Flashcards in Pathophysiology of Atheroma Deck (54)
What is atherosclerosis?
Formation of focal elevated lesions (plaques) in the intima of large and medium sized arteries
What does atheroma in the coronary arteries result in?
Narrowing of the lumen due to atheromatous plaques, this in turn causes ischaemia and angina and can be complicated by thromboembolism
What is arteriosclerosis?
Age-related change in the muscular arteries
What does arteriosclerosis result in?
Smooth muscle hypertrophy
Apparent reduplication of internal elastic laminae
Intimal fibrosis leading to decreased vessel diameter
What does arteriosclerosis contribute to in the elderly?
High frequency of cardiac, cerebral, colonic and renal ischaemia
When are the clinical effects of arteriosclerosis most apparent?
When CVS is further stressed by haemorrhage, major surgery, shock, infection etc.
What is atheroma?
The earliest significant lesion in atherosclerosis
Yellow linear elevation of the intimal lining
What is an atheroma lesion comprised of?
Masses of lipid-laden macrophages
In what way is atheroma relevant?
No clinical significance, only relevant in patients at risk as it may develop into an atheromatous plaque
When are early atheromatous plaques seen?
Young adults onwards
What are the features of early atheromatous plaques?
Smooth yellow patches in the intima
Can progress to established plaques
What are the features of a fully developed plaque?
Central lipid core with fibrous tissue cap
Covered by arterial endothelium
Collagens in the cap provide structural strength
Inflammatory cells reside in the fibrous cap
Central lipid core is rich in cellular lipids and debris derived from the macrophages
Soft, highly thrombogenic ring of foamy macrophages
Extensive dystrophic calcification
Late stage plaques are confluent and cover large areas
What do macrophages in fully developed plaques have a foamy appearance?
Due to uptake of oxidised lipoproteins via specialised membrane bound scavenger receptors
What might provide a marker for atherosclerosis in angiograms and CT scans?
Where do calcifications form?
At arterial branching points and bifurcations due to turbulent flow
What are the features of a complicated atheroma?
Features of established atheromatous plaque plus;
Haemorrhage into the plaque, calcification
What are the two steps involved in the development of atheromatous plaques? How do these steps result in formation of atheromatous plaques?
Injury to the endothelial lining of the artery
Chronic inflammatory and healing response of the vascular wall to the agent causing the injury
Chronic and episodic exposure of arterial wall to these processes is what results in the formation of atheromatous plaques
What is the order of events in atherosclerosis development?
Endothelial injury and dysfunction
Accumulation of lipoproteins in the vessel wall
Monocyte adhesion to the endothelium, migration into the intima and transformation to foamy macrophages
Factor release from activated platelets and macrophages causing smooth muscle cell recruitment
Smooth muscle cell proliferation, ECM production and T-cell recruitment
What are the most important causes of endothelial injury?
Haemodynamic disturbances e.g. turbulent flow, hypercholesterolaemia
How can chronic hypercholesterolaemia directly impair endothelial cell function?
By increasing local production of reactive oxygen species;
Lipoproteins aggregate in the intima and are modified by free radicals produced by inflammatory cells
Modified LDL accumulated by macrophages but not completely degraded
Foamy macrophages accumulate
These are toxic to endothelial cells plus release growth factor and cytokines
How are injured endothelial cells functionally altered?
Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin)
High permeability for LDL
Inflammatory cells and lipids accumulate in intimal layer and form plaques
In advanced plaque formation there are large number of what cells?
Macrophages and T-lymphocytes
What does response to endothelial injury involve?
The chronic inflammatory process
What do growth factors cause in the intimal smooth muscle cells?
Proliferation of the intimal smooth muscle cells and subsequent synthesis of collagen, elastin and mucopolysaccharides
What are growth factors secreted by?
Smooth muscle cells
In established plaques, what is plaque growth initiated by (besides growth factors)?
Small areas of endothelial loss
Microthrombi formed at denuded areas of the plaque surface are organised by the same rear process
Repeated cycles gradually increase the plaque volume
What are the main components of an atheromatous plaque?
Central lipid core
Fibrous tissue cap
Arterial endothelial lining
Collagen in fibrous cap
Inflammatory cells in fibrous cap
Rim of foamy macrophages
What is the most important risk factor for atheroma? Why?
It causes plaque formation and growth in the absence of other known risk factors
What proportion of Caucasians are heterozygous for a mutation resulting in genetically determined lack of cell membrane receptors for LDL?