Pathology

Pathology/A/12

Atherosclerosis

アテローム性動脈硬化症（アテローム硬化）

タグ
Mechanism / 機序High-yield / ポイント

1. Definition

  • Arteriosclerosis = general arterial wall thickening + loss of elasticity.
  • Atherosclerosis (AS) = a subtype; a chronic inflammatory response of the vessel wall (endothelial injury, lipid accumulation in macrophages/SMCs, thrombosis).
  • An intimal plaque = lipid (necrotic) core (cholesterol crystals, debris, foam cells) + fibrous cap (SMCs, collagen, endothelium, neovascularization).

2. Risk Factors

Non-modifiable

  • Age (organ damage in middle age+), male/post-menopausal (estrogen protects pre-menopause), genetics (familial hypercholesterolemia, DM, HTN).

Modifiable (major)

  • Hyperlipidemia: ↑LDL (“bad”, delivers cholesterol to tissues), ↓HDL (“good”, returns cholesterol to liver). Lipoprotein(a) ↑ coronary risk.
  • Hypertension (vessel injury), smoking (1 pack/day → ~200× risk), diabetes mellitus.
  • Risk multiplies with combined factors (2 factors ~3×, 3 factors ~7×).

Additional

  • Inflammation (↑CRP), obesity, physical inactivity, stress, type A personality.

3. Pathogenesis (Response-to-Injury)

  1. Chronic endothelial injury (non-denuding; HTN turbulence, hyperlipidemia) → ↑ROS, ↓NO.
  2. Lipoprotein accumulation in intima → LDL oxidation (oxidized LDL).
  3. Monocyte adhesion/migration → macrophages take up oxidized LDL via scavenger receptors → foam cells.
  4. Platelet adhesion + growth factors (macrophages, EC, platelets) → SMC migration/proliferation + ECM (stabilizes cap).
  5. Lipid accumulation (intra- and extracellular).

4. Morphology

  1. Fatty streak — intimal foam cells; no flow disturbance; even in infants.
  2. Atherosclerotic plaque — white-yellow raised lesion (cells + ECM + lipid core); peripheral neovascularization.
  3. Complicated plaque — aneurysm (media weakening), ulcer/rupture, thrombus (→ MI/stroke/embolism), intraplaque haemorrhage, atheroembolism, calcification.

5. Sites & Prevention

  • Sites/clinical: coronary (MI), carotid/cerebral (stroke), aorta (AAA), peripheral (claudication).
  • Primary prevention: control risk factors, diet/exercise, no smoking.
  • Secondary prevention: statins, aspirin, BP control, coronary bypass.

💡 High-yield: Plaque = lipid core + fibrous cap; oxidized LDL → foam cells is the key early step. Plaque rupture → acute thrombosis is the basis of MI/stroke. Smoking and ↑LDL are leading modifiable risks.