A chronic lesion in the intima that occurs in the arteries, producing narrowing of the lumen and weakening of the vessel wall.
Hardening of the arteries characteries by intimal lesions (atheromas) that protrude into the vessel lumen.
Hardening of the arteries and arterioles which results in thickening of the vessel wall and loss of elasticity
State 5 risk factors for atherosclerosis
Hyperlipidaemia (LDLs, cholesterol): increases risk of lesion development
Diabetes Mellitus: induces high cholesterol
Aging: progressive disease, doesn't manifest til 40+
Male: premenopausal women protected by oestrogen
Genetic abnormalities e.g. familial hypercholesterolemia
Risk factors have a multiplicative effect
Name 5 risk markers for atherosclerosis
High carbohydrate intake
Low oestrogen post-menopause
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?
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
Inflammation: complement, cytokines,
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?
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 can the circadian pattern of onset of acute MI be explained?
Blood pressure is an extrinsic factor that affects stability of atheromatous plaques. Adrenergic stimulation can increase systemic blood pressure or induce local vasoconstriction which increases the stress on the plaque.
Adrenergic stimulation is involved in standing from a horizontal/seated position causing a sudden increase in blood pressure.
What determines the effect of atheroma on distal tissue?
Effects of atheroma on the tissue supplied distally is determined by:
size of the lumen
stability of the plaque
degree of degeneration of the underlying wall
natural history of the plaque
type of blood supply
What is an aneurysm?
Localised abnormal dilation of a blood vessel or the heart
True aneurysm involves an intact, attenuated arterial wall or a thinned ventricular wall of the heart.
Occur when the structure or function of the connective tissue in the vascular wall is compromised
What are the two most common disorders that predispose to aortic aneurysms?
athersclerosis (abdominal aorta) and hypertension (ascending aorta)
Other conditions; trauma, vasculitis
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.
What is endothlial dysfuntion?
Altered phenot type of the endothelial cells that impairs vasoreactivity or induces a thrombogenic surface
What are the symptoms of peripheral vascular disease?
Intermittent claudication (muscle cramp normally in the calf, during exercise which resolves with rest)
Pain at rest (unremitting pain in the foot)
Ischaemic limb (ulceration or gangrene)
Cold limbs with dry skin and lack of hair
What are the effects of atherosclerotic plaques in the mesenteric arteries?
Chronic bowel ischemia
Can result in mesenteric angina (pain following a meal)
or ischemic colitis (necrosis of the bowel tissue causing diarrhoea)
What are the effects of atherosclorotic plaques in the cerebral arteries
Vascular dementia - occurs due to small emboli lodging in the vessels causing cellular damage. Presents as a stepwise decline with each new emboli (not progressive)
TIA: neurological symptoms due to ischemia (dizzyness, parasthesia)
Cerebrovascular accident: affects vision, cognition, motor function
What is the effects of atherosclerosis on the heart?
Myocardial ischemia (90% caused by atherosclerotic plaques in the coronary arteries).
Can result in MI, angina, heart failure or sudden cardiac death
Obstruction of 75% of the lumen is required to cause symptoms (angina) beause compensatory vasodilation is no longer sufficient to meet increases in myocardial demand.
Name four effects of atheroma
Plaque rupture: leading to thrombus formation and/or emboli which causes occlusion
Bleeding into atheroma: causes occlusion
Chronic narrowing of the lumen: reduces blood flow, causes chronis ischemia
Weakening of vessel wall: aneurysm