Pathophysiology of atheroma 2

Question 1

What two step process is involved in the development of atheromatous plaques?

Answer 1

• Injury to endothelial lining of artery
• Chronic inflammatory and healing response of vascular wall to agent causing injury

Chronic/episodic exposure of arterial wall to these processes cause the formation of atheromatous plaques

Question 2

What are the first 3 in the order of events for pathogenesis of atherosclerosis?

Answer 2

• Endothelial injury and dysfunction
• Accumulation of LDL in vessel wall
• Monocyte adhesion to endothelium - they migrate into intima and transform to foamy macrophages

Question 3

What are the last 3 in the order of events for pathogenesis of atherosclerosis?

Answer 3

• Platelet Adhesion
• Factor release from activated platelets, macrophages - smooth muscle cell recruitment
• Smooth muscle cell proliferation, extracellular matrix production and T-cell recruitment
• Lipid accumulation (extracellular and in foamy macrophages).

Question 4

What are the most important causes of endothelial injury?

Answer 4

• Haemodynamic disturbances (turbulent flow)
• Hypercholesterolaemia

Question 5

How can chronic hypercholesterolaemia directly impair endothelial cell function?

Answer 5

By increasing local production of reactive oxygen species

Question 6

What can injured endothelial cells functionally alter?

Answer 6

• Enhanced expression of cell adhesion
• High permeability for LDL
• Increased thrombogenicity
• Inflammatory cells, lipids - intimal layer - plaques

Question 7

What can advanced plaque formation cause?

Answer 7

• Large numbers macrophages, T-lymphocytes
• Lipid-laden macrophages die through apoptosis - lipid into lipid core

Question 8

How does advanced plaque formation affect response to injury?

Answer 8

It causes a chronic inflammatory process

• Inflammatory process
• Alters process of tissue repair

Question 9

How does advanced plaque formation affect growth factors?

Answer 9

• Stimulation of proliferation of smooth muscle cells
• It affects subsequent synthesis collagen
• Causes elastin degradation
• Alterations in Mucopolysaccharide deposition

Question 10

What can plaque growth be initiated by?

Answer 10

Small areas of endothelial cells

Question 11

What can advanced plaque formation affect?

Answer 11

Secretion of growth factors by cells such as platelets, injured endothelium, macrophages and smooth muscle cells

Question 12

How does advanced plaque formation affect microthrombi formed at denuded areas of plaque surface?

Answer 12

• Increase in thrombus formation
• Altered repair process such as smooth muscle cell invasion and collagen deposition

Question 13

What are the consequences of atheroma clinical manifestations?

Answer 13

• Progressive lumen narrowing due to high grade plaque stenosis
• Acute atherothrombotic occlusion
• Embolization of the distal arterial bed
• Ruptured atheromatous abdominal aortic aneurysm

Question 14

What is progressive lumen narrowing due to high grade plaque stenosis?

Answer 14

Stenosis of > 50-75% of vessel lumen which leads to a critical reduction of blood flow in distal arterial bed, then causing reversible tissue ischaemia

E.g stenosed atheromatous coronary artery which leads to stable angina

Question 15

What can very severe stenosis cause?

Answer 15

• Ischaemic pain at rest (very unstable angina)
• Severe stenosis in arteries such as ilea, femoral, popliteal arteries can lead to intermittent claudication (peripheral arterial disease

Question 16

What can longstanding tissue ischaemia cause?

Answer 16

-Atrophy of affected organ eg atherosclerotic renal artery stenosis can lead to renal atrophy

Question 17

What is acute atherothrombotic occlusion?

Answer 17

Rupture of plaque which is an acute event

• This rupture exposes highly thrombogenic plaque contents (collagen, lipid, debris) to blood stream leading to activation of coagulation cascade and thrombotic occlusion in very short time

Question 18

What does total occlusion cause?

Answer 18

Irreversible ischaemia which leads to necrosis (infarction of tissues)

Question 19

What are some arteries can acute atherothrombotic occlusion affect?

Answer 19

• Coronary artery which can lead to myocardial infarct
• Carotid and cerebral artery which can lead to stroke
• Ileal, femoral and popliteal artery which can lead to lower limb gangrene.

Question 20

What is embolization of the distal arterial bed?

Answer 20

Detachment of small thrombus fragments from thrombosed atheromatous arteries can lead to embolization distal to ruptured plaque

Embolic occlusion of small vessels lead to small infarcts in organ.

Question 21

What can embolization of the distal arterial bed lead to?

Answer 21

• In the heart, it can cause dangerous small foci of necrosis which can lead to life-threatening arrhythmias
• It can lead to large ulcerating aortic plaques, lipid rich fragments of plaque
• It can lead to cholesterol emboli in kidney, leg, skin
• It can lead to carotid artery atheromatous debris which is a common cause of stroke.

Question 22

What is ruptured atheromatous abdominal aortic aneurysm?

Answer 22

• Media beneath atheromatous plaques gradually weakened (lipid-related inflammatory activity in plaque)
• It is a gradual dilation of vessel
• It is slow but progressive, seen in elderly, often asymptomatic.

Question 23

What can a sudden rupture cause?

Answer 23

Massive retroperitoneal haemorrhage which has a high mortality

Question 24

What can ruptured atheromatous abdominal aortic aneurysm lead to?

Answer 24

• Aneurysms > 5cm diameter at high risk of rupture
• Mural thrombus causing emboli to legs.

Question 25

What are vulnerable atheromatous plaques?

Answer 25

-Ones that rupture with subsequent thrombosis and they have distinct morphological features

• Recognition of these plaques means a high risk of developing thrombotic complications

Question 26

What can vulnerable atheromatous plaques cause?

Answer 26

• Pronounced inflammatory activities such as degradation and weakening of plaque which increases risk of plaque rupture
• Increased secretion of proteolytic enzymes, cytokines and reactive oxygen species by plaque inflammatory cells
• Highly stenotic plaques often large fibrocalcific component, little inflammation.

Question 27

How to identify vulnerable atheromatous plaques?

Answer 27

• Typically thin fibrous cap
• Large lipid core
• Prominent inflammation

Question 28

What are some preventative and therapeutic approaches?

Answer 28

• Stop smoking
• Control blood pressure
• Weight loss
• Regular exercise
• Dietary modifications

Question 29

What are the secondary preventions?

Answer 29

• Cholesterol lowering drugs such as aspirin
• Surgical options

Question 30

Why can aspirin be used in atheroma?

Answer 30

It inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques