病理生理 心血管系統疾病

1、Diseases of the Cardiovascular System心血管系統疾病 (1),,Heart Disease will kill 1 in 3,,CVD is the #1 cause of death in most countries.,,結構,血 管,心瓣膜,心 肌,心 包,大中動脈 動脈粥樣硬化,小動脈 高血壓病,,內膜炎瓣膜病,心 肌 炎,心臟腫瘤,風濕病,心 包 炎,心

2、臟,血管,血管壁 動脈瘤,Major Disorders of CVS,Atherosclerosis Ischemic Heart Disease (IHD) Hypertension Rheumatic Heart Disease (RHD) Infective Endocarditis Valvular Heart Disease (VHD),Atherosclerosis,動脈粥樣硬化,Introduct

3、ion,Disease of the large and medium-sized arteries.Fat deposits, hardening and destruction.Major cause of IHD, MI and Stroke.Major primary cause of death in most countries.,Arteriosclerosis,AtherosclerosisLarge BVIn

4、tima,Hyaline,M?nckeberg Medial SclerosisMedial BV,AteriolosclerosisSmall BVFull Thickness,Hyperplastic,atheroma,artery,arteriole,細動脈硬化,動脈硬化,動脈粥樣硬化,動脈中層鈣化,Etiology 病因學,Exact cause is unknown.Risk Factors…,Age - the

5、 older you get, the greater the chance.Sex - males have a greater risk, even after women pass menopause.Family history (Genetic factors) - if family members have had CHD, there is a greater chance.,Unchangeable Risk Fa

6、ctors,HyperlipidemiaHypertensionCigarette SmokingDiabetes MellitusObesityPhysical Inactivity Alcohol Intake,Changeable Risk Factors,Hyperlipidemia,Hypercholesterolemia – risk 高膽固醇血癥Hypertriglyceridemia - less s

7、ignificant 高甘油三酯血癥,高脂血癥,Types of Cholesterol,Chylomicrons (CM)Very low density lipoproteins (VLDL)Low density Lipoprotein (LDL)High density Lipoprotein (HDL),LDL,The liver A major component of the tis

8、sues and cellsAtherosclerotic plaque that clogs arteriesIncreases risk of CHD,,,,tissues and cells,Bad cholesterol !,HDL,Tissues and cells It does not have the tendency to clog arteries.,,,the liver,Good cholesterol

9、!,Hypertension,A major risk factor at all agesBlood pressure exceeds 160/95mmHg more than five fold greater risk than those with blood pressures of 140/90 mmHg or lower,,Cigarette Smoking,Smoking aggravates th

10、e injury of endothelial cells. Carbon monoxideNicotine,Diabetes Mellitus 糖尿病,Uncontrolled blood sugar encourages the build up of fatty deposits within the arterial walls.A diabetic person has 2 or 3 x higher risk of

11、atherosclerosis!,,Obesity,Can lead to high blood pressure, raised blood cholesterol levels, and diabetes,Physical Inactivity,Physical activity Blood pressure HDL levelRegular, moderate intensity activity brisk

12、 walking, swimming, cycling, dancing, skipping, tennis, etc.,,,,In small amounts it acts as a vasodilator. 1-2 drinks is good!In large amounts it acts as a vasoconstrictor. 3-4 drinks is bad!,Alcohol C

13、onsumption,Risk Factors,Non modifiableAge Sex Family history (Genetic),Potentially modifiableHyperlipidemiaHypertensionSmokingDiabetesLife style, diet, and exercise,Pathogenesis,Reaction to vascular injury hypoth

14、esislipid infiltration/insudation hypothesis …,Atherosclerosis,Artery Wall,Atherosclerosis,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Monocytes,Lumen,Intima,Macrophage,Foam Cell,Endothelial Cells,Modified LDL,Adhesion & Di

15、apedesis,SRs,LDLR,CytoplasmicLD,,,Chemotaxis,,,,,,,,,,,,,,,,,,,,,,,Cytoplasmic LD,,,,,Endosome,LateEndosome,,CE,TG,FC,SR-A,CD36,ABCA1,ABCG1,HDL,,,Cholesterol Crystal,,,,LAL,,ACAT,,,,,,Transcription Factors,nCEH,,Choles

16、terol Crystal,ApoA1,ER,LD Proteins,FA,Modified LDL,,,,,Oxidation,,,,,,,,,,,CholesterolEfflux,,,,,,,,,,,,,,,ATGLHSL,,Nucleus,,,,ADRP,Perilipin,,Atheroma,Morphology,Development,Fatty Streak（脂紋）Fibrous Plaque（纖維斑塊）Athe

17、romatous Plaque （Atheroma） 粥樣斑塊（粥瘤）,Fatty Streaks 脂 紋,,Atheroma 粥瘤,Fibrous CapNecrotic centerCholesterol Cry.Macrophages,,,,,Complications - development,Ischemia,Rupture,Erosion, ulceration,Thrombosis,embolism,

18、Infarction,Brain, myocardial, renal, gangrene,,,,Angina pectoris, atrophy, intermittent claudication,,Hemorrhage,,,,,Rupture,Atherosclerosis,Atrophy of the media,Aneurysm,Dissecting aneurysms,,,,,Complications - devel

19、opment,Coronary Atherosclerosis冠狀動脈粥樣硬化,狹窄程度,I 級≦25%II級26%-50%III級51%-75%IV級>75%,Coronary AS,Coronary Heart Disease （CHD）冠狀動脈性心臟病（冠狀動脈粥樣硬化性心臟?。?Coronary Heart Disease , CHD,Any vascular disorder that nar

20、rows or occludes the coronary arteries.Atherosclerosis is the most common cause.Risk factors,臨床表現,心絞痛心肌梗死心肌纖維化冠狀動脈性猝死……,冠狀動脈供血不足 心肌耗氧量劇增,Myocardial ischemia心肌缺血,Local, temporary deprivation of the coronary blood

21、supplyAngina pectoris 心絞痛Transient cardiac ischemia without cell death resulting in substernal chest pain.,Angina Pectoris心絞痛,Stabile angina 穩(wěn)定性心絞痛Most common type, coronary artery atherosclerosis, increased card

22、iac demand Unstabile angina 不穩(wěn)定性心絞痛nonocclusive thrombus, occurs at rest Prinzmetal angina 變異性心絞痛coronary artery vasospasmoften occurring at rest,Myocardial infarction, MI心肌梗死,MI is the death of cardiac muscle resu

23、lting from ischemia . The most important form of IHD The leading cause of death,A heart attack occurs when one of the arteries that supplies the heart muscle becomes blocked.Blockage may be caused by spasm of the ar

24、tery or by atheriosclerosis with clot formation. The blockage results in damaged tissue and a permanent loss of contraction of this portion of the heart muscle.,Myocardial Infarction, MI,胸骨后劇烈疼痛，難以緩解發(fā)熱、白細胞增高、血沉加快心肌酶譜增

25、高心電圖變化,Angina vs MI,Anginanarrowed coronary arterytightness or ache in the chest, breathlessness, sick feeling, dizzinesscomes on with exertion or emotiongoes away with rest - usually 2-10 mins,MI (heart attack)due

26、 to sudden blockage of the coronary arterychest pain “l(fā)ike a band”, indigestion, breathlessness, sickness, looking palecomes on at any timedoesn’t go away - if still there in 15 minutes,類型,Subendocardial Myocardial In

27、farction心內膜下心肌梗死Transmural Myocardial Infarction透壁性心肌梗死,Transmural infarction,The ischemic necrosis involves the full or nearly full thickness of the ventricular wall in the distribution of a single coronary artery.,S

28、ubendocardial infarction,Constitutes an area of ischemic necrosis limited to the inner one third or at most one half of the ventricular wall.,Morphology,The microscopic and gross changes represent a spectrum.,,Gross,0-18

29、 h No gross change 18-24 h Vague pallor and softening 1- 7 d Yellow pallor 7-28 d Central pallor with a red border Months White, firm scar,Microscopic Sequence of Changes,1-4h Wavy myoc

30、yte fibers4-24 h Coagulative necrosis1-4 d Neutrophilic infiltrate4-7 d Macrophages7-28 d Granulation tissueMonths Fibrotic scar,生化改變,30min，糖原減少或消失肌紅蛋白、肌凝蛋白、肌鈣蛋白肌酸磷酸激酶（CK）、AST、LDH1,合并癥,乳頭肌功能失調或斷裂心臟破裂室壁瘤

31、附壁血栓急性心包炎,Complications,Heart failureCardiac ruptureVentricular aneurysm Mural thrombus and thromboembolismCardiogenic shockFibrinous pericarditisCardiac arrhythmias,心肌纖維化Myocardial Fibrosis,Chronic Ischemic Hea

32、rt Disease慢性缺血性心臟病Ischemic Cardiomyopathy缺血性心肌病,Myocardial Fibrosis心肌纖維化,Sudden cardiac death心源性猝死,Death within 1 hour of the onset of symptomsfatal cardiac arrhythmia, ventricular fibrillationCoronary artery di

33、sease (80%)Hypertrophic cardiomyopathyMitral valveprolapseAortic valvestenosisCongenital heart abnormalitiesMyocarditis,120,急性冠狀動脈綜合征Acute Coronary Syndrome，ACS,不穩(wěn)定性心絞痛急性心肌梗死冠狀動脈性猝死,缺血心肌再灌注,溶栓經皮冠狀動脈成型術（PTCA）血栓旋