Pathophysiology of Atheroma Flashcards
What is atheroma/atherosclerosis?
Formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries
What is formation of focal elevated lesions (plaques) in intima of large and medium sized arteries called?
Atheroma/athersclerosis
What is the difference in atheroma and atherosclerosis?
Atherosclerosis is the condiction caused by atheroma
What is an example of an atheroma?
In coronary artieries atheramatous plaques narrow lumen and lead to ischaemia
This leads to angina due to myocardial ischaemia
What is a thromboembolism?
Obstruction of a blood vesssel by a blood clot that has become dislodged from another site in the circulation
What is the obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation called?
Thromboembolism
What leads to arteriosclerosis?
Age related change in muscular arteries caused by:
Smooth muscle hypertrophy
Reduplication of internal elastic laminae
Intimal fibrosis
What does arteriosclerosis contribute to?
High frequency of cardiac, cerebral, colonic and renal ischaemia in the elderly
What is arteriosclerosis?
Age related change in muscular arteries causing the walls to thicken and harden
When are the clinical effects of arteriosclerosis most apparent?
When cardiovascular system is further stressed by haemorrhage, major surgery, infection or shock
What is the difference between atherosclerosis and arteriosclerosis?
Arteriosclerosis is the hardening of the artery walls with age
Atherosclerosis is where plaques build up inside the lumen of arteries
What are the 3 different kinds of atheroma?
Fatty streak
Early atheromatous plaque
Fully developed atheromatous plaque
What are fatty streak atheroma composed of?
Masses of lipid-laden macrophages
Who are fatty streaks often seen in?
Young children
Who are early atheromatous plaques often seen in?
Young adults onwards
What are early atheromatous plaques composed of?
Lipid-laden macrophages
What can fatty streaks progress to?
Early atheromatous plaques
What can early atheromatous plaques progress onto?
Fully developed atheromatous plaques
What are fully developed atheromatous plaques composed of?
Central lipid core with fibrous tissued cap, covered by arterial endothelium
What provides strength to a fully developed atheromatous plaque?
Collagens produced by smooth muscle cells in the cap
What resides in the fibrous cap of a fully developmed atheromatous plaque?
Inflammatory cells (macrophages, T-cells, mast cells)
What is the central lipid core of a fully developmed atheromatous plaque rich in?
Cellular lipids/debris derived from macrophaes (died in the plaque)
What rim is often present around fully developed atheromatous plaques?
Rim of foamy macrophages
Why are the rim of macrophages in a fully developed atheromatous plaque foamy?
Uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor
What occurs late in the development of fully developed atheromatous plaques?
Dystophic calcification
Where do fully developed atheromatous plaques often form?
Arterial branching points
What is an atheroma?
Degeneration of the walls of the arterires caused by accumulated fatty deposites and scar tissue, leading to restriction of the circulation and risk of thrombosis
What is degeneration of the walls of the arteries caused by accumulated fatty deposites and scar tissue called?
Atheroma
What is atherosclerosis?
Plaque builds up insides your artiers, which hardens over time and narrows the artery
What is it called when a plaque builds up inside your arteries which hardens over time and narrows the artery?
Atherosclerosis
What features do complicated atheroma have?
Features of established athermatous plaques plus:
Haemorrhage into plaque (calcification)
Plaque rupture
Thrombosis
What is a haemorrhage?
An escape of blood from a ruptured blood vessel
What is an escape of blood from a ruptured blood vessel called?
Haemorrhage
What is thrombosis?
Formation of a blood clot inside a blood vessel
What is formation of a thrombus inside of a blood vessel called?
Thrombosis
What is hypercholesterolaemia?
Excess of cholesterol in the bloodstream
What is excess of cholesterol in the bloodstream called?
Hypercholesterolaemia
What is the most important risk factor for an atheroma?
Hypercholesteroaemia
What do some people have, due to genetics, that leads to high levels of LDL?
Mutation where there are less functional receptors on cell membrane for LDL
What are some signs of major hyperlipidaemia?
Biochemical evidence (LDL, HDL, total cholesterol, triglycerides)
Corneal arcus
Tendon xanthomata
Xanthelasmata
What are some risk factors for atheroma?
Hypercholesteroaemia
Smoking
Hypertension
Diabetes mellitus
Male
Elderly
Less strong ones (obesity. sedemtary, lifestyle, low economic status, low birthweight)
What are the different kinds of hyperlipidaemia?
Familial/primary or acquired/secondary
What is the process for the development of atheromatous plaques?
1) Injury to endothelial lining of artery
2) Chronic inflammatory and healing response of vascular wall to agent causing injury
3) Chronic/episodic exposure of arterial wall to this process leads to formation of atheromatous plaques
What is the pathogenesis of atherosclerosis?
1) Endothelial injury and dysfunction
2) Accumulation of lipoproteins (LDL) in vessel wall
3) Monocyte adhesion to endothelium, which migrate into intima and transform to foamy macrophages
4) Platelet adhesion
5) Factor release from activated platelets and macrophages which leads to smooth muscle cell rectruitment
6) Smooth muscle cell proliferation, extracellular matrix production and T-cell recruitment
7) Lipid accumulation (extracellular and in foamy macrophages)
What are some possible causes of the initial endothelial injury that leads to the pathogenesis of atheroma?
Haemodynamic disturbances (turbulent flow)
Hypercholesterolaemia
How can hypercholesterolaemia damage endothelial?
Impairs endothelial cell function by increased local production of reactive oxygen species
Lipoproteins aggregate in intima and are modified by free radicals produced by inflammatory cells, then picked up by macrophages which become foamy macrophages that are toxic to endothelial
What happens to the function of injurted endothelial cells?
Function is altered
How is the function of injured endothelial cells altered?
Enhanced expression of cell adhesion molecules (such as ICAM-1, E-selectin)
High permeability for LDL
Increased thrombogenecity
What is thrombogenecity?
Tendency of a material in contract with the blood to produced a thrombus
What is the tendency of a material in contact with the blood to produce a thrombus called?
Thombogenecity
What is the process of advanced plaque formation?
1) Large numbers of macrophages and T-cells
2) Lipid laden macrophages die through apoptosis and become the lipid core
3) Response to the injury is the chronic inflammatory process
4) Growth factors (PDGF) lead to proliferation on intimal smooth muscle cells, subsequent synthesis of collagen, elastin and mucopolysaccharide
5) Fibrous cap encloses lipid rich core
6) Growth factors secreted by platelets, injured endothelium, macrophages and smooth muscle cells
What is the process of plaque growth being initiated by small areas of endothelial loss?
1) Microthrombi formed at denuded areas of plaque surface
2) Organised by some repair process (smooth muscle invasion and collagen deposition)
3) Repeated cycle gradually increases plaque volume
Are all plaques clinically noticed?
No, many plaques develop over a lifetime and go clinically unnoticed
What does clinical disease due to plaques range from in terms of seriousness?
Relatively benign to life-threatening
What are some examples of clinical manifestations as a consequence to atheroma?
Progressive lumen narrowing due to high grade plaque stenosis
Acute atherothombotic occlusion
Embolism of the distal arterial bed
Ruptured atheromatous abdominal aortic aneurysm
What is an example of progresssive lumen narrowing due to high grade plaque stenosis?
Stenosis atheromatous coronary artery
Stenosis of what leads to peripheral arterial disease?
Stenosis of ileal, femoral or popliteal artery
What does longstanding tissue ischaemia lead to?
Atrophy of the affected organ
What is acute atherothombotic occlusion?
Rupture of plaque leads to acute event
Rupture exposes highly thombogenic plaque contents (collagen, lipid, debris) to bloodstream leading to activation of coagulation cascade
What does total occlusion (blockage) of a vessel lead to?
Irreversible ischaemia and necrosis of tissued
What are examples of things that can occur due to total occlusion of a vessel?
Myocardial infarction (blocked coronary artery)
Stroke (blocked carotid, cerebral artery)
Lower limb gangrene (blocked ileal, femoral, popliteal artery)
What blocked arteries leads to a stroke?
Carotide or cerebral
What blocked artery leads to myocardial infarction?
Coronary
What blocked artery leads to lower limb gangrene?
Ileal, femoral or popliteal
What is embolism of distal arterial bed?
Detachment of small thrombus fragments which embolised distal to ruptured plaque
Leads to embolic occlusion of small vessels, leading to small infarcts in organs
What is ruptured atheromatous abdominal aortic aneurysm?
Media beneath atheromatous plaque gradually weakens
Leads to gradual dilation of the vessel
Then sudden rupture causing haemorrhage
What is ischaemia?
Restriction if the blood supply to tissue
What is a restriction in the blood supply to a tissue called?
Ischaemia
What are vulnerable atheromatous plaques?
Ones that are prone to rupturing with subsequent thrombosis
Typically thin fibrous cap, large lipid core, prominent inflammation
What can be done to prevent atheromatous plaques?
Stop smoking
Control blood pressure
Weight loss
Regular exercise
Dietary modifications
Cholesterol lowering drugs
Aspirin
Surgical options
How do aspirin help to prevent plaques?
Inhibit platelet aggregation to decrease risk of thrombosis on established atheromatous plaques
