Pathophysiology of Atheroma Flashcards
1
Q
Describe the process of atherogenesis and understand how atheromatous plaques form
A
- Endothelial injury and dysfunction
- Accumulation of LDL in vessel wall
- Monocyte adhesion to wall –> migration into intima –> become foamy macrophages
- Platelet adhesion
- Factor release from activated platelets/macrophages –> smooth muscle cell recruitment
- smooth muscle cell proliferation, ECM production and T-cell recruitment
- Lipid accumulation
2
Q
Understand the role of lipids in the aetiology of atheroma
A
- Hypercholesterolaemia: genetically determined lack of LDL receptors cause plaque formation
- Smoking
- Hypertension
- DM
- Sex: male
- Age: elderly
3
Q
Know the signs of major hyperlipidaemia
A
- Familial/primary vs acquired/secondary
- Biochemical evidence: LDL, HDL, total cholesterol, triglycerides
- Corneal arcus (premature)
- Tendon xanthomata (knuckles, Achilles)
- Xanthelasmata
- Risk/premature/family history of MI/atheroma
4
Q
Define atheroma
A
- Fatty streak
- Earliest significant lesion: begin in childhood
- Yellow linear elevation of intimal lining
- Masses of lipid-laden macrophages
- No clinical significance: may disappear
- May become atheromatous plaques
5
Q
Define fully developed atheromatous plaques
A
- Central lipid core with fibrous tissue cap, surrounded by arterial endothelium
6
Q
Define fully developed atheromatous plaques
A
- Central lipid core with fibrous tissue cap, surrounded by arterial endothelium
- ## Collagen (produced by smooth muscle cells) in cap provides structural strength
7
Q
Define fully developed atheromatous plaques
A
- Central lipid core with fibrous tissue cap, surrounded by arterial endothelium
- Collagen (produced by smooth muscle cells) in cap provides structural strength
- Inflammatory cells reside in cap (recruited by arterial endothelium)
8
Q
Define fully developed atheromatous plaques
A
- Central lipid core rich in cellular lipids/debris derived from macrophages
- Fibrous tissue cap surrounded by arterial endothelium
- Collagen (produced by smooth muscle cells) in cap provides structural strength
- Inflammatory cells in cap (recruited by arterial endothelium) secrete proteases, cytokines, reactive oxygen species
- Soft, highly thrombogenic rim of ‘foamy’ macrophages
9
Q
Define dystrophic calcification
A
- Occurs in generated/necrotic tissue
- Reaction to tissue damage
- Marker for atherosclerosis in angiograms/CT
10
Q
Define complicated atheroma
A
- Haemorrhage into plaque (calcification)
11
Q
Define complicated atheroma
A
- Haemorrhage into plaque (calcification)
- Plaque rupture/fissuring
- Thrombosis
12
Q
Name less strong risk factors of atherosclerosis
A
- Obesity
- Sedentary lifestyle
- Low socio-economic status
- Low birthweight
13
Q
Name causes of endothelial injury
A
- Turbulent flow
- Hypercholesterolaemia
14
Q
Describe how endothelial cells are functionally altered in atherosclerosis
A
- Enhanced permeability of cell adhesion molecules
- High permeability for LDL
- Increased thrombogenicity
15
Q
Describe clinical manifestations of atheromatous plaques
A
- 50-75% stenosis of lumen –> reversible tissue ischaemia
- Coronary artery stenosis –> stable angina
- Very severe stenosis –> unstable angina
- Ileal, femoral, popliteal artery stenosis –> intermittent claudication
- Long standing tissue ischaemia –> atrophy of affected organ
