atherosclerosis Flashcards
define atheroma
accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
define atherosclerosis
the thickening and hardening of arterial walls as a consequence of atheroma
define arteriosclerosis
the thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
what are the macroscopic features of aatherosclerosis
fatty streak -represents earliest stage of atherosclerosis. lipid deposits in intimate of artery. yellow and slightly raised
the simple plaque - raised yellow/white. irregular outline. enlarge and coalesce
the complicated plaque- thrombosis, haemorrhage into plaque, calcification and aneurysm formation
what are the common sites of atherosclerosis
aorta coronary arteries carotid arteries cerebral arteries leg arteries
describe normal arterial structure
endothelium internal elastic lamina muscular media external elastic lamina adventitia
what are the early microscopic features of atherosclerosis
proliferation of smooth muscle cells
accumulations of foam cells
extracellular lipid
what are the late microscopic features of atherosclerosis
fibrosis
necrosis
cholesterol clefts
increase/ decrease in inflammatory cells
disruption of internal elastic lamina and then damage extending to media
ingrowth of blood vessels
plaque fissuring (surface of plaque ruptures)
how do cholesterol clefts appear in microscopy
needle shaped holes in tissue as cholesterol gets dissolved out when we prepare cell for microscopy
what are the clinical affects of ischaemic heart disease
sudden death myocardial infarction angina pectoris -chest pain on exertion due to poor blood supply arrhythmias cardiac failure
clinical effects of cerebral ischaemia
transient ischaemic attack (mini stroke)
cerebral infarction (stroke)
multi-infarct dementia
clinical effects of mesenteric ischaemia
ischaemic colitis - characterised by bleeding in rectum malabsorption (chronic form) intestinal infarction (acute form)
clinical affects of peripheral vascular disease
intermittent claudication- pain in calves on exercise
leriche syndrome -buttock pain & impotence
ischaemic rest pain
gangrene- blood flow to large areas of tissue is cut off. skin becomes greenish-black colour
risk factors of atherosclerosis
age gender- women protected before menopause due to hormones hyperlipidaemia cigarette smoking hypertension diabetes mellitus alcohol infection obesity
how does smoking cause atherosclerosis
reduced PG12
Increased platelet aggregation
what are the theories behind atherosclerosis
thrombogenic theory-plaques formed by repeated thrombi, lipid derived from thrombi, overlying fibrous cap
insudation theory- endothelial injury, inflammation, increased permeability to lipid from plasma
reaction to injury hypothesis-plaques form in response to endothelial injury, hypercholestrolaemia leads to endothelial damage, injury increases permeability and allows platelet adhesion, monocytes penetrate endothelium , smooth muscle cells proliferate and migrate.
the monoclonal hypothesis- each plaque is monoclonal, might represent abnormal growth control, each plaque might be a benign tumour , viral cause ?
what processes are involved in atherosclerosis
thrombosis
lipid accumulation
production of intercellular matrix
interactions between cell types
what cells are involved in atherosclerosis
endothelial cells platelets smooth muscles macrophages lymphocytes neutrophils
how are endothelial cells involved in atherosclerosis
key role in Haemostasis
altered permeability to lipoproteins
production of collagen
stimulation of proliferation and migration of smooth muscle cells
how are platelets involved in atherosclerosis
key role in Haemostasis
stimulate proliferation and migration of smooth muscle cells (PDGF)
how are smooth muscle cells involved in atherosclerosis
take up LDL and other lipid to become foam cells
synthesise collagen and proteoglycans
how are macrophages involved in atherosclerosis
oxidise LDL (they are more damaging in oxidising form)
take up lipids to become foam cells
secrete proteases which modify matrix
stimulate proliferation and migration of smooth muscle cells
how are lymphocytes involved in atherosclerosis
TNF (tumour necrosi factor) may affect lipoprotein metabolism
stimulate proliferation and migration of smooth muscle cells
how are neutrophils involved in atherosclerosis
secrete proteases leading to continued local damage and inflammation
what causes endothelial injury
raised LDL
toxins - cigarette smoke
hypertension
haemodynamic stress
what does endothelial injury cause
platelet adhesion , PDGF release, SMC proliferation and migration
insulation of lipid , LDL oxidation, uptake of lipid by SMC and macrophages
migration of monocytes into intima
foam cells produce cytokines what does this cause
further SMC stimulation
recruitment of other inflammatory cells
how can atherosclerosis be prevented
no smoking reduced fat intake treat hypertension decrease alcohol intake regular exercise
atherosclerosis intervention
stop smoking modify diet treat hypertension treat diabetes lipid lowering drugs
