Atherosclerosis Flashcards
What is the etymology of atherosclerosis?
• Athere = gruel; Sclerosis = hardness
Where does atherosclerosis occur?
Elastic and medium to large muscular arteries
What is an atheroma?
(fibro-fatty plaques)
• Intimal fibrous cap
• Central core rich in lipids
What is the clinical significance of atherosclerosis?
A fuckton of people die of it, in fact the most
- Symptomatic atherosclerosis
- Contributes 1⁄2 of all deaths (Western world)
- . MI, Stroke, Aneurysms, Peripheral vascular disease
How has the rate of symptomatic atherosclerosis changed through the years?
- 1963 (peak) –> 2000
- 50% decreased death rate heart attack
- .70% decreased death rate stroke
Due to
1. Prevention of atherosclerosis 2. Improved methods of treatment 3. Prevention of recurrences
What are the risk factors of atherosclerosis?
- Age
- Sex
- Genetics
- Hyperlipidaemia
- Hypertension
- Smoking
- Diabetes mellitus
What are the different stages of the pathogenesis of atherosclerosis?
Initiation/formation stage (subclinical)
Adaptation stage (subclinical)
Clinical stage
Describe the pathogenesis of atherosclerosis
Precursor lesions (fatty streak, internal hyperplasia) undergoes atherogenic injury and so forms:
Fibroinflammatory lipid atheroma which then undergoes atheroma and wall remodelling forming an atheroma
At this stage and henceforth it may destabilise and so cause acute complications
The atheroma will undergo plaque enlargement, lumen stenosis then become a complicated plaque
Through further lumen stenosis the complicated plaque will cause occlusion, though this can also occur due to thrombosis as an acute complication of the atheroma
What are the different processes involved in atherosclerosis pathogenesis?
- Chronic endothelial injury / dysfunction
- Role of lipids
- Role of macrophages
- Smooth muscle proliferation
- Formation of a fibro-lipid plaque
- Injury to the plaque – thrombus formation
What may cause chronic endothelial injury / dysfunction?
- Haemodynamic disturbances
- Hypercholesterolemia
- Hypertension
- Smoking
- Toxins
- Viruses
- Immune reactions
What effects do chronic endothelial injury / dysfunction have on the artery wall?
- Increase in Endothelial permeability
- Increase in Leukocyte adhesion
- Vascular cell adhesion molecule 1 (VCAM-1)
- Intercellular adhesion molecule- 1 (ICAM-1)
- P-selectin
- E-selectin
- Increase in Monocyte adhesion and migration
What is the role of lipids in the arterial wall during atherosclerosis?
The lipid involved is hyperlipidaemia (LDL cholesterol)
- Impairs endothelial function
- Accumulates within intima
- Causes oxidative modification of LDL:
- Ingested by macrophages via SCAVANGER 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 arterial wall during atherosclerosis?
• Engulf oxidised LDL = foam cells
• Secrete:
• IL1 (interleukin 1)
• TNF (tumour necrosis factor)
• MCP1 (monocyte
chemotactic protein 1) and
• growth factors (PDGF, FGF, TNF)
• Interferon α, TGFβ
• FATTY streak
What is the role of smooth muscles proliferation in the arterial wall during atherosclerosis?
• Collagen and Extracellular matrix deposition • Fatty streak I I v • Mature fibro-fatty Atheroma
What is the morphology of the atheromatous plaque?
It is a fibro-fatty, fibro-lipid plaque
• Patchy and raised white to yellow 0.3-1.5cm
• Core of lipid
• Fibrous cap
It also has a necrotic centre between the media and the fibrous cap
Found in: • Abdominal aorta • Coronary arteries • Popliteal arteries • Descending thoracic aorta • Internal carotid arteries • Vessels of the circle of Willis
