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📚 SYSTEMIC PATHOLOGY - EXAM NOTES (Harsh Mohan / Robbins)

Tamil Nadu 2nd Year MBBS - Most Repeated Topics

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🫀 CARDIOVASCULAR SYSTEM

1. MYOCARDIAL INFARCTION (MI) ⭐⭐⭐ (Most Repeated Long Q)

• Atherosclerosis (major cause)
• Hypertension, DM, dyslipidemia, smoking
• Men > Women (women protected pre-menopause; post-menopause risk equalizes)
• ~10% MIs occur before 40 years; 45% before 65 years

1. Atheromatous plaque rupture/erosion → exposes subendothelial collagen
2. Platelets adhere → release TXA2, ADP, serotonin → further platelet aggregation + vasospasm
3. Tissue factor activates coagulation → thrombus grows
4. Thrombus completely occludes coronary artery within minutes

• STEMI (Transmural MI): Full thickness necrosis, ST elevation, Q waves
• NSTEMI (Subendocardial MI): Inner 1/3 of wall, no Q waves

• Arrhythmias (most common cause of death)
• Cardiogenic shock
• Pericarditis (Dressler syndrome - late)
• Mural thrombus
• Ventricular aneurysm
• Cardiac rupture (3-7 days - peak time)
• Papillary muscle rupture → mitral regurgitation

• Troponin I & T - Most sensitive and specific; rise in 3-4 hrs, peak 24-48 hrs, last 7-10 days
• CK-MB - Rises 4-8 hrs, peak 24 hrs, normalizes in 72 hrs (good for reinfarction)
• Myoglobin - Earliest (rises 1-4 hrs) but not specific
• LDH - Rises late (24-48 hrs), peaks 3-6 days, last 8-14 days

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2. ISCHEMIC HEART DISEASE (IHD) - Short Notes

1. Stable angina - fixed plaque >70% occlusion; pain with exertion, relieved by rest
2. Unstable angina - plaque rupture + thrombosis; pain at rest; treated aggressively
3. MI (see above)
4. Sudden cardiac death - fatal arrhythmia, often first presentation of IHD

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🫘 KIDNEY / URINARY SYSTEM

3. NEPHROTIC SYNDROME ⭐⭐⭐ (Most Repeated)

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4. MINIMAL CHANGE DISEASE ⭐⭐ (Short Q)

• Most common cause of nephrotic syndrome in children (1-7 years)
• Normal on light microscopy (hence the name)
• No deposits on immunofluorescence
• Key finding: Diffuse effacement of podocyte foot processes on electron microscopy
• Selective proteinuria (mainly albumin)
• Responds dramatically to corticosteroids (>90% in children)
• Pathogenesis: circulating factors (possibly antibodies against slit diaphragm proteins) damage podocytes

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5. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS (RPGN) / CRESCENTIC GN ⭐⭐

1. Type I (Anti-GBM): Linear IgG deposits; Goodpasture syndrome (lung + kidney)
2. Type II (Immune complex): Granular deposits; post-streptococcal, SLE, IgA nephropathy
3. Type III (Pauci-immune): No deposits; ANCA-associated vasculitis

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6. NEPHRITIC vs NEPHROTIC SYNDROME

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🫁 RESPIRATORY SYSTEM

7. CARCINOMA OF THE LUNG ⭐⭐⭐ (Most Repeated Long Q)

• Small cell → SIADH (hyponatremia), ACTH (Cushing), Lambert-Eaton myasthenic syndrome
• Squamous cell → Hypercalcemia (PTHrP)
• Any lung cancer → Hypertrophic pulmonary osteoarthropathy, clubbing

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8. TUBERCULOSIS - Pulmonary ⭐⭐ (Short Q)

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🫃 GI TRACT

9. PEPTIC ULCER DISEASE ⭐⭐⭐ (Repeated)

1. H. pylori infection (>70% cases)
2. NSAIDs / Aspirin use (increasing now)
3. Zollinger-Ellison syndrome (gastrin-secreting tumor → massive acid)

• Urease → ammonia → local injury
• CagA gene → virulence, gastric cancer risk
• VacA → vacuolization of gastric cells

• Round/oval, punched-out edges, smooth base
• Mucosal folds radiate to ulcer margin
• Usually < 2 cm

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10. ULCERATIVE COLITIS vs CROHN'S DISEASE ⭐⭐ (Comparison Q)

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🦠 LIVER / HEPATOBILIARY

11. CIRRHOSIS ⭐⭐ (Long Q)

1. Alcoholic liver disease (most common in India / TN)
2. Viral hepatitis (HBV, HCV)
3. Non-alcoholic fatty liver disease (NAFLD)
4. Biliary cirrhosis (primary, secondary)
5. Wilson's disease, hemochromatosis

• Hepatocyte injury → activation of hepatic stellate cells (Ito cells) → collagen deposition → fibrosis
• Portal hypertension develops as fibrous bands compress portal venules

• Portal hypertension → esophageal varices (most dangerous), caput medusae, splenomegaly
• Ascites (low-protein transudative)
• Hepatic encephalopathy (NH3 accumulation)
• Hepatorenal syndrome
• Coagulopathy (liver makes clotting factors)
• Hepatocellular carcinoma (HCC) - complication in HBV/HCV cirrhosis; AFP elevated

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12. HEPATOCELLULAR CARCINOMA ⭐⭐ (Short Q)

• Arises from hepatocytes; most common primary liver malignancy
• Risk: HBV > HCV > cirrhosis > aflatoxin B1
• Tumor marker: AFP (Alpha-fetoprotein) - elevated in 70%
• Gross: Green color (bile production), often multinodular
• Microscopy: Trabecular, acinar, or solid pattern
• Spreads: Portal vein invasion (characteristic), hematogenous

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🦋 ENDOCRINE

13. PAPILLARY CARCINOMA THYROID ⭐⭐⭐ (Most Repeated)

• Most common thyroid malignancy (80-85%)
• Associated with prior radiation exposure (most important risk)
• Spreads via lymphatics to cervical lymph nodes (50% cases)
• Excellent prognosis (10-year survival >95%)

1. Branching papillae with fibrovascular stalks
2. Ground-glass (Orphan Annie Eye) nuclei - finely dispersed chromatin, optically clear appearance
3. Intranuclear inclusions (pseudo-inclusions) and intranuclear grooves
4. Psammoma bodies (concentric calcified structures) - almost never in follicular/medullary Ca
5. Lymphatic invasion common; blood vessel invasion uncommon in small lesions

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14. HASHIMOTO'S THYROIDITIS ⭐⭐ (Short Q)

• Most common cause of hypothyroidism in iodine-sufficient areas
• Autoimmune - anti-TPO, anti-thyroglobulin antibodies
• HLA-DR3, DR5 associated
• Microscopy: Lymphocytic infiltration with germinal center formation + Hürthle cell (oxyphilic) change of follicular epithelium
• Gross: Diffuse, firm, pale gray enlargement
• Risk of B-cell lymphoma (low)

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15. DIABETES MELLITUS - Pathology ⭐⭐⭐ (Long Q)

• Autoimmune destruction of beta cells
• HLA-DR3, DR4
• Insulitis (lymphocytic infiltration of islets)
• Total insulin deficiency; ketosis-prone

• Insulin resistance + relative insulin deficiency
• Amyloid deposition in islets (islet amyloid polypeptide / IAPP)
• Obesity-associated; strong genetic component

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👩 FEMALE GENITAL SYSTEM

16. CERVICAL CARCINOMA ⭐⭐⭐ (Tamil Nadu Fav Long Q)

• Average age: 45-50 years
• Squamous cell carcinoma = 80% (most common)
• Adenocarcinoma = 15%

• HPV E6 protein → binds and degrades p53 (tumor suppressor)
• HPV E7 protein → binds and inactivates Rb (tumor suppressor)
• High-risk HPV types: 16, 18, 31, 33, 45

• CIN I = Mild dysplasia (lower 1/3 epithelium affected)
• CIN II = Moderate dysplasia (lower 2/3)
• CIN III = Severe dysplasia + CIS (full thickness)
• CIN III → Invasive carcinoma over 10+ years

• Fungating (exophytic) or infiltrative ulcerative mass
• Squamous cell: nests/tongues of malignant squamous epithelium with keratin pearls (keratinizing type)
• Koilocytes: cells with perinuclear halo + nuclear enlargement (HPV cytopathic effect)

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17. OVARIAN TUMORS ⭐⭐ (Classification Q)

1. Surface epithelial tumors (most common, 65-70%)
   • Serous cystadenoma/cystadenocarcinoma (most common malignant)
   • Mucinous cystadenoma/cystadenocarcinoma
   • Endometrioid carcinoma
   • Brenner tumor (transitional cell type)
2. Germ cell tumors (20%)
   • Teratoma (most common benign ovarian tumor overall in young)
   • Dysgerminoma (female equivalent of seminoma)
   • Yolk sac tumor (AFP elevated)
   • Choriocarcinoma (beta-hCG elevated)
3. Sex cord-stromal tumors
   • Granulosa cell tumor (estrogen → precocious puberty/postmenopausal bleeding)
   • Thecoma, Sertoli-Leydig cell tumor (androgen → virilization)

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🧫 MALE GENITAL SYSTEM

18. SEMINOMA TESTIS ⭐⭐ (Short Q)

• Most common testicular tumor (40%)
• Peak age: 30-40 years
• Arises from undifferentiated germ cells
• Associated with cryptorchidism

• Large cells with clear glycogen-rich cytoplasm arranged in sheets/lobules
• Prominent nuclei with 1-2 nucleoli
• Fibrous septa with lymphocytic infiltration
• "Fried-egg" appearance of cells

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🩸 HEMATOPOIETIC SYSTEM

19. LEUKEMIA - Classification ⭐⭐

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20. HODGKIN vs NON-HODGKIN LYMPHOMA ⭐⭐

1. Nodular lymphocyte predominant
2. Nodular sclerosis (most common; young women; mediastinal)
3. Mixed cellularity (EBV-related, good for biopsy)
4. Lymphocyte-rich
5. Lymphocyte-depleted (worst prognosis)

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⚡ QUICK REVISION - MUST KNOW ONE-LINERS

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📋 TAMIL NADU UNIVERSITY - FREQUENTLY REPEATED LONG QUESTIONS

1. Describe the pathogenesis, morphology, and complications of Myocardial Infarction
2. Classify renal tumors. Describe the pathology of renal cell carcinoma
3. Classify glomerulonephritis. Describe post-streptococcal GN
4. Pathology of peptic ulcer disease - etiopathogenesis and morphology
5. Papillary carcinoma thyroid - morphology and clinical features
6. Describe Hashimoto's thyroiditis
7. Diabetes mellitus - morphological changes in kidney (diabetic nephropathy)
8. Classify ovarian neoplasms. Discuss serous tumors in detail
9. Cervical carcinoma - HPV role, CIN, invasive carcinoma
10. Ulcerative colitis vs Crohn's disease
11. Describe cirrhosis liver - causes, pathogenesis, morphology, complications
12. Hodgkin lymphoma - Reed-Sternberg cells, classification

📋 TAMIL NADU - FREQUENTLY REPEATED SHORT QUESTIONS

1. Minimal change disease
2. Nephrotic vs nephritic syndrome
3. Seminoma testis
4. Lung carcinoma and paraneoplastic syndromes
5. Psammoma bodies (list conditions)
6. Kimmelstiel-Wilson nodules
7. Philadelphia chromosome
8. Reed-Sternberg cells
9. Koilocytes
10. Cardiac biomarkers (troponin)
11. Carcinoid tumor
12. Benign vs malignant gastric ulcer
13. Hürthle cell
14. Types of giant cells
15. Ghon complex

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All notes referenced from: Robbins & Kumar Basic Pathology and Robbins, Cotran & Kumar Pathologic Basis of Disease (equivalent to Harsh Mohan's systemic pathology coverage). These are the same core sources used in all Indian MBBS curricula.