Slowly progressive multifactorial degenerative process of the elastic and muscular arteries, characterised by patchy deposition of fatty substances/lipids (intimal plaques), intimal proliferation/enlargement of plaque and intimal tears narrowing of vessel lumen clinical features.
Atherosclerosis is the leading cause of death and disability in the developed world:
• in the coronary arteries angina pectoris, myocardial infarction
• in the CNS arteries transient ischaemic attacks, stroke
• in the splanchnic arteries mesenteric ischaemia, bowel infarction
• in the renal arteries renal artery stenosis, hypertension
• in peripheral arteries arterial insufficiency
Risk factors for athersclerosis – smoking, dyslipidaemia, hypertension, sedentary lifestyle, obesity, diabetes mellitus, male, age, homocystiene
Initial event in pathogenesis is injury to the endothelial cells. Injury may be due to (eg):
• smoking chemical irritation
• hypertension turbulent blood flow
• oxidised LDL
• glycated substances in diabetes mellitus
• immune complexes
• viral or bacterial infection
• vasoactive agents
The injury results in endothelial dysfunction impaired vasodilation, increased permeability to lipoproteins, increased adhesiveness of endothelial cells ( platelet deposition).
LDL changes endothelial cell properties, increasing the potential of adherence of cells and other substances to wall of artery. Platelets adhere to injured endothelium (platelet aggregation), small blood clots form (mural thrombi) release growth factors and vasoactive substances (especially thromboxane A2, a potent vasoconstrictor additional injury).
Lipids taken up by endothelial cells increased adherence to cell endothelium.
Monocytes adhere to endothelium, migrating to the intima transform into macrophages (these convert mildly oxidised LDL to highly oxidised LDL enters endothelial cells more readily).
Growth factors (eg platelet derived growth factor) increase binding of monocytes to endothelium and increase the number of LDL receptors greater deposition of cholesterol in endothelium and in macrophages.
Smooth muscle cells and fibroblasts migrate from media to intima in response to growth factors. Some cells accumulate cholesterol (foam cells) release cholesterol into extracellular space fatty streaks (first visible lesion of atherosclerosis).
Smooth muscle, fibrous connective tissue, cholesterol and fibrous debris continues to proliferate and accumulate progression in size (appears as a firm fibromuscular plaque with a cholesterol core – ‘atheroma’)
With advanced atherosclerosis (especially the aorta), cholesterol crystals can microembolise to the lower extremities (especially following vascular surgery).
Clinical features – pulse’s often normal; restless leg type symptoms are common; digital cyanosis; livedo reticularis