Define arteriosclerosis.
Thickening and loss of elasticity of arterial walls
Hardening of the arteries
Differentiate atherosclerosis, arteriolosclerosis, and Monkeberg medial calcific sclerosis.
Atherosclerosis: in LARGE arteries, localized thickening of the wall with lumen NARROWING
Arteriolosclerosis: SMALL arteries and arterioles, thickening of the wall with lumen NARROWING
Monkeberg medial calcific sclerosis: CALCIFIC deposits in MUSCULAR arteries, do NOT encroach the vessel lumen
Define atherosclerosis.
A chronic inflammatory disease of large arteries
Affects everyone
Progresses with age, asymptomatic until a certain stage
Discuss the stages in the natural history of atherosclerosis.
Type I - Initial lesion: isolated macrophage foam cells
Type II - Fatty streak lesion: mainly intracellular lipid accumulation (lots of foam cells together)
Type III - Intermediate lesion: like type II, but with small extracellular lipid pools
Type IV - Atheroma lesion: core of extracellular lipid
Type V - Fibroatheroma lesion: lipid core and fibrotic layer, or mainly calcific, or mainly fibrotic
Type VI - Complicated lesion: surface defect, hematoma/hemorrhage, thrombus
Review the gross anatomy and histology of each atherosclerosis stage.
Type I - foam cells
Type II and III- yellowy streaks of foam cells
Type IV - intimal thickening -> raised lesion, lipid accumulation, lumen obscured
Type V - same as IV, but see collagen production to form a fibrous cap
Type VI - calcification, ulceration, thrombosis, hemorrhage
–Clinical manifestations occur at this stage
Discuss the consequences on CV function and clinical outcomes of each atherosclerosis stage, with emphasis on the complicated stage. (3)
Lesions can…
- Mechanically obstruct blood flow
- Rupture -> atheroemboli and thrombosis
- Weaken underlying media -> aneurysms
Review the endothelial injury hypothesis of atherosclerosis pathogenesis. (7 steps)
Atherosclerosis = chronic inflammatory response of arterial wall initiated by injury to endothelium
-> endothelial cell dysfunction -> increased adhesion of monocytes and platelets -> migration of smooth muscle cells and macrophages into intima -> formation of foam cells -> smooth muscle proliferation -> collagen and lipid deposition
Review the risk factors of atherosclerosis and their contribution to endothelial activation. (9)
Age
Male gender
Family history
Genetic abnormalities
Hyperlipidemia HTN Smoking Diabetes C-reactive protein (indicative of inflammation)
