, thrombosis (loss of antithrombin III), malnutrition
Nephritic Syndrome
- Haematuria with red cell casts and dysmorphic red cells
- Hypertension, oliguria, mild to moderate proteinuria (<3.5 g/day)
- Azotaemia; mild periorbital oedema
- Causes: post-streptococcal, IgA nephropathy, crescentic glomerulonephritis, lupus nephritis
Leakiness versus inflammation defines the two syndromes. Feature Nephrotic Nephritic Proteinuria >3.5 g/day <3.5 g/day Haematuria Minimal Marked, RBC casts Blood pressure Normal Raised Oedema Severe Mild Applied
- Red cell casts are diagnostic of glomerular inflammation
- Minimal change disease responds well to steroids
🔑KEY POINTS TO REMEMBER- Nephrotic: proteinuria >3.5 g/day, hypoalbuminaemia, oedema, hyperlipidaemia.
- Nephritic: haematuria with red cell casts, hypertension, oliguria.
- Minimal change in children, membranous in adults for nephrotic syndrome.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Renal failure is loss of excretory kidney function with retention of nitrogenous waste; it may be acute or chronic.
Acute Kidney Injury
- Pre-renal — hypoperfusion: haemorrhage, shock, dehydration, cardiac failure
- Renal (intrinsic) — acute tubular necrosis (commonest), glomerulonephritis, interstitial nephritis
- Post-renal — obstruction: stones, prostate, tumour
- Rapid rise in urea and creatinine, oliguria, hyperkalaemia, metabolic acidosis
- Often reversible
Chronic Kidney Disease
- Progressive irreversible nephron loss over months to years
- Causes: diabetes mellitus (commonest), hypertension, chronic glomerulonephritis, polycystic disease
- Uraemia — anaemia (↓ erythropoietin), renal osteodystrophy, pericarditis, encephalopathy, pruritus
- Small contracted granular kidneys; hypocalcaemia with hyperphosphataemia
Falling filtration allows waste and potassium to accumulate. Feature Acute Chronic Onset Sudden Gradual Kidney size Normal Small, contracted Anaemia Absent Present Applied
- Hyperkalaemia is the commonest immediate cause of death
- Treatment: correct cause; dialysis or transplantation in end-stage disease
🔑KEY POINTS TO REMEMBER- Acute kidney injury: pre-renal, renal (ATN) or post-renal; often reversible.
- Chronic kidney disease is irreversible — diabetes and hypertension lead.
- Hyperkalaemia is the most dangerous acute complication.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Renal cell carcinoma is the commonest malignant tumour of the adult kidney, arising from proximal tubular epithelium.
Types & Risk Factors
- Clear cell (~70–80%) — VHL gene on chromosome 3p; lipid-rich clear cytoplasm
- Papillary, chromophobe, collecting duct types
- Risk: smoking (strongest), obesity, hypertension, dialysis-associated cystic disease
- Von Hippel-Lindau syndrome — bilateral, multiple tumours
- Gross: yellow-golden, well-circumscribed, with haemorrhage and necrosis
Clinical Features
- Classic triad (only ~10%): haematuria, flank pain, palpable mass
- ‘Internist’s tumour’ — varied presentations; often silent until advanced
- Paraneoplastic: polycythaemia (erythropoietin), hypercalcaemia (PTHrP), hypertension (renin), Cushing, fever
- Invades renal vein and inferior vena cava; left-sided varicocele
- Metastasis: lung (cannonball) and bone
Loss of the VHL gene drives angiogenesis and tumour growth. Feature Detail Commonest type Clear cell Gene VHL (3p) Metastasis Lung, bone Applied
- Radioresistant and chemoresistant — treated by nephrectomy
- Targeted therapy (anti-VEGF, tyrosine kinase inhibitors) in advanced disease
🔑KEY POINTS TO REMEMBER- Renal cell carcinoma arises from proximal tubules; clear cell type commonest.
- VHL gene on 3p; smoking is the main risk factor.
- Triad of haematuria, flank pain and mass; invades renal vein, spreads to lung.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
The prostate is commonly affected by benign prostatic hyperplasia, prostatitis and carcinoma in older men.
Benign Prostatic Hyperplasia
- Very common after age 50; androgen (dihydrotestosterone) dependent
- Arises in the transitional (periurethral) zone
- Hyperplasia of both glandular and stromal elements; nodular
- Obstructive symptoms — hesitancy, poor stream, frequency, nocturia, retention
- Complications: urinary infection, hydronephrosis, bladder hypertrophy and diverticula
- Not premalignant
Carcinoma Prostate
- Commonest in the peripheral zone — palpable as a hard nodule on rectal examination
- Adenocarcinoma; graded by Gleason score
- ↑ PSA; ↑ serum acid phosphatase in advanced disease
- Osteoblastic (sclerotic) bone metastases — lumbar spine via Batson venous plexus
- Treatment: surgery, radiotherapy, androgen deprivation
Zone of origin explains why BPH obstructs early and cancer presents late. Feature BPH Carcinoma Zone Transitional Peripheral Rectal exam Smooth, elastic Hard nodule Metastasis None Osteoblastic Applied
- BPH treated with α-blockers and 5α-reductase inhibitors; TURP if severe
- Prostate cancer often detected by raised PSA before symptoms
🔑KEY POINTS TO REMEMBER- BPH arises in the transitional zone and causes obstruction; not premalignant.
- Carcinoma arises peripherally, graded by Gleason score, raises PSA.
- Prostate cancer produces osteoblastic vertebral metastases.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Nephrotic syndrome is a clinical complex of massive proteinuria, hypoalbuminaemia, generalised oedema and hyperlipidaemia.
Diagnostic Tetrad
- Proteinuria >3.5 g/day (selective in minimal change disease)
- Hypoalbuminaemia <3 g/dL
- Generalised oedema — periorbital first, then anasarca and ascites
- Hyperlipidaemia and lipiduria — oval fat bodies, Maltese cross under polarised light
Causes & Complications
- Children — minimal change disease (commonest; steroid-responsive)
- Adults — membranous nephropathy, focal segmental glomerulosclerosis
- Secondary — diabetes mellitus, SLE, amyloidosis, drugs, infections
- Complications: infections (loss of immunoglobulins), thrombosis (loss of antithrombin III → renal vein thrombosis), protein malnutrition, accelerated atherosclerosis
Albumin loss explains the oedema and the compensatory hyperlipidaemia. Age Commonest cause Children Minimal change Adults Membranous Diabetics Diabetic nephropathy Applied
- Minimal change disease shows foot process effacement only on electron microscopy
- Treatment: steroids, salt restriction, diuretics, statins
🔑KEY POINTS TO REMEMBER- Tetrad: proteinuria >3.5 g/day, hypoalbuminaemia, oedema, hyperlipidaemia.
- Minimal change in children; membranous nephropathy in adults.
- Complications: infection and thrombosis from urinary protein loss.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Acute tubular necrosis (ATN) is destruction of renal tubular epithelium and is the commonest cause of acute kidney injury.
Types & Causes
- Ischaemic ATN — shock, haemorrhage, sepsis, burns, major surgery; patchy tubular necrosis with skip areas
- Nephrotoxic ATN — aminoglycosides, radiocontrast, heavy metals, myoglobin (crush injury), haemoglobin, ethylene glycol
- Proximal tubule and thick ascending limb are most vulnerable
- Tubular casts obstruct the lumen; back-leak of filtrate
Clinical Phases
- Initiation (~36 h) — declining urine output
- Maintenance (oliguric, 1–2 weeks) — oliguria, rising urea and creatinine, hyperkalaemia, acidosis, fluid overload
- Recovery (diuretic) phase — polyuria with potassium and water loss; tubules regenerate
- Urine: muddy brown granular casts, high sodium, low osmolality
Tubules can regenerate, so ATN is potentially reversible. Feature Pre-renal ATN Urine sodium <20 mmol/L >40 mmol/L Urine osmolality High Low Casts Hyaline Muddy brown Applied
- Reversible because tubular basement membrane is preserved
- Manage fluid balance, treat hyperkalaemia, dialyse if needed
🔑KEY POINTS TO REMEMBER- ATN is the commonest cause of acute kidney injury — ischaemic or nephrotoxic.
- Three phases: initiation, maintenance (oliguric), recovery (diuretic).
- Muddy brown granular casts with high urine sodium; potentially reversible.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Pyelonephritis is bacterial infection of the renal pelvis, tubules and interstitium, occurring in acute and chronic forms.
Acute Pyelonephritis
- E. coli commonest; also Proteus, Klebsiella, Enterococcus
- Route: ascending (commonest) from bladder; less often haematogenous
- Risk: females, urinary obstruction, vesicoureteric reflux, catheters, diabetes, pregnancy
- Fever with rigors, loin pain, dysuria; white cell casts in urine (diagnostic of renal origin)
- Gross: yellow abscesses on the surface; neutrophilic tubular infiltration
Chronic Pyelonephritis
- Recurrent infection with reflux or obstruction
- Coarse, asymmetrical scarring with deformed calyces — characteristic
- Thyroidisation of tubules (colloid-like casts)
- Leads to hypertension and chronic kidney disease
- Xanthogranulomatous variant with foamy macrophages
Reflux allows infected urine to reach the renal parenchyma. Feature Acute Chronic Onset Sudden, febrile Insidious Urine White cell casts Variable Kidney Abscesses Coarse scars Applied
- White cell casts distinguish pyelonephritis from cystitis
- Chronic pyelonephritis is an important cause of end-stage renal disease in children
🔑KEY POINTS TO REMEMBER- E. coli ascending infection is the commonest cause.
- Acute: fever, loin pain, white cell casts, cortical abscesses.
- Chronic: coarse scars with deformed calyces and tubular thyroidisation.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Renal calculi are stones formed in the urinary tract from crystallisation of solutes in supersaturated urine.
Types
- Calcium oxalate/phosphate (~75–80%) — commonest; hypercalciuria, hyperparathyroidism; radio-opaque
- Struvite (triple phosphate, ~10–15%) — urease-producing organisms (Proteus); alkaline urine; form staghorn calculi
- Uric acid (~5–10%) — gout, acid urine, high cell turnover; radiolucent
- Cystine — cystinuria (inherited); childhood stones
Features & Complications
- Renal colic — severe loin-to-groin pain, restlessness
- Haematuria, dysuria, nausea, vomiting
- Predisposing: dehydration, immobilisation, urinary infection, hot climate, diet
- Complications: obstruction, hydronephrosis, recurrent infection, chronic kidney disease, squamous metaplasia → carcinoma
- Investigation: non-contrast CT (gold standard), ultrasound, X-ray KUB
Concentrated urine plus a nucleus allows crystals to aggregate. Stone Frequency X-ray Calcium 75–80% Opaque Struvite 10–15% Opaque (staghorn) Uric acid 5–10% Lucent Applied
- High fluid intake is the single best preventive measure
- Staghorn calculi suggest Proteus infection
🔑KEY POINTS TO REMEMBER- Calcium stones are commonest and radio-opaque.
- Struvite stones follow urease-producing infection and form staghorn calculi.
- Uric acid stones are radiolucent; non-contrast CT is the best investigation.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Wilms tumour (nephroblastoma) is the commonest primary renal malignancy of childhood, arising from embryonic nephrogenic tissue.
Features
- Peak age 2–5 years
- WT1 gene on chromosome 11p13
- Associations: WAGR syndrome (Wilms, Aniridia, Genitourinary anomalies, mental Retardation), Denys-Drash, Beckwith-Wiedemann syndrome
- Triphasic histology — blastemal, epithelial and stromal components
- Arises from persistent nephrogenic rests
Presentation & Management
- Large abdominal mass — smooth, does not cross the midline (unlike neuroblastoma)
- Haematuria, hypertension (renin), abdominal pain, fever
- Metastasis to lung
- Investigation: ultrasound and CT; avoid biopsy (risk of tumour spillage)
- Treatment: nephrectomy with chemotherapy; excellent prognosis (>90% survival)
Failure of embryonic kidney tissue to mature produces the tumour. Feature Wilms Neuroblastoma Origin Kidney Adrenal medulla Midline Does not cross Crosses Marker — VMA/HVA raised Applied
- Palpate gently — vigorous examination risks rupture
- One of the great successes of paediatric oncology
🔑KEY POINTS TO REMEMBER- Wilms tumour is the commonest childhood renal cancer, peak age 2–5 years.
- WT1 gene on 11p13; triphasic blastemal, epithelial and stromal histology.
- Smooth mass not crossing the midline; excellent prognosis with treatment.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Bladder carcinoma is usually urothelial (transitional cell) carcinoma, presenting characteristically with painless haematuria.
Risk Factors
- Smoking — the commonest risk factor
- Aniline dyes / β-naphthylamine — rubber, dye, leather industries
- Schistosoma haematobium → squamous cell carcinoma
- Cyclophosphamide, chronic irritation (stones, long-term catheter)
- Adenocarcinoma from urachal remnants
Pathology & Presentation
- Painless intermittent gross haematuria — hallmark; frequency, urgency, dysuria
- Papillary or flat (carcinoma in situ, more aggressive) growth patterns
- Graded low or high; staging depends on muscle invasion
- Commonly multifocal with a strong tendency to recur (field change effect)
- Diagnosis: cystoscopy with biopsy, urine cytology, imaging
Urine stores carcinogens in contact with the urothelium. Type Association Transitional cell Smoking, dyes Squamous cell Schistosomiasis Adenocarcinoma Urachal remnant Applied
- Painless haematuria in an adult is bladder cancer until proved otherwise
- Superficial tumours: resection + intravesical BCG; muscle-invasive: cystectomy
🔑KEY POINTS TO REMEMBER- Transitional cell carcinoma is commonest; smoking and aniline dyes are key risks.
- Schistosoma haematobium causes squamous cell carcinoma.
- Painless haematuria is the hallmark; tumours are multifocal and recur.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Adult polycystic kidney disease is an autosomal dominant disorder in which both kidneys are progressively replaced by multiple cysts.
Genetics & Pathology
- PKD1 on chromosome 16 (~85%, more severe) and PKD2 on chromosome 4
- Defective polycystin proteins
- Bilateral, massively enlarged kidneys (may weigh several kilograms)
- Cysts arise from all parts of the nephron; intervening parenchyma compressed
- Presents in the third to fifth decade
Features & Associations
- Bilateral flank masses, loin pain, haematuria, recurrent infection, stones
- Hypertension — early and common
- Progressive chronic kidney disease → end-stage renal failure
- Berry aneurysms of circle of Willis → subarachnoid haemorrhage
- Cysts in liver (commonest extrarenal), pancreas, spleen; mitral valve prolapse
- Diagnosis: ultrasound; screen family members
Expanding cysts destroy the intervening functioning parenchyma. Feature Adult (AD) Infantile (AR) Inheritance Dominant Recessive Onset Adulthood Infancy Liver Cysts Fibrosis Applied
- Screen for berry aneurysms if there is a family history of subarachnoid haemorrhage
- Control of hypertension slows renal decline
🔑KEY POINTS TO REMEMBER- Autosomal dominant, PKD1 (chromosome 16) and PKD2; defective polycystin.
- Bilateral enlarged cystic kidneys with hypertension and progressive renal failure.
- Associated with liver cysts and berry aneurysms.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.