Pathophysiology of atheroma Flashcards
What is athersclerosis
-Formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries
What is an atheroma?
degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis.
What is the serious consequence of atheroma?
Angia due to myocardial ischaemia
What happens in arteriosclerosis?
-Age related change in muscular arteries
-Reduplication of internal elastic laminae and intimal fibrosis
Causing a decrease in vessel diameter
What does arteriosclerosis contribute to?
cardiac
cerebral
colonic
and renal ischemia
What is a fatty streak ?
Earliest significant lesion
Who is effected by fatty streak?
Young children
What does a fatty streak look like?
Yellow linear elevation of intimal lining
What makes up a fatty streak?
lipid -laden macrophages
Is there any clinical significance to the fatty streak?
NOPE
Who is affected by early atheromatus plaque?
Young adults onwards
What does an early atheromatous plaque look like?
Smooth yellow patches in intima
What do fully developed atheromatus plaque look like?
Central lipid core with fibrous tissue cap covered by arterial endothelium
What provides strength to atheroma when fully developed?
Collagens
What type of cells can be found in fully developed atheroma and where?
Inflammatory cells- (macrophages, T-lymphocytes, mast cells) in fibrous cap
What is the central core of a fully developed atheromatous plaque made from?
Lipids rich in cellular debris derived from macrophages
What are the characteristics of an atheroma?
- Soft
- High thrombogenic
- often rim of foamy macrophages
Why are macrophages described as foamy?
Uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor
What makes an atheroma complicated?
Feature of established atheromatous plaque plus haemorrhage into plaque or fissuring or thrombosis
What happens to haemorrhage when it heals?
Turns to calcification which shows up on angiograms and CT`s
What is the most important risk factor of atheroma?
HYPERCHOLSTEROLAEMIA
What happens in hypercholestrolaemia?
Genetically determined lack of LDL receptors
Caucasians inherit this how?
heterozygously
How many people have hypercholesterolaemia?
1/500
What is corneal arcus?
white rim outside iris
What is tendon xanthomata?
Lumps of fat on knuckles ,achilles
What are some major risks factors of atheroma? (6)
- Smoker
- Hypertensive
- Diabetes mellitus
- Male
- Elderly
- Accelerate process of plaque formation driven by lipids
What is the two step process of developing atheromatous plaque?
- Injury to endothelial of artery
2. Chronic inflammatory and healing response of vascular wall to agent causing injury
What is the sequence of developing atheromatous plaques?
- Endothelial injury
- Accumulation of lipoproteins (LDL)
- Monocyte adhesion-transform into foamy
- Platelet adhesion
- Factor release from activated platelets, macrophages–smooth muscle recruitment
- Smooth muscle cell proliferation, extracellular matrix production and t-cell recruitment
- Lipid accumulation (extracelluar and foamy)
What is the possible causes of endothelial injury?
- Haemodynamic disturbances
- hypercholsterolaemia
How does chronic hypercholesterolaemia damage endothelium
Increasing local production of reactive oxgyen species
How does local hypercholesterolaemia release reactive oxygen species?
liporoteins aggregate in intima and are modified by free radicals produced by inflammatory cells. Modified LDL accumulated by macrophages but not completely degraded –foamy macrophages- toxic to endothelial cells plus release of growth factors, cytokines
How do injured endothelial cells function differently?
- Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin)
- High permeability for LDL
- Increased thrombogenicity
What is formed at denuded areas of plaque surface?
Microthrombi
What happens 50-70% of vessel lumen is stenosed?
critical reduction of blood flow in distal arterial bed-> reversible tissue ischaemia
What does a stenosed atheromatous coronary artery
Stable angia
What happens with a ruptured atheromatous abdominal aortic aneursym suddenly ruptures?
Massive retroperitoneal haemorrhage
What does a typical vunerable atheromatous plaques?
Typically thin fibrous cap, large lipid core, prominent inflammation
What can prevent atheroma build up?
- Stop smoking
- control blood pressure
- Weight-loss
- Regular exercise
- Dietary modifications
Secondary prevention?
Cholesterol lowering drugs, aspirin
