Pathophysiology of atheroma Flashcards
What is atheroma/atherosclerosis?
Formation of focal elevated lesions (plaques) in intima of large and medium-sized arteries
What can atheromas cause?
Serious consequences: angina due to myocardial ischaemia
- Complicated by thromboembolism
What is arteriosclerosis?
- It is not atheromatous.
- Age-related change in muscular arteries
- Age-related change in muscular arteries
- Smooth muscle hypertrophy, apparent reduplicationof internal elastic laminae, intimal fibrosis causes a decrease in vessel diameter
How does arteriosclerosis affect the body?
Contributes to high frequency of cardiac, cerebral, colonic and renal ischaemia in elderly.
When are clinical features of arteriosclerosis most apparent?
They are most apparent when CVS further stressed by haemorrage, major surgery, infection, shock.
Is it possible to have arteriosclerosis and atheromatous together?
YES
What is a Fatty streak in atherosclerosis?
- It is the earliest visible lesion of atherosclerosis
- It is due to an accumulation of lipid-laden foam cells in the intimal layer of the artery.
What is the main hallmark of established atherosclerosis?
Over time , the fatty streak evolves into a fibrous plaque, the hallmark of established atherosclerosis.
- Patients are at risk when there are atheromatous plaques
Features of a Fatty streak
- Earliest significant lesion
- Seen in young children
- Yellow linear elevation of intimal lining
- Comprises masses of lipid-laden macrophages
- No clinical significance
- May disappear
Features of early atheromatous plaque
- Seen in young adults onwards
- Smooth yellow patches in intima
- Lipid-laden macrophages
- Progress to established plaques
What does a fully developed atheromatous plaque contain?
- Central lipid core with fibrous tissue cap, covered by arterial endothelium
- Collagens (produced by smooth muscle cells) in cap provide structural strength
- Inflammatory cells (macrophages, T-lymphocytes, mast cells) reside in fibrous cap: recruited from arterial endothelium.
- Central lipid core rich in cellular lipids/debris derived from macrophages (died in plaque)
- Soft, highly thrombogenic, often rim of “foamy” macrophages
Features of complicated atheroma
- It has the same features of established atheromatous plaque (lipid-rich core, fibrous cap) plus:
- Haemorrhage into plaque (calcification)
- Plaque rupture/fissuring
- Thrombosis
What is calcified atheroma?
Aortic valve calcification is a condition in which calcium deposits form on the aortic valve in the heart.
- These deposits can cause narrowing at the opening of the aortic valve. This narrowing can become severe enough to reduce blood flow through the aortic valve — a condition called aortic valve stenosis.
Aetiology of atheroma
- Hypercholesterolaemia is the most important risk factor.
- Causes plaque formation and growth in absence of other known risk factors
- Importance of LDL cholesterol: studies of patients/animals with genetically determined lack of cell membrane receptors for LDL.
What is hypercholesterolaemia?
Hypercholesterolemia (high cholesterol), is the presence of high levels of cholesterol in the blood.
- It is a form of hyperlipidemia, high blood lipids, and hyperlipoproteinemia (elevated levels of lipoproteins in the blood).
What is the LDL cholesterol problem in 1/500 caucasians?
- Decreased functional receptors on cell surfaces.
- Elevated plasma LDL cholesterol levels.
What are signs of major hyperlipidaemia?
- Familial/primary vs acquired/secondary
- Biochemical evidence: LDL, HDL, total cholesterol, triglycerides
- Corneal arcus (premature)
- Tendon xanthomata (knuckles, achilles)
- Xanthelasmata
- Risk/premature/family history MI/atheroma
Risk factors for atheroma
- Smoking
- Hypertension
- Diabetes mellitus
- Being male
- Being old
These accelerate process of plaque formation driven by lipids.
Other risk factors: huge variation in disease severity among patients with same cholesterol levels.
Less strong risk factors for atheroma
- Obesity
- Sedentary lifestyle
- Low socio-economic status
- Low birthweight
- ?role of micro-organisms?
Two step process in the development of atheromatous plaques
- Injury to endothelial lining of artery
- Chronic inflammatory and healing response of vascular wall to agent causing injury
Chronic/episodic exposure of arterial wall to these processes causes formation of atheromatous plaques.
Order of events in the pathogenesis of atherosclerosis
- Endothelial injury and dysfunction
- Accumulation of lipoproteins (LDL) in vessel wall
- Monocyte adhesion to endothelium > migration into intima and transformation to foamy macrophages.
- Platelet adhesion
- Factor release from activated platelets, macrophages > smooth muscle cell recruitment
- Smooth muscle cell proliferation, extracellular matrix production and T-cell recruitment.
- Lipid accumulation (extracellular and in foamy macrophages).
What are the most important causes of endothelial injury?
- Haemodynamic disturbances (turbulent flow)
- Hypercholesterolaemia (chronic hypercholesterolaemia can directly impair endothelial cell function by increasing local production of reactive oxygen species)
In hypercholesterolaemia, how do lipoproteins aggregate?
- lipoproteins 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 are injured endothelial cells functionally altered?
- Enhanced expression of cell adhesion molecules (ICAM-1, E-selectin)
- High permeability for LDL
- Increased thrombogenecity
Inflammatory cells, lipids → intimal layer → plaques
