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General Pathology — MBBS Viva Questions

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1. Cell Injury, Death & Adaptation

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• Cellular swelling (hydropic change)
• Fatty change (especially liver, heart, kidney)
• Plasma membrane blebbing
• Clumping of nuclear chromatin
• ER dilation, ribosome detachment

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1. ATP depletion → Na/K pump failure → cell swelling
2. Mitochondrial damage → cytochrome c release → apoptosis
3. Intracellular Ca²⁺ increase → activates phospholipases, proteases, endonucleases
4. Free radical injury (ROS) — lipid peroxidation, protein oxidation, DNA damage
5. Membrane permeability defects
6. DNA/protein damage

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• Superoxide dismutase → H₂O₂
• Catalase → H₂O + O₂
• Glutathione peroxidase → detoxifies H₂O₂ and lipid peroxides
• Vitamins C, E, A; ceruloplasmin, transferrin (chelate iron)

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• Hypertrophy — increased cell size (e.g., cardiac hypertrophy in hypertension)
• Hyperplasia — increased cell number (e.g., endometrial hyperplasia under estrogen)
• Atrophy — decreased cell size/number (e.g., disuse atrophy, denervation)
• Metaplasia — one differentiated cell type replaced by another (e.g., Barrett esophagus, squamous metaplasia in bronchus of smokers)
• Dysplasia — disordered growth, pre-neoplastic (not strictly an adaptation)

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• Papillary thyroid carcinoma
• Papillary serous ovarian carcinoma
• Meningioma
• Mesothelioma

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2. Inflammation

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1. Transient vasoconstriction (seconds)
2. Vasodilation → increased blood flow (redness, heat)
3. Increased vascular permeability → protein-rich exudate leaks
4. Stasis → margination of leukocytes

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• Endothelial contraction (most common) — histamine, bradykinin, leukotrienes → gaps form in venular endothelium
• Endothelial injury — direct damage (burns, toxins), neutrophil-mediated
• Transcytosis — VEGF-induced (through vesicular channels)
• Leakiness in new vessels (angiogenesis)

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1. Margination — leukocytes move to vessel periphery
2. Rolling — selectin-PSGL-1 interactions (E-selectin, P-selectin, L-selectin)
3. Adhesion — integrins (LFA-1, Mac-1) bind ICAM-1 on endothelium; activated by chemokines
4. Transmigration (diapedesis) — through intercellular junctions via PECAM-1 (CD31)
5. Chemotaxis — toward the injury site via C5a, IL-8, LTB₄, bacterial products (fMLP)

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• Preformed: histamine (mast cells), serotonin (platelets)
• Newly synthesized: prostaglandins, leukotrienes, PAF, cytokines (TNF, IL-1, IL-6), NO, lysosomal enzymes, ROS

• Complement system (C3a, C5a — anaphylatoxins; C5b-9 MAC)
• Kinin system (bradykinin)
• Coagulation/fibrinolytic system

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• COX pathway → PGE₂ (fever, pain), PGI₂ (vasodilation), TXA₂ (platelet aggregation)
• LOX pathway → LTB₄ (neutrophil chemotaxis), LTC₄, LTD₄, LTE₄ (bronchoconstriction, vasoconstriction — slow reacting substances of anaphylaxis)

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1. Resolution — complete restoration (if minimal necrosis)
2. Healing by fibrosis — if extensive tissue destruction
3. Abscess formation — walled-off collection of pus
4. Progression to chronic inflammation
5. Lymphangitis/bacteremia — spread

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• Macrophages (dominant — secrete cytokines, growth factors, enzymes)
• Lymphocytes (T and B)
• Plasma cells
• Eosinophils (parasitic, allergic)
• Mast cells
• Fibroblasts (repair)

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• Langhans giant cell — nuclei arranged in a horseshoe/peripheral pattern (TB)
• Foreign body giant cell — nuclei scattered randomly
• Touton giant cell — ring of nuclei with foamy cytoplasm peripherally (fat necrosis, xanthoma)
• Osteoclast-type giant cell — in bone tumors
• Reed-Sternberg cell — Hodgkin lymphoma (not a true giant cell but resembles)

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3. Healing and Repair

1. Hemostasis (minutes) — platelet plug, fibrin clot
2. Inflammation (1–3 days) — neutrophils, then macrophages
3. Proliferation (3–14 days) — angiogenesis, fibroblast proliferation, collagen deposition, epithelialization
4. Remodeling (weeks–months) — type III → type I collagen; MMPs degrade excess ECM; tensile strength increases (never exceeds ~80% of original)

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• New capillaries (angiogenesis — VEGF, bFGF driven)
• Proliferating fibroblasts
• Loose ECM (fibronectin, proteoglycans)
• Macrophages
• Myofibroblasts (wound contraction)

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• Local: infection, foreign body, poor blood supply, movement, radiation, hematoma
• Systemic: malnutrition (especially vitamin C — collagen synthesis), diabetes mellitus, corticosteroids, aging, uremia, chemotherapy/immunosuppression

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• Deficient healing — wound dehiscence, ulceration
• Excessive healing — keloid (extends beyond wound margins; type I collagen; more common in dark-skinned individuals), hypertrophic scar (stays within margins)
• Contracture — serious across joints (burn wounds)
• Desmoid tumor — exuberant fibromatosis
• Proud flesh — excessive granulation tissue

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4. Hemodynamic Disorders

• Increased hydrostatic pressure — CCF, portal hypertension, venous obstruction
• Decreased oncotic pressure — nephrotic syndrome, cirrhosis, protein-losing enteropathy, malnutrition
• Lymphatic obstruction — filariasis (elephantiasis), post-mastectomy
• Na⁺ retention — renal failure
• Increased vascular permeability — inflammation, burns

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1. Endothelial injury (most important) — atherosclerosis, trauma, inflammation
2. Stasis or turbulence — atrial fibrillation, prolonged immobility, aneurysm
3. Hypercoagulability — factor V Leiden, antiphospholipid syndrome, pregnancy, malignancy

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• Thromboembolism — most common (DVT → pulmonary embolism)
• Fat embolism — long bone fractures, liposuction
• Air/gas embolism — IV lines, decompression sickness (caisson disease)
• Amniotic fluid embolism — obstetric emergency (DIC)
• Tumor embolism
• Septic embolism — infective endocarditis

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• Nature of blood supply (dual → liver, lung more resistant)
• Rate of occlusion (gradual → collaterals develop)
• Tissue vulnerability (neurons — 3–5 min; myocardium — 20–30 min; fibroblasts — hours)
• Oxygen-carrying capacity of blood

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5. Neoplasia

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• Hyperplasia — increased number of cells (reversible, stimulus-dependent)
• Metaplasia — replacement of one cell type by another (e.g., columnar → squamous in bronchus); reversible; pre-malignant risk if persistent
• Dysplasia — disordered growth with loss of uniformity and architectural orientation; considered pre-neoplastic; hallmarks: nuclear pleomorphism, increased mitoses, abnormal differentiation

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• Pleomorphism — variable size and shape of cells and nuclei
• Hyperchromasia — dark-staining nuclei with coarse chromatin
• Increased nuclear:cytoplasmic ratio (N:C ratio ↑)
• Abnormal mitoses — tripolar, ring-shaped spindles
• Giant cells — tumor giant cells with one large or two nuclei
• Loss of polarity — disordered arrangement

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1. Lymphatic spread — most common for carcinomas; regional nodes first
2. Hematogenous spread — most common for sarcomas; via veins (portal → liver; IVC → lungs)
3. Seeding of body cavities (transcoelomic) — ovarian cancer → peritoneal spread ("omental cake")
4. Perineural spread — adenoid cystic carcinoma, prostate cancer
5. Direct extension

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1. Sustaining proliferative signaling
2. Evading growth suppressors
3. Resisting cell death
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Activating invasion and metastasis
7. (Emerging): Reprogramming energy metabolism (Warburg effect)
8. Evading immune destruction
9. Tumor-promoting inflammation
10. Genomic instability and mutation

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• RAS — most commonly mutated oncogene (colorectal, pancreatic)
• MYC — Burkitt lymphoma (t[8;14])
• HER2/NEU — breast cancer
• BCL-ABL — CML (Philadelphia chromosome t[9;22])
• EGFR — lung adenocarcinoma

• TP53 — most commonly mutated TSG (Li-Fraumeni syndrome)
• RB1 — retinoblastoma (familial bilateral)
• APC — FAP (colorectal)
• BRCA1/2 — breast, ovarian
• CDKN2A (p16) — melanoma, pancreatic

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• Activates CDKN1A (p21) → G1 arrest (allows repair)
• Activates DNA repair genes
• If damage is irreparable → activates BAX → apoptosis
• Mutated in >50% of human cancers; germline mutation → Li-Fraumeni syndrome

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• Hypercalcemia — PTHrP (squamous cell lung, breast, renal carcinoma)
• SIADH — small cell lung carcinoma (ADH)
• Cushing syndrome — ACTH (small cell lung)
• Polycythemia — EPO (renal cell carcinoma, cerebellar hemangioblastoma)
• Eaton-Lambert syndrome — small cell lung (anti-VGCC antibodies)
• Acanthosis nigricans — gastric, lung carcinoma
• Migratory thrombophlebitis (Trousseau sign) — pancreatic adenocarcinoma

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6. Immunopathology

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• Breakdown of self-tolerance (failure of clonal deletion/anergy)
• Molecular mimicry (e.g., rheumatic fever — streptococcal M protein → cardiac myosin)
• Bystander activation
• Epitope spreading
• HLA associations

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• AL (primary) — immunoglobulin light chains (multiple myeloma, plasma cell dyscrasias)
• AA (secondary) — serum amyloid A protein (chronic inflammation — TB, RA, Crohn's)
• Aβ — Alzheimer's disease
• ATTR — transthyretin (senile systemic, familial)
• Aβ₂M — β₂-microglobulin (dialysis)

• H&E: amorphous eosinophilic deposits
• Congo red stain → apple-green birefringence under polarized light (most specific)
• Thioflavine T/S → yellow-green fluorescence
• Electron microscopy: non-branching fibrils, 7.5–10 nm diameter

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7. Genetic & Pediatric Disorders

1. Single-gene (Mendelian) — autosomal dominant (Marfan, NF1), autosomal recessive (cystic fibrosis, PKU), X-linked (hemophilia, DMD)
2. Chromosomal disorders — trisomies (Down, Edwards, Patau), monosomy (Turner's), sex chromosome (Klinefelter's)
3. Multifactorial — polygenic + environment (diabetes, hypertension, congenital heart disease)
4. Mitochondrial — maternal inheritance (MELAS, Leber's optic neuropathy)
5. Trinucleotide repeat disorders — anticipation (Huntington's, fragile X, myotonic dystrophy)

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• Deletion — loss of chromosomal segment (e.g., 5p deletion → cri-du-chat)
• Translocation — segment moved to another chromosome; balanced (no loss) vs. unbalanced
• Inversion — segment reversed; pericentric (includes centromere) vs. paracentric
• Isochromosome — abnormal chromosome with identical arms
• Ring chromosome — ends of chromosome fuse

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• Prader-Willi syndrome if paternal chromosome 15 deleted (maternal allele silenced by imprinting)
• Angelman syndrome if maternal chromosome 15 deleted (paternal allele silenced by imprinting)

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Quick-Fire Staining & Special Tests

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Examiner Tips

• Always start answers by defining the term asked.
• For necrosis questions, know the histology AND clinical example.
• For neoplasia, be ready to compare benign vs. malignant and give examples for each feature.
• Know the four cardinal signs of inflammation and be able to explain each at the molecular level.
• Virchow's triad is a must-know for thrombosis questions.
• When asked about staining, mention the stain name, color produced, AND what it identifies.
• Link granuloma always to TB vs. sarcoidosis — examiners test the distinction repeatedly.

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