Atherogenesis

Question 1

What is the definition of atherogenesis? [2]

Answer 1

the process of forming plaques / in the intima layer of arteries

Question 2

What is the definition of atherosclerosis? [2]

Answer 2

a disease characterised by the formation of atherosclerotic plaques / in the intima of arteries

Question 3

What is the definition of atherothrombosis? [2]

Answer 3

1. characterised by atherosclerotic lesion disruption with thrombus formation
2. the major cause of acute coronary syndrome (ACS) and cardiovascular death

Question 4

What are some complications of atherosclerosis/atherothrombosis? [8]

Answer 4

1. ischaemic damage to organs
2. cerebral infarction
3. myocardial infarction
4. strokes
5. transient ischaemic attacks
6. aortic aneurysm
7. peripheral vascular disease
8. gangrene

Question 5

What are the risk factors of atherosclerosis? [8]

Answer 5

1. increasing age - weaker arterial walls and more time to form plaques
2. smoking - damages endothelial cells
3. hypercholesterolaemia - most important risk factor; lipids damage endothelial cells
4. obesity - more pericardial fat and increase in inflammation
5. diabetes - hyperglycaemia damages endothelium
6. hypertension - added pressure on arterial walls
7. family history
8. male gender - oestrogen is protective?

Question 6

What are the preventative measures to stop atherosclerosis? [5]

Answer 6

1. smoking cessation
2. control of blood pressure - betablockers i.e. ramipril
3. statins to reduce cholesterol
4. low dose aspirin - inhibits the aggregation of platelets
5. weight reduction

Question 7

What is the distribution of atherosclerosis plaques? [3]

Answer 7

1. found within peripheral and coronary arteries
2. focal distribution along the artery length
3. tend to form at arterial branching points and bifurcations

Question 8

What is the composition of plaque? [4]

Answer 8

1. a complex lesion consisting of -
2. central lipid core
3. connective tissue - produced by smooth muscle cells provide structural strength
4. fibrous cap - inflammatory cells reside in fibrous cap

Question 9

How is plaque formed? [4]

Answer 9

1. initiated by injury to endothelial cells which leads to endothelial dysfunction
2. endothelial cells undergo functional alterations and have increased proinflammatory and thrombogenicity
3. chemoattractants released from the site of injury attract leukocytes
4. they accumulate and migrate into the vessel wall

Question 10

What inflammatory cytokines are found in plaques? [3]

Answer 10

1. IL-1
2. IL-6
3. IFN-gamma

Question 11

What are fatty streaks? [3]

Answer 11

1. the earliest significant lesions is called a fatty streak
2. which are composed of lipid-laden macrophages (foam cells) and T lymphocytes within the intimal layer of the artery
3. appears at very early age (<10)

Question 12

What are intermediate lesions? [4]

Answer 12

composed of layers of -

1. lipid-laden macrophages (foam cells)
2. vascular smooth muscle cells
3. T lymphocytes
4. there is adhesion and aggregation of platelets to the vessel wall

Question 13

What are fibrous plaques/advanced lesions? [5]

Answer 13

1. stenosis of arteries and impede blood flow
2. are prone to rupture
3. growth factors (e.g. PDGF) stimulate the proliferation of smooth muscle cells and synthesis of collagen and elastin to form dense fibrous cap which encloses lipid-rich core
4. haemorrhage within the plaque allows for plaque growth
5. dystrophic calcification occurs in the late development of the plaque

Question 14

What is plaque rupture? [4]

Answer 14

1. the plaque is constantly growing and receding
2. the fibrous cap needs to be resorbed and redeposited, so if balance shifts in favour of inflammatory conditions, the fibrous cap will weaken and the plaque ruptures
3. basement membrane, collagen and necrotic tissue exposed to platelets, leading to thrombus formation and subsequent vessel occlusion
4. leads to irreversible ischaemia and infarction of tissue

Question 15

How can coronary artery disease be treated? [3]

Answer 15

1. percutaneous coronary intervention (PCI) - angioplasty (stent implantation)
2. limitations - restenosis following PCI, however drug-eluting stents have decreased stenosis
3. drugs - aspirin, clopidogrel/ticagrelor, statins

Question 16

What are the clinical manifestations of atherosclerosis? [4]

Answer 16

1. progressive lumen narrowing due to plaque stenosis
2. acute atherothrombotic occlusion
3. embolisation of distal arterial bed
4. ruptured abdominal aneurysm

Question 17

What is the cause/consequence of progressive lumen narrowing? [2]

Answer 17

1. stenosis of more than 50-70% of the vessel lumen leads to a critical reduction of blood flow in the distal arterial
2. reversible tissue ischaemia develops, especially during activity (angina) but in severe ischaemic pain even at rest

Question 18

What is the cause/consequence of acute atherothrombotic occlusion? [3]

Answer 18

1. plaque rupture exposes highly thrombogenic plaque components to blood stream
2. leading to activation of the coagulation cascade by platelets and thrombotic occlusion of the vessel lumen
3. total occlusion leads to irreversible ischaemia and infarction of tissues supplied by the obstructed artery

Question 19

What is the cause/consequence of embolisation of the distal arterial bed? [2]

Answer 19

1. atherothrombosis may also result in the formation of emboli, which will embolise the distal arterial bed
2. embolic occlusion of small vessels may cause small infarctions

Question 20

What is the cause/consequence of abdominal aneurysm? [1]

Answer 20

1. rupture of a weakened dilated abdominal aneurysm causes retroperitoneal haemorrhage and death