The nature and pathogenesis of atheroma Flashcards

1
Q

Define atherosclerosis

A

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

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2
Q

Define atherothrombosis

A

When an occlusive thrombosis forms on a spontaneously disrupted plaque

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3
Q

How has the frequency of atherothrombosis changed over the years

A

Become more frequent in recent years

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4
Q

In which societies do atherosclerotic lesions form in

A

Those who have a high dietary fat intake

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5
Q

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

A

A fatty streak

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6
Q

Where is the fatty streak

A

A yellow elevation of the intimal lining made of macrophages

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7
Q

Do fatty streaks have an impact on health

A

No

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8
Q

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

A
  1. Disappear from arterial intimal

2. Progression to atherosclerotic plaque

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9
Q

Describe the structure of an atherosclerotic lesion

A

Lesion with central lipid core

Cap of fibrous tissue covered by arterial endothelium

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10
Q

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

A

Provides structural strength of th plaque

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11
Q

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

A

Smooth muscle cells

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12
Q

What cells reside in the fibrous cap of an atherosclerotic lesion

A
  1. Macrophages
  2. T cells
  3. Mast cells
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13
Q

What cells border atherosclerotic lesions

A

foam cells

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14
Q

What type of cell are foam cells

A

Macrophages that have phagocytose oxidised lipoproteins

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15
Q

When does dystrophic calcification of the plaque occur

A

Late in the process of plaque development

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16
Q

What is dystrophic calcification

A

Calcification in necrotic tissue

17
Q

What can dystrophic calcification show us clinically

A

A marker for an atherosclerotic vessel

18
Q

Where do plaques have a tendency to form at

A

bifurcations

19
Q

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

A

Hypercholesterolaemia

20
Q

Why is hypercholesterolaemia the most important risk factor for atherosclerosis

A

It causes plaque formation and growth

21
Q

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

A
  1. Obesity
  2. Sedentary life
  3. Low socio-economic status
  4. Low birth weight
22
Q

How do bacteria such as chlamydia pneumonia increase risk of atherosclerosis

A

By switching on evolutionary conserved pathways of inflammation

23
Q

How do high-fat diets contribute to atherosclerosis

A

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

24
Q

How do lesions develop

A
  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
25
Role of PDGF
1. Synthesis of collagen, elastin and mucopolysaccharide by smooth muscle cells 2. Proliferation of smooth muscle cells
26
What cell secretes PDGF
Platelets, injured endothelium, macrophages and smooth muscle cells
27
Three clinical manifestations of atherosclerosis
1. Progressive lumen narrowing due to high-grade plaque stenosis 2. Acute atherothrombotic occlusion 3. Embolisation of the distal arterial bed
28
What is the consequence of progressive lumen narrowing due to high-grade plaque stenosis
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
29
What happens during an acute atherothrombotic occlusion
Plaque rupture exposes highly thrombogenic plaque components to the blood stream Activates coagulation cascade and thrombotic occlusion of the vessel lumen
30
What is the consequence of total atherthrombotic occlusion
Irreversible ischaemia causing necrosis of tissues supplied by obstructed artery
31
What is the embolisation of the distal arterial bed
Where detachment of small thrombus fragments attach to the arterial bed distal to the plaque rupture
32
How does hyperlipothemia effect endothelial cells
Damages them