Atherosclerosis Flashcards
what is meant by the term arteriosclerosis?
thickening of walls of arteries + arterioles
usually as a result of hypertension or diabetes melitus - often associated with loss of elasticity
what are the consequences of arteriosclerosis?
- poor tissue perfusion
- inelastic/weak vessels
- increased risk of thrombus formation
what is meant by the term atheroscleorsis?
accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is meant by the term atheroma?
necrotic core of the atherosclerotic plaque
results in thickening and hardening of arterial walls as a consequence of atherosclerosis
what are the different theories to explain atherosclerosis?
- thrombogenic theory
- insudation theory
- monoclonal hypothesis
- reaction to injury hypothesis
what are the principles of the thrombogenic theory?
- plaques form by repeated thrombi
- lipid derived from thrombi
- overlying fibrous cap
- inflammation is a secondary effect
what are the principles of the insudation theory?
- endothelial injury
- inflammation
- increased permeability to lipid from plasma
what are the principles of the reaction to injury hypothesis?
- plaques form in response to endothelial injury
- hypercholesterolaemia causes endothelial damage
- injury increases permeability and allows platelet adhesion
- monocytes penetrate endothelium
- smooth muscles cells proliferate and migrate
what are the principles of the monoclonal hypothesis?
crucial role for smooth muscle proliferation
each plaque is monoclonal
represents abnormal growth
what cellular events lead to atherosclerotic lesions?
endothelial dysfunction causes:
1. platelet adhesion occurs (platelet derived growth factors are released)
2. smooth muscle cells proliferate and migrate
3. lipids (LDL and cholesterol) cross into the tunica intima
4. monocytes cross into intima
Foam cells secrete cytokines which leads to:
1. further smooth muscle stimulation
2. recruitment of other inflammatory cells
smooth muscle cells:
1. produce matrix material (roof) formed of collagen, elastin + other protiens
what are the different components of atherosclerotic plaques?
cells:
* endothelial cells
* platelets
* neutrophils
* macrophages
* leucocytes
* smooth muscle cells
lipid:
* extracellular pools and intracellular foam cells
extracellular matrix:
* collagen
* elastin
* proteoglycans
what is the role of endothelial cells in atherosclerotic plaque formation?
- role in haemostasis
- altered permeability to lipoproteins
- produce collagen
- stimulate proliferation + migration of smooth muscle cells
what is the role of platelets in atherosclerotic plaque formation?
- role in haemostasis
- stimulate proliferation + migration of smooth muscle cells
what is the role of smooth muscle cells in atherosclerotic plaque formation?
- synthesise collagen and proteoglycans
what is the role of macrophages in atherosclerotic plaque formation?
- take up oxidised LDL to become foam cells
- secrete proteases which modify matrix
- stimulate proliferation + migration of smooth muscle cells
what is the role of lymphocytes in atherosclerotic plaque formation?
releases TNF (tumour necrosis factor) affects lipoprotein metabolism
stimualte proliferation + migration of smooth muscle cells
what is the role of neutrophils in atherosclerotic plaque formation?
secrete proteases leading to continued local damage and inflammation
what is the microscopic appearance of atherosclerotic plaques?
fatty streak contains:
* proliferation of smooth muscle cells
* accumulation of foam cells
* extracellular lipid
stable/simple plaque contains:
* fibrosis
* necrosis
* cholesterol clefts
* may contain inflammatory cells
unstable/complicated/vulnerable plaque contains:
* disruption of internal elastic lamina
* damage extends into media
* new vessels grow into plaque
* plaque erodes
what is the macroscopic appeareance of fatty streak?
lipid deposition, slightly raised yellow area in intima
what is the macroscopic appeareance of stable or simple plaque?
raised yellow/white, irregular outline, widely distributed, enlarge and coalsece
what is the macroscopic appeareance of a vulnerable or unstable plaque?
yellow and red, irregular, rough, hard and calcified
what are the different risk factors for development of atherosclerosis?
- age
- gender
- geography
- smoking
- hypertension
- alcohol
- hyperlipidaemia
what are the different interventions to prevent atherosclerotic disease?
- stop smoking
- decrease fat intake
- control hypertension
- increase exercise
- aspirin
what are the different interventions to manage atherosclerotic disease?
- weight management
- manage diabetes melitus
- take lipid lowering drugs
- lower alcohol intake
what is the affect of atherosclerosis in heart?
- ischaemia
- MI
- arrhythmias
- heart failure
- ischaemic heart disease
what is the affect of atherosclerosis in brain?
transient ischaemic attack (TIA)
cerebral infarction (stroke)
vascular dementia
what is the affect of atherosclerosis in the GI tract?
- mesenteric ischaemia
what is the affect of atherosclerosis in peripheral arteries?
- peripheral vascular disease
- acute limb ischaemia
- intermittent claudication
- ischaemic rest pain
what is the affect of atherosclerosis in abdominal aorta?
- aneurysmal formation
- rupture of AAA
- thrombosis and emboli (can cause acute limb ischaemia)
