Atherosclerosis

Question 1

What is atherosclerosis

Answer 1

hardening of the arteries (usually affecting medium-large arteries)

Question 2

Describe an atheroma

Answer 2

(fibro-fatty plaque)
intimal fibrous cap
with a central core rich in lipids

Question 3

Risk factors for atherosclerosis

Answer 3

age
sex
genetics
hypertension
diabetes mellitus 
hyperlipidaemia 
smoking

Question 4

3 Acute complications of destabilised atheroma

Answer 4

plaque rupture/ulceration
plaque haemorrhage
thrombosis (+/- emboli)

also calcification
aneurysmal dilatation

Question 5

Describe the pathogenesis of atherosclerosis

Answer 5

1. Chronic endothelial injury caused by: haemodynamic disturbance, hypercholesterolaemia, hypertension, smoking, toxins, viruses, immune reactions.
2. Endothelial dysfunction:
   - increased permeability
   - increased leukocyte adhesion (VCAM1, ICAM1, P-selectin, E-selectin)
   - increased monocyte adhesion and migration (from lumen into tunica intima where they become macrophages)
   - LDLs also migrate lumen –> intima
3. Smooth muscle emigration from media to intima and macrophage activation. (creates fatty streak.
4. macrophages engulf oxidised LDL and become FOAM cells. Secrete LI1, TNF, MCP1, growth factors. Smooth muscle also engulfs lipid.
5. Smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid (fatty streak –> mature fibro-fatty atheroma)

Question 6

What causes oxidation of LDL?

Answer 6

hyperlipidemia impairs endothelial function and accumulates within intima which causes oxidative modification of LDL

Question 7

oxidation of LDL allows what?

Answer 7

ingestion by macrophages via scavenger receptors => FOAM cells

Question 8

When macrophages become foam cells, what do they secrete

Answer 8

IL1
TNF (tumour necrosis factor)
MCP1 (monocyte chemotactic protein 1)
growth factors (PDGR, FGF, TNF)
Interferon alpha, TGF beta

Question 9

What causes conversation of fatty streak into mature fibro-fatty atheroma?

Answer 9

when smooth muscles proliferatie
collagen and other ECM deposition occurs
extracellular lipid accumulation

Question 10

Where does atherosclerosis most likely occur?

Answer 10

at bifurcations

1. abdominal aorta
2. coronary arteries
3. popliteal arteries
4. descending thoracic aorta
5. internal carotid arteries
6. vessels of circle of Willis

Question 11

Primary prevention of atherosclerosis

Answer 11

stop smoking 
control HT
weight reduction 
lowering total LDL
reduce calorie intake

Question 12

secondary prevention

Answer 12

prevent complications
anti platelet drugs in thrombosis
lower blood lipid levels

Question 13

Histologically, where would you see cholesterol crystals

Answer 13

in the tunica intima (might also see foam cells)