Atherosclerosis Flashcards
Define atherosclerosis (2 definitions)
-Atherosclerosis is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
-The thickening and hardening of arterial
walls as a consequence of atherosclerosis
Define arteriosclerosis
The thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
Describe the macroscopic features of atherosclerosis
Fatty streak
Simple plaque
Complicated plaques
What is a fatty streak?
Lipid deposits in intima. Yellow, slightly raisde. Relationship to atherosclerosis somewhat debatable.
What is a simple plaque?
Raised yellow/white. Irregular outline. Widely distributed. Enlarge and coalesce.
What is a complicated plaque?
Formed from:
- Thrombosis
- Haemorrhage into plaque
- Calcification
- Aneurysm formation
What are common sites of atherosclerosis?
Aorta - especially abdominal Coronary arteries Carotid arteries Cerebral arteries Leg arteries
How may atherosclerosis appear microscopically?
Early changes:
- proliferation of smooth muscle cells
- accumulation of foam cells
- extracellular lipid
Later changes:
- fibrosis
- necrosis
- cholesterol clefts
- +/- inflammatory cells
- disruption of internal elastic lamina
- damage extends into media
- ingrowth of blood vessels
- plaque fissuring
What are the potential clinical effects of ischaemic heart disease?
- sudden death - myocardial infarction - angina pectoris - arrhythmias - cardiac failure
What are the potential clinical effects of cerebral ischaemia?
- transient ischaemic attack
- cerebral infarction (stroke)
- multi-infarct dementia
What are the potential clinical effects of mesenteric ischaemia?
- ischaemic colitis
- malabsorption
- intestinal infarction
What are the potential clinical effects of peripheral vascular disease?
- intermittent claudication
- Leriche syndrome
- ischaemic rest pain
- gangrene
What are risk factors for atherosclerosis?
- Age
- Gender
- Hyperlipidaemia
- Cigarette smoking
- Hypertension
- Diabetes mellitus
- Alcohol
- Infection
- Genetics
- Familial Hyperlipidaemia
What is the role of endothelial cells in atheroma?
-Key role in haemostasis
-Altered permeability to lipoproteins
-Production of collagen
-Stimulation of proliferation and migration
of smooth muscle cells
What is the role of platelets in atheroma?
-Key role in haemostasis
-Stimulate proliferation and migration of
smooth muscle cells (PDGF)
What is the role of smooth muscle cells in atheroma?
- Take up LDL and other lipid to become foam cells
- Synthesise collagen and proteoglycans which are present in excess in atheromatous plaques
What is the role of macrophages in atheroma?
- Oxidise LDL
- Take up lipids to become foam cells
- Secrete proteases which modify matrix
- Stimulate proliferation and migration of smooth muscle cells
What is the role of lymphocytes in atheroma?
- TNF may affect lipoprotein metabolism
- Stimulate proliferation and migration of smooth muscle cells
What is the role of neutrophils on atheroma?
-Secrete proteases leading to continued local damage and inflammation
Give a unifying hypothesis for atheroma formation
1) Endothelial injury due to:
- raised LDL
- ‘toxins’ e.g. cigarette smoke
- hypertension
- haemodynamic stress
2) Endothelial injury causes:
-platelet adhesion, PDGF release, SMC proliferation and migration
-insudation of lipid, LDL oxidation, uptake of
lipid by SMC and macrophages
-migration of monocytes into intima
3)
- Stimulated SMC produce matrix material
- Foam cells secrete cytokines causing further SMC stimulation
- recruitment of other inflammatory cells
