Atherosclerosis

  • Arteriosclerosis means hardening of arteries.
  • It is a generic term for arterial wall thickening and loss of elasticity.
  • There are 3 general patterns
  1. Arteriosclerosis
  2. Monckeberg medial sclerosis
  3. Atherosclerosis

 

  • Arteriosclerosis affects small arteries and arterioles,the 2 anatomical Variants are
  1. Hyaline
  2. Hyperplastic atherosclerosis
  • Monckeberg medial sclerosis is characterized by the calcification of the walls of the muscular arteries.
  1. Persons older than age 50 are most commonly affected.
  2. Usually not clinically significant.
  • Atherosclerosis means hardening and is the most frequent and clinically important pattern

 

Atherosclerosis:

  • The likelihood of atherosclerosis is determined by the combination of acquired and inherited risk factors.
  • Acting together they cause intimal lesions called atheromas that protude into vessel lumens.
  • An atheroma or atheromatous plaque consists of raised lesions with a soft grumous core of lipid covered by a fibrous cap.
  • Besides mechanically obstructing blood flow , atherosclerotic plaques can rupture leading to catastrophic obstructive vascular thrombosis.
  • Atherosclerotic plaque can also increase the diffusion distance from lumen to media, leading to ischemic injury and weakening of the vessel wall, changes that may result in aneurysm formation.

 

Major risk factors for atherosclerosis:

  • Nonmodifiable(constitutional)
  1. Genetic abnormalities
  2. Family history
  3. Increasing age
  4. Male gender
  • Modifiable
  1. Hyperlipidemia
  2. Hypertension
  3. Cigarette smoking
  4. Diabetes
  5. Inflammation

 

Constitutional risk factors:

  • Genetics: family history is the most important independent risk factor for atherosclerosis.
  • Age is dominant influence. Thus ages between 40-60,the incidence of myocardial infarction increases five -fold.
  • Gender: other factors being equal , premenopausal women are relatively protected against atherosclerosis and it’s consequences compared to age-matched men.
  • After menopause , the incidence of atherosclerosis related diseases increase in women and at older ages actually exceeds that of men.

 

 

Modifiable major risk factors:

  • Hyperlipidemia: and more specifically hypercholesterolemia is a major risk factor for atherosclerosis; even in the absence of other risk factors, hypercholesterolemia is sufficient to initiate lesion development.

 

Note:

  • LDL is the complex that delivers cholesterol to peripheral tissues;in contrast, HDL is the complex that mobilizes Cholesterol from periphery and transport it to liver for excretion in bile.
  • Hence LDL is called bad Cholesterol and HDL as good cholesterol.

 

  • Omega-3fatty acids are beneficial, whereas unsaturated fats produced by artificial hydrogenation of polyunsaturated oils adversely affect cholesterol profile

Hypertension:

  • It is another major risk factor for atherosclerosis;both systolic and diastolic levels are important.
  • Chronic hypertension is the most common cause of left ventricular hypertrophy, and hence the latter is also a surrogate marker for cardiovascular risk.

 

Cigarette smoking:

  • It is a well established risk factor in men and likely accounts for increasing incidence and severity of atherosclerosis in women.

 

Diabetes mellitus:

  • Diabetes mellitus induces hypercholesterolemia and markedly increases the risk of atherosclerosis.

 

Additional risk factors are:

  • Inflammation
  • Hyperhomocystinemia
  • Metabolic syndrome
  • Lipoprotein a levels
  • Factors affecting hemostasis

 

Pathogenesis of atherosclerosis:

  • The hypothesis that explains the pathogenesis is known as response to injury hypothesis.
  • This model views atherosclerosis as a chronic inflammatory and healing response of the arterial wall to endothelial injury.
  • Lesion progression occurs through interaction of modified lipoproteins,monocyte-derived macrophages, and T-lymphocytes with endothelial cells and smooth muscle cells of the arterial wall

 

  • The sequence of events according to this scheme are:
  1. Endothelial injury and dysfunction, causing increased vascular permeability, leucocyte adhesion and thrombosis.
  2. Accumulation of lipoproteins in the vessel wall
  3. Monocyte adhesion to the endothelium, followed by migration into the intima and transformation into macrophages and foam cells
  4. Platelet adhesion
  5. Factors release from activated platelets, macrophages, and vascular wall cells, inducing smooth muscle cell recruitment,either from the media or from circulating precursors.
  6. Smooth muscle cell proliferation, extracellular matrix production,and recruitment of T cells.
  7. Lipid accumulation both extracellularly and within cells.

 

Morphology:

Fatty streaks:

  • Fatty streaks are composed of lipid-filled foamy macrophages.
  • Beginning as multiple minute flat yellow spots, they eventually coalesce into elongated streaks 1cm long or longer.
  • These lesions are not sufficiently raised to cause any significant flow disturbances.

 

Atherosclerotic plaque:

  • The key process in the atherosclerosis are intimal thickening and lipid accumulation, which together form plaques.
  • Atherosclerotic plaques are white-yellow and encroach on the lumen of the artery; superimposed thrombus over ulcerated plaques is red-brown.
  • Atherosclerotic lesions are patchy, rarely circumferential on cross-section
  • In descending order , the most extensively involved vessels are the
  1. Lower abdominal aorta
  2. The coronary arteries
  3. The popliteal arteries
  4. The internal carotid arteries and the
  5. Vessels of the circle of Willis

 

  • In humans, the abdominal aorta is typically involved to much greater degree than the thoracic aorta.
  • Atherosclerotic plaques have 3 principal components
  1. Smooth muscle cells, macrophages,and T cells
  2. Extracellular matrix, including collagen, elastic fibres and proteoglycans
  3. Intracellular and extracellular lipid

 

  • Atherosclerotic plaques are susceptible to the following clinically important pathologic changes
  1. Rupture, ulceration, or erosion of the surface atherosclerotic plaques
  2. Hemorrhage into a plaque
  3. Atheroembolism
  4. Aneurysm formation

 

Consequences of atherosclerotic disease:

  • Large elastic arteries and large and medium-sized muscular arteries are the major targets of atherosclerosis.
  • Myocardial infarction, cerebral infarction, aortic aneurysms and peripheral vascular disease (gangrene of the legs) are the major consequences of atherosclerosis.

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