Pathophysiology of Atheroma

Question 1

What is atheroma?

Answer 1

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

Question 2

What is arteriosclerosis?

Answer 2

Age related changes in muscular arteries - smooth muscle hypertrophy and apparent reduplication of the internal elastic laminae(not atheromatous)

Question 3

What is a fatty streak?

Answer 3

The earliest significant lesion which is comprised of masses of lipid laden macrophages

Question 4

When do early atheromatous plaques develop?

Answer 4

Early adulthood onwards

Question 5

What is the structure of a fully developed atheromatous plaque?

Answer 5

A central lipid core with a fibrous cap covered by arterial endothelium

Question 6

What type of cells reside in the fibrous cap of an atheromatous plaque?

Answer 6

Inflammatory cells such as macrophages, T-lymphocytes and mast cells

Question 7

What is the central lipid core of an atheromatous plaque made up of?

Answer 7

Cellular lipids and debris derived from macrophages

Question 8

Where do fully developed atheromatous plaques form?

Answer 8

At arterial branching points/bifurcations

Question 9

What features make an atheroma complicated?

Answer 9

Haemorrhage into the plaque (calcification), plaque rupture/fissuring and thrombosis

Question 10

What is the most important risk factor of atheroma?

Answer 10

Hypercholesterolaemia

Question 11

Why does high cholesterol levels increase the risk of atheroma?

Answer 11

It causes plaque formation and growth in the absence of other known risk factors

Question 12

What are the signs of major lipidaemia?

Answer 12

Biochemical evidence: LDL, HDL, total cholesterol and triglycerides, corneal arcus, tendon xanthomata, xanthelasmata and risk/family history of MI/atheroma

Question 13

Besides Hypercholesterolaemia, what are the risk factors for atheroma?

Answer 13

Smoking, hypertension, diabetes mellitus, male, elderly and an accelerate process of plaque formation driven by lipids

Question 14

What are the less strong risk factors?

Answer 14

Obesity, sedentary lifestyle, low socio-economic status and low birthweight

Question 15

What are the two steps in the development of atheromatous plaques?

Answer 15

Injury to the endothelial lining and chronic inflammation and healing of vascular wall to the agent causing the injury

Question 16

What role do monocytes play in the development of plaques?

Answer 16

They adhere to the endothelium and migrate into the intima where they transform into foamy macrophages

Question 17

What do the factors released from the platelets and macrophages in plaque formation do?

Answer 17

Recruit smooth muscle which results in smooth muscle cell proliferation

Question 18

What are the causes of endothelial injury?

Answer 18

Haemodynamic disturbances (turbulent flow) and hypercholesterolaemia

Question 19

What effect does injury to the endothelial cells have on their function?

Answer 19

Enhanced expression of cell adhesion molecules, high permeability for LDL and increased thrombogenecity

Question 20

What effect does stenosis of 50-75% have on the vessel lumen?

Answer 20

It causes critical reduction of blood flow in the distal arterial bed which causes reversible tissue ischaemia

Question 21

What are the major complications of atheroma?

Answer 21

Rupture of the plaque - leads to thrombotic occlusion, which if it causes total occlusion could lead to MI, stroke or lower limb gangrene.
Embolism of the distal arterial bed - can lead to small infarcts, life-threatening arrhythmias, cholesterol emboli in the kidneys and sin etc. or cerebral infarct/TIA
Abdominal aortic aneurysm - sudden rupture or emboli to the legs

Question 22

What are the features of vulnerable plaques?

Answer 22

Thin fibrous cap, large lipid core and prominent inflammation

Question 23

What are the non-pharmacological preventative and therapeutic approaches?

Answer 23

Smoking cessation, control of blood pressure, weight loss, regular exercise and dietary modifications

Question 24

What are the pharmacological approaches?

Answer 24

Cholesterol lowering drugs and aspirin (inhibits platelet aggregation)