The Common Vein Copyright 2007
Athersclerosis is a degenerative disorder of the vascular wall characterised by a fibrofatty deposition (plaque) in the inner lining (subendothelial) of the artery.
Cause: It occurs as a normal course of aging, but it is accelerated by genetic, dietary and behavioral factors.
Result: The accumulation of plaque in the wall causes narrowing of the lumen of the arteries progressively restricting flow. In addition, the normal smooth and glistening lining of the arteries are replaced by a rough irregular inner wall that is a factor that predisposes to thrombosis, sometimes an acute life threatening event if the arteries of the heart or brain are affected.
Diagnosis: The clinical presentation depends on the organ involved and the degree of narrowing. In the heart for example simple narrowing results in chest pain called angina. When total acute obstruction occurs with thrombosis of the artery, severe unremitting chest pain occurs, and myocardial infarction ensues.Each organ has varied manifestations of clinical presentation, all relating to reduced perfusion of the end organ due to narrowing. Imaging plays an essential role in diagnosis. Ultrasound can directly view the lumen and wall of accessible vessels, while CT scan and MRI are advancing to be the mainstay of diagnosis for the deeper arteries. Angiography was the gold standard of the past, is still used and is invaluable in selected circumstances, particularly if therapeutic intervention is needed.
Treatment is usually directed at maintaining flow to the end organs. Medical therapy is often directed at the smooth muscle components of the vessel wall in order to dilate the vessels. Minimally invasive methods use angioplasty and stents to expand the narrowing directly, while surgery often employs bypass methods.
Atheromatous plaque is an accumulation of fatty and fibrous elements within the intima of the arterial wall. The multifactorial causes of atherosclerosis include age, sex, genetics, lifestyle and dietary factors. among many other unfolding factors. The recognizable “phases” of atherosclerosis include ;
1) Breach of the endothelium
2) Migration of lipoproteins from the lumen into the intima.
The result is a breach in the intima and migration of lipoproteins into the subendothelial layer. The lipoproteins and proteoglycans form a complex compound that traps the fat complex in the subepithelial layer.
3) Formation of a lipoprotein-proteoglycan complex that traps the lipoprotein in the intima
4) Migration of monocytes and lymphocytes from the lumen into the intima.
The next phase heralds the migration of leukocytes and platelets into the subendothelial layer.
5) Transformation of the monocytes into macrophages and phagocytosis of the fat complexes to form fat laden foamy macrophages. (33792h)
The monocytes, phagocytose the lipoprotein-proteoglycan complex forming the lipid laden foamy histiocytes. These macrophages can apparently repllicate. At this stage the macroscopic appearance is the well known “fatty streak”.
6) Migration of smooth muscle cells from the media into the intima and transformation into fibrocytes. A fibrous capsule around the fatty complex is formed. (33792i, 33801b)
The next phase of atherosclerosis occurs following smooth muscle proliferation and migration from the media into the evolving plaque. Smooth muscle also undergoes apoptosis and death. The vascular smooth muscle produces the extracellular matrix has major contribution to the atheromatous lesion. Interstitial collagens (types I and III) and proteoglycans such and elastin fibers also accumulate in atherosclerotic plaques. Accumlation of cholesterol and cholesterol esters occur.
A fibrous capsule around the fatty complex is formed. (33792i, 33801b)
Smooth muscle migrates from the media into the intima and transform into fibrous elements both within the lesion as well superficial to the lesion forming a fibrous plaque.The monocytes and macrophages ingest the fat and foamy fat laden macrophages result. An inflammatory reaction evolves. Continued accumulation of lipid, macrophages, foamy cells, extracellular matrix result in a fibrofatty complex that grows in size over time. As it enlarges it bulges and thins the intima and eventually erodes the surface.
As the disease progresses, cell death within the plaque results, and dystrophic calcification
8) Growth of the atheromatous complex with impingement on the lumen. (33801b)
The progressive impingement on the lumen causes reduction of blood flow, usually manifesting clinically with angina when the lumen is reduced by 70% of its original size.
9) Potential of the complex to rupture.
801d) Acute rupture of a plaque predisposes to superadded thrombosis and occlusion of the lumen.
This diagram shows denudation of the endothelial layer with exposure and rupture of the contents of the atherosclerotic plaque in volcanic fashion into the lumen. This event is catastrophic and can result in acute thrombosis and may even be a fatal event. 33801d Courtesy Ashley Davidoff MD. code heart artery atherosclerosis atheroma vulnerable plaque drawing Davidoff art
Acute myocardial infarction and death are complications of this event. The initial phase of endothelial injury has multifactorial contributing factors including hypertension, hemodynamic factors, hyperlipidemia, homocysteine, smoking, toxins, immune reactions, and viral disease.
The American Heart Association classification divides atherosclerotic lesions into six types; foam cells ( fatty dots) – Type I fatty streaks, – Type II atheromas, – Type III fibroatheromas, – Type IV complicated lesions (Stary)
This diagram shows the yellow spheroidal lipoproteins traverse the injured epithelium (2) from the lumen (red) and binding to the linear shaped proteoglycan molecules in the intimal layer. (3) In essence the lipoprotein is “captured”, because it has been altered structurally and is unable to return to the circulation. Courtesy Ashley Davidoff MD. 33792e code heart artery intima endothelium histopathology pathogenesis atherosclerosis atheroma drawing
The diagram shows an evolving atheromatous plaque with inflammatory cells, monocytes, and lymphocytes infiltrating the intima which contains the lipoprotein- proteoglycan complex, extracellular lipid , and cholesterol crystals. 33792g Courtesy Ashley Davidoff MD. code heart artery intima endothelium histopathology pathogenesis atherosclerosis atheroma drawing
This drawing shows migration of the monocytes into the intima. These monocytes transform into macrophages in the intima and phagocytose the lipid products to become lipid laden foamy cells. The macroscopic correlate at this stage is the fatty streak. Courtesy Ashley Davidoff MD 33792h . code heart artery intima endothelium histopathology pathogenesis atherosclerosis atheroma drawing
This diagram shows the reaction of the smooth muscle cells (b) to the formation of foam cells (a) in the subendothelial layer of the intima. The smooth muscle cells migrate from the muscular layer (4) into the intima. Here they undergo dedifferentiation into fibrocytes. 33792i Courtesy Ashley Davidoff MD. code heart artery intima endothelium histopathology pathogenesis atherosclerosis atheroma drawing
The diagram shows the atherosclerotic lesion in the subepithelial layer of the intima which at first bulges toward the media or muscular layer. 33801a Courtesy Ashley Davidoff MD. code heart artery intima endothelium histopathology pathogenesis atherosclerosis atheroma drawing
The diagram shows the atherosclerotic lesion in the subepithelial layer of the intima which is bulging both toward the media and toward the lumen. There is a central core of fat and necrotic debris, surrounded by fibrous elements which give the plaque its hardness to the feel. The accumulation of fibrous tissue heralds an advanced atherosclerotic lesion. 33801b Courtesy Ashley Davidoff MD. code heart artery