The nature and pathogenesis of atheroma

Question 1

Define atherosclerosis

Answer 1

Formation of focal elevated lesions in the intimal of large and medium-sized arteries

Question 2

Define atherothrombosis

Answer 2

When an occlusive thrombosis forms on a spontaneously disrupted plaque

Question 3

How has the frequency of atherothrombosis changed over the years

Answer 3

Become more frequent in recent years

Question 4

In which societies do atherosclerotic lesions form in

Answer 4

Those who have a high dietary fat intake

Question 5

What is the earliest significant lesion that results in an atherosclerotic lesions

Answer 5

A fatty streak

Question 6

Where is the fatty streak

Answer 6

A yellow elevation of the intimal lining made of macrophages

Question 7

Do fatty streaks have an impact on health

Answer 7

No

Question 8

What two things can happen following the formation of a fatty streak

Answer 8

1. Disappear from arterial intimal

2. Progression to atherosclerotic plaque

Question 9

Describe the structure of an atherosclerotic lesion

Answer 9

Lesion with central lipid core

Cap of fibrous tissue covered by arterial endothelium

Question 10

Role of collagen in the cap of fibrous tissue of an atherosclerotic lesion

Answer 10

Provides structural strength of th plaque

Question 11

What produces the connective tissue in the cap of the fibrous tissue of an atherosclerotic lesion

Answer 11

Smooth muscle cells

Question 12

What cells reside in the fibrous cap of an atherosclerotic lesion

Answer 12

1. Macrophages
2. T cells
3. Mast cells

Question 13

What cells border atherosclerotic lesions

Answer 13

foam cells

Question 14

What type of cell are foam cells

Answer 14

Macrophages that have phagocytose oxidised lipoproteins

Question 15

When does dystrophic calcification of the plaque occur

Answer 15

Late in the process of plaque development

Question 16

What is dystrophic calcification

Answer 16

Calcification in necrotic tissue

Question 17

What can dystrophic calcification show us clinically

Answer 17

A marker for an atherosclerotic vessel

Question 18

Where do plaques have a tendency to form at

Answer 18

bifurcations

Question 19

What is the most important risk factor which can result in atherosclerosis

Answer 19

Hypercholesterolaemia

Question 20

Why is hypercholesterolaemia the most important risk factor for atherosclerosis

Answer 20

It causes plaque formation and growth

Question 21

What are other factors other than hypercholesterolaemia that can cause atherosclerotic lesions

Answer 21

1. Obesity
2. Sedentary life
3. Low socio-economic status
4. Low birth weight

Question 22

How do bacteria such as chlamydia pneumonia increase risk of atherosclerosis

Answer 22

By switching on evolutionary conserved pathways of inflammation

Question 23

How do high-fat diets contribute to atherosclerosis

Answer 23

Promote translocation of commensal-derived endotoxin from the gut into the general circulation = inflammation

Question 24

How do lesions develop

Answer 24

1. Damage to endothelium of arterial wall
2. Injured endothelial cells have enhanced expression of cell adhesion molecules + high permeability for LDL + increased thrombogenicity
3. This allows inflammatory cells and lipids to enter intimal layer and form plaques
4. Large amounts of macrophages and T cells accumulate in the plaque tissues
5. Foam cells die via apoptosis
6. Foam cells spill lipid into lipid core- chronic inflammation
7. Growth factor PDGF stimulate tissue repair

Question 25

Role of PDGF

Answer 25

1. Synthesis of collagen, elastin and mucopolysaccharide by smooth muscle cells
2. Proliferation of smooth muscle cells

Question 26

What cell secretes PDGF

Answer 26

Platelets, injured endothelium, macrophages and smooth muscle cells

Question 27

Three clinical manifestations of atherosclerosis

Answer 27

1. Progressive lumen narrowing due to high-grade plaque stenosis
2. Acute atherothrombotic occlusion
3. Embolisation of the distal arterial bed

Question 28

What is the consequence of progressive lumen narrowing due to high-grade plaque stenosis

Answer 28

1. Stenosis leads to reduction of blood flow in distal arterial bed
2. Reversible tissue ischaemia develops
3. Ischaemic pain occurs when stenosis is severe

Question 29

What happens during an acute atherothrombotic occlusion

Answer 29

Plaque rupture exposes highly thrombogenic plaque components to the blood stream
Activates coagulation cascade and thrombotic occlusion of the vessel lumen

Question 30

What is the consequence of total atherthrombotic occlusion

Answer 30

Irreversible ischaemia causing necrosis of tissues supplied by obstructed artery

Question 31

What is the embolisation of the distal arterial bed

Answer 31

Where detachment of small thrombus fragments attach to the arterial bed distal to the plaque rupture

Question 32

How does hyperlipothemia effect endothelial cells

Answer 32

Damages them