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
Cell injury occurs when a cell can no longer adapt to stress, resulting in reversible or irreversible damage.
Causes
- Hypoxia/ischaemia — commonest cause
- Physical agents — trauma, heat, radiation
- Chemicals, drugs, poisons
- Infections; immunological reactions
- Genetic defects; nutritional imbalance
Mechanisms
- ATP depletion → sodium pump failure → cell swelling
- Mitochondrial damage → ↓ ATP, free radicals
- ↑ Intracellular calcium → activates enzymes
- Free-radical injury → membrane lipid peroxidation
- Membrane and DNA/protein damage
Loss of ATP and calcium influx decide whether injury can be reversed. Feature Reversible Irreversible Cell swelling Present Marked Membrane Intact Ruptured Nucleus Normal Pyknosis Applied
- Reperfusion injury worsens damage through free radicals
- Enzyme leak (troponin, transaminases) marks irreversible injury
🔑KEY POINTS TO REMEMBER- Hypoxia is the commonest cause of cell injury.
- Mechanisms: ATP depletion, ↑ calcium, free radicals, membrane damage.
- Membrane rupture marks the point of irreversibility.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Cellular adaptations are reversible changes in cell size, number, phenotype or function in response to altered demand or stress.
Types
- Hypertrophy — ↑ cell size (cardiac, skeletal muscle)
- Hyperplasia — ↑ cell number (endometrium, prostate)
- Atrophy — ↓ cell size and function (disuse, denervation, ischaemia)
- Metaplasia — one differentiated cell type replaced by another
- Dysplasia — disordered growth (pre-neoplastic, not a true adaptation)
Physiological vs Pathological
- Physiological — uterine hypertrophy in pregnancy, breast hyperplasia in lactation
- Pathological — left ventricular hypertrophy in hypertension, endometrial hyperplasia
Adaptation buys time; when its limit is exceeded, injury follows. Adaptation Change Example Hypertrophy ↑ Size Cardiac muscle Hyperplasia ↑ Number Endometrium Atrophy ↓ Size Disuse Applied
- Adaptations are reversible if the stimulus is removed
- Persistent metaplasia may progress to dysplasia and cancer
🔑KEY POINTS TO REMEMBER- Adaptations: hypertrophy, hyperplasia, atrophy, metaplasia.
- Hypertrophy = bigger cells; hyperplasia = more cells.
- Reversible, but persistent stress leads to injury or dysplasia.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Necrosis is the death of cells in living tissue accompanied by enzymatic digestion and inflammation.
Nuclear Changes
- Pyknosis — nuclear shrinkage and condensation
- Karyorrhexis — fragmentation
- Karyolysis — dissolution (fading)
Types
- Coagulative — ischaemia in solid organs; architecture preserved
- Liquefactive — brain infarct, abscess
- Caseous — tuberculosis; cheesy, granuloma
- Fat necrosis — acute pancreatitis (saponification)
- Fibrinoid — vasculitis, malignant hypertension
- Gangrenous — limb ischaemia (dry/wet)
Leakage of cell contents triggers the inflammation that defines necrosis. Type Typical site Coagulative Myocardial infarct Liquefactive Brain Caseous Tuberculosis Applied
- Serum enzymes (troponin, amylase) rise after necrosis
- Always pathological — unlike apoptosis
🔑KEY POINTS TO REMEMBER- Necrosis = cell death with enzymatic digestion and inflammation.
- Nuclear changes: pyknosis, karyorrhexis, karyolysis.
- Types: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Apoptosis is programmed, energy-dependent cell death of single cells without inflammation.
Pathways
- Intrinsic (mitochondrial) — ↓ Bcl-2, ↑ Bax → cytochrome c release → caspase 9
- Extrinsic (death receptor) — Fas/FasL, TNF → caspase 8
- Both converge on executioner caspases 3 and 6
- Regulated by p53 (DNA damage)
Morphology & Situations
- Cell shrinkage, chromatin condensation, apoptotic bodies
- Membrane remains intact → no inflammation
- Phagocytosed by neighbouring cells
- Physiological — embryogenesis, menstruation, involution
- Pathological — viral hepatitis (Councilman bodies), radiation, tumour cell death
Controlled dismantling avoids leakage, so no inflammation occurs. Pathway Trigger Caspase Intrinsic Mitochondrial 9 Extrinsic Death receptor 8 Applied
- Excess apoptosis → neurodegeneration; too little → cancer
- Bcl-2 overexpression (follicular lymphoma) blocks apoptosis
🔑KEY POINTS TO REMEMBER- Apoptosis is programmed, energy-dependent, without inflammation.
- Intrinsic (mitochondrial, caspase 9) and extrinsic (death receptor, caspase 8).
- p53 and Bcl-2 regulate it; defects contribute to cancer.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Intracellular accumulations are abnormal deposits of substances within cells; pathological calcification is abnormal deposition of calcium salts in tissues.
Intracellular Accumulations
- Lipid — fatty change (liver), cholesterol (atheroma, xanthoma)
- Protein — Russell bodies, Mallory hyaline, α₁-antitrypsin
- Glycogen — diabetes, glycogen storage disease
- Pigments — exogenous (carbon/anthracosis) and endogenous (lipofuscin, melanin, haemosiderin)
Pathological Calcification
- Dystrophic — in dead/damaged tissue; serum calcium normal (atheroma, TB, damaged valves)
- Metastatic — in normal tissue; hypercalcaemia (hyperparathyroidism, bone metastases, vitamin D excess)
- Metastatic calcification favours kidney, lung, gastric mucosa, vessels
The serum calcium level distinguishes the two forms. Feature Dystrophic Metastatic Tissue Dead/damaged Normal Serum calcium Normal Raised Example Atheroma Hyperparathyroidism Applied
- Psammoma bodies — laminated calcification (papillary thyroid carcinoma, meningioma)
- Lipofuscin is the ‘wear and tear’ pigment of ageing
🔑KEY POINTS TO REMEMBER- Accumulations: lipid, protein, glycogen, pigments.
- Dystrophic calcification: damaged tissue, normal serum calcium.
- Metastatic calcification: normal tissue with hypercalcaemia.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Necrosis is classified morphologically into distinct types that indicate the underlying cause.
Types
- Coagulative — ischaemic infarct of solid organs; tissue architecture preserved, nuclei lost
- Liquefactive — brain infarct, pyogenic abscess; tissue digested to liquid
- Caseous — tuberculosis; cheese-like, granulomatous, structure destroyed
- Fat necrosis — acute pancreatitis, breast trauma; chalky-white saponification
- Fibrinoid — immune vasculitis, malignant hypertension; bright pink vessel walls
- Gangrenous — dry (coagulative, limb) or wet (with infection)
Whether proteins denature or enzymes digest decides the pattern. Type Cause Coagulative Ischaemia Liquefactive Brain, abscess Caseous Tuberculosis Fat Pancreatitis Applied
- Brain is the exception — ischaemia causes liquefactive necrosis
- Caseous necrosis suggests tuberculosis until proved otherwise
🔑KEY POINTS TO REMEMBER- Coagulative (ischaemia), liquefactive (brain/abscess), caseous (TB).
- Fat necrosis in pancreatitis; fibrinoid in vasculitis.
- Brain infarct is liquefactive despite being ischaemic.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Apoptosis and necrosis are the two patterns of cell death, differing fundamentally in mechanism and consequence.
Apoptosis
- Programmed, energy (ATP)-dependent
- Affects single cells
- Cell shrinks; membrane intact; apoptotic bodies formed
- No inflammation; may be physiological or pathological
Necrosis
- Always pathological, passive, no energy required
- Affects groups of cells
- Cell swells; membrane ruptures; contents leak
- Inflammation present
Membrane integrity is the crucial difference between the two. Feature Apoptosis Necrosis Energy Required Not required Membrane Intact Ruptured Inflammation Absent Present Extent Single cell Groups Applied
- DNA laddering in apoptosis; random DNA breakdown in necrosis
- Anticancer drugs act largely by inducing apoptosis
🔑KEY POINTS TO REMEMBER- Apoptosis: programmed, ATP-dependent, single cells, no inflammation.
- Necrosis: pathological, cell swelling and rupture, with inflammation.
- Membrane integrity is preserved only in apoptosis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Fatty change (steatosis) is the abnormal accumulation of triglycerides within parenchymal cells, most often the liver.
Causes
- Alcohol — commonest cause
- Obesity, diabetes mellitus (non-alcoholic fatty liver disease)
- Protein malnutrition (kwashiorkor)
- Toxins — carbon tetrachloride; drugs; pregnancy; hypoxia
Mechanism & Morphology
- ↑ Free fatty acid delivery, ↑ triglyceride synthesis
- ↓ Apoprotein synthesis → impaired lipoprotein export
- ↓ Fatty acid oxidation
- Liver enlarged, soft, yellow, greasy
- Microscopy: clear fat vacuoles displacing the nucleus
Imbalance between fat delivery and export loads the hepatocyte. Feature Detail Commonest cause Alcohol Appearance Yellow greasy liver Reversible Yes, early Applied
- Reversible if the cause is removed
- May progress to steatohepatitis, fibrosis and cirrhosis
🔑KEY POINTS TO REMEMBER- Fatty change is triglyceride accumulation, commonest in the liver.
- Alcohol is the leading cause; also obesity, diabetes, malnutrition.
- Reversible early but may progress to cirrhosis.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Metaplasia is a reversible change in which one differentiated cell type is replaced by another differentiated cell type better able to withstand stress.
Types & Examples
- Squamous metaplasia — bronchus in smokers (columnar → squamous)
- Cervix (endocervical columnar → squamous)
- Columnar (glandular) metaplasia — Barrett’s oesophagus (squamous → columnar) in reflux
- Osseous metaplasia — bone in soft tissue
- Intestinal metaplasia of stomach in chronic gastritis
Mechanism & Significance
- Reprogramming of stem cells, not transdifferentiation of mature cells
- Adaptive but with a cost — loss of protective function (loss of cilia and mucus in bronchus)
- Reversible if the stimulus is removed
- Persistent stimulus → dysplasia → carcinoma
The tissue trades specialised function for durability. Site Change Bronchus Columnar → squamous Oesophagus Squamous → columnar Cervix Columnar → squamous Applied
- Barrett’s oesophagus is premalignant (adenocarcinoma)
- Squamous metaplasia of bronchus precedes squamous cell carcinoma
🔑KEY POINTS TO REMEMBER- Metaplasia = one differentiated cell type replaced by another.
- Occurs by stem cell reprogramming and is reversible.
- Barrett’s oesophagus is premalignant.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Free radicals are chemical species with a single unpaired electron that damage cells by initiating chain reactions — oxidative stress.
Sources
- Normal metabolism — mitochondrial oxidative phosphorylation
- Reperfusion after ischaemia
- Radiation (radiolysis of water), toxins (carbon tetrachloride)
- Inflammation — respiratory burst of neutrophils
- Species: superoxide, hydrogen peroxide, hydroxyl radical, nitric oxide
Mechanisms of Damage & Defences
- Lipid peroxidation of membranes
- Protein cross-linking and fragmentation; DNA damage (mutations, ageing, cancer)
- Antioxidant defences: superoxide dismutase, catalase, glutathione peroxidase
- Vitamins A, C, E; transport proteins (transferrin, ceruloplasmin) bind free metals
One radical starts a self-propagating chain unless antioxidants intervene. Enzyme Action Superoxide dismutase Superoxide → H₂O₂ Catalase H₂O₂ → water Glutathione peroxidase Removes H₂O₂ Applied
- Reperfusion injury after thrombolysis or angioplasty
- Implicated in ageing, atherosclerosis and carcinogenesis
🔑KEY POINTS TO REMEMBER- Free radicals have unpaired electrons and cause oxidative stress.
- Damage by lipid peroxidation, protein and DNA injury.
- Defences: superoxide dismutase, catalase, glutathione peroxidase, vitamins.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Pathological calcification is the abnormal deposition of calcium salts, with or without iron and magnesium, in tissues.
Dystrophic Calcification
- In dead or degenerated tissue
- Serum calcium normal
- Examples: atheromatous plaques, damaged heart valves, tuberculous lymph nodes, old scars, dead parasites
- Psammoma bodies in papillary thyroid carcinoma and meningioma
Metastatic Calcification
- In normal tissue, always with hypercalcaemia
- Causes: hyperparathyroidism, bone destruction (metastases, myeloma), vitamin D excess, renal failure, sarcoidosis
- Sites: kidney (nephrocalcinosis), lung, gastric mucosa, blood vessels, cornea
- Preferentially in tissues that secrete acid (internal alkalinity)
Serum calcium is the single distinguishing feature. Feature Dystrophic Metastatic Serum calcium Normal Raised Tissue Damaged Normal Example Atheroma Nephrocalcinosis Applied
- Calcification on X-ray may be the first clue to old tuberculosis
- Correct the underlying hypercalcaemia in metastatic calcification
🔑KEY POINTS TO REMEMBER- Dystrophic calcification occurs in damaged tissue with normal calcium.
- Metastatic calcification occurs in normal tissue with hypercalcaemia.
- Metastatic type affects kidney, lung, stomach and vessels.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.Definition
Hypertrophy is an increase in cell size, whereas hyperplasia is an increase in cell number; both enlarge the organ.
Hypertrophy
- ↑ Synthesis of structural proteins and organelles
- Occurs in permanent (non-dividing) cells — cardiac and skeletal muscle, neurons
- Physiological — skeletal muscle in athletes, uterus in pregnancy
- Pathological — left ventricular hypertrophy in hypertension
Hyperplasia
- Occurs only in dividing (labile/stable) cells
- Physiological — breast in lactation, liver regeneration
- Pathological — endometrial hyperplasia, benign prostatic hyperplasia
- Hormonal or compensatory stimuli
Whether the cell can divide determines which response occurs. Feature Hypertrophy Hyperplasia Change Cell size Cell number Cell type Permanent Dividing Example Cardiac muscle Endometrium Applied
- Uterus in pregnancy shows both hypertrophy and hyperplasia
- Pathological hyperplasia may progress to dysplasia and cancer
🔑KEY POINTS TO REMEMBER- Hypertrophy = ↑ cell size (permanent cells like cardiac muscle).
- Hyperplasia = ↑ cell number (dividing cells like endometrium).
- Pregnant uterus shows both; pathological hyperplasia can precede cancer.
📚SOURCES: Robbins & Cotran Pathologic Basis of Disease; Textbook of Pathology (Harsh Mohan); Robbins Basic Pathology.