Thrombus, Embolus, & Atherosclerosis

Question 1

Thrombosis

Answer 1

• the pathologic formation of a blood clot (vs. physiologic)

Question 2

How can we distinguish a Thrombus from a post-mortem clot?

Answer 2

• via lines of Zahn (alternating lines of RBCs and fibrin)

- via attachment to vessel wall

Question 3

Give an example of a genetic cause of hypercoagulability.

Answer 3

• mutations in Factor V Leiden prevent its inactivation from Protein S and Protein C, leading to a hypercoagulable state

Question 4

Protein C and Protein S

Answer 4

• inactivate Factor V and Factor VIII, preventing thrombus formation
• vitamin K dependent; inactivated by warfarin –> there is actually an initial INCREASE in risk of thrombosis as a result, which is why we give heparin at this time

Question 5

What are the different types of emboli?

Answer 5

• F.A.T. B.A.T.

- fat, amniotic fluid, thrombus, bacteria, air, tumor

Question 6

What is an atheromatous plaque made up of?

Answer 6

• a necrotic lipid (cholesterol) core with a fibromuscular cap

Question 7

What happens when an atheromatous plaque ruptures?

Answer 7

• the necrotic contents of the lipid core are exposed, resulting in coagulation –> thrombosis –> partial/total occlusion

Question 8

Why does atherosclerosis weaken the affected vessel wall?

Answer 8

• because the plaque prevents blood from supplying the deeper parts of the vessel (the media and adventitia), resulting in weakening

Question 9

What are the three major hypotheses for atheroma formation?

Answer 9

• endothelial injury, oxidative modification of lipids, and a response to retention (lipoproteins retained in the subendothelial space trigger a reaction)

Question 10

Foam Cell

Answer 10

• a macrophage that has phagocytosed a modified (oxidized) lipid/LDL

Question 11

Pathogenesis of Atherosclerosis

Answer 11

• endothelial injury –> increased blood flow and permeability –> accumulation of lipoproteins and macrophages –> lipids get oxidized –> oxidized lipids get taken up by macrophages –> foam cells and fatty streak –> proliferation of smooth muscle and ECM production –> atherosclerotic genesis

Question 12

The ECM proliferation during atherosclerosis stabilizes the plaques, so how do these end up potentially rupturing?

Answer 12

• the inflammation causes macrophages to secrete MMPs (matrix metalloproteinases), which breakdown the ECM
• creates unstable plaques that are prone to rupture