Pathophysiology of atheroma

Question 1

What is athersclerosis

Answer 1

-Formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries

Question 2

What is an atheroma?

Answer 2

degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis.

Question 3

What is the serious consequence of atheroma?

Answer 3

Angia due to myocardial ischaemia

Question 4

What happens in arteriosclerosis?

Answer 4

-Age related change in muscular arteries
-Reduplication of internal elastic laminae and intimal fibrosis
Causing a decrease in vessel diameter

Question 5

What does arteriosclerosis contribute to?

Answer 5

cardiac
cerebral
colonic
and renal ischemia

Question 6

What is a fatty streak ?

Answer 6

Earliest significant lesion

Question 7

Who is effected by fatty streak?

Answer 7

Young children

Question 8

What does a fatty streak look like?

Answer 8

Yellow linear elevation of intimal lining

Question 9

What makes up a fatty streak?

Answer 9

lipid -laden macrophages

Question 10

Is there any clinical significance to the fatty streak?

Answer 10

NOPE

Question 11

Who is affected by early atheromatus plaque?

Answer 11

Young adults onwards

Question 12

What does an early atheromatous plaque look like?

Answer 12

Smooth yellow patches in intima

Question 13

What do fully developed atheromatus plaque look like?

Answer 13

Central lipid core with fibrous tissue cap covered by arterial endothelium

Question 14

What provides strength to atheroma when fully developed?

Answer 14

Collagens

Question 15

What type of cells can be found in fully developed atheroma and where?

Answer 15

Inflammatory cells- (macrophages, T-lymphocytes, mast cells) in fibrous cap

Question 16

What is the central core of a fully developed atheromatous plaque made from?

Answer 16

Lipids rich in cellular debris derived from macrophages

Question 17

What are the characteristics of an atheroma?

Answer 17

• Soft
• High thrombogenic
• often rim of foamy macrophages

Question 18

Why are macrophages described as foamy?

Answer 18

Uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor

Question 19

What makes an atheroma complicated?

Answer 19

Feature of established atheromatous plaque plus haemorrhage into plaque or fissuring or thrombosis

Question 20

What happens to haemorrhage when it heals?

Answer 20

Turns to calcification which shows up on angiograms and CT`s

Question 21

What is the most important risk factor of atheroma?

Answer 21

HYPERCHOLSTEROLAEMIA

Question 22

What happens in hypercholestrolaemia?

Answer 22

Genetically determined lack of LDL receptors

Question 23

Caucasians inherit this how?

Answer 23

heterozygously

Question 24

How many people have hypercholesterolaemia?

Answer 24

1/500

Question 25

What is corneal arcus?

Answer 25

white rim outside iris

Question 26

What is tendon xanthomata?

Answer 26

Lumps of fat on knuckles ,achilles

Question 27

What are some major risks factors of atheroma? (6)

Answer 27

- Smoker - Hypertensive - Diabetes mellitus - Male - Elderly - Accelerate process of plaque formation driven by lipids

Question 28

What is the two step process of developing atheromatous plaque?

Answer 28

1. Injury to endothelial of artery | 2. Chronic inflammatory and healing response of vascular wall to agent causing injury

Question 29

What is the sequence of developing atheromatous plaques?

Answer 29

- Endothelial injury - Accumulation of lipoproteins (LDL) - Monocyte adhesion-transform into foamy - Platelet adhesion - Factor release from activated platelets, macrophages--smooth muscle recruitment - Smooth muscle cell proliferation, extracellular matrix production and t-cell recruitment - Lipid accumulation (extracelluar and foamy)

Question 30

What is the possible causes of endothelial injury?

Answer 30

- Haemodynamic disturbances | - hypercholsterolaemia

Question 31

How does chronic hypercholesterolaemia damage endothelium

Answer 31

Increasing local production of reactive oxgyen species

Question 32

How does local hypercholesterolaemia release reactive oxygen species?

Answer 32

liporoteins aggregate in intima and are modified by free radicals produced by inflammatory cells. Modified LDL accumulated by macrophages but not completely degraded --foamy macrophages- toxic to endothelial cells plus release of growth factors, cytokines

Question 33

How do injured endothelial cells function differently?

Answer 33

- Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin) - High permeability for LDL - Increased thrombogenicity

Question 34

What is formed at denuded areas of plaque surface?

Answer 34

Microthrombi

Question 35

What happens 50-70% of vessel lumen is stenosed?

Answer 35

critical reduction of blood flow in distal arterial bed-> reversible tissue ischaemia

Question 36

What does a stenosed atheromatous coronary artery

Answer 36

Stable angia

Question 37

What happens with a ruptured atheromatous abdominal aortic aneursym suddenly ruptures?

Answer 37

Massive retroperitoneal haemorrhage

Question 38

What does a typical vunerable atheromatous plaques?

Answer 38

Typically thin fibrous cap, large lipid core, prominent inflammation

Question 39

What can prevent atheroma build up?

Answer 39

- Stop smoking - control blood pressure - Weight-loss - Regular exercise - Dietary modifications

Question 40

Secondary prevention?

Answer 40

Cholesterol lowering drugs, aspirin