The nature and pathogenesis of atheroma Flashcards
Define atherosclerosis
Formation of focal elevated lesions in the intimal of large and medium-sized arteries
Define atherothrombosis
When an occlusive thrombosis forms on a spontaneously disrupted plaque
How has the frequency of atherothrombosis changed over the years
Become more frequent in recent years
In which societies do atherosclerotic lesions form in
Those who have a high dietary fat intake
What is the earliest significant lesion that results in an atherosclerotic lesions
A fatty streak
Where is the fatty streak
A yellow elevation of the intimal lining made of macrophages
Do fatty streaks have an impact on health
No
What two things can happen following the formation of a fatty streak
- Disappear from arterial intimal
2. Progression to atherosclerotic plaque
Describe the structure of an atherosclerotic lesion
Lesion with central lipid core
Cap of fibrous tissue covered by arterial endothelium
Role of collagen in the cap of fibrous tissue of an atherosclerotic lesion
Provides structural strength of th plaque
What produces the connective tissue in the cap of the fibrous tissue of an atherosclerotic lesion
Smooth muscle cells
What cells reside in the fibrous cap of an atherosclerotic lesion
- Macrophages
- T cells
- Mast cells
What cells border atherosclerotic lesions
foam cells
What type of cell are foam cells
Macrophages that have phagocytose oxidised lipoproteins
When does dystrophic calcification of the plaque occur
Late in the process of plaque development
What is dystrophic calcification
Calcification in necrotic tissue
What can dystrophic calcification show us clinically
A marker for an atherosclerotic vessel
Where do plaques have a tendency to form at
bifurcations
What is the most important risk factor which can result in atherosclerosis
Hypercholesterolaemia
Why is hypercholesterolaemia the most important risk factor for atherosclerosis
It causes plaque formation and growth
What are other factors other than hypercholesterolaemia that can cause atherosclerotic lesions
- Obesity
- Sedentary life
- Low socio-economic status
- Low birth weight
How do bacteria such as chlamydia pneumonia increase risk of atherosclerosis
By switching on evolutionary conserved pathways of inflammation
How do high-fat diets contribute to atherosclerosis
Promote translocation of commensal-derived endotoxin from the gut into the general circulation = inflammation
How do lesions develop
- Damage to endothelium of arterial wall
- Injured endothelial cells have enhanced expression of cell adhesion molecules + high permeability for LDL + increased thrombogenicity
- This allows inflammatory cells and lipids to enter intimal layer and form plaques
- Large amounts of macrophages and T cells accumulate in the plaque tissues
- Foam cells die via apoptosis
- Foam cells spill lipid into lipid core- chronic inflammation
- Growth factor PDGF stimulate tissue repair
Role of PDGF
- Synthesis of collagen, elastin and mucopolysaccharide by smooth muscle cells
- Proliferation of smooth muscle cells
What cell secretes PDGF
Platelets, injured endothelium, macrophages and smooth muscle cells
Three clinical manifestations of atherosclerosis
- Progressive lumen narrowing due to high-grade plaque stenosis
- Acute atherothrombotic occlusion
- Embolisation of the distal arterial bed
What is the consequence of progressive lumen narrowing due to high-grade plaque stenosis
- Stenosis leads to reduction of blood flow in distal arterial bed
- Reversible tissue ischaemia develops
- Ischaemic pain occurs when stenosis is severe
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
What is the consequence of total atherthrombotic occlusion
Irreversible ischaemia causing necrosis of tissues supplied by obstructed artery
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
How does hyperlipothemia effect endothelial cells
Damages them
