Pathophysiology of atheroma Flashcards
What is an atheroma/atherosclerosis?
- formation of focal eleveted lesions ( plaques) in T.intima of large + medium sized arteries
- hardening of artery
Describe features of arteriosclerosis
- umberella term
- when muscular arteries change with age due to hardening.
- atherosclerosis/arteriolosclerosis
Describe the formation of an atheroma
- Damage to the endothelium will cause the LDL to enter the endothelial cells. Monocytes (transforms into foamy macrophages) will follow the LDL and attempt to break them down through oxidation.
- High LDL means that macrophages will engulf too much LDL > death.
- dead macrophages(foamy macrophages) will deposit under the damaged endothelium and releases cytokines which signals other monocytes > dead.
- The foam cells will accumulate into a lesion = FATTY STREAK(earliest stage)
- This fatty streak is thrombogenic and can cause blood to clot on it.
- Platelet(activated) adhesion to endothelium and migrates to the damaged endothelium and release a growth factor which encourages growth of SM cells whichrecruit in the fatty streak in the T.intima.
- SM cells will release collagen, mucopolysaccharidess + elastin > ECM production ). This forms the FIBROUS CAP which encloses lipid rich core.
- Plaque prevents removal of Ca2+ by LDL due to HDL unable to do its job ( remove). In turn, calcium builds up in vessel wall + crystalises (calcification) on walls of artery.
- This process causes inflammation. C -reactive protein increases ( indication of infection/inflammation. Inflammatory reaction takes place and process of tissue repair.
- proteolytic ennzymes, cytokines and RAS will be produced by plaque inflammatory cells in attempt to degrade plaque
- Growth factors will also be secreted by platelets, SM, macrophages and injured endothelium
- endothelial loss can also cause plaque growth
When can fatty streaks be found? What is it?
- young children.
- can disappear
- Yellow linear elevation of intimal lining
- composed of lipid0laden macrophages
When can an early atheromatous plaque be formed and what is it?
- Young adults onwards
- smooth yellow patches in intima
- lipid laden macrophages
What may be found in the central lipid core of a fully developed atheromatous plaque?
- rich in cellular lipid/debris from dead macrophages ( died in plaque)
- fibrous tissue cap surrounds it
- collagen ( produced by SM cells) provide it structural strength.
- inflammatory cells such as macrophages, T.lymphocytes, mast cells ( C.reactive protein produced) reside in fibrous cap
Microthrombi in established plaques
-formed at plaque surface + organised by same repair process ( SM cell invasion, collagen deposition)
Why are the macrophages ‘Foamy’?
-due to the uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor
When may calcification occur? And where?
- occurs in late plaque development and forms at arterial branching points/bifurcations(turbulent flow)
- late stage plaques cover large areas
Complicated atheroma
REMVOE
- features of established atheromatous plaque ( lipid-rich core, fibrous cap) + haemorrhage into plaque (calcification)
- plaque rupture/fissuring + thrombosis may occur
What is hypercholesterolaemia?
-high blood cholesterol
Effect of hypercholesterolaemia
-LDL deposits on the walls of arteries and macrophages engulf this. Overtime leads to astherosclerotic plaques.
Mutation of hypercholestorolaemia
- lack of LDL membrane receptors. Prevents uptake of LDL of peripheral cells so > high plasma LDL cholesterol
- caucasions is heterozygous for this mutation
- rare patients homozygous with a much higher cholesterol level and die from coronary artery atheroma in infancy/teens
Types of hypercholesterolaemia
hyperlipidaemia, hyperlipidproteinaemia..
Biochemical Signs of major hyperlipidaemia
Biochemical evidence: LDL, HDL, total cholesterol, triglycerides
