Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

The formation of focal elevated lesions (plaques) in the intima of medium and large arteries.

Question 2

How can atherosclerosis cause ischaemia?

Answer 2

Atheromatous plaques narrow the lumen of coronary arteries.
Angina is a complication of atherosclerosis, due to myocardial ischaemia.

Question 3

What is arteriosclerosis?

Answer 3

No atheromatous.
An age-related change in muscular arteries, leading to a decrease in vessel diameter.
Smooth muscle hypertrophy, apparent reduplication of internal elastic laminae, and intimal fibrosis can occur.

Question 4

What does arteriosclerosis cause?

Answer 4

Contributes to cardiac, cerebral, colonic, and renal ischaemia in the elderly.
Clinical effects are most apparent when the CVS is stressed by haemorrhage, major surgery, infection, or shock.

Question 5

What is the earliest significant lesion in atherosclerosis?

Answer 5

The earliest significant lesion, often found in young children, is a fatty streak.
A yellow linear elevation of intimal lining, made of masses of lipid-laden macrophages.
No clinical significance; may disappear.
Will form a plaque in patients at risk.

Question 6

What are early atheromatous plaques?

Answer 6

Can be seen in young adults and onwards.
Smooth yellow patches in the intima.
Lipid-laden macrophages.
Progresses to established plaques.

Question 7

What is a fully developed atheromatous plaque composed of?

Answer 7

A central lipid core - rich in cellular lipids and debris, derived from macrophages that have died in plaque.
A fibrous tissue cap, covered by arterial endothelium.

Question 8

What is the histology of a plaque?

Answer 8

Collagens (produced by smooth muscle cells) in the cap - structural strength.
Inflammatory cells (macrophages, T Cells, mast cells) - in the cap.
Soft and highly thrombogenic.
Often has a rim of ‘foamy’ (due to uptake of oxidised lipoproteins) macrophages.

Question 9

What can occur late in plaque development?

Answer 9

Extensive dystrophic calcification.
May be a marker for atherosclerosis in angiograms or CT.
Forms at arterial bifurcations (turbulent flow).
Late-stage plaques can be confluent and cover large areas.

Question 10

What are the features of complicated atheroma?

Answer 10

Calcification (haemorrhage in plaque).
Plaque rupture or fissuring.
Thrombosis.
Usually leads to clinical consequences.

Question 11

What is the aetiology of atherosclerosis?

Answer 11

Hypercholesterolaemia - the most important risk factor. Causes plaque formation and growth, in the absence of other known risk factors.
High LDL cholesterol.

Question 12

What are the signs of major hyperlipidaemia?

Answer 12

Familial (primary).
Acquired (secondary).
Biochemical evidence (LDL, HDL, total cholesterol, TAGs).
Corneal arcus (premature).
Tendon xanthomata (knuckles, Achilles).
Xanthelasmata.
Family history of MI or atheroma.

Question 13

What are the risk factors of atherosclerosis?

Answer 13

Smoking.
Hypertension.
Diabetes mellitus.
Male.
Elderly.

Question 14

How does plaque develop?

Answer 14

The endothelial artery lining gets injured.
Chronic inflammation and healing of the vascular wall occurs in response.
Chronic or episodic exposure of the arterial wall to these processes forms plaques.

Question 15

What accumulates on damaged endothelial cells in the formation of atherosclerosis?

Answer 15

Damaged endothelial accumulate LDL and monocytes (transforms into ‘foamy’ macrophages).
Platelets adhere to the endothelium.

Question 16

What is the pathogenesis of atherosclerosis, once platelets and macrophages are activated?

Answer 16

Tissue factors are released from activated platelets and macrophages.
Smooth muscle cells proliferate; ECM is produced; and T Cells are recruited.
Lipid accumulates in the ECM and macrophages.

Question 17

How are injured endothelial cells functionally altered?

Answer 17

Enhanced expression of cell adhesion molecules.
High permeability for LDL.
Increased thrombogenicity.
This allows inflammatory cells and lipids to get into the intimal layer and form plaques.

Question 18

What occurs in advanced plaque formation?

Answer 18

Lipid-laden macrophages die through apoptosis, releasing lipids into the core.
Growth factors cause smooth muscle cell proliferation and the synthesis of collagen, elastin, and mucopolysaccharides.
The fibrous cap encloses the lipid core.

Question 19

What occurs in established plaques?

Answer 19

Microthrombi form at denuded areas of the plaque surface (organised by smooth muscle cell invasion and collagen deposition).
Repeated cycles increase plaque volume.

Question 20

What is the management and treatment of atherosclerosis?

Answer 20

Smoking cessation.
Controlling BP.
Weight loss, exercise, dietary modification.
Cholesterol-lowering drugs.
Aspirin - inhibits platelet aggregation to decrease thrombosis risk on plaques.
Surgical options.

Question 21

How can atherosclerosis cause progressive lumen narrowing?

Answer 21

Reduces blood flow in distal arterial beds.
Long-standing tissue ischaemia causes atrophy of the affected organ.

Question 22

What are the clinical causes of progressive lumen narrowing?

Answer 22

Stenosed coronary artery - stable angina.
Severe stenosis - ischaemic pain at rest, unstable angina.
Ileal, femoral, or popliteal artery stenosis.
Intermittent claudication - peripheral arterial disease (calf pain on walking).

Question 23

How can atherosclerosis cause acute atherothrombotic occlusion?

Answer 23

An acute event causes plaque rupture and exposes highly thrombogenic plaque contents (collagen, lipid, debris) to the bloodstream.
The clotting cascade is activated and thrombotic occlusion occurs.

Question 24

What are the effects of total occlusion?

Answer 24

Irreversible ischaemia and necrosis (infarction) of tissues.
Coronary artery - MI.
Carotid or cerebral artery - stroke.
Ileal, femoral or popliteal artery - lower limb gangrene.

Question 25

How can atherosclerosis cause embolisation of the distal arterial bed?

Answer 25

Detachment of small thrombus fragments from thrombosed atheromatous arteries embolise distal to ruptured plaque.
Embolic occlusion of small vessels causes small infarcts in organs.

Question 26

What are examples of embolic occlusion of small vessels?

Answer 26

Small foci of necrosis in the heart - life- threatening arrhythmias.
Large ulcerating aortic plaques, or lipid rich fragments of plaque - cholesterol emboli in kidney/leg/skin.
Carotid artery atheromatous debris - stroke or cerebral infarct.

Question 27

How can atherosclerosis cause a ruptured abdominal aortic aneurysm?

Answer 27

The media beneath atheromatous plaques gradually weakens (lipid-related inflammatory activity in the plaque).
Causes gradual dilatation of the vessel.
Slow but progressive, seen in the elderly, often asymptomatic.

Question 28

What can sudden ruptures of plaques cause?

Answer 28

Massive retroperitoneal haemorrhage (high mortality).
Aneurysms >5cm in diameter - high risk of rupture.

Question 29

What are distinct features of inflammation in vulnerable plaques?

Answer 29

Degradation and weakening of plaque, increasing risk of rupture.
Secretion of enzymes, cytokines and ROSs by plaque inflammatory cells.

Question 30

What are the features of highly stenotic plaques?

Answer 30

Large fibrocalcific components.
Little inflammation.