SECTION 01
Atherosclerosis (AS)
Overview — Arteriosclerosis
Arteriosclerosis
Any condition causing thickening / hardening of arterial walls + loss of elasticity. Three patterns:
✓ Atherosclerosis
- Large & medium arteries
- Intimal fatty deposits + SMC proliferation
- Main focus of this section
Mönckeberg Calcification
- Medial calcification
- Less clinically significant
Arteriolosclerosis
- Affects small arteries & arterioles
- Associated with hypertension
Definition & Risk Factors
Atherosclerosis
Disease of large and medium-sized arteries characterised by intimal fatty deposits → SMC + connective tissue proliferation → ultimately arteriolosclerosis. Fundamentally a lipid metabolism disorder.
Risk Factors
- Hyperlipidaemia KEY
- Hypertension
- Smoking
- Diabetes & hyperinsulinaemia
- Heredity
- Age 40–60, male sex
Lipoproteins
- ↑ Risk Chylomicron (CM)
- ↑ Risk VLDL, LDL, oxidised LDL, IDL
- Protective HDL
Pathogenesis — Hypotheses
4 Hypotheses
- Response to injury — endothelial damage → monocyte/platelet adhesion
- Lipid infiltration — lipid enters intima, engulfed by Mφ → foam cells
- Smooth muscle mutagenic — SMC proliferation
- Macrophage receptor defect — impaired LDL clearance
Cellular Sequence
- Endothelial injury → monocyte & platelet adhesion
- Monocytes & SMCs migrate into intima
- Engulf lipid → foam cells
- Foam cells accumulate → well-developed plaque
Morphology — Plaque Progression
Stage 1 — Fatty Streaks (Early)
- Lipid-filled foam cells in intima
- Grossly: yellow, flat spots/streaks, 1–2 mm wide, slightly raised
- Form at ostia of branch vessels
- LM: foam cells (Mφ + SMC that engulfed lipid)
- Reversible — can regress
- Seen even in infants/children
Stage 2 — Fibrous Plaque
- Grossly: pale yellow/waxy, slightly protuberant
- Superficial fibrous cap — SMC + ECM
- Lipid zone — deep foam cells, free lipid, debris
- Basal zone — SMC, connective tissue, inflammatory cells
Stage 3 — Atheroma (Advanced Plaque)
- Grossly: grey-yellow lesions impinging on lumen
- Yellow grumous lipid core + firm white fibrous cap
- LM: dense fibrous cap (hyaline collagen + SMC in ECM)
- Necrotic core — lipid, cholesterol clefts, cell debris, fibrin
- Foam cells + T lymphocytes + neovascularisation around lesion
- Calcium deposits (stain blue)
- Ischaemic atrophy of underlying media
Plaque Complications (memorise all 5)
Haemorrhage into Plaque
- Rupture of fibrous cap or thin neovascularisation vessels
- Contained haematoma → expands or ruptures plaque
Rupture / Ulceration / Erosion
- Exposes bloodstream to thrombogenic material
- Triggers thrombus formation
- Acute coronary syndrome mechanism
Atheroembolism
- Plaque debris discharged into bloodstream
- Forms microemboli → distal ischaemia
Aneurysm
- Ischaemic atrophy of media → loss of elastic tissue
- Vessel wall weakens → aneurysm may rupture
Calcification
- Ca²⁺ deposits in necrotic material
- Arterial wall becomes hard and fragile
Key Locations: Aorta (posterior wall, ostia — most severe at abdominal aorta) · Coronary arteries · Renal · Mesenteric · Carotid/Cerebral · Lower extremity arteries
SECTION 02
Ischemic Heart Disease (IHD)
IHD — Definition
A group of syndromes from myocardial ischaemia: imbalance between coronary perfusion ↓ and cardiac O₂ demand ↑.
Coronary Atherosclerosis — Distribution
Affected Vessels (by frequency)
- 40–50% Left anterior descending (LAD)
- 30–40% Right coronary artery (RCA)
- 15–20% Left circumflex (LCX)
- Left > Right; large branch > small; proximal > distal
Stenosis Grading
Critical stenosis ≥70–75% → symptomatic angina on exertion. Fixed 90% stenosis → ischaemia at rest.
IHD Types
Type 1 — Angina Pectoris
Paroxysmal substernal/precordial chest discomfort (constricting / squeezing / knife-like)
| Type | Trigger | Key Feature | ECG |
|---|---|---|---|
| Stable (Typical) | Exertion / stress | Stenosis >75%; relieved by rest or nitroglycerine | ST depression |
| Prinzmetal (Variant) | Rest | Coronary vasospasm | ST elevation |
| Unstable | Any / progressive | AS plaque rupture + partial thrombosis; pre-infarction angina | Variable |
Type 2 — Myocardial Infarction (MI)
Definition: Acute ischaemic necrosis from severe sustained ischaemia. 95% involve left ventricle.
Subendocardial MI
- Necrosis limited to inner ⅓ of ventricular wall
- Involves papillary muscle & trabeculae carneae
- Multi-focal / circumferential
Transmural MI
- Full/nearly full thickness (>⅔) necrosis
- Distribution of a single coronary artery
- Anemic infarct: yellow/grey-red, dry, irregular
- Visible macroscopically at 6 hours
Infarct Favourite Sites by Vessel
| Vessel | Freq. | Territory |
|---|---|---|
| LAD | 40–50% | Anterior LV wall near apex, anterior septum, apex |
| RCA | 30–40% | Inferior-posterior LV wall, posterior septum, inferior RV |
| LCX | 15–20% | Lateral LV wall (except apex) |
Progression of Transmural MI over Time
½–4 hr
Gross: none · Micro: wavy fiber border4–12 hr
Gross: occasional dark mottling · Micro: coagulation necrosis begins, oedema, haemorrhage12–24 hr
Gross: dark mottling · Micro: myocyte hypereosinophilia, marginal contraction band necrosis1–3 days
Gross: yellow-tan centre · Micro: coagulation necrosis, neutrophil infiltrate, loss of nuclei & striation3–7 days
Gross: hyperaemic border, soft centre · Micro: early macrophage phagocytosis7–10 days
Gross: maximally soft & yellow-tan · Micro: well-developed phagocytosis, early granulation tissue at margin10–14 days
Gross: red-grey borders · Micro: well-established granulation tissue + collagen deposition2–8 weeks
Gross: grey-white scar (border → core) · Micro: increased collagen>2 months
Dense collagenous scar — complete
Lab markers: TnT ↑, TnI ↑ (most specific) · CK-MB ↑ · Myoglobin · LDH
MI Complications
| Complication | Timing / Details |
|---|---|
| Contractile dysfunction | Early — degree depends on infarct size |
| Arrhythmias | Most common cause of death in first hour |
| Myocardial rupture | 3–7 days: free wall → haemopericardium/tamponade; septum → L-to-R shunt; papillary muscle → mitral regurgitation |
| Pericarditis | Fibrinous; rough dark epicardial surface |
| Infarct expansion | Wall thinning + mural thrombus |
| Mural thrombus | Risk of systemic embolism |
| Ventricular aneurysm | Large apical bulge → stasis → thrombus |
| Papillary muscle dysfunction | Mitral regurgitation |
| Progressive heart failure | Late complication |
Type 3 — Chronic Ischaemic HD
- Cause: moderate–severe coronary stenosis or occlusion
- Gross: LV hypertrophy + dilation, grey-white scars
- LM: diffuse myocardial fibrosis + myocardial hypertrophy/atrophy
- Clinical: heart failure
Type 4 — Sudden Cardiac Death
- Unexpected death from cardiac cause
- Most common cause: ischaemic heart disease
- Mechanism: lethal ventricular arrhythmia
- Triggers: AP/MI, acute myocardial ischaemia, coronary spasm
SECTION 03
Hypertension
Definition
Persistent elevation of systemic arterial BP above normal. Normal: ≤140/90 mmHg. Hypertension: ≥140/90 mmHg.
Classification
- Essential (primary): 90–95% — unknown cause
- Secondary: 5–10% — renal or endocrine cause
Causes of Essential Hypertension
- Genetic factors
- High salt intake
- Chronic stress
- Obesity, smoking, physical inactivity, age
- ↑ cardiac output OR ↑ peripheral vascular resistance
Benign vs. Malignant Hypertension
Benign Hypertension (95%)
Compatible with long life; slow progression over decades.
Stage 1
Functional disorders
- Intermittent arteriole/small artery constriction
- Headaches, dizzy spells; labile BP
- Reversible with rest
Stage 2
Arterial changes
- Hyaline arteriolosclerosis: pink hyaline thickening, lumen narrowing
- Often: afferent glomerular arteriole, splenic central arteriole
- Small/medium arteries: medial muscular hypertrophy + fibrosis
- Large arteries: often accompanied by atherosclerosis
Stage 3
Visceral changes
| Organ | Changes |
|---|---|
| Heart | LV hypertrophy (>400 g wall >1.5–2 cm) → concentric → eccentric → CHF |
| Kidneys | "Primary granular atrophic kidney" — small, firm, fine granular surface; hyaline arteriolosclerosis + glomerular hyalinisation + tubular atrophy |
| Brain | Cerebral oedema (hypertensive encephalopathy) · encephalomalacia (small infarcts) · cerebral haemorrhage (most severe) |
| Retina | Arterial narrowing and haemorrhage |
Malignant Hypertension (5%)
BP >200/120 mmHg, diastolic usually >130 mmHg. Younger patients. Rapid progression.
- Rapidly progressive organ damage
- Renal failure
- Hypertensive encephalopathy
- Left ventricular failure
Pathological changes:
- Necrotising arteriolitis
- Hyperplastic arteriolosclerosis ("onion-skinning") → luminal obliteration
- Major organs: kidney and brain
Death within 2 years (avg 8 months) from uremia, CHF, or cerebral haemorrhage if untreated.
Quick Comparison
| Benign HT | Malignant HT | |
|---|---|---|
| Prevalence | ~95% | ~5% |
| Onset | Gradual, older | Rapid, younger |
| BP | Moderate elevation | >200/120 mmHg |
| Vascular lesion | Hyaline arteriolosclerosis | Necrotising arteriolitis + onion-skinning |
| Prognosis | Decades if controlled | Months without treatment |
SECTION 04
Valvular Heart Disease
Rheumatic Heart Disease
Rheumatic Fever (RF)
Immunologically mediated inflammatory disease triggered by Group A β-haemolytic streptococcal infection. Occurs 2–3 weeks after strep throat, most common age 5–15. Pathognomonic feature: Aschoff body.
Pathogenesis
- Ag-Ab cross-reaction: streptococcal M-protein Ab attacks heart valve glycoprotein
- Autoimmune mechanism
- Hereditary susceptibility
Aschoff Body — Key Lesion
- Centre: fibrinoid necrosis
- Nearby: Anitschkow cells (also called Aschoff cells / "owl-eye" / "caterpillar" cells) — activated macrophages
- Periphery: lymphocytes + monocytes
- Origin: monocyte-macrophage lineage
Acute Rheumatic Carditis — 3 Components
Endocarditis
- Mainly mitral valve (± aortic)
- Active stage: tiny wart-like vegetations along closure lines → "verrucous endocardium"
- Vegetations = white thrombus (platelets + fibrin)
- Inactive: fibroplastic proliferation → valve thickening, shortening, hardening → stenosis/insufficiency
Myocarditis
- Adults: Aschoff bodies near small vessels
- Children: diffuse mesenchymal inflammation
- Result: scar
- Clinic: fever, prolonged P-R interval, WBC↑, ASO↑
Pericarditis
- Serous/fibrinous pericarditis
- "Cor villosum" — heavy shaggy fibrinous coat
- Outcome: absorption (recovery) OR organisation → constrictive pericarditis
- Clinic: friction rub, enlarged cardiac border on X-ray
Infective Endocarditis
Definition
Invasion of heart valves by a microbiologic agent (streptococci, fungi, virus) with vegetation formation.
Acute Infective Endocarditis
- High-virulence organisms (e.g. S. aureus)
- Affects normal endocardium — aortic and mitral valves
- Bulky, friable, dirty, grey-yellow vegetations (several cm)
- Rapid valve destruction
- Systemic embolisation → septic infarcts
- >50% mortality despite treatment
Subacute Bacterial Endocarditis (SBE)
- Low-virulence organisms (viridans strep, enterococcus, fungi)
- Occurs in vulnerable hosts with pre-existing heart disease
- Large, friable, irregular masses; may extend onto chordae
- Ulceration/perforation; fall off easily → emboli
- LM: granulation tissue at base, eventual fibrosis + calcification
- Recoverable with appropriate antibiotics
Endocarditis Comparison
| Rheumatic Endocarditis | Acute IE | SBE | |
|---|---|---|---|
| Organism | Post-strep (immune) | High virulence | Low virulence |
| Vegetation size | Tiny, wart-like | Bulky, several cm | Large, irregular |
| Vegetation character | Along closure line, firm, white | Friable, dirty, grey-yellow | Friable, grey-yellow, granulation at base |
| Valve affected | Mainly mitral | Aortic + mitral | Mitral or aortic |
| Pre-existing disease | No | No | Yes |
| Prognosis | Chronic valve disease | High mortality | Recoverable |
Chronic Valvular Disease
Stenosis = valve fails to open completely (leaflets thick, rigid, inter-adherent → narrow orifice)
Insufficiency/Regurgitation = valve fails to close completely (leaflets thick, convoluted, retracted, or perforated → backflow)
Insufficiency/Regurgitation = valve fails to close completely (leaflets thick, convoluted, retracted, or perforated → backflow)
Mitral Stenosis
- Cause: chronic rheumatic endocarditis (mainly)
- Orifice reduced from 5 cm² → 1–2 cm² (sometimes 0.5 cm²)
- "Fish-mouth" deformity
- Haemodynamics: left atrial dilation → pulmonary congestion → RV hypertrophy
- X-ray: inverted "pear-shaped heart" — 3 chambers enlarged (LA, RV, RA)
Mitral Insufficiency
- Cause: rheumatic endocarditis
- Blood regurgitates into LA at systole → LV volume overload
- Haemodynamics: all 4 chambers enlarge
- X-ray: spherical heart
- Clinical: whole heart failure
Combined Mitral Stenosis & Insufficiency
- Globoid heart — all chambers dilated
- Leaflets markedly thickened and opaque
- LV wall thickened
Aortic Stenosis
- Cause: chronic aortic valvulitis / congenital / AS
- LV hypertrophy (pressure overload)
- X-ray: boot-shaped heart
- Pulse pressure ↓, angina pectoris
REVIEW
Key Exam Questions
Questions to Master
- Gross pathological changes of atherosclerosis + 5 complications
- Heart, kidney & brain changes in benign hypertension
- Basic pathological changes of rheumatism + Aschoff body
- Morphologic differences: rheumatic endocarditis vs. infective endocarditis
- Complications of myocardial infarction
Key Terms to Define
- Atheroma
- Foam cell
- Aschoff body
- Verrucous endocardium
- Cor villosum
- Fish-mouth deformity
- Onion-skinning
- Critical stenosis
- Transmural MI
- SBE