Atherosclerosis

Question 1

Define arteriosclerosis.

Answer 1

Thickening and loss of elasticity of arterial walls

Hardening of the arteries

Question 2

Differentiate atherosclerosis, arteriolosclerosis, and Monkeberg medial calcific sclerosis.

Answer 2

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

Question 3

Define atherosclerosis.

Answer 3

A chronic inflammatory disease of large arteries
Affects everyone
Progresses with age, asymptomatic until a certain stage

Question 4

Discuss the stages in the natural history of atherosclerosis.

Answer 4

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

Question 5

Review the gross anatomy and histology of each atherosclerosis stage.

Answer 5

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

Question 6

Discuss the consequences on CV function and clinical outcomes of each atherosclerosis stage, with emphasis on the complicated stage. (3)

Answer 6

Lesions can…

• Mechanically obstruct blood flow
• Rupture -> atheroemboli and thrombosis
• Weaken underlying media -> aneurysms

Question 7

Review the endothelial injury hypothesis of atherosclerosis pathogenesis. (7 steps)

Answer 7

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

Question 8

Review the risk factors of atherosclerosis and their contribution to endothelial activation. (9)

Answer 8

Age
Male gender
Family history
Genetic abnormalities

Hyperlipidemia
HTN
Smoking
Diabetes
C-reactive protein (indicative of inflammation)