• Atherosclerosis is characterized by intimal lesions called atheromas that protrude into vessel lumens.
  • An atheromatous plaque consists of a raised lesion with a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol esterscocered by a white fibrous cap.

Major risk factors for atherosclerosis:

Non modifiable factors –

  1. Age : atherosclerosis is typically progressive, it does not usually manifest clinically until middle age or later
  2. Gender : premenopausal women are relatively protected aginst atherosclerosis compared to age-matched men. After menopause, however, the incidence of atherosclerosis related diseases increases and at older ages actually exceeds that of men
  3. Genetics : family history is theost significant independent risk factor for atherosclerosis. The well established familial predisposition to atherosclerosis is usually multifactorial, relating to inheritance of various genetic polymorphisms and hypertension or diabetes

Modifiable risk factors :

  1. Hyperlipidemia : and more specifically hypercholesterolemia is a major risk factor for atherosclerosis, hypercholesterolemia is sufficient to stimulate lesion development. LDL cholesterol is the form of cholesterol that is delivered to peripheral tissues. In contrast, HDL mobilizes cholesterol from tissue and transports it to the liver for excretion in the bile.
  2. Hypertension : it is the most important cause of left ventricular hypertrophy and hence the latter is also related to IHD
  3. Cigarette smoking : the increased risk and severity of atherosclerosis in smokers is due to reduced level of HDL, deranged coagulation system and accumulation of carbon monoxide in the blood that produces carboxyhemoglobin and eventually hypoxia in arterial wall favouring atherosclerosis.
  4. Diabetes mellitus : the incidence of atherosclerosis is twice as high in diabetics as in non diabetics. There is also an increased fold of strokes and a 100-fold increased risk of atherosclerosis induced gangrene of the lower extremities.

Pathogenesis of atherosclerosis :

  • Endothelial injury – endothelial loss due to any kind of injury results in intimal thickening.
  • The etiological culprits contributing to endothelial cell dysfunction in early atherosclerosis include hypertension, hyperlipidemia, toxins from cigarette smoke, homocysteine and even infectious agents
  • Hemodynamic disturbances – plaques tend to occur at Ostia of existing vessels, branch points, and along the posterior wall of the abdominal aorta, where there are disturbed flow patterns
  • Lipids – the dominant lipids in atheromatous plaques are cholesterol and cholesterol esters. Chronic hypercholesterolemia can directly impair endothelial cell function by increasing local oxygen free radical production; oxygen free radicals can injure tissues and accelerate nitric oxide decay, reducing its vasodulator activity
  • Inflammation – monocytes transform into macrophages and avidly engulf lipoproteins including oxidised LDL . Activated macrophages produce reactive oxygen species that aggrevate LDL oxidation and elaborate growth factors that drive smooth muscle cell proliferation
  • Infection – herpes virus, cytomegalovirus, Chlamydia pneumoniae have all been detected in Atherosclerotic plaques but not in normal arteries.
  • Smooth muscle cell proliferation – initial smooth muscle cell proliferation and ECM deposition convert a fatty streak, the earliest lesion into a mature atheroma and contribute to progressive growth of atherosclerotic lesions

Morphological features of atherosclerosis:

  1. Fatty streaks and dots : they may be the precursor lesions of atheromatous plaques and are prominent in aorta and major arteries
  2. Gelatinous lesions : they develop in the intima of the aorta and may also be the precursora of plaques
  3. Atheromatous plaques : a fully developed atheromatous lesion is called atheromatous plaque. Most often and severely affected is the abdominal aorta. Grossly they are white to yellowish white lesions varying in diameter from 1-2 cm. Microscopically, superficial luminal part of fibrous cap is covered by endothelium, and is composed of smooth muscle xells; cellular area under the fibrous cap is composed of mixture of macrophages, foam cells, lymphocytes; deeper central soft core consists of extracellular lipid material, cholesterol clefts,fibrin; in oldrr and more advanced lesions, the collagen in the fibrous cap may be dense and hyalinised
  4. Complicated plaques – various pathologic changes that occur in fully developed atheromatous plaques are called the complicated lesions. Calcification, ulceration, thrombosis, hemorrhage , aneurysm formation are the complications

Source : Robbins and Cotran’s book of pathology and Harsh Mohan’s textbook of pathology

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