---

MUHS 2nd MBBS Pathology - Cardiovascular System: Complete Exam Notes

Source: Robbins & Kumar Pathologic Basis of Disease (9e) | Robbins & Kumar Basic Pathology | Harshmohan Pathology correlation included

---

TOPIC 1: ISCHEMIC HEART DISEASE (IHD) - Classification

Definition

Classification of IHD (MUHS Exam High Yield)

IHD
├── 1. Angina Pectoris
│     ├── Stable angina (exertional)
│     ├── Unstable angina (crescendo/pre-infarction)
│     └── Prinzmetal / Vasospastic angina
├── 2. Myocardial Infarction (MI)
│     ├── STEMI (ST-elevation MI)
│     └── NSTEMI (Non-ST elevation MI)
├── 3. Chronic IHD with CHF (Ischemic cardiomyopathy)
└── 4. Sudden Cardiac Death (SCD)

---

Pathogenesis of IHD

1. Fixed ("preexisting") atherosclerotic occlusion - slowly progressive; causes stable angina
2. Acute plaque change + superimposed thrombosis/vasospasm - causes MI, unstable angina, SCD

---

TOPIC 2: MYOCARDIAL INFARCTION (MI)

Definition of Infarct

Pathogenesis of MI

1. Atheromatous plaque disrupted by endothelial injury, intraplaque hemorrhage, or shear forces
2. Subendothelial collagen + necrotic plaque contents exposed to blood
3. Platelet adhesion, aggregation, activation → release of TXA2, ADP, serotonin → vasospasm
4. Coagulation activation by tissue factor → growing thrombus
5. Within minutes → complete coronary occlusion → ischemia → necrosis

90% of MIs are due to coronary atherothrombosis. Angiography within 4 hours shows thrombosis in ~90% of STEMI cases.

• Coronary vasospasm (cocaine, ephedrine)
• Emboli (from mural thrombus in AF, IE vegetations, prosthetic valves)
• Vasculitis, sickle cell disease, amyloid deposition

---

Morphological Changes in MI as per Age of Infarct

Exam Tip (MUHS): Earliest change visible on electron microscopy = swelling of mitochondria + amorphous densities in matrix within 30 minutes. First light microscopy change = wavy myocyte fibers at 4-12 hrs.

Key Microscopic Stages:

• Coagulative necrosis - cell outlines preserved but nucleus lost
• Karyolysis (nuclear dissolution)
• Dense neutrophil infiltration (neutrophils peak at 24-48 hrs)
• "Wavy fiber" change at edges (due to stretching of viable myocytes)

• Macrophages replace neutrophils (mononuclear cells)
• Phagocytosis of dead debris
• Most vulnerable time for rupture!

• Granulation tissue at periphery
• Angiogenesis (new capillary buds)
• Fibroblast proliferation
• Collagen deposition

• Dense collagenous scar
• Thin gray-white fibrous tissue

---

Laboratory Diagnosis / Evaluation of MI

Cardiac Biomarkers (Enzymes used in diagnosis)

• Troponin = gold standard for MI diagnosis (most sensitive and specific)
• CK-MB = best marker for detecting re-infarction (returns to normal quickly)
• Myoglobin = earliest marker (rises within 1-3 hrs)
• LDH "flip" = LDH1 > LDH2 (normally LDH2 > LDH1) - diagnostic of MI

Other Lab Findings:

• ECG changes: ST elevation (STEMI), ST depression (NSTEMI), Q waves (transmural infarct)
• Leukocytosis: neutrophilia within 24-48 hrs
• ESR elevation: raised (due to inflammatory response)
• Echocardiography: wall motion abnormalities
• Imaging: Coronary angiography (gold standard for CAD)

---

Gross Appearance of MI

• Transmural MI: Full thickness of wall - due to complete coronary occlusion
• Subendocardial MI: Inner 1/3 of myocardium - due to hypoperfusion/shock

• LAD occlusion → Anterior wall + anterior septum of LV (most common)
• RCA occlusion → Posterior wall + posterior septum of LV + RV
• LCX occlusion → Lateral wall of LV

• 0-12 hours: Normal or slightly pale area
• 12-24 hours: Pale, slightly mottled area
• 1-3 days: Pale yellow-tan, hyperemic border (red-brown rim)
• 3-7 days: Central yellow-tan softening, prominent red hyperemic border
• 1-2 weeks: Depressed, red-brown gelatinous area (granulation)
• Weeks-months: Gray-white fibrous scar

---

Consequences and Complications of MI

Immediate/Early Complications (1st Week):

Late Complications (After 1st Week):

Summary Diagram of MI Complications:

MYOCARDIAL INFARCTION
        │
        ├─ EARLY (1-7 days)
        │     ├─ Arrhythmias (VF → Sudden Death) ⭐
        │     ├─ Cardiogenic shock (>40% LV damage)
        │     ├─ Acute LV failure / pulmonary edema
        │     ├─ Papillary muscle dysfunction → MR
        │     └─ Right ventricular infarction
        │
        ├─ INTERMEDIATE (3-14 days)
        │     ├─ Myocardial RUPTURE (free wall → tamponade)
        │     ├─ Ventricular SEPTAL RUPTURE → VSD
        │     ├─ Papillary RUPTURE → acute MR
        │     └─ Mural thrombus → embolism
        │
        └─ LATE (weeks-months)
              ├─ Fibrinous pericarditis / Dressler syndrome
              ├─ Ventricular aneurysm
              └─ Chronic IHD / CHF

---

TOPIC 3: HYPERTENSIVE HEART DISEASE - Morphology

Definition

1. Left ventricular hypertrophy in the absence of other cardiovascular pathology
2. Clinical history or pathologic evidence of hypertension in other organs (kidneys)

Morphology

GROSS:

• Concentric left ventricular hypertrophy (increased wall thickness WITHOUT early dilation)
• Heart weight may exceed 500 g (normal 320-360 g for a 60-70 kg individual)
• LV wall thickness may exceed 2.0 cm (normal 1.2-1.4 cm)
• Left atrial dilation (due to stiff LV impairing diastolic filling)
• In long-standing decompensated disease: LV dilation (eccentric hypertrophy)
• Right-sided changes: RV hypertrophy in pulmonary hypertension (Cor Pulmonale)

MICROSCOPIC:

• Increased transverse diameter of cardiomyocytes (hypertrophy)
• Nuclear enlargement and hyperchromasia - "boxcar nuclei" (prominent, enlarged, squared-off nuclei)
• Interstitial fibrosis (perivascular and interstitial connective tissue increase)
• Thickened intramural coronary arteries (medial hypertrophy)

Clinical Features:

• Asymptomatic initially (detected on ECG/echo as LV hypertrophy)
• May present with atrial fibrillation (due to left atrial dilation)
• Progressive CHF
• Higher risk of MI, sudden cardiac death, ventricular arrhythmias, stroke

HYPERTENSIVE HEART DISEASE - KEY POINTS

Systemic Hypertension
        ↓
Pressure Overload on LV
        ↓
Concentric LV Hypertrophy (adaptive)
   - Heart wt >500g
   - LV wall >2.0 cm
   - Boxcar nuclei
   - Interstitial fibrosis
        ↓
Diastolic Dysfunction → LA Dilation → AF
        ↓
Progressive pump failure → CHF / SCD

---

TOPIC 4: RHEUMATIC HEART DISEASE (RHD)

Etiopathogenesis

Etiology:

• Preceded by Group A beta-hemolytic Streptococcal pharyngitis (Streptococcus pyogenes)
• Latent period: 2-3 weeks between throat infection and symptoms of acute rheumatic fever (ARF)
• Occurs in 0.3-3% of patients with streptococcal pharyngitis

Pathogenesis - Molecular Mimicry (Cross-Reactivity Hypothesis):

1. Streptococcal M protein antigens are similar to cardiac antigens (myosin, tropomyosin, sarcolemmal proteins, valvular glycoproteins)
2. Antibodies + CD4+ T cells raised against Streptococcal M proteins cross-react with cardiac proteins
3. Antibody binding activates complement and Fc-receptor cells (neutrophils, macrophages)
4. T cells stimulate cytokine production → macrophage activation → Aschoff bodies
5. Streptococci are absent from the lesions (purely immunologic damage)
6. Genetic susceptibility: certain HLA alleles predispose to cross-reactive immune responses

Group A Strep Pharyngitis
        ↓
Anti-Strep Antibodies (esp. anti-M protein)
        ↓
MOLECULAR MIMICRY
(Cross-reaction with cardiac antigens: myosin, sarcolemma, valve glycoproteins)
        ↓
T-cell and Antibody-mediated cardiac injury
        ↓
ACUTE RHEUMATIC FEVER → PANCARDITIS
        ↓
Repeated attacks → CHRONIC RHD

Morphology of Acute Rheumatic Fever - Pancarditis

PERICARDITIS:

• "Bread and butter" pericarditis - fibrinous pericarditis with characteristic shaggy exudate
• Usually resolves without significant sequelae

MYOCARDITIS:

• Aschoff Bodies (pathognomonic lesion of acute RF) - circumscribed granulomatous foci containing:
  • Anitschkow cells (caterpillar cells) - plump activated macrophages with:
    • Abundant cytoplasm
    • Large round-to-ovoid nucleus
    • Central chromatin condensed into a central wavy ribbon - "caterpillar" or "owl-eye" appearance
  • Occasional multinucleated giant cells (Aschoff giant cells)
  • T lymphocytes, plasma cells
  • Central fibrinoid necrosis
• Diffuse Aschoff body distribution in myocardium
• Interstitial edema and mononuclear infiltration

ENDOCARDITIS:

• Fibrinoid necrosis within valve cusps
• Small (1-2 mm) verrucous vegetations (verrucae) along the line of closure of valves
• MacCallum plaques: irregular subendocardial thickenings in left atrium (at posterior wall)

Morphology of Chronic RHD

• Leaflet thickening
• Commissural fusion and shortening → "fish-mouth" or "button-hole" stenosis
• Thickening and fusion of chordae tendineae (calcification common)
• Left atrial dilation (result of mitral stenosis/regurgitation)

• Mitral alone: ~65-70%
• Mitral + Aortic: ~25%
• Tricuspid: infrequent
• Pulmonary: rare

---

Extracardiac Lesions in Rheumatic Heart Disease

• Fever
• Prolonged PR interval on ECG
• Raised ESR / CRP
• Leukocytosis
• Arthralgia (if arthritis is not a major criterion)

MUHS Exam Tip: Erythema Marginatum + Subcutaneous nodules are minor in UPDATED Jones criteria. The classic 5 major criteria = Carditis, Polyarthritis, Chorea, Erythema Marginatum, Subcutaneous Nodules (CEPSS mnemonic).

---

TOPIC 5: CAUSES OF VEGETATIONS IN HEART

Types of Vegetative Endocarditis

---

TOPIC 6: RHEUMATIC vs. BACTERIAL ENDOCARDITIS - Differentiation

Comparison Table (MUHS Exam Favorite)

---

Subacute Bacterial Endocarditis (SBE) - Detailed

Definition:

Most Common Organism:

Predisposing Conditions:

• Previously damaged valves (RHD, congenital bicuspid aortic valve, MVP)
• Dental procedures (bacteremia)
• IV drug abuse (right-sided endocarditis)
• Prosthetic valves (Staphylococcus epidermidis common)

Morphology:

• Vegetations: Irregular, friable, bulky (0.5-2 cm); contain fibrin, inflammatory cells, bacteria
• Located at irregular positions on valve leaflets
• Less destructive than acute endocarditis (ABE)
• Microscopy: Granulation tissue at base of vegetation (indicates healing/subacute nature)
• With time: fibrosis, calcification, chronic inflammatory infiltrate

Systemic/Embolic Manifestations of IE:

• Osler nodes: Painful nodules on fingertips/toes (immune complex-mediated)
• Janeway lesions: Painless hemorrhagic lesions on palms/soles (embolic)
• Roth spots: Oval retinal hemorrhages with pale centers
• Splinter hemorrhages: Linear subungual hemorrhages
• Glomerulonephritis: Antigen-antibody complex deposition
• Petechiae: On skin and mucous membranes
• Splenomegaly: Due to immune stimulation

Complications:

• Septic emboli → Brain (septic meningitis/abscess), kidneys (septic infarcts), spleen
• Mycotic aneurysms (cerebral vasculature most commonly)
• Ring abscess formation (especially ABE)
• Valvular regurgitation → acute CHF (if untreated)

---

QUICK REVISION TABLE - MUHS Exam

---