Pathophysiology of Atheroma Flashcards
(43 cards)
What is an atheroma/atherosclerosis?
Formation of focal elevated lesions (plaques) in intima of large and medium sized arteries.
Give an example of the implications of an atheroma.
E.g. in coronary arteries, atheromatous plaques narrow lumen –> ischaemia.
Serious consequences - angina due to myocardial ischaemia.
How can atheromas be complicated?
By thromboembolisms.
What is arteriosclerosis?
Not atheromatous.
Age related change in muscular arteries.
Smooth muscle hypertrophy, apparent reduplication of internal elastic laminae, intimal fibrosis –> decrease in vessel diameter.
What does arteriosclerosis contribute to?
High frequency of cardiac cerebral, colonic and renal ischaemia in elderly.
When are clinical effects most apparent?
When CVS further stressed by haemorrhage, major surgery, infection, shock…
What is the earliest significant lesion of an atheroma?
A fatty streak..
When will this fatty streak develop?
Probably in childhood.
What will this fatty streak look like?
Yellow, linear elevation of intimal lining.
What is the fatty streak comprised of? What is the risk associated with this streak?
Masses of lipid laden macrophages. No clinical significance and may disappear but at risk of developing atheromatous plaques.
When does an early atheromatous plaque develop? What does it look like and what is it composed of?
Young adulthood onwards.
Smooth yellow patches in intima.
Lipid-laden macrophages.
Progress to established plaques.
What is the fully developed atheromatous plaque composed of?
Central lipid core (rich in cellular lipids/debris from macrophages (died in plaque)) with fibrous tissue cap, covered by arterial endothelium. Collagens (produced by smooth muscle cells) in cap provide structural strength. Inflammatory cells (macrophages, T-lymphocytes, mast cells), reside in fibrous cap - recruited from arterial endothelium.
What often forms the rim of the fully developed atheroma?
Soft, highly thrombogenic foamy macrophages - foamy appearance due to uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor.
What may also happen to a fully developed atheromatous plaque?
Dystrophic calcification (occurs late) - (?marker for atherosclerosis in angiograms/CT). Form at arterial branching points/bifurcations (turbulent flow).
What are late stage plaques like?
Confluent, cover large areas.
Describe what a complicated atheroma is like.
Features of established atheromatous plaque plus haemorrhage into plaque (calcification), plaque rupture/fissuring, thrombosis –> clinical consequences.
What is the most important risk factor for developing atheromas?
Hypercholesterolaemia - causes plaque formation and growth in absence of other risk factors.
What is the prevalence of hypercholesterolaemia and how does it present?
1/500 Caucasians heterozygous for this type of mutation: decreased functional receptors on cell surfaces, elevated plasma LDL cholesterol levels.
Homozygous (1/mil) - much higher cholesterol levels, usually due from coronary artery atheroma in infancy/teens.
What are the signs for major hyperlipidaemia?
Familial/primary vs acquired/secondary. Biochemical evidence - LDL, HDL, total cholesterol, triglycerides. Corneal arcus (premature) Tendon xanthomata (knuckles, Achilles) Xanthelasmata Risk/premature/FH of MI/atheroma.
What are the major risk factors for atheroma?
Hypercholesterolaemia Smoking Hypertension Diabetes mellitus Male Elderly Accelerate process of plaque formation driven by lipids.
What are less strong risk factors for atherosclerosis?
Obesity Sedentary lifestyle Low socio-economic status Low birth weight ?role of microorganisms
Describe the two step process leading to the formation of atheromatous plaques.
Injury to endothelial lining of artery.
Chronic inflammation and healing response of vascular wall to agent causing injury.
Chronic/episodic exposure of arterial wall to these processes –> formation of atheromatous plaques.
Describe the pathogenesis of atherosclerosis.
Endothelial injury and dysfunction
Accumulation of lipoproteins (LDL) in vessel wall
Monocyte adhesion to endothelium –> migration into intima and transformation to foamy macrophages
Platelet adhesion
Factor release from activated platelets, macrophages (smooth muscle recruitment)
Smooth muscle cell proliferation, extracellular matrix production and T-cell recruitment
Lipid accumulation (extracellular and in foamy macrophages).
How are the injured endothelial cells functionally altered?
Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin)
High permeability for LDL
Increased thrombogenicity.
Inflammation cells, lipids –> intimal layer –> plaques.
