L1, CVS Pathology PDF

pathology - CVS Atherosclerosis LECTURE (1) Atherosclerosis Dr. M. Shalaby pathology - CVS Atherosclerosis  Chronic, progressive, multifocal disease of th...

pathology - CVS Atherosclerosis LECTURE (1) Atherosclerosis Dr. M. Shalaby pathology - CVS Atherosclerosis  Chronic, progressive, multifocal disease of the vessel wall. DEFINITION  Characterized by formation of fibro-fatty plaques.  Before menopause: Males ˃ females. INCIDENCE  After menopause: males = females.  More in developed countries. MAJOR MINOR (MODIFIABLE) NON-modifiable ① Increasing age ① High carbohydrate intake ② Male gender ② Obesity ③ Family history ③ Physical inactivity ④ Genetic abnormalities ④ Stress ("type A" personality) Modifiable ⑤ Postmenopausal ① Hyperlipidemia ⑥ Alcohol ② Hypertension ⑦ Lipoprotein Lp(a) ③ Cigarette smoking ⑧ Unsaturated fat intake ④ Diabetes Dr. M. Shalaby pathology - CVS Atherosclerosis ① Aorta, especially descending. ② Coronaries ③ Cerebral & internal carotids. ④ Femoral , renal, superior mesenteric Dr. M. Shalaby pathology - CVS Atherosclerosis  Development of focal chronic endothelial cell injury:  Caused by endotoxins, hypoxia, cigarettes, virus, stress  Entry of lipoproteins into intima of the vessel? LDL,VLDL  Migration of monocytes into intima.  Monocytes are transformed into macrophages and foam cells  due to engulfing lipid causing lipoproteins oxidation  Adhesion of platelets and secrete platelet derived growth factor (PDGF)  Smooth-muscle migration: mediated by mitogenic factors released from activated platelets, macrophages, endothelial cells.  Proliferation of smooth muscle cells in the intima and deposition of Extracellular matrix and collagen and proteoglycans.  Lipid accumulation:  extra-and intra-cellular in macrophages and smooth muscle that become foam cells.  Formation of fibrous cap that separate the lesion from the lumen Dr. M. Shalaby pathology - CVS Atherosclerosis Dr. M. Shalaby pathology - CVS Atherosclerosis 1 Gross  Multiple, smooth, yellowish fatty dots. FATTY STREAK  Not raised above endothelial surface (flat)  Coalesce to form larger ones  Disc- like patches.  Color ranges from yellow to white according to relative amount of fat and UNCOMPLICATED fibrous tissue ATHEROMA  Covered by glistening intima.  More around the mouths of the branches.  Grayish white, firm CUT SURFACE  Fibrous coat and a yellow soft center  Calcification. COMPLICATED  Ulceration. ATHEROMA  Thrombosis FATTY STREAK UNCOMPLICATED ATHEROMA CUT SURFACE COMPLICATED ATHEROMA Dr. M. Shalaby pathology - CVS Atherosclerosis 2 Microscopic ① Cholesterol clefts. ② Lipid-laden foam cells ③ Extracellular lipid ④ Lymphoplasmacytic infiltrate FATTY STREAK ① Subendothelial fibrous cap: formed of proliferated smooth muscle cells, foam cells and extra cellular matrix ② Central core: of cholesterol and cholesterol esters, lipid laden UNCOMPLICATED macrophages (foam cells), necrotic debris and calcification. ATHEROMA ③ Neovascularization around the periphery. ④ Media:  Disrupted elastic lamina.  Atrophy of the media deep to the plaque Dr. M. Shalaby pathology - CVS Atherosclerosis UNCOMPLICATED ATHEROMA NORMAL CORONARY ARTERY CORONARY ARTERY ATHEROSCLEROSIS Dr. M. Shalaby pathology - CVS Atherosclerosis ① Narrowing of vascular lumen → chronic ischemia. ② Superimposed thrombosis → acute ischemia & Infarction. ③ Ulceration with liberation of fatty core → acute ischemia, fat emboli & Infarction. ④ Pressure atrophy of the media with fibrosis → weakening of the wall → Aneurysm. ⑤ Dystrophic calcification. ULCERATION & HEMORRHAGE THROMBOSIS THROMBOSIS & RECANALIZATION CALCIFICATION Dr. M. Shalaby