Atherosclerosis Flashcards
Define atheriosclerosis
The thickening of the walls of arteries and arterioles usually as a result of hypertension or diabetes mellitus
Define atherosclerosis
the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
Define atheroma
The thickening and hardening of arterial walls as a consequence of atherosclerosis
Describe the macroscopic morphological appearance of atherosclerosis
Fatty streak = lipid deposits in intima, yellow, raised.
Simple plaque = raised, yellow/white, irregular, widely distributed.
Complicated plaque = thrombosis, haemorrhage into plaque, calcification, aneurysm
Describe the microscopic morphological appearance of atherosclerosis
early changes = accumulation of foam cells, proliferation of smooth muscle cells, extracellular lipid deposition
later changes = fibrosis, necrosis, cholesterol clefts, disruption of internal elastic lamina, extension into media, ingrowth of blood vessels, plaque fissuring
What are the cells and their role in the formation of atherosclerosis?
Endothelial cells = altered permeability to lipoproteins, collagen prod, stim of prolif/migration of smooth muscle (SM) cells.
Platelets = stim prolif/migration of SM cells.
SM cells = take up LDL to become foam cells.
Macrophages = oxidise LDL, take up lipids to become foam cells, secrete proteases, stim prolif/migration of SM cells.
Lymphocytes = TNF may affect lipoprotein met, stim prolif/migration of SM cells.
Neutrophils = secrete proteases causing local damage/inflam
What are the common site for atherosclerosis?
Aorta, coronary arteries, carotid arteries, cerebral arteries, leg arteries
What are the risk factors for atherosclerosis?
Smoking (effect on coag), hypertension (increased pressure = endothelial damage), impaired glucose tolerance, age, gender, hyperlipidaemia (LDL most significant), alcohol, apolipoprotein E genotype, familial hyperlipidaemia (abnormal lipoprotein = early devel), geography, infection, oral contraceptives, obesity
What are the stages leading to atherosclerosis?
Chronic endothelial injury.
Platelet adhesion and monocyte accumulation with release of growth factors and cytokines.
SM emigration from media into intima.
Macrophages and smooth muscle cells = engulf lipid to form foam cells
SM proliferation, collagen and matrix deposition, extracellular lipid deposition, neovascularisation
What are the complications of severe atherosclerosis?
Ischaemic heart disease (sudden death, MI, angina, arrhythmias),
Cerebral ischaemia (TIA, stroke, dementia),
Mesenteric ischaemia (malabsorption)
Peripheral vascular disease (intermittent claudication),
Abdominal aortic aneurysm (weakens)
What is the unified hypothesis of atherosclerosis?
Endothelial injury, followed by platelets adhesion, PDGF, SMC prolif/migration, LDL oxidation, uptake of lipid, migration of monocyte into intima, SMC prod matrix material, foam cells secrete cytokines
What is the reaction to injury hypothesis in regards to atherosclerosis?
Plaques in response to endothelial injury, hypercholesterolaemia leads to endothelial injury, injury increases permeability and allows platelet adhesion
Describe the monoclonal hypothesis
Crucial role for smooth muscle proliferation,
each plaque is monoclonal
might represent abnormal growth
is each plaque a benign tumour?
could atherosclerosis have a viral aetiology?
How can atherosclerosis be prevented?
Stop smoking, Decrease fat intake, Treat hypertension, Aspirin, Sensible alcohol intake, Regular exercise and control of weight, Treat DM, Lipid lowering drugs (statins)
What is familial hypercholesterolemia?
genetic disorder = high LDL
complications = heart attack, stroke, atheroscleosis
