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CARDIAC PATHOLOGY - COMPLETE ANSWER GUIDE

SAQ Section (Questions 1-29)

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1. Gross & Microscopy of Infective Endocarditis

• Vegetations - friable, bulky, irregular, destructive masses on valve leaflets (typically on the line of closure)
• Located on the atrial surface of AV valves and ventricular surface of semilunar valves
• In acute IE (S. aureus): large, bulky, destructive vegetations with ulceration/perforation of leaflets
• In subacute IE (S. viridans): smaller, less destructive vegetations on previously damaged valves
• Underlying valve may show ulceration, perforation, chordal rupture

• Vegetations composed of: fibrin, platelets, inflammatory cells (neutrophils/macrophages), and bacteria/fungal colonies
• Underlying valve shows coagulative necrosis with acute inflammatory infiltrate
• Granulation tissue and fibrosis in older lesions
• Bacteria visible as "colonies" embedded within fibrin mesh

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2. Investigations & Interpretation in Acute Myocardial Infarction

• Troponin I/T is the gold standard - most sensitive and specific. A single high-sensitivity troponin at presentation + clinical features confirms MI
• CK-MB useful for detecting re-infarction (returns to normal faster)
• ECG changes: ST elevation (STEMI) or depression, T-wave inversion, new LBBB, Q waves (old infarct)
• Echocardiography: wall motion abnormality in affected segment
• Coronary angiography: confirms occlusion; used for PCI

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3. Morphology & Complications (Cardiac) in Bacterial Endocarditis

1. Valvular insufficiency/regurgitation - from leaflet destruction
2. Valvular perforation - particularly aortic and mitral leaflets
3. Chordae tendineae rupture - causes acute mitral regurgitation
4. Ring abscess - spread of infection to valve annulus and adjacent myocardium (most common with S. aureus)
5. Myocarditis - direct extension of infection
6. Pericarditis - via direct spread
7. Conduction abnormalities - aortic root abscess extends into conduction system causing heart block
8. Intracardiac fistula formation

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4. Complications of Myocardial Infarction

• Arrhythmias (most common cause of death in first 24 hrs) - VF, VT
• Cardiogenic shock (large infarct >40% LV)
• Acute left heart failure / pulmonary edema
• Mural thrombus (days 2-3)
• Fibrinous pericarditis (days 2-3)

• Cardiac rupture - free wall rupture (peak at day 4-7) causing hemopericardium and tamponade
• Ventricular septal defect - septal rupture
• Papillary muscle rupture - acute mitral regurgitation
• Ventricular aneurysm (fibrotic wall bulge, especially anterior wall after LAD occlusion)
• Dressler's syndrome (autoimmune pericarditis, weeks later)
• Reinfarction, sudden cardiac death

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5. Aschoff Body

• Central zone of fibrinoid necrosis
• Surrounding activated macrophages called Anitschkow cells (pathognomonic):
  • Large pale histiocytes
  • Nuclei with central bar of chromatin resembling a "caterpillar" or "owl eye" appearance
  • Also called "caterpillar cells"
• Occasional Aschoff giant cells (multinucleated Anitschkow cells)
• Peripheral lymphocytes and plasma cells

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6. Serum Cardiac Markers / Complications of Atherosclerosis in Myocardial Infarction

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7. Classification of Endocarditis

1. Acute IE - virulent organisms (S. aureus), normal or abnormal valves, rapid destruction, high mortality
2. Subacute IE (SABE) - low virulence (S. viridans), pre-existing valve disease, weeks-months course

1. Infective - bacterial, fungal, rickettsial
2. Non-infective (Non-bacterial thrombotic endocarditis, NBTE) - marantic endocarditis (cancer, debility), small sterile vegetations on line of closure
3. Libman-Sacks endocarditis - SLE, small vegetations on both surfaces of leaflets
4. Rheumatic endocarditis - post-group A streptococcal, verrucous vegetations on line of closure (mitral most common)

• Mitral > Aortic > Tricuspid (right-sided in IV drug users)

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8. Complications of Coronary Atherosclerosis

1. Angina pectoris (stable, unstable, Prinzmetal variant)
2. Acute MI (STEMI and NSTEMI)
3. Sudden cardiac death (ischemic arrhythmia - VF)
4. Chronic ischemic heart disease - progressive pump failure
5. Congestive heart failure - after repeated infarcts
6. Ventricular aneurysm
7. Stroke/TIA - if atheroembolism involves carotids (though mechanism different)
8. Renal artery involvement - hypertension, renal failure
9. Peripheral artery disease

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9. Features of Tetralogy of Fallot

1. Ventricular septal defect (VSD) - large, subarterial/perimembranous
2. Pulmonary stenosis - subvalvular (infundibular), valvular, or supravalvular outflow obstruction
3. Overriding aorta - aorta positioned above/overrides the VSD
4. Right ventricular hypertrophy - compensatory, due to RV pressure overload

• Cyanosis (early if severe PS - "blue baby") - right-to-left shunt through VSD
• Tet spells (hypercyanotic attacks)
• Squatting posture (increases SVR, reduces right-to-left shunting)
• Clubbing of fingers/toes
• Polycythemia
• "Boot-shaped heart" on CXR (coeur en sabot)

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10. Four Important Complications Following Acute MI

1. Arrhythmias - VF (commonest cause of early death), VT, AF, heart block
2. Cardiac rupture - free wall (hemopericardium/tamponade), septum (VSD), papillary muscle (acute MR)
3. Left ventricular failure + cardiogenic shock - pump failure from necrotic myocardium
4. Mural thrombus + systemic embolism - thrombus on endocardial surface of infarct zone

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11. Major Pathologic Changes in Left-Sided Heart Failure

• Hypertrophy (initially concentric, then dilated)
• Myocyte hypertrophy, interstitial fibrosis
• Subendocardial ischemia and infarcts

• Dilation (backs up from LV)
• Risk of AF, mural thrombus

• Pulmonary venous congestion and hypertension
• Pulmonary edema - pink frothy fluid in alveoli
• "Heart failure cells" - hemosiderin-laden alveolar macrophages from RBC extravasation
• Alveolar capillary congestion, thickening of alveolar walls
• Pleural effusions (especially right-sided)

• Reduced cardiac output causing peripheral organ hypoperfusion

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12. Define Hypertension - Etiopathogenesis & Classification

• JNC/ACC/AHA (2017): BP ≥130/80 mmHg (new criteria)
• Traditional: Sustained BP >140/90 mmHg
• Hypertensive crisis: >180/120 mmHg

• Primary (essential) - 90-95%, no identifiable cause
• Secondary - 5-10%, identifiable cause: renal disease (most common), renovascular, endocrine (Conn's, Cushing's, pheochromocytoma), coarctation of aorta, drugs (OCPs)

• Genetic predisposition + environmental factors
• Increased sodium retention - reduced renal Na+ excretion → volume expansion
• RAAS activation - angiotensin II vasoconstriction + aldosterone Na retention
• Increased sympathetic activity - neurogenic vasoconstriction
• Endothelial dysfunction - reduced NO, increased endothelin
• Vascular remodeling - arteriolar wall thickening (hyaline or hyperplastic arteriolosclerosis)
• Obesity, insulin resistance, dyslipidemia as contributing factors

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13. Extracardiac Lesions in Rheumatic Heart Disease

1. Joints - migratory polyarthritis (most common manifestation, not destructive)
2. Skin:
   • Erythema marginatum (pink, non-pruritic, spreading rash)
   • Subcutaneous nodules (Aschoff-like granulomas over bony prominences)
3. CNS - Sydenham's chorea (St. Vitus' dance) - involuntary movements, emotional lability
4. Lungs - rheumatic pneumonitis (rare)
5. Blood vessels - arteritis (coronary, renal, mesenteric)
6. Kidney - mild glomerulitis (uncommon)

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14. Morphology of Hypertensive Disease

• Left ventricular hypertrophy (concentric) - LV wall >2 cm, heart weight >500 g
• Microscopically: myocyte hypertrophy, "boxcar nuclei," interstitial fibrosis

• Benign nephrosclerosis: hyaline arteriolosclerosis, glomerular sclerosis, tubular atrophy, cortical granularity ("flea-bitten" kidney)
• Malignant nephrosclerosis: fibrinoid necrosis of arterioles, "onion-skin" (hyperplastic) arteriolosclerosis, petechiae on surface

• Hyaline arteriolosclerosis (benign HT) - protein/lipid deposition in arteriolar walls
• Hyperplastic arteriolosclerosis (malignant HT) - "onion skin" concentric laminated thickening
• Large vessels - accelerated atherosclerosis

• Lacunar infarcts, hypertensive encephalopathy, intracerebral hemorrhage (Charcot-Bouchard microaneurysms in basal ganglia)

• AV nicking, copper/silver wiring, papilledema, flame hemorrhages

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15. Laboratory Diagnosis of Acute Myocardial Infarction

• Troponin I/T (gold standard) - rises 3-6 hrs, peaks 24-48 hrs, remains elevated 7-10 days
• CK-MB - rises 4-8 hrs, peaks 24 hrs; useful for re-infarction detection
• Myoglobin - earliest (1-2 hrs) but non-specific
• LDH1 > LDH2 ("flipped LDH pattern") - historical marker

• ST elevation (STEMI) or depression (NSTEMI)
• T-wave inversion
• Pathological Q waves (>0.04s wide, >25% of R-wave height) - old infarct

• Echocardiography - regional wall motion abnormality
• Coronary angiography - identifies culprit lesion
• Radionuclide scan (Technetium pyrophosphate) - "hot spot" in acute MI

• CBC: leukocytosis (neutrophilia) within 24 hrs
• ESR: elevated
• Blood glucose: hyperglycemia (stress response)

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16. Complications of Acute Myocardial Infarction

• Immediate (mins-hrs): Arrhythmias, sudden cardiac death
• 1-3 days: Fibrinous pericarditis, mural thrombus, continuing pump failure
• 4-7 days: Free wall rupture (peak), papillary muscle rupture, VSD (septal rupture)
• Weeks: Ventricular aneurysm, Dressler's syndrome (2-10 weeks post-MI), thromboembolic events

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17. Rheumatic Endocarditis

• MacCallum's plaque - irregular thickening of left atrial posterior wall
• Verrucous vegetations - small (1-2 mm), warty, firmly adherent, along the line of valve closure
• Leaflets show edema and inflammatory infiltrate
• Subvalvular Aschoff bodies
• With repeated attacks: commissural fusion, leaflet thickening, fibrosis, calcification, shortened/fused chordae → mitral stenosis

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18. Heart in SABE (Subacute Bacterial Endocarditis)

• Organism: Usually S. viridans (oral flora), also Streptococcus bovis, HACEK group
• Pre-existing valve disease: Always present (rheumatic, congenital, degenerative)
• Vegetations: Smaller than acute IE, less destructive, attached to line of closure
• Microscopically: fibrin, bacteria, inflammatory cells; less necrosis than acute IE
• Complications: Embolic phenomena (spleen, kidney, brain), immune complex deposition
• Osler's nodes (painful fingertip nodules - immune complex), Janeway lesions (painless palmar hemorrhages - embolic), Roth spots (retinal hemorrhages), splinter hemorrhages
• Splenomegaly - from chronic bacteremia + immune stimulation
• Clubbing - with long-standing disease

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19. Serum Enzymes in Myocardial Infarction

• CK-MB isoform most specific for myocardial damage
• LDH flipped pattern: LDH1 > LDH2 (normal ratio reversed) - historic marker
• Troponin is standard of care - high sensitivity assays detect micro-infarction

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20. Lab Diagnosis of Rheumatic Heart Disease

• Throat culture - Group A Strep (may be negative by time of carditis)
• ASO titer (Anti-Streptolysin O) - elevated (>200 Todd units in adults, >333 in children) - most important
• Anti-DNase B, anti-streptokinase, anti-hyaluronidase - additional strep antibodies

• ESR elevated
• CRP elevated
• Leukocytosis

• Prolonged PR interval (1st degree AV block) - most common ECG finding in carditis

• Valvular abnormalities, pericardial effusion

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21. Lab Diagnosis of Chronic Heart Failure

• BNP (Brain Natriuretic Peptide) and NT-proBNP - most important; elevated proportional to degree of ventricular stress; used for diagnosis and prognosis
• Troponin (mild elevation in severe CHF)

• CBC: Dilutional anemia, or polycythemia (right HF)
• Renal function: Elevated BUN/creatinine ("cardiorenal syndrome")
• LFTs: Elevated (hepatic congestion - "nutmeg liver" in right HF)
• Serum electrolytes: Hyponatremia (poor prognosis marker)
• Thyroid function: To exclude thyroid cause
• Urinalysis: Proteinuria (from renal congestion)

• Chest X-ray: Cardiomegaly, pulmonary congestion, Kerley B lines, pleural effusion
• Echocardiography: EF measurement, wall motion, diastolic dysfunction assessment

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22. Recent Myocardial Infarct

• Coagulative necrosis - loss of nuclei, striations preserved, ghost outlines of cells
• Neutrophilic infiltration - peaks at 2-3 days
• Wavy fiber change at border
• Yellow-tan soft center

• Macrophage infiltration begins (replaces neutrophils)
• Removal of necrotic debris begins
• Granulation tissue starts at periphery

• Ongoing phagocytosis of necrotic myocytes
• Progressive granulation tissue with vascular proliferation and fibroblasts

• Yellow-tan/gray area of necrosis
• Hyperemic (red) border
• Soft, friable tissue (highest risk of rupture at day 4-7)

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23. Serum Enzymes in Myocardial Infarction

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24. Etiopathology & Laboratory Diagnosis of Rheumatic Heart Disease

1. Group A beta-hemolytic Streptococcus pharyngitis triggers immune response
2. Molecular mimicry: Strep M-protein epitopes share structural similarity with cardiac myosin, valve glycoproteins, neuronal antigens
3. Antibodies (anti-GlcNAc, anti-cardiac) cross-react with cardiac endothelium
4. Two-hit hypothesis: Antibody attack on valve endothelium → T-cell extravasation into valve → Aschoff body granuloma formation
5. Repeated strep infections cause cumulative valve damage → scarring, stenosis, regurgitation

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25. Bacterial Endocarditis

• S. viridans - subacute, on abnormal valves
• S. aureus - acute, on normal or abnormal valves; #1 in healthcare/IV drug users
• Enterococcus - elderly, GI/GU procedures
• HACEK - culture-negative, fastidious organisms
• Strep bovis - associated with colon cancer

• Cardiac: valve destruction, abscess, conduction block
• Embolic: septic emboli to brain (cerebral abscess/stroke), kidneys (abscess), spleen, coronaries
• Immunologic: Osler's nodes, Roth spots, glomerulonephritis (immune complex deposition)
• Mycotic aneurysms from septic emboli to vessel walls

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26. Pathogenesis of Acute Rheumatic Fever

1. Precipitating event: Pharyngitis with Group A beta-hemolytic Streptococcus (GAS) - S. pyogenes
2. Immune response: 2-4 weeks later, antibodies develop against GAS (ASO, anti-DNase B)
3. Molecular mimicry: Antibodies cross-react with:
   • Cardiac sarcolemmal antigens
   • Valve glycoproteins (cross-reactive with hyaluronate)
   • Brain gangliosides (→ chorea)
   • Synovial tissue (→ arthritis)
4. T-cell mediated damage: CD4+ T cells infiltrate cardiac valves
5. Aschoff body formation in myocardium
6. Pancarditis: pericarditis, myocarditis, endocarditis

• Throat (NOT skin) strep infection triggers ARF
• Streptococcal skin infections (impetigo) do NOT cause ARF
• Rheumatic fever does NOT recur unless there is another strep pharyngitis episode
• Prevention: Benzathine penicillin prophylaxis for 10 years / life

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27. Gross & Microscopic Picture of Myocardial Infarction

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28. Utility of Laboratory in Diagnosis of MI

• High-sensitivity troponin (hsTnI/hsTnT): Allows rapid 0/1h or 0/3h protocols for rule-in/rule-out
• Serial troponins: A rising pattern (delta troponin) is more specific than a single elevated value
• CK-MB: Useful when troponin cannot distinguish skeletal from cardiac muscle injury; useful for re-infarction (returns to baseline faster)
• BNP/NT-proBNP: Not diagnostic of MI but helps assess LV function and prognosis
• Coronary angiography: The definitive "laboratory test" for identifying culprit lesion in STEMI - guides PCI

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29. Isoenzymes in Acute Myocardial Infarction

• CK-MM: skeletal muscle (normal)
• CK-MB: myocardium (rises in MI, >6% of total CK = myocardial specific)
• CK-BB: brain

• CK-MB1 (tissue form) and CK-MB2 (plasma form)
• CK-MB2 > 1.0 U/L or CK-MB2/CK-MB1 ratio >1.5 = early indicator of MI (detectable at 2-4 hrs)

• LDH1 (H4) and LDH2 (H3M1) - cardiac
• LDH5 (M4) - liver/skeletal muscle
• Normal: LDH2 > LDH1
• "Flipped pattern" in MI: LDH1 > LDH2 (appears 8-24 hrs after MI, persists 5-10 days)
• Useful when patient presents late (after CK-MB returns to normal)

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LAQ Section

LAQ 1. Pathology & Pathogenesis of Rheumatic Heart Disease

Pathogenesis

• GAS M-protein shares epitopes with cardiac antigens
• Anti-GlcNAc antibodies cross-react with cardiac valve laminin
• Anti-cardiac myosin antibodies cross-react with valve endothelium
• T-cell mediated damage follows: CD4+ T cells infiltrate valves via activated endothelium (expressing VCAM-1)
• Granuloma (Aschoff body) formation in myocardium

Pathology

1. Pericarditis (serous/fibrinous):
   • "Bread-and-butter" pericarditis
   • Fibrinous exudate on epicardial surface
   • Usually resolves; rarely constrictive
2. Myocarditis:
   • Aschoff bodies (pathognomonic) - focus of fibrinoid necrosis surrounded by Anitschkow cells
   • Diffuse myocardial inflammation
   • Aschoff giant cells (Aschoff cells fused)
   • Edema and interstitial inflammation
3. Endocarditis (Valvulitis):
   • Most important because leads to chronic sequelae
   • Verrucous vegetations (1-2 mm) along line of valve closure
   • Mitral valve most commonly involved
   • MacCallum's plaque on posterior left atrial wall

• Fibrous thickening of valve leaflets
• Commissural fusion → stenosis
• Shortened, fused, thickened chordae tendineae
• Calcification of valve
• Mitral stenosis - classic end result ("fish mouth" or "buttonhole" opening)
• Left atrial dilation → AF, thrombus → systemic embolism
• Pulmonary hypertension → right heart failure

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LAQ 2. Etiopathogenesis & Morphological Changes in Acute MI

Etiopathogenesis

• Atherosclerosis (primary cause)
• Hypertension, diabetes, smoking, dyslipidemia, obesity, family history

1. Plaque disruption: Erosion or rupture of vulnerable atherosclerotic plaque (thin-cap fibroatheroma) exposes collagen and lipid core
2. Platelet adhesion and aggregation: via GPIb to vWF; GPIIb/IIIa to fibrinogen; release of TxA2, ADP, serotonin → amplification loop
3. Coagulation cascade activation: Tissue factor exposure → thrombin generation → fibrin formation
4. Thrombotic occlusion: Complete within minutes; 90% of STEMI have total occlusion on early angiography

• STEMI (transmural): LAD occlusion → anterior MI (most common); RCA → inferior MI; LCx → lateral MI
• NSTEMI (subendocardial): Partial occlusion or demand-supply mismatch

Morphological Changes

• Contraction band necrosis at periphery of infarct = hypercontracted sarcomeres due to Ca2+ influx; also seen in reperfusion injury
• Reperfusion injury: Paradoxical cell death after restoration of blood flow; contraction band necrosis, free radical burst, calcium overload
• Coagulative necrosis is the predominant pattern
• No regeneration - myocytes are terminally differentiated; repair is by fibrosis only

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Sources: Robbins & Kumar Basic Pathology (Robbins Pathology) | Braunwald's Heart Disease | Goldman-Cecil Medicine | Fuster and Hurst's The Heart 15th Ed.

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CARDIAC PATHOLOGY - LAQ COMPLETE ANSWERS

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LAQ 1. Pathology & Pathogenesis of Rheumatic Heart Disease

Pathogenesis

• Trigger: Group A beta-hemolytic Streptococcus (GAS) pharyngitis (NOT skin)
• Latent period: 2-4 weeks after sore throat
• Mechanism - Molecular Mimicry:
  • GAS M-protein and streptococcal carbohydrate (N-acetyl glucosamine / GlcNAc) share structural epitopes with cardiac proteins
  • Antibodies against GAS cross-react with: cardiac valve laminin, cardiac myosin heavy chain, valve glycoproteins
  • "Two-hit hypothesis": Antibody attack on valve endothelium activates it (VCAM-1 expression) → CD4+ T cells extravasate into valve tissue → granulomatous inflammation → Aschoff body formation

Pathology - Acute Rheumatic Carditis

• Fibrinous or serofibrinous exudate on both pericardial surfaces
• "Bread-and-butter" pericarditis
• Causes chest pain and pericardial friction rub
• Usually resolves; rarely causes constrictive pericarditis

• Aschoff bodies (pathognomonic) - perivascular location in myocardium
  • Central fibrinoid necrosis
  • Anitschkow cells (caterpillar cells) - activated macrophages with owl-eye/caterpillar nuclei
  • Aschoff giant cells (multinucleate)
  • Peripheral lymphocytes and plasma cells
• Causes PR interval prolongation on ECG

• Verrucous vegetations: Small (1-2 mm), firm, warty, along line of valve closure
• MacCallum's plaque: Irregular fibrotic thickening of posterior left atrial wall (from jet-stream injury)
• Valves: Mitral > Mitral + Aortic > Aortic alone > Tricuspid (right-sided rare)

Pathology - Chronic Healed Phase (repeated attacks)

• Progressive fibrosis, thickening, and retraction of valve leaflets
• Commissural fusion → stenosis
• Subcommissural fibrous bridges
• Shortened, thickened, fused chordae tendineae
• Calcification
• End result: Mitral stenosis ("fish-mouth" / "buttonhole" orifice)

• Left atrial dilation → AF → mural thrombus → systemic embolism
• Pulmonary hypertension → RV hypertrophy → right heart failure

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LAQ 2. Etiopathogenesis & Morphological Changes in Acute Myocardial Infarction

Etiopathogenesis

• Non-modifiable: Age, male sex, family history
• Modifiable: Hypertension, diabetes, smoking, hypercholesterolemia (LDL), obesity, physical inactivity

1. Vulnerable atherosclerotic plaque (thin fibrous cap, large lipid core, inflammatory cells) undergoes sudden rupture or erosion
2. Subendothelial collagen and lipid core exposed to circulating blood
3. Platelet adhesion via GPIb-vWF interaction → platelet activation → release of TxA2, ADP, serotonin → vasoconstriction + further platelet aggregation
4. Coagulation activation: Tissue factor on plaque debris → thrombin generation → fibrin → thrombus propagation
5. Complete occlusion within minutes → STEMI; partial occlusion or distal embolization → NSTEMI/UA

• LAD occlusion → anterior/anteroseptal MI (most common)
• RCA occlusion → inferior/posterior MI; can involve SA/AV node
• LCx occlusion → lateral MI

Morphological Changes

• Contraction band necrosis: Hypercontracted sarcomeres at border + in reperfusion zones - calcium overload
• Coagulative necrosis: Ghost cells with preserved outlines but no nuclei
• No regeneration: Cardiac myocytes are terminally differentiated - purely fibrotic repair

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LAQ 3. Etiology of Rheumatic Fever + Clinical Manifestations + Pathologic Changes in Acute Rheumatic Heart Disease

Etiology

• Causative organism: Group A beta-hemolytic Streptococcus (Streptococcus pyogenes)
• Site of infection: Pharynx ONLY (skin strep does not cause RF)
• M-protein serotypes most associated: M1, M3, M5, M6, M18, M24
• Predisposing factors: Age 5-15 years, poverty, overcrowding, recurrent strep infections

Clinical Manifestations - Jones Criteria (2015 revised)

• Carditis (clinical or subclinical/echocardiographic) - most serious
• Arthritis - migratory polyarthritis, large joints, very painful, responds to aspirin
• Chorea (Sydenham's) - involuntary purposeless movements, emotional lability, "milkmaid grip"
• Erythema marginatum - pink, non-pruritic spreading skin rash with central clearing
• Subcutaneous nodules - painless, hard, over bony prominences (elbows, knees, scalp)

• Fever (>38.5°C)
• Elevated ESR, CRP
• Prolonged PR interval on ECG
• Arthralgia (only if arthritis not counted as major)
• Previous RF or rheumatic heart disease

Pathologic Changes in Acute Rheumatic Heart Disease

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LAQ 4. Gross & Microscopic Changes in Myocardial Infarction

• Early (<6h): No change, or TTC staining shows pale zone
• 6-24h: Dark mottling
• 1-3 days: Yellow-tan center, red border
• 4-7 days: Soft, yellow, friable - RUPTURE RISK HIGHEST
• 2 weeks onward: Progressive gray-white scarring

• 2 months: Dense white fibrous scar

• Reversible: Wavy fibers, mitochondrial swelling
• Irreversible: Coagulative necrosis → pyknotic nuclei → ghost cells
• Neutrophils (days 1-3) → Macrophages (days 3-7) → Granulation tissue (week 1-2) → Fibrosis (>6 weeks)
• Contraction band necrosis at border/reperfusion zones

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LAQ 5. Define Rheumatic Fever & Rheumatic Heart Disease + Jones Criteria + Aschoff Nodule + Complications of RHD

Definitions

Jones Criteria

Aschoff Nodule - Formation & Fate

• Triggered by molecular mimicry-mediated immune response
• Located perivascularly in myocardium
• Composition:
  • Central fibrinoid necrosis (acidophilic, structureless debris)
  • Anitschkow cells (Caterpillar cells): Large activated macrophages; pale abundant cytoplasm; central nucleus with undulating chromatin ribbon ("owl eye" or "caterpillar")
  • Aschoff giant cells: Multinucleated Anitschkow cells
  • Peripheral lymphocytes (CD4+ T cells), occasional plasma cells

1. Resolution - complete healing in mild cases
2. Fibrosis - scar formation (Aschoff bodies → small fibrous scars in myocardium)
3. Persistence - active Aschoff bodies can persist for years after clinical recovery, indicating ongoing subclinical carditis
4. Repeated attacks → progressive accumulation of fibrous tissue → chronic RHD

Complications of Rheumatic Heart Disease

1. Mitral stenosis (most common) - "fish mouth" valve
2. Mitral regurgitation
3. Aortic stenosis / regurgitation
4. Tricuspid and pulmonary valve involvement (rare)
5. Infective endocarditis (on damaged valve)
6. Atrial fibrillation (from LA dilation)
7. Congestive heart failure

• Mural thrombus in LA/LAA → systemic embolism → stroke, renal/splenic infarcts

• Pulmonary hypertension → cor pulmonale

• Damaged valves susceptible to IE

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LAQ 6. Pathogenesis, Gross & Microscopic Picture of Infective Endocarditis

Pathogenesis

• Pre-existing valve disease: RHD > mitral valve prolapse > bicuspid aortic valve > calcific stenosis
• Prosthetic heart valves (10-20% of IE)
• IV drug use (right-sided - tricuspid)
• Immunosuppression, diabetes, malignancy, hemodialysis

1. Bacteremia - transient (dental procedures, GI/GU instrumentation, IV drug use, IV lines)
2. Sterile platelet-fibrin thrombus forms at site of endothelial injury (jet lesion, turbulence)
3. Bacterial adherence to platelet-fibrin nidus - via bacterial surface adhesins (fibronectin-binding proteins of S. aureus, FimA of strep)
4. Bacterial proliferation within the vegetation - protected from antibiotics and immune cells
5. Vegetation growth - continues to incorporate fibrin, platelets, bacteria, and inflammatory cells
6. Valve destruction - proteases, toxins, and direct invasion destroy leaflets

Gross Picture

• Vegetations: Friable, bulky, irregular, destructive masses on valve cusps/leaflets
• Location: Along the line of valve closure
  • AV valves: atrial surface
  • Semilunar valves: ventricular surface
• Vegetations can be single or multiple, extending onto chordae and mural endocardium
• Underlying leaflet may show: ulceration, perforation, erosion
• In acute IE (S. aureus): large, very destructive vegetations; tissue destruction with abscess
• In subacute IE: smaller vegetations; less tissue destruction; may show healing at base
• Embolized vegetations may leave "punched-out" defects in valve

Microscopic Picture

• Vegetation core: Fibrin meshwork + platelet aggregates + bacteria/fungi (visible as colonies)
• Inflammatory infiltrate: Neutrophils and macrophages
• Underlying valve: Acute inflammatory infiltrate, coagulative necrosis, abscess formation
• Healing areas: Granulation tissue, fibroblast proliferation, neovascularization
• In subacute IE: Less necrosis, more fibrous organization, calcification at base of vegetation
• Microorganisms: Gram-positive cocci in clusters (staph) or chains (strep) visible on Gram stain within vegetation

Complications

• Valve destruction → regurgitation (acute hemodynamic collapse in acute IE)
• Perforation of leaflets
• Chordal rupture
• Ring abscess (extends to annulus + myocardium)
• Conduction abnormalities (AV block) from aortic root abscess
• Pericarditis, myocarditis
• Fistula formation

• Septic emboli → brain abscess, stroke (MCA territory)
• Mycotic aneurysm (septic emboli in arterial wall → aneurysm → rupture)
• Renal abscess/infarct
• Splenic abscess/infarct
• Pulmonary emboli (right-sided IE)

• Immune complex glomerulonephritis (focal embolic or diffuse proliferative GN)
• Osler's nodes: Painful, tender nodules on finger/toe pads - immune complex vasculitis
• Janeway lesions: Painless hemorrhagic macules on palms/soles - septic emboli
• Roth spots: Oval retinal hemorrhages with pale centers

• Splenomegaly (chronic bacteremia + immune stimulation)
• Anemia of chronic disease
• Clubbing (long-standing)

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LAQ 7. Morphology & Lab Diagnosis in Acute MI

Laboratory Diagnosis - Complete

• Single elevated troponin + clinical symptoms = MI
• Delta troponin (rising pattern over 3-6 h serial measurements) confirms acute injury vs chronic elevation
• CK-MB >6% of total CK = cardiac specific
• LDH flipped pattern (LDH1 > LDH2) - useful in late presenters

• Hyperacute T waves: Tall peaked T waves - very early (minutes)
• ST elevation: >1 mm in 2 contiguous leads = STEMI; ST depression = NSTEMI or posterior MI
• T-wave inversion: Subacute phase
• Pathological Q waves: >0.04s wide, >25% of R wave - evolve over hours-days; indicate transmural necrosis (permanent)
• New LBBB: Treated as STEMI equivalent

• Echocardiography: Regional wall motion abnormality (earliest) - even before enzyme rise
• Coronary angiography: Identifies culprit vessel, guides PCI - the definitive diagnostic + therapeutic tool
• Radionuclide imaging: Technetium-99m pyrophosphate ("hot spot" scan); thallium-201 ("cold spot")
• Cardiac MRI: Best for assessing viability, scar extent (late gadolinium enhancement)

• Leukocytosis (neutrophilia) within 24 h - peaks day 2-4
• Elevated ESR (peaks day 4-5)
• Hyperglycemia (stress response)
• Elevated CRP

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LAQ 8. Differentiate Between Rheumatic and Bacterial Endocarditis

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LAQ 9. Classify Ischemic Heart Disease + Gross & Microscopy of MI

Classification of Ischemic Heart Disease (IHD)

1. Angina Pectoris
   • Stable angina: Predictable exertional chest pain; >70% fixed stenosis; relieved by rest/nitrates
   • Unstable angina: Increasing frequency/severity; at rest; plaque disruption + partial thrombus
   • Prinzmetal (variant) angina: Coronary vasospasm; ST elevation at rest; normal coronaries on angio
2. Acute MI (see below)
   • STEMI (transmural, complete occlusion)
   • NSTEMI (subendocardial, partial occlusion)
3. Sudden Cardiac Death
   • Ischemia-triggered fatal arrhythmia (VF) without tissue necrosis
   • Most common presentation of IHD
4. Chronic Ischemic Heart Disease (CIHD)
   • Progressive heart failure from repeated infarcts + ischemic cardiomyopathy
   • Large areas of fibrosis + viable but hibernating myocardium

Gross & Microscopy of MI

• <6h: invisible (TTC staining pallor)
• 6-24h: dark mottling
• 1-7 days: yellow-tan; soft; highest rupture risk at days 4-7
• Weeks: progressive white scar formation

• Coagulative necrosis → ghost cells
• Neutrophils (days 1-3) → Macrophages (3-7 days) → Granulation (1-2 weeks) → Fibrosis (>6 weeks)
• Contraction band necrosis at margins

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LAQ 10. Etiopathogenesis, Morphology & Clinical Features of Rheumatic Heart Disease

Etiopathogenesis

Morphology

Clinical Features

• Age: 5-15 years (rare <5 and >25)
• 2-4 weeks after GAS pharyngitis
• Migratory polyarthritis (most common - 75%)
• Carditis (50-65%): tachycardia, murmurs (mitral regurgitation), pericardial friction rub, cardiomegaly
• Sydenham's chorea (10-15%): weeks-months after acute phase
• Erythema marginatum, subcutaneous nodules (less common)
• Fever, elevated inflammatory markers

• Mitral stenosis (dominant): dyspnea, orthopnea, hemoptysis, atrial fibrillation, systemic emboli, pulmonary hypertension
  • Signs: Malar flush, opening snap + mid-diastolic rumbling murmur at apex
• Mitral regurgitation: pansystolic murmur, LA/LV dilation, eventually LV failure
• Aortic valve disease: aortic stenosis or regurgitation
• Progressive CHF if untreated
• Susceptibility to IE

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LAQ 11. Morphological Changes in MI + Complications of MI

Complications of MI - Comprehensive

• Ventricular fibrillation - most common cause of death in first hour
• Ventricular tachycardia
• Bradyarrhythmias, heart block (inferior MI involving AV node - RCA territory)
• AF

• Acute left heart failure / pulmonary edema - large infarcts (>25% LV)
• Cardiogenic shock - >40% LV necrosis; mortality 70-80%
• Mitral regurgitation: Papillary muscle dysfunction or rupture (day 3-7)
• Free wall rupture: Days 4-7 (peak); → hemopericardium → cardiac tamponade → sudden death
• Ventricular septal rupture: Septal infarct → VSD → biventricular failure
• Ventricular aneurysm: Thinned, fibrotic wall that bulges paradoxically; site for mural thrombus

• Fibrinous pericarditis: Days 2-3; chest pain + friction rub; self-limiting
• Dressler's syndrome: 2-10 weeks post-MI; autoimmune pleuropericarditis; fever, chest pain, pericardial effusion

• Mural thrombus: On endocardium overlying infarct zone (days 2-7); risk of systemic embolism → stroke, renal infarct

• Reinfarction
• Chronic ischemic cardiomyopathy
• Sudden cardiac death (late arrhythmia from scar)

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LAQ 12. Causes of Vegetations in Heart + Subacute Bacterial Endocarditis

Causes of Vegetations in Heart

Subacute Bacterial Endocarditis (SABE) - In Brief

• Osler's nodes: Painful nodules on finger/toe pads (immune complex vasculitis)
• Janeway lesions: Painless hemorrhagic palmar/plantar macules (septic emboli)
• Roth spots: Oval pale-centered retinal hemorrhages (immune complex)
• Splinter hemorrhages: Linear subungual hemorrhages (emboli)
• Splenomegaly: Chronic immune stimulation
• Clubbing: Late feature
• Fever, weight loss, night sweats, anemia, hematuria (immune GN)

• Major: Positive blood culture (≥2), endocardial involvement on echo
• Minor: Predisposition, fever, vascular phenomena, immunologic phenomena, microbiological evidence

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LAQ 13. Lab Evaluation of MI + Consequences & Complications

Lab Evaluation

Consequences of MI

1. Loss of contractile function: Each 1g of necrotic myocardium = loss of contractile units
2. Electrical instability: Ischemic myocytes have abnormal action potentials → re-entry arrhythmias
3. Ventricular remodeling: Infarct zone thins, non-infarct zone hypertrophies (eccentric hypertrophy)
4. Neurohormonal activation: RAAS, sympathetic → initially compensatory but long-term detrimental (Starling curve decompensation)
5. Hemodynamic compromise: Reduced CO → hypotension → shock (large infarcts)

Complications

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LAQ 14. Define Infarct + Enzymes in Diagnosis of MI + Gross & Microscopic Features by Age

Definition of Infarct

• Red (hemorrhagic) infarct: Loose tissue (lung, intestine) or dual blood supply; reperfused tissue
• White (pale/anemic) infarct: Solid organs with end-arterial supply (heart, kidney, spleen)
• Myocardial infarct: White infarct; becomes hemorrhagic only at margins or after reperfusion

Enzymes in Diagnosis

Gross & Microscopic Features by Age of Infarct

• <6 hours: Gross-none; Micro-wavy fibers
• 6-24 hours: Gross-mottling; Micro-coagulative necrosis + neutrophils start
• 1-3 days: Gross-yellow-tan; Micro-maximal neutrophils, loss of nuclei
• 3-7 days: Gross-soft yellow, hyperemic border; Micro-macrophages, granulation starts; RUPTURE RISK PEAK
• 1-2 weeks: Gross-depressed, vascularized granulation; Micro-granulation tissue
• >6 weeks: Gross-white scar; Micro-dense collagen fibrosis

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LAQ 15. Presenting Features & Complications of Infective Endocarditis

Presenting Features

• Fever (most common symptom, 90%) - low-grade/intermittent (subacute) or high/sustained (acute)
• Rigors, night sweats, malaise, weight loss
• Anemia of chronic inflammation

• New or changing heart murmur (regurgitant murmur most common)
• Features of heart failure (acute severe regurgitation)
• Conduction abnormalities (PR prolongation, AV block) - aortic root abscess

• Osler's nodes, Janeway lesions, Roth spots, splinter hemorrhages (see LAQ 12)
• Clubbing (late)
• Splenomegaly

• Stroke (MCA), visual loss, hematuria, flank pain, abdominal pain

Complications

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LAQ 16. Gross & Microscopic Appearance of MI at Various Stages + Enumerate Complications

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LAQ 17. Pathogenesis, Gross & Microscopic Pathology, Lab Diagnosis & Complications of Bacterial Endocarditis

Pathogenesis

Gross Pathology

Microscopic Pathology

Lab Diagnosis

• 3 sets from different sites, 30 min apart, before starting antibiotics
• Positive in 90% of cases
• Identifies organism + antibiotic sensitivity

• TTE (transthoracic): First-line; sensitivity ~60-75%
• TOE/TEE (transesophageal): Sensitivity >90%; better for prosthetic valves, small vegetations, abscesses

• CBC: Normocytic normochromic anemia, leukocytosis, elevated ESR, elevated CRP
• Rheumatoid factor: Positive in SABE (>50%) from polyclonal immune stimulation
• Low complement (C3/C4) - in immune complex GN

• Hematuria, proteinuria, red cell casts (immune complex GN)

1. Positive blood culture with typical IE organism (≥2 separate cultures)
2. Echocardiographic evidence (vegetation, abscess, or new prosthetic valve dehiscence; new valvular regurgitation)

1. Predisposing heart condition or IV drug use
2. Fever ≥38°C
3. Vascular phenomena (arterial emboli, septic pulmonary infarcts, mycotic aneurysm, Janeway lesions)
4. Immunologic phenomena (GN, Osler's nodes, Roth spots, RF+)
5. Microbiological evidence not meeting major criteria

Complications

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Sources: Robbins & Kumar Basic Pathology (Robbins Pathology) | Braunwald's Heart Disease 12th Ed | Goldman-Cecil Medicine | Fuster and Hurst's The Heart 15th Ed | Sherris & Ryan Medical Microbiology

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Infectious Diseases in Pediatrics

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VIRAL INFECTIONS

Respiratory Viruses

Exanthematous (Rash) Diseases - "The Classic Six"

Herpesvirus Group

• Herpes Simplex Virus (HSV-1): Gingivostomatitis, cold sores, herpetic whitlow, neonatal herpes (HSV-2 more common neonatally)
• HSV-2: Neonatal herpes - highest risk during vaginal delivery with active lesions; encephalitis, disseminated disease
• CMV (HHV-5): Congenital CMV - most common congenital infection; sensorineural hearing loss, periventricular calcifications
• EBV (HHV-4): Infectious mononucleosis - fever, exudative pharyngitis, cervical LAD, splenomegaly; monospot test; avoid ampicillin (rash)
• HHV-6: Roseola (above)
• VZV: Chickenpox + Zoster (above)

Enteroviruses

• Poliomyelitis: Poliovirus; anterior horn cell destruction → flaccid paralysis; vaccine-preventable
• Hand-Foot-Mouth Disease: Coxsackie A16, Enterovirus 71; oral ulcers + vesicles on palms/soles
• Herpangina: Coxsackie A; painful vesicles/ulcers on soft palate/tonsillar pillars
• Aseptic Meningitis: Most common cause = enterovirus (echovirus, coxsackie)
• Viral Myocarditis: Coxsackie B - most important cardiac cause in children

Gastrointestinal Viruses

• Rotavirus: #1 cause of severe dehydrating diarrhea in children worldwide under 5; vaccine available
• Norovirus: Epidemic vomiting illness; all ages; gastroenteritis outbreaks
• Astrovirus: Mild diarrhea in young children
• Adenovirus (enteric types 40/41): Diarrhea in infants/young children
• Hepatitis A: Fecal-oral; usually benign self-limiting in children; vaccine-preventable
• Hepatitis B: Vertical transmission (mother to baby); chronic infection more likely if acquired in childhood; vaccine from birth
• Hepatitis C: Can be acquired perinatally; chronic hepatitis/cirrhosis

CNS Viruses

• Viral Encephalitis: Herpes simplex (most common treatable cause), arboviruses (West Nile, Japanese encephalitis, La Crosse, Eastern Equine)
• Rabies: Uniformly fatal once symptomatic; from animal bite
• Progressive Multifocal Leukoencephalopathy (PML): JC virus; in immunocompromised

Other Important Viruses

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BACTERIAL INFECTIONS

Respiratory Tract

CNS Infections

Gastrointestinal

Skin & Soft Tissue

Systemic Bacterial Infections

Vaccine-Preventable Bacterial Diseases

• Tetanus (Clostridium tetani) - neonatal tetanus (umbilical stump), lockjaw
• Pertussis
• Diphtheria
• H. influenzae type b disease
• Pneumococcal disease
• Meningococcal disease
• Typhoid

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FUNGAL INFECTIONS

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PARASITIC INFECTIONS

Protozoa

Helminths (Worms)

Ectoparasites

• Pediculosis (Lice): Head lice (Pediculus capitis) - very common in school-age children
• Scabies: Sarcoptes scabiei - intense itching, burrows; Norwegian (crusted) scabies in immunocompromised

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CONGENITAL INFECTIONS (TORCH)

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TICK-BORNE & VECTOR-BORNE DISEASES

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NEONATAL INFECTIONS (Special Category)

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HOSPITAL-ACQUIRED (NOSOCOMIAL) INFECTIONS IN CHILDREN

• MRSA (Methicillin-resistant S. aureus): Skin/soft tissue, BSI, pneumonia
• C. difficile: Antibiotic-associated diarrhea
• Gram-negative sepsis: Klebsiella, Pseudomonas, E. coli (esp. in ICU, immunocompromised)
• Fungal infections: Candida BSI (central line-associated)

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SUMMARY TABLE BY ORGAN SYSTEM

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Source: Red Book 2021 - AAP Committee on Infectious Diseases | Robbins & Kumar Basic Pathology | The Harriet Lane Handbook (Johns Hopkins, 23rd ed.)