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PA26.1-2 | Atherosclerosis & Aneurysms — SDL Guide (Part 2)

The Atheromatous Plaque: Morphology

A four-panel medical diagram shows the morphology, gross appearance, distribution, and stability features of mature atheromatous plaques in arteries. — **Panel A:** Mature atheromatous plaque cross-section showing lumen, overlying endothelium, fibrous cap, smooth muscle cells, collagen/proteoglycan matrix, macrophages, foam cells, lymphocytes, shoulder region, necrotic lipid core, cholesterol clefts, necrotic debris, calcium deposits, internal elastic lamina, and tunica media.. **Panel B:** Gross opened artery showing raised white-to-yellow intimal plaque and yellow porridge-like necrotic atheromatous center.. **Panel C:** Ranked distribution of plaques: abdominal aorta below renal arteries, proximal coronary arteries, popliteal artery, internal carotid artery, and Circle of Willis; note that veins and pulmonary vessels are rarely affected at normal pressures.. **Panel D:** Stable plaque versus vulnerable plaque showing thick versus thin fibrous cap, small versus large lipid core, fewer versus many macrophages, prominent shoulder inflammation, and rupture risk..

The mature atheromatous plaque (fibrous plaque, atheroma) is the signature lesion of atherosclerosis:

Gross appearance: white-to-yellow, raised intimal lesion; size from a few mm to several cm; may have yellowish, porridge-like necrotic centre ('atheroma' = Greek for gruel).

Microscopic components:
• Fibrous cap — superficial layer composed of SMCs, macrophages, foam cells, lymphocytes embedded in a dense collagen and proteoglycan matrix. Provides structural integrity.
• Necrotic lipid core — central acellular zone of cholesterol crystals, necrotic debris, foam cell remnants, calcium deposits.
• Shoulder region — lateral edges where active inflammation predominates; most vulnerable to rupture.

A labelled medical diagram shows the structure, stability features, and common distribution sites of mature atheromatous plaques. — **Panel A:** Arterial lumen, overlying endothelium, fibrous cap, shoulder region, necrotic lipid core, cholesterol clefts, foam cells/macrophages, smooth muscle cells, collagen, calcification, tunica media, adventitia.. **Panel B:** Vulnerable plaque: thin fibrous cap, large lipid core, many macrophages, few smooth muscle cells, rupture-prone shoulder; Stable plaque: thick fibrous cap, small lipid core, smooth muscle cells, collagen, calcification.. **Panel C:** Distribution ranking: abdominal aorta below renal arteries, proximal coronary arteries, popliteal artery, internal carotid artery, Circle of Willis; veins and pulmonary vessels usually spared under normal pressure..

Distribution of plaques (highest to lowest frequency):
1. Abdominal aorta (below renal arteries) — most heavily affected
2. Coronary arteries (proximal segments)
3. Popliteal artery (claudication in peripheral arterial disease)
4. Internal carotid artery (stroke)
5. Circle of Willis

Note: Veins and pulmonary vessels are virtually never affected under normal (non-elevated) pressures — reinforcing the haemodynamic/pressure component of injury.

Plaque stability: A plaque with a thin fibrous cap + large lipid core + many macrophages/few SMCs is vulnerable (high rupture risk) even if it causes <50% stenosis. A thick cap + small core + heavy calcification is stable (less rupture risk, more stenosis).

CLINICAL PEARL

Thin-cap fibroatheroma (TCFA) is the pathological definition of the 'vulnerable plaque' responsible for most acute MI events. Paradoxically, many MI patients had <50% stenosis on their last angiogram — the plaque ruptured before it caused significant obstruction. This is why statin therapy (plaque stabilisation, not just cholesterol-lowering) reduces MI events even in patients without high-grade stenosis. The clinical lesson: don't wait for flow-limiting disease to start secondary prevention.

SELF-CHECK

In the response-to-injury hypothesis, which receptor on macrophages is primarily responsible for ox-LDL uptake leading to foam cell formation?

A. LDL receptor (LDLR / ApoB-100 receptor)

B. Scavenger receptor (SR-A / CD36)

C. VLDL receptor

D. Toll-like receptor 4 (TLR-4)

Reveal Answer

Answer: B. Scavenger receptor (SR-A / CD36)

Scavenger receptors (SR-A, CD36) on macrophages have low affinity for native LDL but high affinity for ox-LDL. Critically, scavenger receptors are NOT downregulated by cholesterol accumulation (unlike the LDL receptor which is downregulated by cellular cholesterol via SREBP), so macrophages continue engulfing ox-LDL until they are massively lipid-laden — this is the molecular basis for uncontrolled foam cell formation. TLR-4 also binds ox-LDL and triggers inflammatory signalling but is not the primary uptake receptor.

Complications of Atherosclerosis

A multi-panel medical diagram shows how atherosclerotic plaques cause chronic ischaemia, thrombosis, plaque erosion, intraplaque haemorrhage, calcification, aneurysm formation, and atheroembolism. — **Panel A:** Overview of chronic ischaemia from progressive luminal narrowing versus acute plaque disruption causing thrombosis.. **Panel B:** Plaque rupture at thin fibrous cap shoulder, exposed collagen and tissue factor, platelet adhesion, thrombus, acute MI, stroke, acute limb ischaemia.. **Panel C:** Plaque erosion with endothelial loss, intact fibrous cap, superficial platelet-rich thrombus.. **Panel D:** Haemorrhage into plaque from ruptured vasa vasorum, intraplaque haematoma, sudden plaque expansion, rapid luminal narrowing.. **Panel E:** Dystrophic calcification of necrotic core, rigid brittle plaque, eggshell calcification on X-ray inset.. **Panel F:** Abdominal aortic aneurysm from media destruction by macrophage MMPs and atheroembolism with cholesterol crystals causing blue toe syndrome..

Atheromatous plaques cause disease through two broad mechanisms: chronic ischaemia (progressive luminal narrowing → haemodynamic compromise) and acute events (sudden plaque disruption → thrombosis).

1. Plaque rupture / erosion → thrombosis (most dangerous)
• Rupture: thin fibrous cap breaks (often at the shoulder); lipid core exposes collagen and tissue factor → platelet adhesion → thrombus.
• Result: acute MI (coronary), stroke (carotid), acute limb ischaemia (peripheral). Responsible for ~75% of fatal MIs.
• Plaque erosion (endothelial loss without frank rupture) causes remaining ~25%.

2. Haemorrhage into plaque
• Disruption of thin-walled vasa vasorum within the plaque → intraplaque haematoma → sudden plaque expansion → rapid luminal narrowing without rupture. Contributes to unstable angina and acute coronary syndromes.

3. Calcification
• Dystrophic calcification of the necrotic core → rigid, brittle plaque. May cause 'eggshell' calcification visible on X-ray. Paradoxically associated with stable lesions but complicates percutaneous interventions.

4. Aneurysm formation
• Atherosclerotic plaques in the aortic wall destroy the media → weakened wall → aneurysmal dilation. The mechanism: inflammation, proteases (MMPs) from macrophages degrade elastin and collagen. Most commonly: abdominal aortic aneurysm (AAA).

5. Atheroembolism
• Plaque rupture → release of cholesterol crystals / thrombotic debris → emboli to distal vessels → 'blue toe syndrome', renal infarcts, mesenteric ischaemia.

6. Progressive stenosis → chronic ischaemia
• Coronary: stable angina → chronic heart failure
• Renal: renovascular hypertension, ischaemic nephropathy
• Mesenteric: intestinal ischaemia / 'abdominal angina'
• Peripheral: intermittent claudication → rest pain → gangrene

SELF-CHECK

A 55-year-old man develops an acute MI. Coronary angiography performed 24 hours earlier showed only 45% stenosis at the culprit site. What pathological finding at the plaque BEST explains this acute event?

A. Heavy calcification of the fibrous cap causing embolisation

B. Rupture of a thin fibrous cap exposing the lipid core with thrombosis

C. Plaque with a thick fibrous cap and dense SMC content

D. Intraplaque haemorrhage from well-formed vasa vasorum

Reveal Answer

Answer: B. Rupture of a thin fibrous cap exposing the lipid core with thrombosis

Thin-cap fibroatheroma (TCFA) — the vulnerable plaque — typically causes <50% stenosis because most of its volume is occupied by a large lipid core with eccentric remodelling rather than lumen-encroachment. Rupture of the thin cap exposes the highly thrombogenic lipid core (collagen, tissue factor) to blood, triggering rapid platelet aggregation and thrombus formation that abruptly occludes the vessel. Option D (intraplaque haemorrhage) can also precipitate ACS but is the less common mechanism; option A and C describe stable lesions.

Aneurysms: Definition and Classification

Four-panel medical diagram comparing true and false aneurysm wall anatomy and fusiform versus saccular aneurysm morphology. — **Panel A:** True aneurysm showing dilated arterial lumen with intact intima, media, and adventitia; label all three vessel wall layers and the aneurysmal dilation.. **Panel B:** False aneurysm or pseudoaneurysm showing arterial wall defect, escaping blood, contained haematoma, adventitia/perivascular tissue, and disrupted vessel wall.. **Panel C:** Fusiform aneurysm showing circumferential symmetric spindle-shaped dilation involving the full vessel circumference, with normal vessel diameter indicated for comparison.. **Panel D:** Saccular aneurysm showing one-sided spherical outpouching involving part of the vessel circumference, with aneurysm neck, sac, and parent vessel labeled..

An aneurysm is a localised, abnormal, permanent dilation of a blood vessel (or cardiac chamber) to at least 1.5× its normal diameter.

True vs False aneurysm:

Type	Wall	Example
True aneurysm	All three layers of the vessel wall (intima, media, adventitia)	Atherosclerotic AAA, syphilitic, berry
False aneurysm (pseudoaneurysm)	Haematoma contained by only adventitia and/or perivascular tissue — NOT a complete vessel wall	Post-catheterisation femoral artery, traumatic, anastomotic leak

Morphological classification:
• Fusiform aneurysm — circumferential, symmetric dilation involving the full circumference of the vessel wall; spindle-shaped. Typical of atherosclerotic AAA.
• Saccular aneurysm — one-sided, spherical outpouching involving only part of the circumference. Typical of berry aneurysms at the circle of Willis and syphilitic aortitis.

A multi-panel medical diagram compares fusiform and saccular aneurysm shapes, true and false aneurysm wall anatomy, and key aetiological classifications. — **Panel A:** Fusiform aneurysm with circumferential spindle-shaped arterial dilatation, arterial lumen, normal proximal artery, normal distal artery, and uniformly dilated vessel wall.. **Panel B:** Saccular aneurysm with one-sided pouch, narrow neck, asymmetric outpouching, arterial lumen, and parent artery.. **Panel C:** True aneurysm cross-section showing intact but dilated tunica intima, tunica media, tunica adventitia, vessel lumen, and stretched vessel wall.. **Panel D:** False aneurysm or pseudoaneurysm cross-section showing wall defect through all three layers, escaped blood, haematoma cavity, compressed vessel lumen, tunica intima, tunica media, and tunica adventitia.. **Panel E:** Aetiological classification icons for atherosclerotic infrarenal AAA, hypertensive Charcot-Bouchard microaneurysm, cystic medial degeneration with dissection, syphilitic thoracic aneurysm, mycotic aneurysm, and berry aneurysm at circle of Willis branch points..

Aetiological classification (MOST IMPORTANT for exam):
1. Atherosclerotic — commonest overall; abdominal aorta below renal arteries (AAA)
2. Hypertensive — small cerebral arteries (Charcot-Bouchard microaneurysms) → intracerebral haemorrhage
3. Cystic medial degeneration → dissecting aneurysm / aortic dissection (Marfan syndrome, HTN)
4. Syphilitic (luetic) — tertiary syphilis; thoracic aorta (ascending + arch)
5. Mycotic — infected emboli lodge in vasa vasorum → septic weakening; any artery
6. Berry (saccular cerebral) — congenital defect in media at circle of Willis branch points