Atherosclerosis Flashcards
what is an atheroma
accumulation of intracellular and extracellular lipids in the intima and media of large and medium sized arteries
what are the 3 possible macroscopic features of atheromas
- fatty streak
- simple plaque
- complicated plaque
what are fatty streaks
lipid depositions in the intima giving a yellow and slightly raised appearance
what are simple plaques
depositions of lipids giving raised white/yellow areas which are irregularly shaped and widely distributed
they can merge together to form large areas
what are complicated plaques
simple plaques which have had something happen to them e.g. a haemorrhage of the plaque, a thrombosis, calcification or aneurysm formation
where are the most common sites for atherosclerosis
- aorta
- coronary arteries
- leg arteries
- cerebral arteries
- carotid arteries
what are the layers of normal arteries
- endothelium
- sub endothelium CT
- internal elastic lamina
- muscular media
- external elastic lamina
- adventita
what are the microscopic features of atheromas
- proliferation of smooth muscle cells
- accumulation of foam cells
- extracellular lipid
what are some of the later microscopic changes seen in atheromas
fibrosis, necrosis, cholesterol clefts, inflammatory cells, disruption of internal elastic lamina and so damage extends to media and plaque fissuring
what is fissuring
a split of the plaque, which exposures the vessel wall so leads to a thrombosis
what are the clinical affects of atherosclerosis
ischaemic heart disease giving:
- death
- MI
- angina
- cardiac failure
Cerebral ischaemia giving:
- cerebral infarction
- dementia
Mesenteric Ischaemia giving:
- malabsorption
- intestinal infarction
Peripheral Ischaemia giving:
- gangrene
-intermittent claudication
Leriche syndrome
what is intermittent claudication
there is pain in the calf muscles when walking which reduces with rest
what increases the chance of atherosclerosis
- age
- gender
- smoking
- hyperlipidaemia
- diabetes
- alcohol
- infection
which gender are better protected from atherosclerosis
women
why does hyperlipidaemia cause atherosclerosis
there is a high plasma cholesterol and so particularly more LDLs are deposited and HDLs are protective
what are the physical signs of hyperlipidaemia
- arcus
- tendon xanthomas
- xanthelasma
how does hypertension cause atherosclerosis
high pressure causes endothelial damage
what factors cause hereditary predisposition of atherosclerosis
- variations in apoprotein metabolism and receptors
what is atherosclerosis
the thickening and hardening of the arterial walls as a result of atheromas
what are the 4 theories of the pathogenesis of atherosclerosis
- thrombogenic theory
- insudation theory
- monoclonal hypothesis
- reaction to cell injury
what is the thrombogenic theory
that plaques formed due to repeated lipid derived thrombi with an overlying fibrous cap
what is the insudation theory
where endothelial injury causes inflammation and increases the permeability of lipid from plasma
what is the reaction to cell injury hypothesis
where plaques form in response to endothelial injury which increases permeability and allows platelet adhesion. monocytes can enter endothelium and smooth muscle cells proliferate and migrate
what is the monoclonal hypothesis
where each plaque is monoclonal representing abnormal growth control
what are the cells involved in atherosclerosis
- endothelial cells
- platelets
- smooth muscle cells
- macrophages
- lymphocytes
- neutrophils
what do the endothelial cells do in atherosclerosis
cause an altered permeability to lipoproteins, cause the production of collagen and stimulate proliferation and migration of smooth muscle cells
what do the platelets do in atherosclerosis
involved in homoeostasis, stimulation proliferation and migration of smooth muscle cells
what do the smooth muscle cells do in atherosclerosis
take up LDLs and other lipids to become foam cells
synthesise collagen and proteoglycans
what do the macrophages do in atherosclerosis
oxidise LDLs
take up lipids to become foam cells
secrete proteases which modify the matrix
stimulate proliferation and migration of smooth muscle cells
what do the lymphocytes do in atherosclerosis
they secrete TNF which affects lipoprotein metabolism
stimulate proliferation and migration of smooth muscle cells
what do the neutrophils do in atherosclerosis
secrete proteases leading to continued local damage and inflammation
what causes endothelial damage
raised LDL
toxins
hypertension
stress
what does endothelial damage cause
platelet adhesion growth factor release smooth muscle proliferation and migration LDL oxidation lipid uptake by SMC and macrophages monocyte migration to intima
what do foam cells do
further stimulate SMCs and recruit other inflammatory cells
what can prevent atherosclerosis
no smoking, reduced fat intake, treat hypertension, limit alcohol, exercise
