Atherosclerosis Flashcards
What is an atheroma?
- Fibro-fatty plaques
- 2 components:
- Intimal fibrous cap
- Central core rich in lipids
What are the risk factors for developing atherosclerosis?
- Age
- Usually not clinically relevant until at least middle age
- Sex
- Males are far more prone
- Genetics
- Related to familial clustering of other risk factors such as hypertension or diabetes.
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes Mellitus
Describe the pathogenesis of atherosclerosis.
What are the major risk factors for the pathogenesis which causes atherosclerosis?
- Chronic endothelial injuery / dysfunction
- Role of lipids
- Role of macrophages
- Smooth muscle proliferation
- Formation of a fibro-lipid plaque
- Injury to the plaque - thrombus formation
What are the causes of chronic endothelial injury / dysfunction?
- Haemodynamic disturbances
- Hypercholesterolaemia
- Hypertension
- Smoking
- Toxins
- Viruses
- Immune reactions
- ↑ endothelial permeability
- When endothelium is injured, permeability increases. The blueberry cells are WBCs and they adhere to the injured endothelium.
- ↑ Leukocyte adhesion
- Vascular cell adhesion molecule 1 (VCAM-1)
- Intercellular adhesion molecule-1 (ICAM-1)
- P-selectin
- E-selectin
- ↑ Monocyte adhesion and migration
Describe the role of lipids in the development of atherosclerosis.
- Hyperlipidaemia (LDL)
- Impairs endothelial function
- Accumulates within intima
- Causes oxidative modification of LDL:
- Ingested by macrophages via SCAVENGER receptors = foam cells.
- Chemotactic for monocytes.
- Inhibit the motility of macrophages.
- Stimulates release of cytokines.
- Cytotoxic to endothelial and smooth muscle cells.
What is the role of macrophages in the development of atheromas?
- Engulf oxidised LDL ⇒ foam cells.
- Secrete:
- IL1
- TNF
- MCP1 (monocyte chemotactic protein 1)
- Growth factors
- PDGF - platelet-derived growth factor
- FGF - fibroblast growth factor
- TNF
- Interferon α
- TGFβ
- Formation of fatty streak
- This is the first visible appearance of atheroma.
What is the role of smooth muscle proliferation in the development of atheromas?
Collagen and extracellular matrix deposition
↓
Fatty streak
↓
Mature fibro-fatty atheroma
Describe the morphology of an atheroma.
- Atheromatous (fibro-lipid) plaque
- Patchy and raised white to yellow 0.3-1.5cm
- Core of lipid
- Fibrous cap
Which vessels are most commonly affected by atherosclerosis?
- Abdominal aorta
- AAA
- Coronary arteries
- Ischaemic heart disease
- Popliteal arteries
- Desceneding thoracic aorta
- Internal carotid arteries
- Vessels of the circle of Willis
- Stroke
What features of the morphology would make an atheroma ‘complicated’?
- Complicated lesions:
- Calcification
- Rupture or ulceration
- Haemorrhage
- Thrombosis
- Aneurysmal dilatation
What are the histological features highlighted by the arrows?
- Foam cells - bubbly appearance.
- They originally were WBCs (monocytes) which passed from the lumen into the tunica media, they phagocytosed oxidised LDL and became foam cells.
Describe the morphology of fatty streaks.
- Fatty dots <1mm
- Elongated streaks 1cm or longer
- Foam cells + T lymphocytes
- In aorta age <1 year
- In coronary artery form in adolescence
- May be precursors of plaques
What are the clinical features of atherosclerosis?
-
Only appears if there are complications:
- Thrombosis
- Calcification
- Aneurysmal dilatation
- Ischaemic events:
- Heart
- Brain
- Lower extremities
- Other organs
What are the primary and secondary prevention strategies for atherosclerosis?
- Primary
- Smoking cessation
- Control of HTN
- Weight reduction
- Lowering total LDL
- Reduce calorie intake
- Secondary
- Prevent complications
- Antiplatelet drugs in thrombosis
- Lower blood lipid levels
