Pathophysiology of atheroma

Question 1

What is atheroma ?

Answer 1

It is the formation of focal elevated lesions (plaques) in the intima of large and medium sized arteries

Question 2

what is arteriosclerosis?

Answer 2

• It is the thickening and hardening of the walls of arteries, typically in old age
• not atheromatous
• smooth muscle hypertrophy, apparent duplication of IEL, intimal fibrosis –> decrease vessel lumen diameter

Question 3

What are 3 main steps in atheroma formation?

Answer 3

-FATTY STREAK (earliest significant lesion)
yellow elevation in intima, made up of macrophages
(may disappear/may develop into atheromatous plaque)

-EARLY ATHEROMATOUS PLAQUE
smooth yellow patches in intima

-FULLY DEVELOPED ATHEROMATOUS PLAQUE
central lipid core surrounded by fibrous cap and covered by arterial endothelium
-central lipid core: macrophages/cellular lipids /debris derived from macrophages died through apoptosis/ often rim of foamy macrophages (through uptake of oxidised lipoproteins)
-fibrous cap: inflammatory cells (t-lymphocytes, mast cells) & collagen (produced by smooth muscle)

Question 4

where is the main place of atheroma formation?

Answer 4

arterial branching points / bifurcations

Question 5

what are the features of complicated atheroma?

Answer 5

atheromatous plaque plus:

• haemorrhage into plaque (calcification)
• plaque rupture & formation of clot around it, blocking artery lumen
• thrombosis

Question 6

what is vulnerable atheroma?

Answer 6

Typically have a thin fibrous cap, very large lipid core and prominent inflammation.
High risk of developing thrombotic complications

Question 7

what is the 2 step process of atheromatous plaque formation?

Answer 7

1. injury to endothelial lining of artery

2. chronic inflammatory and healing response of vascular wall

Question 8

what kind of exposure of the artery wall leads to atheromatous plaque formation?

Answer 8

chronic exposure to endothelial injury = endothelial dysfunction

Question 9

what is the pathogenesis of atheromatous plaque formation?

Answer 9

1. endothelial injury & dysfunction
2. accumulation of LDL in vessel wall
3. monocyte adhesion to endothelium –> migration into intima & transformation into foamy macrophages
4. platelet adhesion
5. growth factor release (PGDF) from activated platelets + macrophages –> smooth muscle cell recruitment
6. smooth muscle cell proliferation + ECM production + T cell recruitment
7. lipid accumulation (extracellular and in lipid core)

Question 10

what may plaque growth also be initiated by?

Answer 10

small areas of endothelial loss–> smooth muscle cell invasion + collagen deposition –> formation of micro thrombi

Question 11

what is the aetiology of plaque formation?

Answer 11

-hypercholesterolaemia- LDL (most important)

Question 12

what are signs of hyperlipidaemia?

Answer 12

• corneal arcus (white ring around iris)
• xanthelasmata (fat deposits around eye)
• Tendon axanthomata (swellings on knuckles/ achilles tendon)
• biochemical evidence (LDL, total cholesterol, triglycerides)

Question 13

What are some clinical manifestations of atheromatous plaque formation?

Answer 13

• progressive lumen narrowing due to plaque stenosis –> stable/unstable angina
• acute atherothrombotic occlusion –> MI
• embolization of distal arterial bed –> small infarcts in organs
• Ruptured atheromatous abdominal aortic aneurysm –> due to media beneath atheromatous plaques gradually weakened due to inflammatory activity –> dilation of vessel –> sudden rupture

Question 14

what are the main causes of atheromatous plaque formation once there is endothelial injury?

Answer 14

• haemodynamic disturbances (turbulent flow)

- hypercholesterolaemia