Atherosclerosis - classification, etiology, pathogenesis, and clinical manifestation
Atherosclerosis is a chronic progressive disease of large and medium-sized elastic and muscular arteries, characterized by formation of intimal fibrofatty plaques (atheromas ) that lead to luminal narrowing and vascular complications.
Classification
By vessel involvement
By clinical form
Etiology (risk factors)
Non- modifiable
- Age (risk increases with age).
- Male sex.
- Family history/ genetics.
Modifiable
- Hyperlipidemia (↑ LDL, ↓ HDL).
- Hypertension.
- Smoking.
- Diabetes mellitus.
- Obesity.
- Physical inactivity.
- Hyperhomocysteinemia.
Pathogenesis
Response- to- injury hypothesis
- 1 Endothelial injury or dysfunction
Causes: hypertension, toxins (cigarette smoke), hyperlipidemia, turbulent flow.
- 2 Lipoprotein entry and modification
LDL accumulates in intima → oxidized LDL ( oxLDL) → pro- inflammatory.
- 3 Monocyte adhesion and migration
Monocytes enter intima → transform into macrophages → ingest oxLDL → form foam cells.
- 4 Formation of fatty streaks
Earliest visible lesion, composed of foam cells.
- 5 Smooth muscle cell (SMC) migration and proliferation
SMCs move from media to intima → produce extracellular matrix (collagen, proteoglycans).
- 6 Fibrous cap formation and plaque maturation
Fibrous cap overlies lipid core → forms atheromatous plaque.
- 7 Plaque complications
Calcification.
Ulceration/ rupture → thrombosis.
Hemorrhage into plaque.
Embolization of plaque debris.
Aneurysm formation (weakening of vessel wall).
Clinical manifestations
Asymptomatic phase
Long latent period; plaques develop silently over decades.
Symptomatic phase (complications)
Ischemia due to stenosis
Coronary arteries → stable angina pectoris.
Peripheral arteries → intermittent claudication.
Acute thrombosis due to plaque rupture
Myocardial infarction.
Cerebral infarction (stroke).
Sudden cardiac death.
Aneurysm and dissection
Aorta (especially abdominal aorta).
Embolization
Cholesterol emboli to distal arteries.