Pathophysiology of atheroma Flashcards
what is atherosclerosis?
Formation of focal elevated lesions (plaques) in intima (innermost membrane or layer- nearest lumen) of large and medium-sized arteries
what can the formation of atheromatous plaques in narrow lumen of arteries cause
ischaemia (restriction in blood supply to tissues)
what is a serious consequence of atheroma
angina due to myocardial ischaemia
what is arteriosclerosis
thickening and hardening of the walls of the arteries age-related change in muscular arteries
what things can cause a decrease in vessel diameter? (3)
- smooth muscle hypertrophy (growth and increase of the size of muscle cells)
- apparent reduplication of internal elastic laminae
- intimal fibrosis
what other condition does arteriosclerosis contribute greatly to in the elderly?
cardiac, cerebral, colonic and renal ischaemia (ie reduction of blood flow to these organs/tissues)
When are the clinical affects of arteriosclerosis most apparent?
when the CVS has been further stressed by haemorrhage, major surgery, infection, shock
Describe atheroma being just a fatty streak
- earliest significant lesion
- found in young children
- yellow linear elevation of intimal lining
- no clinical significance - might disappear
- at risk of developing atheromatous plaques
What is atheroma?
the fatty material which forms deposits in the arteries
Early atheromatous plaque?
- Young adults onwards
- •Smooth yellow patches in intima
- •Lipid-laden macrophages
- •Progress to established plaques
Fully developed atheromatous plaque?
Central lipid core with fibrous tissue cap, covered by aterial endothelium
- Collagens in cap provide structural strength - these collagen fibres are produced by smooth muscle cells
- Inflammatory cells (macrophages, T-cells, mast cells) residue in fibrous cap: recruited from arterial endothelium
Soft, highly thrombogenic, often rim of “foamy” macrophages (“foamy” due to uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor)
- Dystrophic calcification extensive, occurs late in plaque development.
- Form at arterial branching points/bifurcations (turbulent flow)
- Late stage plaques: confluent, cover large areas
List the 3 stages of arethoma
Fatty streak
Early atheromatous plaque
Fully eveloped atheromatous plaque
Define ‘dystrophy’
a disorder in which an organ or tissue of the body wastes away
Describe two-step process of atheromatous plaque development
- 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 → formation of atheromatous plaques
Describe ‘complicated atheroma’
Features of established atheromatous plaque (lipid-rich core, fibrous cap)
Haemorrhage into plaque can cause a rapidly developing stenosis or occlusion to vessel
Plaque rupture/fissuring - Scarring transforms “soft” atheromas into “firm” atheromas, which calcify and become extremely hard and brittle
Thrombosis - material in the plaque contains thromboplastin which will trigger blood clotting, and a thrombus will develop at the site of intimal ulceration.
What is the most important risk factor contributing to atheroma formation?
Hypercholesterolaemia - high cholesterol - Causes plaque formation and growth in absence of other known risk factors
Describe why elevated plasma levels of LDL cholesterol is detrimental?
Low-density lipoprotein (LDL) – carries cholesterol to the cells that need it, but if there’s too much cholesterol for the cells to use, it can build up in the artery walls. Important to keep cholesterol levels low. The liver removes LDL and other lipoproteins from the circulation by receptor-mediated endocytosis
What are some signs of major hyperlipidaemia?
- Familial/primary vs acquired/secondary (?idiopathic)
- Biochemical evidence: LDL, HDL, total cholesterol, triglycerides in plasma
- Corneal arcus (if premature)- white, grey, or blue opaque ring in the corneal margin, or white ring in front of the periphery of the iris - often seen in elderly
- Xanthelasmata/ Tendon xanthomata (knuckles, Achilles) skin lesions due to having too much fat in macrophages or more rarely in the adipose tissue
- Risk/premature/family history MI/atheroma
Other more general risk factrs for atheroma
- Smoking
- Hypertension
- Diabetes mellitus
- Male
- Elderly
- Accelerate process of plaque formation driven by lipids
How do endothelial cells become functionally altered when injured?
- Enhanced expression of cell adhesion molecules
- High permeability for LDL
- Increased thrombogenicity
How does plaque volume gradually increase?
Repeated cycles of damage/repair
ileal, femoral, popliteal artery stenosis can cause what
Peripheral arterial disease - build-up of fatty deposits in the arteries restricts blood supply to leg muscles
Total occlusion of blood vessel can lead to what?
Irreversible ischaemia (reduced blood flow to organs) which in turn causes necrosis (infarction) of tissues
E.g myocardial infarction - coronary artery
stroke- carotid, cerebral artery
lower limb gangrene (like necrosis but is tissue death due to some form of interrupted blood supply)- ileal femoral, popliteal artery
Preventative and therapeutic approaches for atheroma?
Stop smoking
control blood pressure
weight loss
regular exercise
dietary modifications
Secondary prevention - cholesterol lowering drugs, aspirin, surgery
How does aspirin work as an atheroma preventative drug?
inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques
summary of atheroma and heart disease
Coronary heart disease is caused by narrowing of the arteries that supply the heart with blood. This narrowing of the arteries is called atherosclerosis. Fatty deposits, such as cholesterol, cellular waste products, calcium and other substances build up in the inner lining of an artery. This build up, known as plaque, usually affects small and medium sized arteries. The flow of blood through the arteries is restricted as the inside diameter is reduced. Blood clots, which often happen in the coronary arteries during a heart attack, are more likely to develop when arterial walls are roughened by the build up of fatty deposits.
Describe hypercholesterolaemia
Familial hypercholesterolaemia (FH) is an inherited disorder that causes high levels of LDLs to be present in the body and is a disorder that is often caused by a mutated LDL receptor gene. FH can lead to early cardiovascular disease and heart attacks at a young age.
When LDL receptors do not function correctly, LDL stays in the bloodstream longer than it should. LDL then gets into the artery walls, where it can harden and narrow the passages in the arteries.
