Chapter 6 The disease of cardiovascular system

Section 1. Atherosclerosis ( AS ) Atherosclerosis is a disease of large and medium-size ateries that result in progressive accumulation within the intima of SMCs, lipids and connective tissue

Arteriosclerosis : Atherosclerosis ( AS ) Monckeberg media calcific sclerosis Arteriolosclerosis

Fibrofatty plaques that protrude into the lumen Atherosclerosis characterized by : Intimal lesions called atheroma Fibrofatty plaques that protrude into the lumen Loss of elasticity of underlying media Undergo a serious of complications

aorta (abdominal) , carotid arteries Primarily affects : Large - sized (elastic) arteries : aorta (abdominal) , carotid arteries Medium - sized muscular arteries : coronary , cerebral

Ⅰ.Etiology and Pathogenesis (Ⅰ) Risk factors 1. Hyperlipidemia : ① LDL cholesterol, VLDL, triglycerides Lp (a) promoting ② HDL/HDL-C, apoA-I inhibiting 2. Hypertension: a major risk factor

4. Diabetes and hyperinsulimemia: 3. Smoking: ① Endothelial damage, CO↑ PDGF↑, SMC proliferation , emigration →media ② LDL oxidation ox-LDL 4. Diabetes and hyperinsulimemia: ① Hyperglycemia LDL glycolate ox-LDL hypertriglyceride ② Hyperinsulimemia SMC↑、HDL↓

5. Heredity: 200genes 6. Age and sex： HDL-receptor gene mutation→ family hypercholesterolemia 6. Age and sex： (1) Age: age↑→AS factors changes arterial wall proliferative change (2) Sex: estrogen → HDL postmenopausal female = male

(Ⅱ) Pathogenesis The mechanism responsible for lipid deposition in the intima and formation of the atheromatous lesion is known. At least six hypotheses have been proposed to explain the origins of atherosclerotic plaques.

1. Response to injury hypothesis : (1) Chronic endothelial injury (2) Insudation of LDL into vessel wall (3) Modification of lipoprotein by oxidatin (4) Adhesion of blood monocyte to the EC (5) Adhesion of platelet (6) Activated platelet , macrophage release factors (7) Proliferation of SMC in the intima and accumulation of extracellular matrix(collagen) (8) Enhanced accumulation of lipid intracellularly and extracellularly.

Central to this thesis are the following events Lipids Endothelial injury SMC proliferation Macrophage(Mφ)

2. Lipid infiltration hypothesis 3. Smooth muscle mutagenic hypothesis 4. Macrophage receptor defect hypothesis

Ⅱ Morphology (Ⅰ) Favorite site: lower abdominal aorta coronary A popliteal A descending thoracic aorta internal carotid A vessels of circle of willis

(Ⅱ) Basic pathologic changes

1. Fatty streak: the early lesion (1) Gross: yellow flat spots or streaks, 1-2mm in width , slightly raised

Fatty streak (sudan red)

(2).LM: (low power lens) Fatty streak

(2) LM: composed of lipid-filled foam cells Fatty streak

(4) Results: reversible (3) Formation： lipid↑→engulfed by Mφ、SMC →foam cell (two sources) (4) Results: reversible could be seen in infants and children

2. Fibrous plaque： (1) Gross: irregular grey-white raised plaque (2) LM: fibrous cap foam cell, lipids inflammatory cell

whitish yellow 3. Atheromatous plaque(atheroma) (1) Gross: yellow irregular elevated plaque

(2) LM: ① Surface: Fibrous cap hyaline degeneration of collagen, SMC embed in extracellular matrix ② Necrotic center: amorphous necrotic materials lipid, cell debris,cholesterol crystals, calcium surrounding: granulation tissue, LC, foam cells ③ Media: atrophy→thin

Lumen Masson trichrome Fibrous cap Lipid core Media thin Calcification,neovascularization

Fibrous cap Foam cells calcification cholesterol crystals muscularis

(三) Complicated lesions: (1) Hemorrhage into a plaque: Acute obstruction of A → infarction ( coronary A →myocardial infarction） (2) Focal rupture: Lower abdominal aorta, iliac A, temporal A Rupture → ulceration → thrombosis ↓ embolism→infarct

(3) Thrombosis： Obstruction → infarction (4) Calcification ： Brittleness → rupture (5) Aneurysm formation： Rupture → hemorrhage

Aneurysm Hemorrhage

Plaque rupture AS focal disruption,thrombomosis

Ⅲ. Lesions in organs & clinical features 1. Aortic AS： (1) Site：abdominal aorta>thoratic A> aorta arch > ascending A (2) Lesions： atheromatous and secondary changes abdominal aortic aneurysm →rupture →death 2. Coronary AS: coronary heart disease

3. Carotid A and Cerebral A AS: (1) Site:basilar A,middle cerebral A,Willis circle (2) Lesion ① Ischemic atrophy of brain ② Infarction：thrombosis temporal lobe, caudate nucleus,lenticular nucleus, thalamus ③ Hemorrhage：AS →aneurysm rupture

4. Renal A AS: (1) Sites： proximal segment of major branch of renal A (2) Lesion: infarct or hypertension

narrowing→claudication 5. AS of extremities: narrowing→claudication →thrombosis→gangrene 6. Small intestine AS: infarction

Small intestine AS