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
Atherosclerosis is a chronic disease of large and medium arteries characterised by fibrofatty intimal plaques (atheromas) that narrow the lumen.
Pathogenesis (response-to-injury hypothesis)
- Endothelial injury — hypertension, smoking, hyperlipidaemia, diabetes
- LDL entry and oxidation in the intima
- Monocytes enter → macrophages engulf lipid → foam cells → fatty streak
- Smooth muscle migration and collagen synthesis → fibrous cap
- Mature plaque: lipid-rich necrotic core + fibrous cap
Sites & Complications
- Commonest: abdominal aorta > coronary > popliteal > carotid > circle of Willis
- Plaque rupture → thrombosis → myocardial infarction, stroke
- Calcification, ulceration, haemorrhage into plaque
- Aneurysm formation from medial weakening; embolisation
Chronic injury converts a lipid deposit into a rupture-prone plaque. Stage Feature Fatty streak Foam cells Fibrous plaque Cap + necrotic core Complicated Rupture, thrombosis Applied
- Vulnerable plaque — thin cap, large lipid core, many inflammatory cells
- Statins stabilise plaques and lower LDL
🔑KEY POINTS TO REMEMBER- Atherosclerosis follows the response-to-injury sequence.
- Foam cells → fatty streak → fibrofatty plaque with necrotic core.
- Plaque rupture with thrombosis causes infarction and stroke.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Ischaemic heart disease results from imbalance between myocardial oxygen supply and demand, usually from coronary atherosclerosis; infarction is ischaemic myocardial necrosis.
Clinical Syndromes
- Angina — stable, unstable (pre-infarction), Prinzmetal (vasospastic)
- Myocardial infarction — usually from plaque rupture with thrombosis
- Chronic ischaemic heart disease; sudden cardiac death
- Commonest artery: left anterior descending (~50%)
Evolution of Infarct
- 0–12 h — no gross change; wavy fibres
- 12–24 h — pale; early coagulative necrosis, contraction bands
- 1–3 days — neutrophil infiltration
- 3–7 days — macrophages, softening (risk of rupture)
- 1–3 weeks — granulation tissue; >6 weeks — dense fibrous scar
Necrosis spreads outwards from the vulnerable subendocardium. Marker Rises Peak Troponin I/T 3–4 h 24 h (7–10 days) CK-MB 4–6 h 24 h Myoglobin 1–2 h Early Applied
- Troponin is the most sensitive and specific marker; CK-MB detects re-infarction
- Complications: arrhythmia, cardiac failure, rupture, aneurysm, Dressler syndrome
🔑KEY POINTS TO REMEMBER- IHD is usually due to coronary atherosclerosis; MI from plaque rupture and thrombosis.
- LAD is the commonest artery involved.
- Neutrophils at 1–3 days, macrophages 3–7 days, scar after 6 weeks; troponin is the key marker.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Systemic hypertension is persistent elevation of blood pressure — ≥140/90 mmHg in adults — producing widespread vascular and organ damage.
Classification
- Primary (essential) — 90–95%; multifactorial (genetic, salt, obesity, stress)
- Secondary — renal (commonest: glomerulonephritis, renal artery stenosis), endocrine (Conn, Cushing, phaeochromocytoma), coarctation, drugs, pregnancy
- Benign — gradual; malignant (accelerated) — diastolic >120 mmHg, papilloedema, rapid organ damage
Vascular & Organ Changes
- Hyaline arteriolosclerosis — benign hypertension and diabetes
- Hyperplastic arteriolosclerosis (‘onion-skin’) ± fibrinoid necrosis — malignant hypertension
- Heart — concentric left ventricular hypertrophy → failure
- Kidney — benign nephrosclerosis; granular contracted kidney
- Brain — haemorrhage (Charcot-Bouchard microaneurysms), stroke; eye — retinopathy
Small-vessel change is the common pathway to end-organ damage. Type Arteriole Course Benign Hyaline Slow Malignant Onion-skin, fibrinoid Rapid Applied
- Malignant hypertension is a medical emergency
- Left ventricular hypertrophy is an independent risk factor for death
🔑KEY POINTS TO REMEMBER- Hypertension: ≥140/90 mmHg; 90–95% primary (essential).
- Benign → hyaline arteriolosclerosis; malignant → onion-skin change and fibrinoid necrosis.
- Target organs: heart, kidney, brain and eye.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Rheumatic fever is an immune-mediated multisystem disease following group A streptococcal pharyngitis, which may lead to chronic valvular disease.
Pathogenesis & Diagnosis
- Molecular mimicry — antibodies to streptococcal M protein cross-react with cardiac tissue
- Latent period 2–3 weeks after sore throat
- Modified Jones criteria — major: carditis, migratory polyarthritis, Sydenham chorea, subcutaneous nodules, erythema marginatum
- Minor: fever, arthralgia, ↑ ESR/CRP, prolonged PR interval
- Plus evidence of streptococcal infection (↑ ASO titre)
Cardiac Pathology
- Pancarditis — endocarditis, myocarditis, pericarditis
- Aschoff bodies — pathognomonic granulomas with Anitschkow cells
- Small, warty, non-embolising vegetations along valve closure lines
- Chronic: mitral stenosis (commonest) — fish-mouth/buttonhole valve, fibrosis and fusion of commissures and chordae
‘It licks the joints but bites the heart.’ Valve Frequency Mitral Commonest Mitral + aortic Next Tricuspid Rare Applied
- Penicillin prophylaxis prevents recurrences
- Treating streptococcal sore throat prevents the first attack
🔑KEY POINTS TO REMEMBER- Rheumatic fever follows streptococcal pharyngitis by molecular mimicry.
- Diagnosed by modified Jones criteria; Aschoff bodies are pathognomonic.
- Chronic disease causes mitral stenosis; prevented by penicillin prophylaxis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Infective endocarditis is microbial infection of the endocardium, usually the valves, producing friable vegetations.
Organisms & Predisposition
- Acute — Staphylococcus aureus; normal valves; rapidly destructive
- Subacute — viridans streptococci; previously damaged valves; insidious
- Prosthetic valve — coagulase-negative staphylococci
- Intravenous drug users — tricuspid valve, S. aureus
- Predisposing: rheumatic valve disease, congenital heart disease, prosthetic valves, dental procedures
Features & Diagnosis
- Fever, new or changing murmur, splenomegaly
- Embolic and immune phenomena — Roth spots, Osler nodes (painful), Janeway lesions (painless), splinter haemorrhages, clubbing, glomerulonephritis
- Vegetations are large, friable and embolise (unlike rheumatic)
- Blood cultures (3 sets) + echocardiography; modified Duke criteria
Bacteria seed a sterile thrombus and build a friable vegetation. Type Organism Valve Acute S. aureus Normal Subacute Viridans strep Damaged IV drug use S. aureus Tricuspid Applied
- Complications: valve destruction, cardiac failure, mycotic aneurysm, abscess, stroke
- Prolonged intravenous antibiotics ± valve surgery
🔑KEY POINTS TO REMEMBER- Acute endocarditis from S. aureus on normal valves; subacute from viridans on damaged valves.
- Vegetations are friable and embolise; Osler nodes, Janeway lesions, Roth spots.
- Diagnosis by blood cultures, echocardiography and modified Duke criteria.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
The atheromatous plaque (atheroma) is the basic lesion of atherosclerosis — a raised fibrofatty intimal lesion.
Structure
- Fibrous cap — smooth muscle cells, collagen, elastin (outer)
- Cellular zone — macrophages, foam cells, T lymphocytes
- Central necrotic core — lipid, cholesterol clefts, cell debris, calcium
- Neovascularisation at the plaque base
- Located in the intima, extending into the media
Complications
- Rupture / fissuring → thrombosis (commonest cause of infarction)
- Haemorrhage into plaque → sudden expansion
- Calcification; ulceration and atheroembolism (cholesterol emboli)
- Aneurysm from medial atrophy
A thin cap over a large lipid core is what makes a plaque dangerous. Component Content Cap Smooth muscle, collagen Core Lipid, cholesterol clefts Cells Foam cells, T cells Applied
- Vulnerable plaques may cause infarction without severe stenosis
- Statins stabilise the fibrous cap
🔑KEY POINTS TO REMEMBER- Plaque = fibrous cap, cellular zone and lipid-rich necrotic core.
- Cholesterol clefts and foam cells are characteristic.
- Rupture with thrombosis is the key complication.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Complications of myocardial infarction arise from loss of contractile muscle, electrical instability and structural weakening, and follow a characteristic timeline.
Early Complications
- Arrhythmias — commonest cause of early death (ventricular fibrillation)
- Cardiogenic shock — with >40% ventricular loss
- Acute left ventricular failure and pulmonary oedema
- Rupture (3–7 days) — free wall (tamponade), septum (VSD), papillary muscle (mitral regurgitation)
- Pericarditis (2–4 days), mural thrombus → embolism
Late Complications
- Ventricular aneurysm — weeks to months; persistent ST elevation
- Dressler syndrome — autoimmune pericarditis after weeks
- Chronic cardiac failure; recurrent infarction
- Arrhythmias from scar tissue
Timing of the complication follows the stage of infarct healing. Time Complication Hours Arrhythmia 3–7 days Rupture Weeks Aneurysm, Dressler Applied
- Rupture risk peaks when macrophages soften the infarct (3–7 days)
- Persistent ST elevation after weeks suggests ventricular aneurysm
🔑KEY POINTS TO REMEMBER- Arrhythmia is the commonest early cause of death after MI.
- Cardiac rupture occurs at 3–7 days when the infarct is softest.
- Late: ventricular aneurysm and Dressler syndrome.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
The Aschoff body is the pathognomonic granulomatous lesion of rheumatic fever, found chiefly in the myocardium.
Structure & Cells
- Focus of fibrinoid necrosis surrounded by inflammatory cells
- Anitschkow cells — activated macrophages with caterpillar-shaped wavy chromatin
- Aschoff giant cells — multinucleate forms
- Lymphocytes and plasma cells at the periphery
- Located perivascularly in the myocardial interstitium
Evolution & Significance
- Early (exudative) — fibrinoid necrosis
- Intermediate (proliferative/granulomatous) — classic Aschoff body
- Late (healing) — replaced by fibrous scar
- Takes several months to evolve; indicates ongoing rheumatic activity
The granuloma marks active rheumatic carditis before scarring occurs. Cell Feature Anitschkow Caterpillar nucleus Aschoff giant cell Multinucleate Core Fibrinoid necrosis Applied
- Presence indicates active rheumatic carditis
- Fibrous healing produces valvular stenosis
🔑KEY POINTS TO REMEMBER- Aschoff body is pathognomonic of rheumatic fever.
- Contains fibrinoid necrosis, Anitschkow (caterpillar) cells and giant cells.
- Heals by fibrosis, contributing to chronic valve disease.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Cardiomyopathies are primary diseases of heart muscle not caused by ischaemic, valvular, hypertensive or congenital disease.
Types
- Dilated (congestive) — commonest (~90%); all chambers dilated, ↓ systolic function; causes: alcohol, viral myocarditis, peripartum, doxorubicin, genetic
- Hypertrophic — asymmetrical septal hypertrophy, myofibre disarray; autosomal dominant (sarcomeric gene mutations); sudden death in young athletes
- Restrictive — rigid, non-compliant ventricle with impaired filling; amyloidosis, endomyocardial fibrosis, haemochromatosis, sarcoidosis
Clinical Features
- Dilated — progressive cardiac failure, arrhythmias, mural thrombus and emboli
- Hypertrophic — dyspnoea, angina, syncope on exertion; systolic murmur; outflow obstruction
- Restrictive — features of right heart failure, raised jugular venous pressure
- Echocardiography is the key investigation
Whether the ventricle fails to contract or to fill defines the type. Type Ventricle Defect Dilated Dilated, thin Systolic Hypertrophic Thick septum Diastolic Restrictive Stiff Filling Applied
- Hypertrophic cardiomyopathy is a leading cause of sudden death in young athletes
- Dilated cardiomyopathy may require transplantation
🔑KEY POINTS TO REMEMBER- Three types: dilated (commonest), hypertrophic, restrictive.
- Hypertrophic shows asymmetrical septal hypertrophy and myofibre disarray.
- Restrictive impairs ventricular filling (amyloid, endomyocardial fibrosis).
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Pericarditis is inflammation of the pericardium, classified by the nature of the exudate and by chronicity.
Types by Exudate
- Serous — viral infection, SLE, rheumatic fever, uraemia
- Fibrinous / serofibrinous — commonest; myocardial infarction, uraemia, Dressler syndrome; bread-and-butter appearance, friction rub
- Purulent (suppurative) — pyogenic bacteria
- Haemorrhagic — tuberculosis, malignancy
- Caseous — tuberculosis (may calcify)
Chronic & Complications
- Constrictive pericarditis — dense fibrous or calcified sac restricting filling; commonly tuberculous
- ‘Concretio cordis’ — encasing calcified pericardium
- Cardiac tamponade — rapid effusion; hypotension, raised JVP, muffled sounds (Beck triad)
- Adhesive mediastinopericarditis
Acute inflammation may end in effusion, tamponade or chronic constriction. Type Cause Fibrinous MI, uraemia Haemorrhagic TB, malignancy Constrictive Tuberculosis Applied
- Pericardial friction rub is the classic clinical sign
- Tamponade requires urgent pericardiocentesis
🔑KEY POINTS TO REMEMBER- Fibrinous pericarditis (bread-and-butter) is commonest — MI, uraemia, Dressler.
- Tuberculosis causes haemorrhagic, caseous and constrictive pericarditis.
- Tamponade presents with Beck triad and needs urgent drainage.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
An aneurysm is a localised abnormal dilatation of a blood vessel or the heart wall, involving all layers (true) or a breach (false).
Classification
- True aneurysm — all three layers intact; fusiform or saccular
- False (pseudo) aneurysm — wall breached, contained by haematoma and adventitia
- Dissecting aneurysm — blood splits the media through an intimal tear
- Berry aneurysm — circle of Willis; mycotic — infective
Causes & Complications
- Atherosclerosis — commonest; abdominal aorta below renal arteries
- Hypertension — dissection, Charcot-Bouchard microaneurysms
- Cystic medial degeneration — Marfan syndrome
- Syphilis — thoracic aorta (tree-bark intima); trauma, infection, vasculitis
- Complications: rupture (often fatal), thrombosis, embolism, pressure erosion
Laplace's law means wall tension rises as the aneurysm enlarges. Aneurysm Site Cause Abdominal aortic Below renal arteries Atherosclerosis Berry Circle of Willis Congenital defect Syphilitic Thoracic aorta Syphilis Applied
- Abdominal aortic aneurysm >5.5 cm warrants repair
- Ruptured berry aneurysm → subarachnoid haemorrhage
🔑KEY POINTS TO REMEMBER- True aneurysm involves all layers; false is contained rupture; dissection splits the media.
- Atherosclerosis is the commonest cause (abdominal aorta below renal arteries).
- Berry aneurysms rupture into the subarachnoid space.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Risk factors for atherosclerosis are conditions that increase the likelihood of plaque formation, divided into modifiable and non-modifiable.
Non-Modifiable
- Age — risk rises progressively
- Male sex (women protected until menopause)
- Family history / genetic — the most significant independent factor
- Familial hypercholesterolaemia (LDL receptor defect)
Modifiable (major)
- Hyperlipidaemia — ↑ LDL, ↓ HDL; the central factor
- Hypertension
- Smoking
- Diabetes mellitus
- Minor: obesity, physical inactivity, stress (type A personality), ↑ homocysteine, ↑ CRP, oral contraceptives
Risk factors multiply rather than simply add when combined. Factor Type Age, sex, genetics Non-modifiable Lipids, BP, smoking, diabetes Modifiable Applied
- The four major modifiable factors together account for most risk
- Controlling lipids, blood pressure, smoking and glucose is the basis of prevention
🔑KEY POINTS TO REMEMBER- Non-modifiable: age, male sex, family history.
- Four major modifiable: hyperlipidaemia, hypertension, smoking, diabetes.
- Risk factors act synergistically, not additively.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.