病理学英文教学课件：ch6 The disease of cardiovascular system

1、 Atherosclerosis ( AS ) Monckeberg media calcific sclerosis ArteriolosclerosisSection 1. Atherosclerosis ( AS ) 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

2、Primarily affects : Large - sized (elastic) arteries : aorta (abdominal) , carotid arteries Medium - sized muscular arteries : coronary , cerebral , popliteal A(一一) Risk factors1. Hyperlipidemia : LDL cholesterol, VLDL, triglycerides Lp (a) promoting HDL/HDL-C, apoA-I inhibiting2. Hypertension: a ma

3、jor risk factor 3. Smoking: Endothelial damage, CO PDGF, SMC proliferation , emigration media LDL oxidation ox-LDL4. Diabetes and hyperinsulimemia: Hyperglycemia LDL glycolate ox-LDL hypertriglyceride Hyperinsulimemia SMC、HDL5. Heredity: 200genes HDL-receptor gene mutation family hypercholesterolemi

4、a 6. Age and sex：(1) Age: ageAS factors changes arterial wall proliferative change (2) Sex: estrogen HDL postmenopausal female = male 7. Others: Obesity , stressful life type , hypoxia , diet lack of Vit. C , infection of bacteria , virus8. Lack of exercise :9. Intake of alcohol : Protective role fo

5、r moderate intake of alcohol : HDL A large amount of intake of alcohol: hypertension, cerebral hemorrhage1. 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) Adhes

6、ion 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 injur

7、y SMC proliferation Macrophage(M)Roles of Role of lipids : Increase endothelial permeability Impair endothelial function OX-LDL ingested by Mform foam cells chemotactic for circulating monocytes increase monocyte adhesion stimulate release of growth factors chemotactic to endothelial cells (EC) smoo

8、th muscle cells (SMC) Role of EC injury: initial lesion Mechanical injury Smoking , Hypoxia Hyperlipidemia Hypertension EC injury Non-denuding EC dysfunction EC denuding Increased EC permeability Enhanced monocyte, platelet adhesion Release GFSMC proliferation Risk Factors Role of macrophage: key st

9、ep Platelet , EC, Monocyte, SMC Growth Factors (PDGF, FGF, etc) emigration proliferation adhereemigrant subendothelially foam cells Matrix GFSMC Role of SMC proliferation: GF SMC proliferation in emigration of media SMC to intima Phenotype change (constrictivesynthesis) surface LDL receptorfoam cell

10、(SMC derived) collagen , elastic fiber protein, proteoglycans Interactionformation of AS plaque 2. Lipid infiltration hypothesis ： Hyperlipidemia EC damagepermeability lipoprotein depositMcleanup SMC Atheroma3. Smooth muscle mutagenic hypothesis SMC in AS plaquemonoclone Causes: chemical mutagenic a

11、gents virus4. Macrophage receptor defect hypothesis(1) Normal Cell membrane: LDL receptorcombine with LDLengulfintracellular IntakeLDL receptorchange with the need of cholesterol (2) AS: LDL receptorsLDL cleaning LDL in blood (2) ox-LDL Not be recognized by native LDL receptor Engulf mediate by scav

12、enger receptor (Msurface）foam cell Chemotactic to monocytes Chemotactic to EC、SMC GF 二二. Morphology (一一) Favorite site: lower abdominal aorta coronary A popliteal A descending thoracic aorta internal carotid A vessels of circle of willis(二二) Basic pathologic changes 1. Fatty streak: the early lesion

13、 (1) Gross: yellow flat spots or streaks, 1-2mm in width , slightly raised Fatty spotFatty spot Fatty streak (sudan red)(2) LM: composed of lipid-filled foam cells Fatty streak(3) Formation： lipidengulfed by M、SMC foam cell (two sources)(4) Results: reversible could be seen in infants and children 2

14、. Fibrous plaque：(1) Gross: irregular grey-white raised plaque(2) LM: fibrous cap foam cell, lipids inflammatory cell 3. Atheromatous plaque(atheroma) (1) Gross: whitish yellowyellowirregular elevated plaque (2) LM: Surface: Fibrous cap hyaline degeneration of collagen, SMC embed in extracellular ma

15、trix Necrotic center: amorphous necrotic materials lipid, cell debris,cholesterol crystals, calcium surrounding: granulation tissue, LC, foam cells Media: atrophythinFibrous capLumenLipid core Masson trichromeMedia thinCalcification,neovascularization(三三) Complicated lesions:(1) Hemorrhage into a pl

16、aque: Acute obstruction of A infarction ( coronary A myocardial infarction）(2) Focal rupture: Lower abdominal aorta, iliac A, temporal A Rupture ulceration thrombosis embolisminfarct(3) Thrombosis： Obstruction infarction(4) Calcification ： Brittleness rupture(5) Aneurysm formation： Rupture hemorrhag

17、eHemorrhageAneurysmAS focal disruption,thrombomosisPlaque rupture1. Aortic AS：(1) Site：abdominal aortathoratic A aorta arch ascending A(2) Lesions： atheromatous and secondary changes abdominal aortic aneurysm rupture death2. Coronary AS: coronary heart disease 三三.Lesions in organs & clinical feature

18、s3. Carotid A and Cerebral A AS:(1) Site:basilar A,middle cerebral A,Willis circle(2) Lesion Ischemic atrophy of brain Infarction：thrombosis temporal lobe, caudate nucleus,lenticular nucleus, thalamus Hemorrhage：AS aneurysm rupture 4. Renal A AS: (1) Sites： proximal segment of major branch of renal

19、A (2) Lesion: infarct or hypertension Renal A AS5. AS of extremities: narrowingclaudication thrombosisgangrene6. Small intestine AS: infarction Small intestine AS(一一) Coronary atherosclerosis 1. Distribution ：Left right，large branchsmall branch， proximal segment distant segment Left anterior descend

20、ing coronary A right CAleft CAleft circumflex CA 2. Features：cutface crescent plaque of myocardial side，eccentric stenosis 4 grades 76% CHD： ischemic heart disease(IHD) a group of closely related syndromes resulting from myocardial ischemia Etiology and pathogenesis： Insufficient blood supply: AS, s

21、pasm Increase in cardiac energy demand: BP，overworked，excite work load of heart An imbalance between the perfusion and demand of the heart for oxygenated blood 1. Angina pectorisA symptom complex of IHD characterized by paroxymal and usually attacks of substernal or precordial chest discomfort (cons

22、tricting, squeezing, chocking or kinfelike) cardiac oxygen demand Acute , temporarily, comparatively coronary A blood supply Clinical types :(1) Stable or typical angina： relived by rest or nitroglycerin, stenosis of coronary AS 75% (2) Prinzmetal or variant angina: episodic angina, occure at rest d

23、ue to coronary vasospasm ECG：S-T elevated （3）Unstable angina： occure with progressively increasing frequency tend to be of more prolonged duration induced by rupture of AS plaque with superimposed partial thrombosis and embolization or vasospasm (preinfarction angina)Concept：acute ischemic necrosis

24、due to severe sustained ischemia Types：95% LV, trnasmural or subendocardial infarction(1) Subendocardial myocardial infarction Concept：an area of ischemic necrosis limited to the inner 1/3 and involve papillary muscle, trabeculae carnae Lesion：multi different in size focal necrosis Circumferential i

25、nfarction: entire LV endocardium(2) Transmural myocardial infarction The ischemic necrosis involves the full or nearly full thickness of the ventricular wall in the distribution of a single coronary artery. 2/3thick layer infarctThe progression of myocardial necrosisRCALADLCX Favorite sites：LAD 40-5

26、0% Anterior wall of LV near apex,anterior portion of ventricular septrm, apex circumferentiallyRCA 30-40%Inferior-posterior wall of LV, posteriole portion of ventricular septum, inferior-posterior RV free wall LCX 15-20%Lateral wall of LV except at apex Lesion：anemic infarct，yellow or gray-red，dryir

27、regular2hr LM change 6hr naked eye-4hrNone4-12hrOccasionally dark motting12-24hrDark motting1-3dMotting with yellow-tan infarct center3-7dHyperemic border, center yellow-tan softing7-10dMaximally yellow-tan and soft with depressed red-tan margins10-14dRed-gray depressed infarct borders2-8wGray-white

28、 scar, progressive from border to core of infarct2mScarring completeLM-4hrVariable waviness of fibers at border4-12hrBeginning coagulation necrosis,edema,hemorrhage12-24hrOngoing coagulation necrosis,myocyte hypereosinophilia, marginal contraction band necrosis1-3dCoagulation necrosis,with loss of n

29、uclei and striation,interstitial infiltrate of neutrophils3-7dBeginning disintegratin of dead myofibers,early phagocytosis7-10dWell-developed phagocytosis of dead cells,early formation of fibrovascular granulation at margin10-14dWell-estabished granulation and collagen deposition2-8wIncreased collag

30、en deposition2mDense collagenous scar梗死梗死48h后，细胞核消失，肌浆均质细颗后，细胞核消失，肌浆均质细颗粒状粒状, 横纹消失。心肌间隙见嗜中性粒细横纹消失。心肌间隙见嗜中性粒细胞浸润。胞浸润。 心肌凝固性坏死（肌浆凝集）心肌凝固性坏死（肌浆凝集）梗死的心肌纤维肌浆内可见明显梗死的心肌纤维肌浆内可见明显增厚的波浪状横带（收缩带）增厚的波浪状横带（收缩带）心肌梗死心肌梗死7天后，心肌细胞核几乎消失，肌天后，心肌细胞核几乎消失，肌浆变成红染无结构。可见增生的肉芽组织。浆变成红染无结构。可见增生的肉芽组织。 Lab： CPK AST LDH GPT GOP Co

31、mplication Papillary muscle dysfunction or rupture： Myocardial rupture：acute,severe，1-3days or 1week（within 2weeks） Favorite site Results Ventricular free wallHemopericardium and cardiac tamponade Ventricular septumLeft-to-right shunt Papillary muscleSevere mitral regurgitation Ventricular aneurysm：

32、from a large transmural anteroseptal infarct Mural thrombosis： Post-myocardial infarct syndrome Acute pericarditis： acute fibrinous inflammation Acute left heart failure Cardiogenic shock: 40%output Arrhythmias: conduction disturbance Mural thrombosis(1) Cause：moderate-severe stenosis of the coronar

33、y A. or total occlusion(2) Gross：LV hypertrophy and dilation, discrete, gray-white scars(3) LM : Diffuse myocardial fibrosis myocardial hypertrophy or atrophy(4) Clinical features：heart failure Van Gieson stainFibrosis(red) , myocardium (yellow)(1) Risk factors： alcohol , strain , smoking athlete, s

34、ome at nigh(2) Lesion： major vessel severe stenosis一一. Introduction1. Hypertension A clinical syndrome clinically characterized by elevated blood pressure of systolic ,diastolic pressure and lead to the lesions of heart,brain, kidney , vessles 2. Normal BP: Systolic130mmHg Diastolic 85mmHg Hypertens

35、ion: Systolic18.4kPa (140mmHg) Diastolic12kPa (90mmHg)CLASSIFICATION OF BLOOD PRESSURE IN ADULTSNormalHigh normalHypertensionStage 1 (mild)Stage2 (moderate)Stage 3 (severe)Stage 4 (very severe) 210 120 Category Systolic (mm Hg) Diastolic (mm Hg) 3. Classification (1) Secondary hypertension: 5%-10% C

36、hronic glomerulonephritis Renal A. stenosis, adrenal,piturary tumor (2) Primary hypertension: 90%-95% Benign hypertension Malignant hypertension(一一) Etiology:1. Genetic factors: Polygenic disorder ( mutations or polymorphisms at several gene loci influence blood pressure , RAS ) 2. Diet: dietary sod

37、ium intake: Na+, K+ 3. Psychological factors: stress 4. Others: obesity , smoking , age humoral factorsangiotensin prostaglandins kallikreinsthrombin NOLT3 （vasodilators）catecholamines（vasoconstrictors）Na+mineralocorticoidscardionatriFluid outputCardiac outputRateContractile force = = peripheral res

38、istance Auto-regulationiron（pH、lonic）-receptor -receptor hormone( (vasoconstrictor) ) (vasodilatro) neuronal factors(二二)Pathogenesis Three pathways overlap : 1. Renal retention of excess sodium (1) Factors（intake、inherit） Na+H2O retention blood volumeBP (2) Salt sensitivitymainly this way 2. Functio

39、nal vasoconstriction: (1) Small artery, arteriole : SMC contract peripheral resistance BP (2) Involved factors: Stress,angstcerebral cortex malfunction catecholamineBP Sympathetic N excitesmall A contract kidney ischemiarenin Extra-kidney(EC,SMC) angiotensin genes: autocrine or paracrinevasoconstric

40、tionBP 3. Structural hypertrophy: Vasoconstriction factors Proliferation and hypertrophy of SMC Small A wall peripheral resistanceBP Types: Benign (Chronic ) hypertension : 95%, Involve Arteriole:12layer SMC(afferent A) Small artery:30.7/17.3kPa （230 / 130mmHg） A rapid course to death: Brain hemorrh

41、age Heart failure Renal failure1. A immunologically mediated inflammatory disease related to the infection of group A beta-hemolytic streptococci2. Sites:Connective tissue, BV, commonly affect heart,joint,skin,brain3. Feature: Aschoff body formation4.clinic：5-15years old, rheumatic fever, rheumatic

42、heart disease. (一一) Etiology Sensitization to streptococcal antigens, follow 1 to 4 weeks after group A beta-hemolytic streptococci infection. A-s. pharyngitis history Often in winter, summer 1. Ag-Ab cross reactions C Ag(glycoprotein): heart valve, joint M Ag(protein): SMC of myocardium , BV2. Auto

43、immune mechanism 3. Heritage susceptibility(一一) Sites: connective tissue of body，heart , joint , blood vessel , skin . ( (二二) )Basic lesions： 1.1.Alterative and exudative phase（1month）：）： Sites: Heart, serosa, joint, skin , brain Lesions: Stromal mucoid degeneration, fibrinoid necrosis 2. Proliferat

44、ive(granulomatous)phase ： Aschoff body formation Sites： Interstitium of myocardium beside BV Subendocardium Subcutaneous CT Pericardium , joint , vessel: less LM：Aschoff body Center: Fibrinoid necrosis Nearby:Aschoff cell awl-eye cell caterpillar cell Periphery: Lymphocyte , monocyte Origin：mono -ma

45、crophage Vimentin, mac387, lysozyme: (+) Actin , desmin : (-) Rheumatic myocarditisAschoff bodyAschoff bodyawl-eye cellcaterpillar cell 3. Healing phase (scar phase) 4. Totally lasts for 4-6months New-old lesions overlap Progressive hyalinization and fibrosis Nonspecific scarring (一一) Rheumatic hear

46、t disease： Pericarditis: Fibrinous pericarditis Myocarditis: Aschoff body Endocarditis: Vegetation 1. Rheumatic endocarditis： (1) Sites： heart valve Mitral(40%) mitral + aortic(40%) aortic alone(10%) tricuspid pulmonary(2) Lesions：verrucous endocarditis Gross：small white vegetations (verrucae) alone

47、 the line of closure of the mitral valve miliary in size , firmly adhere to valve LM：Pale thrombus McCallum patch: back wall of left antrium, endocardium irregular thickeningRheumatic endocarditis vegetationsRheumatic endocarditisPale thrombus Rheumatic endocarditis （3）Results： Repeated organization

48、 of thevegetation valve thicken, hard, adhere chronic valvular vitium of the heart stenosis or insufficiency （4）Clinical：fever , anemia , murmurChronic valvular vitium of the heartstenosis and insufficiency2. Rheumatic myocarditis(1) Sites: Myocardium mesenchyma, near small BV(2) Lesions： In adult：A

49、schoff body In child: Diffuse myocardium mesenchyma inflammation (3) Results: scar (4) Clinic : fever, a prolonged P-R interval in ECG， WBC, antibody titer OAschoff body ( awl-eye,caterpillar cell )3. Rheumatic pericarditis (1) Sites: pericardium(2) Lesions: Serofibrinous pericarditis Cor villosum:

50、a lot of fibrinous exudate and form a heavy shaggy coat with adhesion between the layers of the pericardium Cor villosumFibrinous pericarditis(3) Results Absorption: recovery Originization constrictive pericarditis(4) Clinic features : percussion：limit expand auscultation：fricative X ray：heart enlar

51、ged1. Infective endocarditis characterized by invasion of the heart valves by a microbiologic agent accompanied with vegetation formation2. Pathogens： germ (streptocci), fungi, viruses 3. Classification Acute infective endocarditis Subacute infective endocarditis:common）1. Pathogens: of lower virule

52、nce viridans streptococci enterococci fungi 2.Features： Infective vegetations : Bulky , friable vegetations composed of thrombi and organisms Occure in vulnerable hosts: with preexisting heart conditions:RE, calcific aortic stenosis, aging, septal defects Favorite sites: mitral or aortic valve3. .Pa

53、thologic change(1) Heart : Gross： different in size, large , single or in group, friable , gray-yellow, irregular masses that can extend onto the chorda, ulceration and perforation may occur, fall off easily A row of warty small vegetations along the lines of closure of the valve leafletsLarge irreg

54、ular masses on the valve cusps that can extend onto the cords LM: : vegetation composed of platelet, fibrin, bacteria , neutrophile calcification, necrosis, granulation(2) Blood vessel： Invading organism and vegetation embolism and vasculitis Embolic infarction： brain kidney , spleen , heart Clinic：

55、linear hemorrhages in skin, mucosaRoth point small vasculitisosler nodule 3. Kidney : Microembolism: local GN Ag-Ab complex: diffuse GN4. Septicemia: low grade fever, anemia, debility, spleen enlarged1. Cause：highly virulent organism, staphylococcus aureus(common), 2. Pathogenesis：purulent inflammat

56、ion the septicemia blood stream endocardium，previously normal heart, mainly aortic valve or mitral 3 . Lesion： Acute purulent endocarditis： leaflets perforation, ulceration Vegetation fragileeasily to fall dissemination of organism or fragments of the vegetation septic infarctionAcute infective endo

57、carditisAcute infective endocarditis (1) With high fever (2) Runs a rapidly progressive to death (3) Disseminated infection, embolization or cardiac decompensation secondary to erosion of valves structural changes of valves (stenosis or insufficiency) Congenital abnormal development1.1.Conception:injuries2. Sites : damaged valve（RE） Common: mitral valve , aortic valve Rare: tricuspid , pulmonary 3. Causes : RE , IE AS , syp