Atheroma Pathophysiology Flashcards
What is the difference between atherosclerosis and arteriosclerosis
Arteriosclerosis is not atheromatous
Is an age-related change in muscular arteries
Smooth muscle hypertrophy, apparent reduplication of internal elastic laminae
What is the general structure of a fully developed atheromatous plaque?
Central lipid core with fibrous tissue cap, covered by arterial endothelium.
What is the structure of the fibrous cap in an atheroma?
Collagens provide structural strength
Inflammatory cells reside in cap also (macrophages, lymphocytes, mast cells)
What is in the central lipid core of an atheroma?
Central lipid core rich in cellular lipids/debris derived from macrophages that have died in the plaque
It is soft, highly thrombogenic, often have a rim of ‘foamy’ macrophages.
Dystrophic calcification extensive and occurs late in plaque development
Form at arterial branching points
What are the features of a complicated atheroma?
Features of an established atheromatous plaque
Haemorrhage into plaque (calcification)
Plaque ruptures/fissuring
Thrombosis
What causes atheroma?
Hypercholesterolaemia the most important risk factor.
Importance of LDL - genetic mutation leading to decreased LDL receptors causing hypercholesterolaemia known (1/500 heterozygous)
Rarely, 1/1million are homozygous - usually die from coronary artery atheroma in infancy/teens
What are some signs of major hyperlipidaemia?
Can be familial or acquired.
Biochemical evidence - LDL, HDL, total cholesterol, triglycerides. Corneal arcus Tendon xanthomata Xanthelasma Risk/premature/FH of MI/atheroma
What are some risk factors for atheroma?
Huge variation in disease severity among patients with same cholesterol levels
Smoking Diabetes Male Elderly Hypertension All accelerate process of plaque formation driven by lipids.
Less strong risk factors:
- obesity
- sedentary lifestyle
- socioeconomics
What is the process for the development of an atheromatous plaque in terms of steps, and order of events?
Two step process:
- injury to endothelial lining of artery
- chronic inflammatory and healing response of vascular wall to agent causing injury
Order of events:
Endothelial injury
Accumulation of LDL in vessel wall
Monocyte adhesion and migration into intima (transform to foamy macrophages)
Platelet adhesion
Factor release from activated platelets, macrophages > smooth muscle cell recruitment
Smooth muscle cell proliferation, ECM production and T-cell recruitment
Lipid accumulation - extracellular and in foamy macrophages
What are the main causes of endothelial injury leading to atheroma?
Haemodynamic disturbances
Hypercholesterolaemia
- can directly impair endothelial cell function (by ROS production)
- lipoproteins aggregate in intima and are modified
In what way are injured endothelial cells functionally altered?
Enhanced expression of cell adhesion molecules
High permeability for LDL
Increased thrombogenicity
Inflammatory cells, lipids > intimal layer > plaques
What are the typical features of a vulnerable plaque? (Likely to rupture into thromboses)
Thin fibrous cap
Large lipid core
Prominent inflammation
Pronounced inflammatory activity > degradation, weakening of plaque > risk of rupture
Highly stenotic plaques often have large fibrocalcific component, with little inflammation
Some examples of prevention/therapy for atheroma?
Stop smoking Control BP Weight-loss Regular exercise Dietary modifications
Cholesterol lowering drugs
Aspirin
Surgery
