Atherosclerosis

Definition

  • Chronic inflammatory response of large & medium sized arteries to endothelial injury, characterised by sub-endothelial lipid deposit, inflammation, and fibrosis (plaque)
  • A type of arteriosclerosis in which arterial wall thickens due to atheromatous plaque formed by
    • invasion of WBCs (foam cells)
    • proliferation of intimal smooth muscle cells
  • Clinically: Macroangiopathy
Arteries and veins

Risk Factors

  • Non-modifiable
    • Age, Male gender, family history, genetics
  • Modifiable
    • Hyperlipidemia, hypertension, smoking, DM, lifestyle,
  • Other
    • CRP (inflammation), Hyperhomocysteinemia, Metabolic syndrome, pro-coagulatory state

Pathogenesis

Response to injury hypothesis

  1. Endothelial injury → endothelial dysfunction → increased leukocyte adhesion + thrombosis
    • Causes: mechanical denudation, hemodynamic disturbance, immune complex deposition, irradiation
    • Triggers: Hypertension, hyperlipidemia,
  2. Accumulation of lipoproteins: oxidized LDL & cholesterol crystals in the vessel wall
  3. Platelet adhesion & activation
  4. Monocyte adhesion to endothelium → migration into intima → differentiation into Macrophages engulfment of oxidized LDL thus becoming foam cells (activated macrophages
  5. Lipid accumulation within macrophages → engulfment of oxidized LDL thus becoming foam cells (activated macrophages which have fat inside them) → inflammatory cytokine release
  6. Smooth muscle cell recruitment due to factors released from platelet activation + macrophages + vascular wall cells
  7. Smooth muscle cell proliferation & ECM production (Healing)

Pathology Summary

  • Intimal injury → Lipid/LDL accumulation  inflammation → macrophages → SMC proliferation → fibrosis → necrosis → ulceration → bleeding
  • Dot → streak → soft → hard → complicated plaques →
    • Unstable/Stable
    • TH1 / TH2
    • Inflammation/Healing

Complications

  • Calcification, ulceration, thrombosis, hemorrhage
  • Narrowed lumen, sudden occlusion, superimposed thrombus, local thrombi can cause infarctions in smaller vessels, emboli can cause problems in other areas
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