Pathology of Atherosclerosis

Question 1

How are plaques formed?

Answer 1

Endothelial damage causes lipid accumulation in intima. Lipids oxidized by inflammatory mediators. Smooth muscle cells migrate and proliferate. Oxidized LDL taken into macrophages (which migrate into lipid core via selectins and integrins) to create foam cells. Foam cells also oxidize LDL which creates a vicious cycle.

Question 2

Earliest recognizable form of atherosclerosis?

Answer 2

Fatty streak – layer of intimal foam cells.

Question 3

Steps of plaque progression

Answer 3

Inflammation, neovascularization, intra-plaque hemorrhage.

These things cause lipid core expansion, oxidative stress, and apoptosis

Question 4

How does plaque inflammation occur?

Answer 4

Disrupted endothelium allows for migration of inflammatory cells that can move deeper to the tunica media. This can disrupt the internal elastic lamina.

Question 5

How does neovascularization contribute to plaque rupture

Answer 5

Atherosclerosis causes need for increased vascularization because diffusion barrier increased. Vasa vasorum grow but are thin and weak. They are easily breakable.

Question 6

What are the effects of intra-plaque hemorrhage?

Answer 6

Increases oxidative stress due to free hemoglobin. Lipid core expansion, so plaque size increases.

Question 7

AHA Classes I-VI

Answer 7

I: Isolated foam cells, intimal thickening (initial)
II: Conglomeration of foam cells to form fatty streak
III: Type II changes and small extracellular lipid pools (Intermediate)
IV: Fibrous cap and lipid core (atheroma)
V: Lipid core/calcium/fibrous tissue present (fibroatheroma)
VI: Surface defect – ruptured plaque (complicated lesion)

Question 8

Three types of unstable plaques

Answer 8

Ruptured, erosion thrombi which don’t communicate with lipid core like ruptured do, calcific nodule through thin fibrous cap.

Question 9

Secondary atherosclerosis in vein grafts

Answer 9

Histology differs, concentric lesions that are 90%-100% occlusive. Don’t have fibrous cap, don’t have inflammatory cellular infiltrates. Probably due to surgical injury.

Question 10

Loeys-Dietz Syndrome

Answer 10

Mutations in TGF B, so abnormal collagen and elastin. Can cause aortic aneurysm.

Question 11

Nutritional deficiency that causes aortic aneurysm

Answer 11

Vitamin C deficiency

Question 12

Microscopic changes with aortic aneurysm

Answer 12

Intima is thick and fibrotic, media is thin.

Question 13

Cystic medial degenration

Answer 13

Pathognomonic for marfans syndrome. Get fragmented elastic fibers.