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
Peptic ulcer is a breach in the mucosa of the gastrointestinal tract extending through the muscularis mucosae, caused by acid-pepsin digestion.
Aetiology
- H. pylori — commonest cause (~90% duodenal, ~70% gastric)
- NSAIDs and aspirin — inhibit protective prostaglandins
- Smoking, alcohol, steroids, stress
- Zollinger-Ellison syndrome — gastrinoma with multiple ulcers
- Imbalance between aggressive (acid, pepsin, H. pylori) and defensive factors (mucus, bicarbonate, prostaglandins, blood flow)
Morphology
- Sites: first part of duodenum (commonest), lesser curvature of stomach
- Usually single, round to oval, <2 cm
- Punched-out with clean sloping margins, smooth base
- Four microscopic zones: necrotic, inflammatory, granulation tissue, fibrotic base
Ulcers form where mucosal defence fails against acid and pepsin. Feature Duodenal Gastric Pain Relieved by food Worse with food Acid High/normal Normal/low Malignancy Never Possible Applied
- Complications: haemorrhage (commonest), perforation, penetration, obstruction
- Gastric ulcers must be biopsied to exclude carcinoma
🔑KEY POINTS TO REMEMBER- Peptic ulcer extends through the muscularis mucosae.
- H. pylori and NSAIDs are the main causes; duodenal ulcer is commonest.
- Haemorrhage is the commonest complication; gastric ulcers need biopsy.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Colorectal carcinoma is malignancy of the colon and rectum, almost always adenocarcinoma arising from adenomatous polyps.
Risk Factors & Molecular Pathways
- Age >50, low-fibre high-fat diet, adenomatous polyps
- Familial adenomatous polyposis (APC gene), HNPCC/Lynch (mismatch repair)
- Ulcerative colitis (long-standing)
- Adenoma-carcinoma sequence — APC → KRAS → p53 (chromosomal instability)
- Microsatellite instability pathway in Lynch syndrome
Morphology & Presentation
- Right colon — polypoid/fungating; anaemia, occult bleeding, mass, weight loss
- Left colon — annular ‘napkin-ring’ constricting; obstruction, altered bowel habit, bleeding per rectum
- Spread: direct, lymphatic, blood (liver), transcoelomic
- Dukes and TNM staging; CEA for follow-up
Sequential mutations convert a polyp into invasive carcinoma over years. Feature Right colon Left colon Growth Polypoid Annular Presentation Anaemia Obstruction Stool Occult blood Frank blood Applied
- Screening colonoscopy from age 50 (earlier if family history)
- Polypectomy interrupts the adenoma-carcinoma sequence
🔑KEY POINTS TO REMEMBER- Colorectal carcinoma is adenocarcinoma from the adenoma-carcinoma sequence (APC-KRAS-p53).
- Right-sided lesions cause anaemia; left-sided cause obstruction.
- Liver is the commonest site of metastasis; CEA used for follow-up.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Cirrhosis is diffuse, irreversible liver disease with fibrosis and regenerating nodules replacing normal architecture.
Causes
- Alcohol — commonest in the West
- Viral hepatitis B and C — commonest in Asia
- Non-alcoholic steatohepatitis (obesity, diabetes)
- Biliary (primary biliary cholangitis, obstruction)
- Metabolic: Wilson disease, haemochromatosis, α₁-antitrypsin deficiency
- Autoimmune; cryptogenic
Morphology & Consequences
- Micronodular (<3 mm; alcohol), macronodular (>3 mm; viral), mixed
- Three essentials: bridging fibrosis, nodular regeneration, disruption of architecture
- Hepatocellular failure — jaundice, hypoalbuminaemia, oedema, coagulopathy, encephalopathy, gynaecomastia, spider naevi
- Portal hypertension — varices, splenomegaly, ascites, caput medusae
- Hepatocellular carcinoma — major long-term risk
Fibrosis plus nodular regeneration obstructs portal flow and impairs function. Type Nodules Cause Micronodular <3 mm Alcohol Macronodular >3 mm Viral hepatitis Applied
- Ruptured oesophageal varices — commonest cause of death
- Child-Pugh score grades severity
🔑KEY POINTS TO REMEMBER- Cirrhosis = irreversible fibrosis with regenerating nodules.
- Alcohol and viral hepatitis are the leading causes.
- Leads to liver failure, portal hypertension and hepatocellular carcinoma.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Viral hepatitis is inflammation of the liver caused by hepatotropic viruses A to E, differing in transmission and outcome.
Viruses
- Hepatitis A — RNA, faeco-oral, no chronicity, vaccine available
- Hepatitis B — DNA, parenteral/sexual/vertical; chronicity ~5–10% in adults; vaccine available
- Hepatitis C — RNA, parenteral; high chronicity (~80%); no vaccine
- Hepatitis D — defective, requires HBsAg (co-infection or superinfection)
- Hepatitis E — faeco-oral; high mortality in pregnancy (~20%)
Pathology & Course
- Ballooning degeneration, Councilman (apoptotic) bodies, lobular inflammation
- Portal tract lymphocytic infiltrate; interface hepatitis in chronic disease
- Clinical phases: incubation, pre-icteric (prodrome), icteric, recovery
- Outcomes: recovery, fulminant hepatitis, chronic hepatitis, cirrhosis, hepatocellular carcinoma
- Carrier state (B and C)
Damage is chiefly immune-mediated rather than directly cytopathic. Virus Route Chronic A Faeco-oral No B Parenteral Yes C Parenteral High E Faeco-oral No (severe in pregnancy) Applied
- HBsAg = infection; anti-HBs = immunity; HBeAg = high infectivity
- Hepatitis B and C are the major causes of hepatocellular carcinoma
🔑KEY POINTS TO REMEMBER- A and E spread faeco-orally without chronicity; B, C, D are blood-borne.
- Councilman bodies and ballooning degeneration are characteristic.
- Hepatitis E is severe in pregnancy; B and C cause cirrhosis and liver cancer.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Jaundice (icterus) is yellow discoloration of skin, sclera and mucosae due to hyperbilirubinaemia (serum bilirubin >2 mg/dL).
Types
- Pre-hepatic (haemolytic) — excess bilirubin production; unconjugated; haemolysis, ineffective erythropoiesis
- Hepatic (hepatocellular) — hepatitis, cirrhosis, drugs; mixed hyperbilirubinaemia
- Post-hepatic (obstructive/cholestatic) — gallstones, carcinoma head of pancreas, stricture; conjugated
- Hereditary: Gilbert and Crigler-Najjar (unconjugated), Dubin-Johnson and Rotor (conjugated)
Distinguishing Features
- Haemolytic — lemon-yellow, normal-coloured stool and urine, ↑ reticulocytes, ↑ urobilinogen
- Obstructive — deep yellow-green, pale (clay) stools, dark urine, pruritus, ↑↑ alkaline phosphatase
- Hepatocellular — ↑↑ transaminases, variable stool colour
The type of bilirubin raised localises the level of the problem. Type Bilirubin Urine Haemolytic Unconjugated No bilirubin Obstructive Conjugated Dark, bilirubin + Hepatic Mixed Variable Applied
- Unconjugated bilirubin is water-insoluble → not excreted in urine
- Severe neonatal unconjugated jaundice → kernicterus
🔑KEY POINTS TO REMEMBER- Jaundice appears when serum bilirubin exceeds ~2 mg/dL.
- Pre-hepatic and Gilbert cause unconjugated; obstruction causes conjugated jaundice.
- Obstructive jaundice: pale stools, dark urine, high alkaline phosphatase.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Helicobacter pylori is a curved, microaerophilic Gram-negative bacillus colonising gastric mucosa and causing gastritis, peptic ulcer and gastric malignancy.
Virulence & Pathogenesis
- Urease — splits urea into ammonia, neutralising acid (basis of diagnostic tests)
- Flagella — motility through mucus; adhesins for attachment
- CagA and VacA — cytotoxins causing epithelial injury
- Chronic antral gastritis → ↑ gastrin → ↑ acid → duodenal ulcer
- Chronic pangastritis → atrophy → intestinal metaplasia → carcinoma
Associated Diseases & Diagnosis
- Chronic gastritis, duodenal ulcer (~90%) and gastric ulcer (~70%)
- Gastric adenocarcinoma and MALT lymphoma (WHO class I carcinogen)
- Invasive: biopsy urease test, histology, culture
- Non-invasive: urea breath test (best for confirming eradication), stool antigen, serology
Persistent colonisation drives inflammation towards ulceration or malignancy. Test Type Urea breath test Non-invasive Rapid urease (biopsy) Invasive Stool antigen Non-invasive Applied
- Eradication: PPI + amoxicillin + clarithromycin for 14 days
- MALT lymphoma may regress after eradication alone
🔑KEY POINTS TO REMEMBER- H. pylori is a urease-producing curved Gram-negative bacillus.
- Causes chronic gastritis, peptic ulcer, gastric carcinoma and MALT lymphoma.
- Urea breath test confirms eradication; treat with triple therapy.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Gastric carcinoma is malignancy of the stomach, almost always adenocarcinoma, often diagnosed late.
Risk Factors & Precursors
- H. pylori — chronic gastritis → atrophy → intestinal metaplasia → dysplasia → carcinoma
- Diet: smoked, salted, pickled foods, nitrosamines; low fruit and vegetable intake
- Pernicious anaemia, chronic atrophic gastritis, adenomatous polyps, partial gastrectomy
- Blood group A; smoking; family history (E-cadherin/CDH1 mutation)
Types & Spread
- Intestinal type — gland-forming, bulky, better prognosis; older patients
- Diffuse type — signet-ring cells, infiltrative, linitis plastica (leather-bottle stomach); worse prognosis
- Sites: pylorus and antrum (~50%), lesser curvature
- Virchow node (left supraclavicular), Krukenberg tumour (ovaries), Sister Mary Joseph nodule (umbilical)
A well-defined sequence links chronic infection to carcinoma. Type Cells Prognosis Intestinal Glandular Better Diffuse Signet-ring Worse Applied
- Presents late with weight loss, anaemia, epigastric pain, vomiting
- Endoscopy with biopsy is the diagnostic method
🔑KEY POINTS TO REMEMBER- Gastric adenocarcinoma follows H. pylori gastritis and intestinal metaplasia.
- Intestinal type is glandular; diffuse type has signet-ring cells and linitis plastica.
- Virchow node, Krukenberg tumour and Sister Mary Joseph nodule indicate spread.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Inflammatory bowel disease comprises Crohn disease and ulcerative colitis, chronic idiopathic inflammatory disorders of the bowel.
Crohn Disease
- Any part of gut, mouth to anus; terminal ileum commonest
- Skip lesions, transmural inflammation
- Non-caseating granulomas; cobblestone mucosa, deep fissuring ulcers
- Strictures, fistulae, abscesses; ‘string sign’ on barium
- Diarrhoea without blood, abdominal pain, malabsorption
Ulcerative Colitis
- Rectum and colon only; continuous from rectum proximally
- Mucosal and submucosal inflammation only
- Crypt abscesses, pseudopolyps; no granulomas
- Bloody diarrhoea with mucus, tenesmus
- Complications: toxic megacolon, higher carcinoma risk
Depth and continuity of inflammation separate the two diseases. Feature Crohn UC Site Mouth to anus Colon only Depth Transmural Mucosal Granuloma Present Absent Fistula Common Rare Applied
- Both have extraintestinal features: arthritis, uveitis, erythema nodosum, sclerosing cholangitis
- Long-standing ulcerative colitis requires surveillance colonoscopy
🔑KEY POINTS TO REMEMBER- Crohn: skip lesions, transmural, non-caseating granulomas, fistulae.
- Ulcerative colitis: continuous colonic mucosal disease with crypt abscesses.
- UC causes bloody diarrhoea and carries a higher cancer risk.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Acute pancreatitis is acute inflammation with autodigestion of the pancreas by its own prematurely activated enzymes.
Causes & Pathogenesis
- Gallstones and alcohol — account for about 80%
- Others: trauma, ERCP, drugs (azathioprine, thiazides), hyperlipidaemia, hypercalcaemia, mumps, scorpion sting
- Duct obstruction or acinar injury → premature trypsinogen activation
- Trypsin activates other enzymes → proteolysis, fat necrosis, haemorrhage
- Lipase → fat necrosis with calcium soap (saponification) → hypocalcaemia
Features & Investigations
- Severe epigastric pain radiating to back, vomiting, relieved by leaning forward
- Cullen sign (periumbilical) and Grey Turner sign (flank) bruising in haemorrhagic cases
- ↑ Serum amylase (early, less specific) and ↑ lipase (more specific, longer)
- Hypocalcaemia, hyperglycaemia, leucocytosis; CECT for severity
- Complications: pseudocyst, abscess, ARDS, shock, DIC, chronic pancreatitis
The organ digests itself once trypsin is activated prematurely. Enzyme Effect Trypsin Activates cascade Lipase Fat necrosis Elastase Vessel damage Applied
- Hypocalcaemia results from calcium soap formation and indicates severity
- Management: nil by mouth, fluids, analgesia, treat the cause
🔑KEY POINTS TO REMEMBER- Gallstones and alcohol cause most cases.
- Premature trypsin activation causes autodigestion and fat necrosis.
- Raised lipase is more specific than amylase; hypocalcaemia indicates severity.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Portal hypertension is a sustained rise in portal venous pressure above 10–12 mmHg (normal 5–10 mmHg).
Causes by Site
- Pre-hepatic — portal vein thrombosis, extrinsic compression, splenic vein thrombosis
- Intrahepatic — cirrhosis (commonest), schistosomiasis, non-cirrhotic portal fibrosis
- Post-hepatic — Budd-Chiari syndrome, constrictive pericarditis, right heart failure
Consequences
- Portosystemic collaterals — oesophageal varices (dangerous), caput medusae, haemorrhoids
- Splenomegaly with hypersplenism (pancytopenia)
- Ascites — ↑ hydrostatic pressure, ↓ albumin, ↑ aldosterone, lymph leak
- Hepatic encephalopathy — ammonia bypasses the liver
- Congestive gastropathy
Blood diverts through collateral channels that are prone to bleed. Site Example Pre-hepatic Portal vein thrombosis Intrahepatic Cirrhosis Post-hepatic Budd-Chiari Applied
- Variceal bleeding is the commonest fatal complication
- Managed by propranolol, banding, TIPS shunt
🔑KEY POINTS TO REMEMBER- Portal hypertension = portal pressure >10–12 mmHg; cirrhosis is the commonest cause.
- Classified as pre-hepatic, intrahepatic or post-hepatic.
- Causes varices, splenomegaly, ascites and encephalopathy.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Cholelithiasis is the formation of calculi within the gallbladder, resulting from altered composition of bile.
Types
- Cholesterol stones — commonest in the West; single, large, pale yellow, radiolucent
- Pigment stones — black (chronic haemolysis, cirrhosis) and brown (biliary infection, parasites); small, multiple
- Mixed stones — commonest overall; multiple, faceted, laminated
- Only ~10–20% are radio-opaque
Risk Factors & Complications
- Five Fs: female, fertile (multiparity), fat (obesity), forty, fair
- Also: oral contraceptives, rapid weight loss, diabetes, haemolytic anaemia, ileal disease
- Formation needs supersaturation, nucleation and gallbladder hypomotility
- Complications: biliary colic, acute and chronic cholecystitis, empyema, obstructive jaundice, gallstone pancreatitis, gallstone ileus, carcinoma gallbladder
Supersaturated bile plus stasis allows crystals to grow into stones. Stone Colour Association Cholesterol Pale yellow Obesity Black pigment Black Haemolysis Brown pigment Brown Infection Applied
- Ultrasound is the investigation of choice
- Chronic irritation predisposes to gallbladder carcinoma (porcelain gallbladder)
🔑KEY POINTS TO REMEMBER- Types: cholesterol, pigment (black/brown) and mixed (commonest).
- Risk factors summarised as the five Fs; most stones are radiolucent.
- Complications: cholecystitis, obstructive jaundice, pancreatitis, carcinoma.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Oesophageal carcinoma is malignancy of the oesophagus, presenting late with progressive dysphagia and carrying a poor prognosis.
Squamous Cell Carcinoma
- Upper and middle third; commoner worldwide and in India
- Risk: smoking, alcohol, hot beverages, nitrosamines, achalasia, Plummer-Vinson syndrome, corrosive strictures, tylosis
- Arises from squamous dysplasia
Adenocarcinoma
- Lower third; commoner in the West and rising
- Arises from Barrett’s oesophagus (columnar metaplasia from chronic reflux)
- Risk: GERD, obesity, hiatus hernia
- Sequence: reflux → metaplasia → dysplasia → carcinoma
Site of the tumour predicts its histological type and cause. Feature Squamous Adenocarcinoma Site Upper/middle Lower third Risk Smoking, alcohol Barrett’s, reflux Region Asia, Africa West Applied
- Progressive dysphagia — solids then liquids — with weight loss
- Rich submucosal lymphatics allow early spread; prognosis is poor
🔑KEY POINTS TO REMEMBER- Squamous cell carcinoma affects the upper two-thirds (smoking, alcohol).
- Adenocarcinoma affects the lower third, arising from Barrett’s oesophagus.
- Progressive dysphagia with weight loss; poor prognosis from early spread.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.