Question
Discuss the etiopathogenesis of Atherosclerosis. What are the possible complications that may arise due to the presence of these plaques in different arteries. Draw a labelled diagram depicting the histological appearance of the same. (6+5+4)
Answer
Etiopathogenesis of atherosclerosis (response-to-injury hypothesis)
- Endothelial injury/dysfunction: Caused by risk factors — hypertension, hyperlipidaemia (particularly elevated LDL cholesterol), smoking, diabetes, haemodynamic turbulence at vessel branch points — increases endothelial permeability and adhesion molecule expression
- Lipid entry and modification: LDL cholesterol accumulates in the subendothelial intima and undergoes oxidative modification
- Monocyte recruitment: Monocytes adhere to activated endothelium, migrate into the intima, and differentiate into macrophages, which phagocytose oxidized LDL to become lipid-laden foam cells, forming the initial fatty streak
- Smooth muscle cell migration and proliferation: Growth factors (PDGF, released by activated platelets, macrophages, and endothelium) stimulate migration of smooth muscle cells from the media into the intima, where they proliferate and synthesize extracellular matrix (collagen), forming a fibrous cap over the lipid core
- Plaque maturation: The mature atheromatous plaque consists of a fibrous cap (smooth muscle cells, collagen) overlying a necrotic lipid core (cholesterol clefts, foam cells, debris), with associated inflammatory cells (T lymphocytes, macrophages) and neovascularization
Complications of atherosclerotic plaques in different arteries
- Coronary arteries: Angina, myocardial infarction (from plaque rupture/thrombosis), sudden cardiac death
- Cerebral arteries: Transient ischaemic attack, ischaemic stroke
- Aorta: Aneurysm formation (weakening of the wall), aortic dissection, mural thrombus with distal embolization
- Renal arteries: Renovascular hypertension, ischaemic nephropathy
- Peripheral (lower limb) arteries: Intermittent claudication, critical limb ischaemia, gangrene
General plaque-related complications
- Rupture/fissuring: Exposes thrombogenic plaque contents, triggering acute thrombosis and vessel occlusion
- Haemorrhage into the plaque: Sudden plaque expansion
- Calcification: Increases plaque rigidity/fragility
- Aneurysm formation: From weakening of the underlying media by the atherosclerotic process
(A labelled diagram cannot be rendered in this text-based answer; the histological appearance to be depicted would show, from lumen to outer wall: an intact/disrupted endothelium, a fibrous cap of smooth muscle cells and collagen, an underlying necrotic core containing cholesterol clefts and foam cells, scattered chronic inflammatory cells, and areas of dystrophic calcification, with the underlying media and adventitia labelled for orientation.)