Pathophysiology of atheroma

Question 1

Define atheroma.

Answer 1

Formation of plaques in the intima of large and medium sized arteries.

Question 2

What are the dangers of atheroma?

Answer 2

Atheromatous plaques narrow the lumen which can cause ischaemia. Can have serious consequences –> myocardial ischaemia.

Question 3

What is the difference between ischaemia and infarction?

Answer 3

Ischaemia is a reduced blood supply which can cause pain like angina, infarction is the end point of ischaemia when the tissue dies.

Question 4

What is atherosclerosis?

Answer 4

A disease of muscular arteries. Smooth muscle hypertrophy, reduplication of internal elastic laminae, intimal fibrosis and lessened vessel diameter.

Question 5

Describe the stages in development of an atheromatous plaque.

Answer 5

Fatty streak –> early atheromatous plaque –> fully developed atheromatous plaque.

Fatty streak: earliest significant lesion; can be present in children; yellow elevation of intimal lining comprising lipid-laden macrophages.

Early atheromatous plaque: young adults onwards; smooth, yellow patches in intima filled with lipid-laden macrophages; progress to established plaques.

Fully developed atheromatous plaque: central lipid core with a fibrous cap, covered by arterial endothelium; filled with collagen (strength), inflammatory cells and central lipid core (dead macrophages); soft and highly thrombogenic; form at arterial branching points (turbulent flow).

Question 6

What is a complicated atheroma?

Answer 6

An atheroma that brings clinical consequences - plaque rupture and thrombosis.

Question 7

What is the most important risk factor for atheroma?

Answer 7

Hypercholesterolaemia. Familial type caused by mutations in the LDL receptor.

Question 8

What should the normal cholesterol level be in the blood?

Answer 8

5ml or less.

Question 9

What are the clinical signs of major hyperlipidaemia?

Answer 9

Family history; biochemical evidence (raised cholesterol counts);corneal arcus (discolouration around the eyes); tendon xanthomata; xanthelasmata (yellow patches on inner eyelid).

Question 10

Name some strong risk factors for atheroma.

Answer 10

Smoking, HT, DM, male and elderly.

Question 11

How do atheromatous plaques develop?

Answer 11

1) Injury to endothelial lining of an artery.
2) Chronic inflammatory and healing response in vascular wall to agent, causing injury.

–> formation of atheromatous plaques.

Question 12

Describe the pathogenesis of atherosclerosis.

Answer 12

There is endothelial injury and then accumulation of LDL in vessel wall. Monocytes adhere to the endothelium, migrate to intima and transform into foamy macrophages. Platelet adhesion. Factors released from activated platelets and macrophages cause smooth muscle cell recruitment. Smooth muscle cell proliferation, ECM production and T-cell recruitment –> lipid accumulation.

Question 13

What are the most important causes of endothelial injury?

Answer 13

Haemodynamic disturbances (turbulent flow); and hypercholesterolaemia (> local production of ROS, lipoproteins aggregate in intima and are modified by free radicals from inflammatory cells; modified LDL accumulates in macrophages but is not completely degraded - injured endothelial cells).

Question 14

Once injured, what are the functional alterations of endothelial cells?

Answer 14

• > expression of adhesion molecules
• > permeability for LDL
• > thrombogenicity

Question 15

Describe advanced plaque formation.

Answer 15

Lots of T cells and macrophages –> these die via apoptosis and lipid goes to lipid core. Tissue repair occurs as a response and this creates a fibrous cap (smooth muscle cells, collages, elastin and mucopolysaccharide).

Question 16

Describe progressive lumen narrowing.

Answer 16

Stenosis of over 50-75% of lumen causes a critical reduction in blood flow –> reversible tissue ischaemia eg. stable angina. Very severe stenosis causes ischaemic pain at rest which is unstable angina. If this happens in the ileal, femoral or popliteal arteries –> intermittent claudication. Longstanding tissue ischaemia can cause atrophy of the affected organ –> renal atrophy.

Question 17

What is an acute atherothrombotic occusion?

Answer 17

Rupture of plaque –> an acute event. Thrombogenic plaque contents exposed to blood stream which activates coagulation cascade and thrombotic occlusion occurs. Total occlusion causes irreversible ischaemia and infarction of tissues. Eg. MI, stroke or lower limb gangrene.

Question 18

What is embolisation?

Answer 18

When a small thrombus fragment detaches from main clot and gets stuck in a vessel. This can cause small infarcts in organs. This is a common cause of stroke and life threatening arrythmias in the heart.

Question 19

What is a mural thrombus?

Answer 19

When emboli travel to legs from AAA. In an AAA, media between the atheromatous plaque is gradually weakened which causes gradual dilation of the vessel.

Question 20

Which atheromatous plaques are vulnerable?

Answer 20

Atheromatous plaques that rupture with subsequent thrombosis. Typically have a thin fibrous cap, prominent inflammation and a large lipid core.

Question 21

What are the preventative measures?

Answer 21

Stop smoking, control BP, lose weight, exercise regularly and modify exercise.

Question 22

Describe secondary prevention.

Answer 22

Cholesterol lowering drugs and aspirin (inhibits platelet aggregation).