ATHEROSCLEROSIS زيد ثامر جابر. Zaid. Th. Jaber

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Kristian McDonald
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1 ATHEROSCLEROSIS زيد ثامر جابر Zaid. Th. Jaber

2 Objectives 1- Review the normal histological features of blood vessels walls. 2-define the atherosclerosis. 3- display the risk factors of atherosclerosis. 4- mention the Pathophysiology of atherosclerosis. 5-microscopic and macroscopic pics of atherosclerosis. 6- the outcome of atherosclerosis.

3 normal The 3 concentric layers-intima, media and adventitia-are most clearly defined in the larger vessels particularly arteries. Arteries consist of: 1. Intima. 2. Internal elastic lamina. 3. Media. 4. External elastic lamina. 5. Adventitia. The basic constituents of the wall are: 1. Endothelial cells. 2. Smooth muscle cells. 3. Extracellular matrix (ECM), including elastin, collagen and glycosaminoglycans.

9 Normal coronary artery

10 Definition of atherosclerosis is a slowly progressive inflammatory disorder of the arterial wall. Hardening of arteries. In which the walls of arteries thicken; stiffen; And loose their elastisty.

11 Atherosclerosis is a dominant pattern of arteriosclerosis. It primarily affects elastic and large to medium sized muscular arteries : 1-abdominal oarta 2- coronary artery 3- popliteal artery 4- carotid artery 5- circle of willis.

12 Risk factors

13 Pathophysiology

15 Theories: 1- Endothelial injury 2- Thrombogenic 3- C.pneumoniae

16 The pathogenesis of Ath. remains unexplained, but endothelial damage (and chlamydia infection?,) could be the primary event and the reaction to it may eventually lead to plaque formation (response to injury hypothesis;!). Plaques usually develop at sites of high mechanical stress (vessel bifurcation); in this way also hypertension becomes a risk factor. Among the reactions are an increased lipid uptake in the vessel wall as well as adhesion of monocytes and thrombocytes helped by HoCys. The monocytes penetrate into the intima and are transformed into macrophages.these liberate reactive O2 radicals, especially the superoxide anion

17 O2 (also helped by HoCys), which have a general damaging effect on endothelial cells and inactivate endothelium-formed NO on its way to the endothelium and the vascular musculature: NO + O2! ONOO. This results in the loss of NO action, namely inhibition of platelet and monocyte adhesion to the endothelium as well as antiproliferative and vasodilating effects on the vascular musculature. The latter favor spasms Even in the early stages of Ath., O2 radicalsmodify by oxidation of those LDLs that have entered the endothelium. Oxidized LDLs damage the endothelium and there induce the expression of adhesion molecules which allow vessel musculature to proliferate.

18 Oxidation also results in altered binding of LDLs. They can no longer be recognized by ApoB 100 receptors (!p. 246ff.), but rather by so-called scavenger receptors that are contained in large amounts within the macrophages. Consequently, these now phagocytize large amounts of LDLs and are transformed into sedentary foam cells (!C9). Lipoprotein(a) can be oxidized and phagocytized in a similar fashion. Simultaneously, chemotactic factors of monocytes and thrombocytes trigger the migration of smooth muscle cells from the media into the intima (!C6). Here they are stimulated to proliferate by PDGF and other growth-promoting factors (from macrophages, thrombocytes, damaged endothelium, and the muscle cells themselves). They, too, are transformed into foam cells by uptake of oxidized LDLs (!C10). They form an extracellular matrix (collagen, elastin, proteoglycans) that also contributes to atheroma formation.

35 Atherosclerotic plaque

36 Atherosclerosis with severe narrowing of the lumen & area of calcification at the lower right

37 Atheromatous plaque with recent thrombosis

38 Atheroma at high magnification : numerous foam cells & cholesterol clefts

41 The consequences of plaque deposition are narrowing of the lumen that can lead to ischemia. Coronary heart disease as well as chronic occlusive arterial disease of the limbs with painful ischemia on exercise (intermittent claudication) are examples of this. Other consequences of plaque formation are stiffening of the vessel wall (calcification), thrombus formation that obstructs the residual lumen and can cause peripheral emboli (e.g., cerebral infarction, stroke) as well as bleeding into the plaques (additional narrowing by the haematoma) and the vessel wall. Thus weakened, the wall may be stretched (aneurysm; see below) and even rupture, with dangerous bleeding into the surrounding tissues, for example, from the aorta (see below) or cerebral vessels (massive intracerebral bleeding, stroke.

51 Reference 1-Robbins and Cotran PATHOLOGIC BASIS OF DISEASE. 2-Silbernagl/Lang, Color Atlas of Pathophysiology 2000 Thieme 3- Davidson_ Principles_and_Practice_of_Medicine_21 st 4- diagnosis.com 5- Nature. Macmillan Magazines, London/UK

Arteriosclerosis & Atherosclerosis

Arteriosclerosis & Atherosclerosis Arteriosclerosis = hardening of arteries = arterial wall thickening + loss of elasticity 3 types: -Arteriolosclerosis -Monckeberg medial sclerosis -Atherosclerosis Arteriosclerosis,