Atherosclerosis

Question 1

Definition of atherosclerosis

Answer 1

• degenerative disease of tunica intima affecting large & medium sized arteries
• characterised by atheromas

Question 2

Risk factors of atherosclerosis (2)

Answer 2

1. Constitutional/Non Modifiable
   - age, M, family Hx, genetics
2. Modifiable
   - hyperlipidemia, HTN, diabetes, cigarette smoking, obesity

Question 3

Pathogenesis of atherosclerosis (4)

Answer 3

1. Chronic endothelial injury
   - due to hyperlipidemia, hemodynamic disturbances etc
2. Response to injury
   - Increased permeability & leakage of lipids - lipoprotein accumulation in vessel wall
   - LDL oxidised by free radicals - engulfed by macrophages - forms foam cells + stimulates release of growth factors, cytokines, chemokines
   - Enhanced leukocyte adhesion, platelet adhesion
   - Monocyte migration into intima - transforms into macrophages & foam cells
   - Factors induce smooth muscle recruitment
3. Smooth muscle proliferation & ECM synthesis - stabilises plaque
4. Lipid accumulation (extracellularly & within cells)

Question 4

Effects of atheroma (plaque) (2)

Answer 4

1. Raised lesion - mechanically obstructs blood flow

2. Weakens underlying media - possible aneurysm formation

Question 5

Progression of atheroma (3)

Answer 5

1. Fatty Streak
   - barely visible, smooth, slightly raised, yellow/white
   - contains foamy macrophages
2. Atheroma - Fibrofatty plaque
   - raised lesion, protrudes into vessel lumen
   - superficial fibrous cap (collagen, SM) + softer necrotic core (lipids, macrophages etc)
   - after SM cell prolif & ECM synth
3. Advanced/Unstable Plaque
   - usually smaller, with large lipid core + thin fibrous cap
   - more likely to undergo acute plaque change
   - intrinsic factors - more MMP (degrade collagen & ECM), less TIMP
   - extrinsic factors - bp, platelet reactivity

Question 6

Consequences of atherosclerosis (3)

Answer 6

1. Chronic atherosclerotic stenosis
   - gradual vessel luminal occlusion - compromises blood flow - ischemic injury - stable angina, chronic IHD, intermittent claudication etc
2. Acute plaque changes
   - rupture/fissure, erosion/ulceration, hemorrhage, thrombosis, embolism
3. Aneurysm formation