Atheroma Flashcards
Define atheroma
A chronic lesion in the intima that occurs in the arteries, producing narrowing of the lumen and weakening of the vessel wall.
Define atherosclerosis
Hardening of the arteries characteries by intimal lesions (atheromas) that protrude into the vessel lumen.
Define arteriosclerosis
Hardening of the arteries and arterioles which results in thickening of the vessel wall and loss of elasticity
State 5 risk factors for atherosclerosis
Modifiable:
Hyperlipidaemia (LDLs, cholesterol): increases risk of lesion development
Hypertension
Smoking
Diabetes Mellitus: induces high cholesterol
Non-modifiable:
Aging: progressive disease, doesn’t manifest til 40+
Male: premenopausal women protected by oestrogen
Family history
Genetic abnormalities e.g. familial hypercholesterolemia
Risk factors have a multiplicative effect
Name 5 risk markers for atherosclerosis
Obesity
Low HDLs
Sedentary lifestyle
Alcohol
High carbohydrate intake
Low oestrogen post-menopause
Hypothyroidism
Describe the cellular events leading to the formation of athersclerotic lesions
Endothelial injury causes increased vascular permeability and activates endothelium to release cytokines, chemokines and express adhesion molecules.
Increased vascular permability allows lipids to leak into the intima where they are oxidised by free radicals and enzymes
Monocytes adhere to the endothelium, and migrate to the intima where they digest lipids and are transformed into foam cells. Activated macrophages release cytokines that recruit T-cells and APCs. T-cells release cytokines and promote a chronic inflammatory state
Damage to the endothelum exposes collagen and vWF which activates platelets, promoting thrombosis.
Factors released from activated platelets, macrophages and endothelial cells recruit smooth muscle cells from the intima and circulation, which proliferate and produce ECM.
Smooth muscle cells also take up oxidised lipids to become foam cells. There is also intracellular calcification which is deposited as cells degenerate
What is an atheroma?
An intimal lesion (atherosclerotic plaque) that consists of a lipid core (mostly cholesterol) and an accumulation of inflammatory cells, vascular smooth muscle cells and ECM covered by a white fibrous cap made of smooth muscle cells and collagen.
Often undergo calcification
What are the 5 common arteries involved in atherosclerosis?
Abdominal aorta
Coronoary arteries
Legs (poplitieal)
Internal carotid
Cerebral arteries
How does blood flow affect the development of atheroma?
Plaques tend to occur at opening of vessels, branch points and along the posterior wall of the aorta.
Flow is more turbulent in these areas, and they are therefore more susceptible to endothelial damage.
What is a fatty streak?
Deposition of foam cells, ECM and proliferating smooth muscle in the intima. Early lesion which can later develop into a mature atheroma.
What is the composition of atherosclerotic plaques?
Cells: Smooth muscle cells, macrophages, T-cells
ECM: collage, slastin, proteoglycans
Lipid: intracellular and extracellular cholesterol and LDLs
State four things that can damage the endothelium (favours atheroma formation)
Haemodynamic disturbance: hypertension, turbulent flow
Infection
Inflammation: complement, cytokines,
Lipid products
Toxins: bacterial products, smoking
What are the consequences of atherosclerotic disease?
Ischemia: small vessels can become occluded, compromising tissue perfusion
Thrombosis: rupture, ulceration or erosion of the atheromatous plaque can result in thromosis which can partially or completely occlude the lumen
Haemorrhage into a plaque due to a rupture of the fibrous cap, causing it to expand and occlude the vessel
Atheroembolism: plaque can rupture and release debris into the bloodstream
Aneurysm formation: atherosclerosis induces pressure/ischemic atrophy of the media and there is loss of elastic tissue, causing weakness of the vessel wall.
What are the possible complications of an aortic aneurysm?
Rupture
thrombus
emboli
pressure on structures (e.g. vertebrae)
fistulas to the GI tract
What factors affect plaque stability?
Intrinsic factors: Plaque structure and composition
Extrinsic factors: Blood pressure, Platelet reactivity
The compositon of plaques is dynamic and this can affect stability, those with large areas of foam cells or thin fibrous caps are more likely to rupture
Rupture of a plaque means it was unable to withstand the vascular shear forces of blood flow.
How do abdominal aortic aneurysms develop?
Atherosclerotic plaque in the intima compresses the underlying media and compromoses the blood supply from the vascular lumen to the arterial wall.
Lack of nutrients and waste removal causes atrophy and necrosis that results in weakening and thinning of the arterial wall. This causes it to dilate in response to the high pressure of the blood running through it as the structure cannot be maintained.
