---

Morphology of Infective Endocarditis (IE)

Gross Features

Ring abscess = when vegetation erodes into the myocardium at the valve annulus. Most feared complication of acute IE (especially S. aureus).

---

Microscopy

• Acute IE - minimal healing; rapid destruction
• Subacute IE - granulation tissue at base indicates attempted repair (organism has lower virulence, e.g., Strep viridans)

---

Gross Pathology Images (Robbins)

---

Quick Comparison: Acute vs Subacute IE Morphology

---

Key Points from Your Notes

• Vegetations in IE are on the atrial surface of the mitral valve and the ventricular surface of the aortic valve (the low-pressure side downstream of the regurgitant jet)
• Embolism from left-sided IE → systemic (brain, kidneys, spleen); from right-sided → pulmonary
• Fibrosis and calcification can develop later in both forms
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 528-529

---

Morphology of Acute Rheumatic Heart Disease (RHD)

Overview - Pancarditis

• Pericardium → Rheumatic pericarditis
• Myocardium → Rheumatic myocarditis
• Endocardium → Rheumatic endocarditis

---

i. Rheumatic Pericarditis

Bread and butter pericarditis = fibrinous strands deposited on both visceral and parietal pericardial surfaces that stick and pull apart.

---

ii. Rheumatic Myocarditis

Gross - Sequential Stages:

Microscopic - The Aschoff Body:

1. Foci of lymphocytes (primarily T-cells)
2. Occasional plasma cells
3. Anitschkow cells (plump activated macrophages) - pathognomonic for RF

The Anitschkow Cell (must know for exams):

---

iii. Rheumatic Endocarditis

a. Rheumatic Valvulitis

Key distinction from IE: RHD vegetations are small, sterile, firmly attached along the line of closure. IE vegetations are large, friable, and destructive.

b. Rheumatic Submural Endocarditis - MacCallum Plaques

---

Chronic Rheumatic Heart Disease

Valves Affected (Frequency):

1. Mitral alone: 65-70%
2. Mitral + Aortic: 25%
3. Tricuspid + Pulmonary: Rarely

Morphology of Chronic Mitral Valve Changes:

---

Quick Memory Summary

Acute RHD = PANCARDITIS
├── Pericarditis → Bread & Butter
├── Myocarditis → Aschoff bodies (Anitschkow cells = caterpillar cells)
└── Endocarditis
    ├── Valvulitis → 1-2mm verrucae at lines of closure
    └── Submural → MacCallum plaques (left atrium)

Chronic RHD = MITRAL STENOSIS
→ Fish mouth / Button hole orifice
→ Left atrial dilation + mural thrombi
→ Pulmonary HTN → RVH

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 525-528

---

Myocardial Infarction (MI) - Complete Notes

Definition

• Ischemia lasting 20-30 minutes or longer → irreversible cell injury → MI
• The 2018 joint task force defines it as: "acute myocardial injury detected by abnormal cardiac biomarkers in the setting of evidence of acute myocardial ischemia"

---

Commonly Involved Vessels

---

Risk Factors

• Atherosclerosis - most common risk factor
• Age: 10% MI under 45 yrs; 45% MI under 65 yrs
• Sex: Males > Females (during reproductive years). Post-menopause, risk equalizes - protective effect of estrogen is lost
• Other: hypertension, diabetes, smoking, dyslipidemia, family history

---

Etiology

A. Coronary Atherosclerosis (90% of cases)

• Atherosclerotic narrowing of one or more coronary arteries

B. Non-Atherosclerotic (~10% of cases)

1. Vasospasm without coronary atherosclerosis
2. Emboli from:
   • Left atrium (with atrial fibrillation)
   • Left-sided mural thrombus
   • Vegetations of infective endocarditis
   • Intracardiac prosthetic material
   • Paradoxical emboli - from right heart/peripheral veins through a patent foramen ovale into coronary arteries
3. Other ischemic causes:
   • Vasculitis
   • Sickle cell disease (hematologic)
   • Amyloid deposition in vascular walls
   • Vascular dissection
   • Lowered systemic BP (shock)

---

Pathogenesis

Atheromatous plaque: intraplaque hemorrhage / erosion / ulceration / rupture / fissuring
↓
Exposure of sub-endothelial collagen + necrotic plaque contents
↓
Platelet adherence → activation → release granule contents → aggregate → microthrombi
↓
Vasospasm (from platelet mediators: TXA2, ADP, serotonin)
↓
Activation of coagulation pathway → bulk thrombus → Arterial occlusion

Severe ischemia
↓
Loss of oxidative phosphorylation → decreased ATP generation
↓
Accumulation of noxious metabolites (lactic acid, Ca²⁺ influx)
↓
Loss of contractility
↓
20-30 mins of ischemia → Irreversible cell injury
↓
Microvascular injury → Myocardial Infarction

Why does subendocardium die first? It is the most distal from epicardial vessels, receives blood last, and is exposed to highest intramural pressures. Ischemia progresses as a wavefront from subendocardium outward toward epicardium.

---

Types of Infarct (by Wall Thickness Involved)

---

Morphology - The Key Timeline (MOST EXAM-TESTED)

---

Reperfusion

• Thrombolysis (tPA)
• Angioplasty + stent placement
• CABG (Coronary Artery Bypass Graft)

1. Mitochondrial dysfunction → membrane permeability changes → apoptosis
2. Contraction band necrosis - calcium influx causes hypercontraction of sarcomeres → eosinophilic bands (hallmark of reperfused MI on microscopy)
3. Free radical damage (ROS: O₂⁻, H₂O₂, •OH)
4. "No-reflow" phenomenon - leukocyte aggregation in reperfused microvessels blocks blood flow
5. Platelet and complement activation → further microvascular injury

Contraction band necrosis is the microscopic hallmark of reperfused MI. It is NOT seen in non-reperfused MI.

---

Clinical Features

---

Investigations

---

Complications

Severity depends on: infarct size + location + thickness (transmural vs subendocardial)

---

Quick Summary Diagram

PLAQUE RUPTURE → THROMBUS → OCCLUSION
        ↓
   0-½ hr: Reversible (wavy fibers)
   ½-4 hr: Coagulation necrosis begins
   1-3 days: Neutrophil peak
   3-7 days: Macrophages, softening
   7-14 days: Granulation tissue
   2-8 wks: Collagen scar
   >2 months: Dense fibrotic scar

REPERFUSION → contraction band necrosis
COMPLICATIONS:
  Early → Arrhythmias (VF), rupture (3-7d)
  Mid   → Pericarditis (day 2-3)
  Late  → Aneurysm, HF, Dressler syndrome

• Robbins & Kumar Basic Pathology, p. 353-360

---

Vasculitis - Complete Notes

Classification of Vasculitis (by Vessel Size)

---

ANCA-Associated Vasculitis

Memory: c-ANCA = PR3 = Wegener's (With cytoplasmic staining). p-ANCA = MPO = Microscopic Polyangiitis (Myeloperoxidase + Perinuclear).

---

Polyarteritis Nodosa (PAN)

Definition

Key Features

• About 15% linked to hepatitis B viral infection; most cases are idiopathic
• Lungs are SPARED (pulmonary circulation not involved - important differentiator)
• ANCA is typically negative in classic PAN

Affected Organs (descending order)

Kidney involvement → renal artery vasculitis → renin-mediated hypertension + renal infarctions Nervous system → mononeuritis multiplex in >80% of cases

Morphology

Gross:

• Involves vessel segments especially at bifurcation as tiny beaded nodules
• Aneurysmal bulges visible in gross specimens (microaneurysms)
• Lesions are segmental - skip areas present between affected segments

Microscopic - 3 Sequential Stages:

Note: Granulomatous inflammation is absent in PAN (distinguishes it from Wegener's/GPA and Churg-Strauss)

Clinical Diagnosis:

• Requires tissue biopsy OR angiogram showing microaneurysms
• Simultaneous nerve + muscle biopsy (sural nerve + gastrocnemius) has high yield

Treatment:

• Hepatitis B-associated PAN: anti-viral therapy + plasma exchange + short-course steroids
• Idiopathic PAN: high-dose prednisolone (1 mg/kg/day) → taper; cyclophosphamide for severe disease

---

Thromboangiitis Obliterans (Buerger's Disease)

Definition

Key Features:

• Affects tibial and radial arteries principally (distal vessels)
• Occasionally extends into nerves and veins of extremities
• Finally leads to gangrene of extremities
• Contains hemosiderin-laden macrophages and organized thrombus
• Most common cause of mononeuritis multiplex (per your notes)
• Develops before age of 35 in heavy smokers
• Men <40 years; higher prevalence in Asians and Eastern Europeans

Etiopathogenesis

Morphology

Key distinguishing feature: Internal elastic lamina is preserved in Buerger's (unlike atherosclerosis where it is destroyed). This is a major histologic differentiator.

Clinical Features

Clinical triad: Claudication of extremity + Raynaud phenomenon + Migratory superficial vein thrombophlebitis

Treatment:

---

Quick Comparison: PAN vs Buerger's Disease

• Goldman-Cecil Medicine, p. (medium-vessel vasculitides chapter)
• Harrison's Principles of Internal Medicine, 22nd Edition