1. Chapter 6 The disease of cardiovascular system

2. 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

3. Arteriosclerosis :
Atherosclerosis ( AS )
Monckeberg media calcific sclerosis
Arteriolosclerosis

4. 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

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

6. 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

7. 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↓

8. 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

9. (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.

10. 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.

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

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

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

17. (Ⅱ) Basic pathologic changes

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

19. Fatty streak (sudan red)

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

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

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

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

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

25. (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

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

27. Fibrous cap
Foam cells
calcification
cholesterol crystals
muscularis

28. (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

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

30. Aneurysm
Hemorrhage

31. Plaque rupture
AS focal disruption,thrombomosis

32. 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

33. 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

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

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

38. Small intestine AS