Abdomen, Pelvis, and Perineun

Etiology
Pathogenesis
Pathology
Pathophysiology
Epidemiology
Management & Determining the Cause
Study Question

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The integrative pathophysiology of atherosclerosis, ischemic heart disease, and the systemic inflammatory response.

Atherosclerosis develops over many years (1) and can lead to myocardial infarction (2), while the stress of acute myocardial infarction (2) also produces an “echo” in atherosclerotic plaques (1). Acute myocardial infarction causes pain and anxiety that triggers sympathetic outflow from the central nervous system (3). β3 adrenergic stimulation mobilizes leukocyte progenitors from their bone marrow niche. These progenitor cells can migrate to the spleen, where they can multiply in response to hematopoietic growth factors. The proinflammatory monocytes then leave the spleen and enter the atherosclerotic plaque (1), where they promote inflammation that can render a plaque more likely to provoke thrombosis and hence acute myocardial infarction (2). IL, interleukin. Reproduced with permission from Libby P, Nahrendorf M, Swirski FK: Leukocytes Link Local and Systemic Inflammation in Ischemic Cardiovascular Disease: An Expanded “Cardiovascular Continuum.” J Am Coll Cardiol. 2016 Mar 8;67(9):1091-1103.192

Fibrous plaques, or atheromas, occur within the intima of arteries, most frequently the proximal portions of the coronary arteries, the larger branches of the carotid arteries, the circle of Willis, the large vessels of the lower extremities, and the renal and mesenteric arteries (Figure 9.1).

1. 1. The plaques have a central core of cholesterol and cholesterol esters; lipid-laden macrophages, or foam cells; calcium; and necrotic debris.
  2. The core is covered by a subendothelial fibrous cap, which is made up of smooth muscle cells, foam cells, fibrin and other coagulation proteins, as well as extracellular matrix material, such as collagen, elastin, glycosaminoglycans, and proteoglycans.
  3. The plaques may be complicated by:
    
    Ulceration, hemorrhage into the plaque, or calcification of the plaque
    
    Thrombus formation at the site of the plaque, producing obstructive disease
    
    Embolization of an overlying thrombus or of plaque material itself
  4. The atheromas can develop from the fatty streak, a lesion that is characterized by focal accumulations in the intima of lipid-laden foam cells that may appear as early as the first year of life and that is present in the aorta of most older children.

(A) Fibroinflammatory lipid plaques. Focal elevated plaques in the thoracic aorta. (B) The fibrous cap (asterisks) separates the lumen (L) from the necrotic core (bracket). (C) Hematoxylin and eosin section showing narrowed lumen with atheroma in the intima (including fibrous cap, cholesterol/lipid/necrotic debris core, and calcification).

The most significant consequence is ischemic heart disease and myocardial infarction, the most common cause of death in the United States.

Other significant complications include stroke from cerebral ischemia and infarction, ischemic bowel disease, peripheral vascular occlusive disease with findings varying from claudication to ischemic necrosis and gangrene, and renal arterial ischemia with secondary hypertension.
Weakening of the vessel wall may lead to aneurysm formation.

Atherosclerosis is the most frequent cause of significant morbidity caused by vascular disease. It is seen worldwide, but the highest incidence occurs in Finland, Great Britain, other northern European countries, the United States, and Canada.

The incidence is more than 10-fold greater in Finland than that in Japan.

Atherosclerosis

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Diseases and Disorders