病理学课件：5-心血管-英

1、Diseases of Cardiovascular SystemKey points for studying of systemic pathology 1. Morphology: maropathologic changes:microscopic pathologic changes: histopathology2. Clinical course or features: Functional alterations of tissues and organs Symptoms:Signs: Laboratory analysis:Complications:Outcome an

2、d sequelae:3. Etiology: pathogenic agents, risk or associated factors 4. Pathogenesis: inflammatory, tumorous, metabolic, degenerative, immunologic, genetic, developmentalCategories of Cardiovascular DiseasesInflammatory diseases： infectious: endocarditis, myocarditis, pericarditis non-infectious: r

3、heumatic fever, vasculitis2. Arteriosclerosis: atherosclerosis, hypertension3. Valvular diseases: congenital or acquired4. Cardiomyopathy: primary cardiomyopathy5. Congenital heart diseases:6. Cor pulmonale: 7. Cardiac tumor:Cardiovascular diseases and age distributionChildren, Youth: Congenital hea

4、rt diseases Inflammatory diseases: rheumatic fever, myocarditis, Adults: valvular diseases, cardiomyopathy, vasculitisElderly: arteriosclerosis, cor pulmonaleDiseases in discussionArteriosclerosis:Atherosclerosis: coronary heart diseaseHypertension: hypertensive heart diseaseRheumatic disease：rheuma

5、tic heart diseaseInfectious endocarditis:Valvular diseases:Cardiomyopathymyocarditis Histological structure Blood vessel HeartIntima: endothelium Endocardium: endothelium Media: internal elastic lamina, elastin, SMC Myocardia: myocyte Adventitia: external elastic lamina Adventitia: CT, neurofiber At

6、herosclerosis动脉粥样硬化1. Systemic involvement of large, medium-sized arteries(aorta, coronary, cerebral, renal and iliac).2. Lipids (cholesterol) deposition in intima, hyperplasia of smooth muscle cells, fibrosis and necrosis, formation of characteristic atheroplaque (atheroma，粥瘤), narrowing of arteria

7、l lumen and loss of elasticity.3. Ischemia of organs: atrophy, fibrosis, infarction Epidemiologypopulation：elderlymale femaleIndustrialized: developed countries or regionsurban ruralBasic pathologic changes: 4 stagesPreferable sites: aorta and its main branchesAbdominal aorta, coronary, carotid, ren

8、al and iliac branch ostia, protruding surface of curve1. Fatty streak: lipids deposit Gross：yellow streaks or spots flatten or slightly elevatedL/M： deposited lipids and aggregated foam cells foam cells deriving from: macrophages of blood SMC migrate from media Cautions: 1. Reversible lesion 2. Prog

9、ress to fibro-plaque in only some patientsLipids deposition and formation of foam cells1. chemical modification of LDL: oxidize. 2. Macrophage and SMC infiltration: endothelia-cytokinesMigration of SMC from media Fatty streaks in aortaFatty streaks in aortaFatty streaks in aortaFatty streak: foam ce

10、lls aggregate and thickening of intimaFoam cells：Sudan III staining of lipids Foam cells: small nuclei and vacuous cytoplasmFoam cells: small nuclei and vacuous cytoplasmTrans-differentiation of SMC and collagen production: fibrosis2. Fibrous plaque Gross：elevated, gray-yellow plaques L/M: superfici

11、al fibrous cap: SMCs and extracellular matrix(collagen, elastin, proteoglicans, external lipids). Underlying proliferated SMCs, macophages, foam cells, free lipids and extracellular matrix.Earlier fibrous plaqueIntimaFibrous plaque3. Atheromatous plaque (atheroma) Gross： marked elevated, gray-yellow

12、 plaques. In cross: white, hard fibrous cap, yellow gruel-like materials in central.L/M: hyaline fibrous cap, central amorphous materials(necrosis) containing cellular debris, lipids, cholesterol crystals(or clefts), foam cells, and granulation tissue at edge and inflammatory cells: lymphocytes.Athe

13、roma:Eccentric plaque and narrowing of lumenAtheromatous plaque: fibrosis, necrosis(clefts of cholesterol) and narrowing of lumenAtheromatous plaque: media atrophyAtheromatous plaque: necrosis, cholesterol crystals, foam cells4. Complicated plaque or secondary changes Hemorrhage: intraplaque hemorrh

14、age, hematoma Focal rupture, ulceration: embolism: cholesterol emboli, atheroemboli Thrombosis：infarction Calcification：mineral deposition in cap, necrotic area leading to hardening, rigidity, fragility of arterial wall Aneurysm: segmental dilation in saccular or fusiform due to media atrophy.Hemorr

15、hageThrombosis Aneurysm（动脉瘤）: True aneurysm: segmental dilation in saccular or fusiform due to media atrophy.Dissecting aneurysm: dissection of media, accumulation of blood coming from rupture of cap or vasa vasorum1-4：true aneurysm5：dissecting aneurysm6：false aneurysmdissecting aneurysm of abdomina

16、l aortaLesions involved organs and manifestations1. Narrowing of lumen ischemic atrophy2. Obstruction of lumen infarctionhemorrhage of intra-plaque thrombosis3. Media atrophy aneurysm1. Aorta: aneurysm: abdominal aorta, fatal hemorrhage aortic valves: insufficiencyAtherosclerotic lesions in abdomina

17、l aorta and iliac artery Atherosclerotic lesions in abdominal aortaAtheroma in aortaDissecting aneurysm of aorta: thrombus, double lumen and atherosclerosisMicroscopic appearance of dissecting aneurysm: dissection of aortic media2. Atherosclerosis of coronary arteriesAtherosclerosis of coronary arte

18、ries ischemia of myocardia coronary heart diseaseAngina pectorisMyocardial infarctionChronic ischemic heart diseaseSudden cardiac death3. Atherosclerosis of cerebral arteriesPreferable sites: carotid, basilar artery, circles of Willis, middle cerebral arteryChronic ischemia cerebral atrophydementia,

19、 encephalopathyVascular dementia is the second most common cause of dementia in the USA and Europe, but it is the most common form in some parts of Asia.Acute ischemia: cerebral infarctionAnatomy of cerebral circulation Internal carotid: carotid artery - one middle cerebral artery and one anterior c

20、erebral arteryVertebral: two vertebral arteries - one basilar artery - two posterior cerebral arteries.The circle of Willis: the anterior communicating artery that joins the two anterior cerebral arteries, and the two posterior communicating arteries, each of which joins a posterior cerebral artery

21、with an ipsilateral carotid artery.20% of cardiac output goes to the brain, and 80% of carotid flow goes to the ipsilateral middle cerebral artery. Anatomy of cerebral circulationAnatomy of cerebral circulationAnatomy of cerebral circulation4. Atherosclerosis of renal arteriesSegment: renal artery a

22、nd main branchesChronic ischemia-repeated infarction and scaring- atrophy and fibrosisGross: atherosclerotic atrophy of kidney: bilateral, asymmetric, de-conformation.atherosclerotic atrophy of kidney动脉粥样硬化性肾萎缩5. Atherosclerotic arteries of extremitiesSites：iliac arteriesLower extremities： atrophy o

23、f muscles stumble: gangrene: ischemic infarctionAtherosclerosis and affection on various organsPathogenesisPathogenic agents: risk factorsPathogenesis:basic process components cells cellular factorsHard risk factors (Large contribution to incidence; potentially avoidable or treatable)1. Hyperlipidem

24、ia: Particularly hypercholesterolemia LDL , VLDL , HDL , apo-AI , Lp-a The level of blood lipids (cholesterol) correlate with ASExperiment：high-lipid intake inducing ASMetabolic alterations of lipids inducing AS：endocrine disease, genetic defects: prematured AS lipids deposition is the initial and c

25、ritical event in pathogenesis of ASHard risk factors2. Hypertension: especially after the age of 45 very important promoting factor3. Smoking: predominant atherogenic effects in the aorta and coronary vessels4. Diabetes mellitus: particularly in coronary, cerebral, and peripheral arteries inducing h

26、ypercholesterolemia Constitutional risk factors1. Age: age-related disease. degeneration of arterial wall: decline in potential of lipids-cleaning2. Sex: before menopause: malefemale; menopause: male= female level of estrogen-related.3. Genetic: Single gene: mutation in genes of LDL receptor, apopro

27、tein, lipoprotein esterase multiple genes: predispositionSoft risk factors (Small contribution to incidence in statistical studies)1. Lack of regular exercise2. Obesity3. Stressful lifestyleKey process1. Endothelia injury and lipids deposition2. Endothelia dysfunction3. Macrophage infiltration4. Emi

28、gration and proliferation of SMC5. Fibrosis and necrosisThe components of plaquelipids: LDLLDL: OX-LDL: lipids or apo-B iNOS, 15-LO-mediated，MPOThe role of OX-LDL：Chemotaxis：Inducing expression of adhesion molecules of endothelia：ICAM-1，VCAM-1Scavenger receptor: foam cells formationInitiating immune

29、 reaction Possible Mechanisms by which oxLDL Components Can Exert Proatherogenic EffectsCell, Vol. 104, 503516, February 23, 2001The components of plaque Endothelial cellsChronic injury: necrosis, apoptosis Production: Adhesion molecules: ICAM-1，VCAM-1, selectins - monocyte migration Cytokines: mono

30、cytes/SMC proliferationThe components of plaqueMacrophages: infiltrating, scavenger receptor(SR-A/cd36), cytokines-producingSmooth muscle cells: Migration:Proliferation: PDGF, FGF, etc.Collagen synthesis: TGF-Smad-pathwayThe essence of hyperplasia of SMC： responsive：polyclonal autonomoustumorous, mo

31、noclonal：oncogenes, antioncogenes or genetic mutationFatty streakCell, Vol. 104, 503516, February 23, 2001Fibrous plaqueCell, Vol. 104, 503516, February 23, 2001Atheromatous plaque and secondary changesCell, Vol. 104, 503516, February 23, 2001Reviewing of hypothesis on pathogenesis1. Lipid hypothesi

32、s2. Mutagenesis hypothesis3. Injury and response hypothesis4. Receptor defect hypothesis：germline mutation of LDL receptorExamples of Genes that Influence Development of Atherosclerosis in Hypercholesterolemia MiceCell, Vol. 104, 503516, February 23, 2001Potential Targets for Development of Small Mo

33、lecule Inhibitors of AtherosclerosisCell, Vol. 104, 503516, February 23, 2001Coronary Heart Disease冠心病The narrowing of coronary artery results in hypoperfusion, hypoxia (ischemia) of myocardium Ischemic Heart Disease: IHDPathogenesisAtherosclerosis of coronary arteries：95% the initial and proximal s

34、egments, main branches of left or right coronary artery, especially left anterior descending branchseverity: I75%thrombosis, rupture, intraplaque hemorrhage2. Coronary artery vasospasm：3. Inflammatory diseases of coronary artery: syphilis, some of arteritisTypes and features1. Angina pectoris 心绞痛2.

35、Myocardial infarction 心肌梗死3. Chronic ischemic heart disease 慢性缺血性心脏病4. Sudden cardiac death 急性心源性死亡Angina pectoris 心绞痛Intermittent chest pain, transient, reversible myocardial squeezing, crushing substernal sensation, radiating to left armMechanism: ischemiamyocytes injury, metabolic products accumu

36、lation nerve systemSubtypes and features1. Stable：stress-inducing, relieving by rest or vasodilator cause: fixed narrowing(75%)2. Unstable：increasing frequency and intense, longer lasting preinfarction anginacause: thrombosis, distal embolization, spasm3. Variant/Prinzmetal：non-inducing stress, caus

37、e: vasospasmMyocardial infarction: 心肌梗死Persistent and complete ischemia of local myocardiumnecrosis of myocytesPathogenesis:1. Thrombosis2. Spasm3. Hypoperfusion - increasing demandTypes: left-side heart1. Transmural:2. Subendocardial: Subendocardial MI 心内膜下心肌梗死Features:1. Inner 1/3 of myocardium, i

38、ncluding trabecula, papillary muscles2. Disseminated foci of infarcts, involving entire endocardium (circular MI) , not limited to area of one artery supply3. Severe narrowing of arteries in large parts of arteries4. Vasospasm related主动Pars右 室Anteri bran c右 Ri右 R.右 Ve房左 室 后Rer室 间 隔 R.后 室 间 沟 Ve

39、Sulcus interR.venttri Regional myocardial (or transmural) infarction MI 区域性（或透壁性）心肌梗死Involving area and frequency: left right50%： left anterior descending CA: anterior, apical, 2/3 anterior interventricular septum25%：right CA: left posterior ventricle, 1/3 posterior interventricular septum, right ve

40、ntricle Others：left circumflex: lateral left ventricle Morphology Coagulative necrosisinflammatory responsefibrous healingGross: post-infarctionIrregular shaped areas of infarcts6 hr: pallor 8-9 hr： yellow, dry, firm, mute4 d： hyperemic and hemorrhage border10 d: yellow, soft 2-3 wk： red: granulatio

41、n tissue, 5 wk： gray, firm, shrunk: scaring (organization) Infarct in left anterior wallInfarct in left anterior, interventricular septumScar formation of infarct L/M: coagulative necrosis: No changes in early1-2 hr: wavy fiber change9 hr： neutrophils appear18-24 hr: cytoplasmic condensation (increa

42、sing eosinophilia, contraction bands); Nuclear change: pyknosis, karyorrhexis24-72 hr: neutrophils infiltration4 d： hyperemic and hemorrhage in surrounding 7 d: macrophages, granulation tissue at edge10 d: granulation tissue in surrounding.2-8 wk: scaring (organization)Wavy fiber changeCytoplasmic:

43、condensation(increasing eosinophilia)Nuclear change: pyknosis karyorrhexisCytoplasmic condensation (increasing eosinophilia, contraction bands), karyorrhexis, hyperemiaCytoplasmic condensation (increasing eosinophilia), karyorrhexis, infiltrating neutrophilsInfiltrating neutrophils, myocytolysisMacr

44、ophages:1-2 weekMacrophages phagocytizing necrotic myocytesOrganization by granulation tissue Scaring, hypertrophy of remaining myocytesRepair of myocardial infarctionInjury and repair1. Inflammation 2. Fibrosis: scar formation Hyperplasia of fibroblast and myofibroblastAngiogenesisExtracellular mat

45、rix proteinStem cell transplantationEmbryonic stem cellsSomatic stem cells: bone marrow mesenchymal neonatal cardiomyocytes other sourcesiPS: induced pluripotent cell Biochemical detectionProtein: MyohemoglobulinEnzymes： Creatine kinase(CK): 2-4 hr, 24 peak, 72 normal LDH: Troponins: 2-4 hr, 24 peak

46、, last 4- 7 d indicator of myocyte injuryComplications and sequelae1. rupture ：within 1-2 weeksapical: 1/3tamponadeseptum: heart failurepapillary musclesmitral insufficiencyleft heart failure2. Ventricular aneurysm：acute or healing phaseapical heart failure, mural thrombosis3. Mural thrombi：infarct

47、or Ventricular aneurysm4. Pericarditis：fibrins exudates Left ventricular aneurysm5. Cardiogenic shock The infarct area of left ventricle40%，output shock6. Cardiac arrhythmias：involve conduct system7. Scar formation Organization：small：2 weekslarge：4-6 weeks Hypertension高血压病SystolicDiastolicNormal: 14

48、0 mmHg or90 mmHgHypertension: 160 95Borderline: 140 sys.160 90 dia95 Essential or primary hypertension: idiopathic， arteriolosclerosis Type：benign or malignant(accelerate)Secondary hypertension: as a part of diseases(kidney, endocrine tumor）Benign hypertension良性高血压病 onset at middle or elderly，progre

49、ss slowly Clinical course：1. Functional deregulation: interval vasospasm of arteriole or small arteries，hypertension in fluctuation; asymptomatic2. Arteriosclerosis: persistent hypertension3. Organs: compensatory: hypertrophy of heart, nephrosclerosis, cerebral arteriosclerosis, decompensatory: card

50、iac failure, cerebral hemorrhage, renal failurePathologic changes1. Arteriole2. Heart: left ventricle3. Kidney:4. Cerebral arteriole:5. Retinal:1. Arteriole : generalized Characteristic change: hyaline arteriolosclerosisrenal afferent arteriole, splenic central arteriole, retinal central artery Path

51、ology: Subendothelial protein deposition hyaline degeneration thickening of wall, rigidity, luminal narrowing and occlusion arteriolosclerosishyaline degeneration of splenic central arteriolehyaline degeneration of renal afferent arteriolehyaline degeneration of renal arteriole2. Smaller arteries(mu

52、scular arteries) Intimal thickening: hyperplastic SMC, fibrosis, matrix deposition Duplicate internal elastic lamina Media hyperplastic：SMCs proliferation Result: narrowing of lumenSclerosis of smaller arteries in hypertension3. Organs lesions and manifestations 1) Hypertensive heart disease: left v

53、entricle hypertrophy mechanism：high pressure -increasing systolic load of left ventricleGross： hypertrophy of left ventricle wall，papillary and trabecular muscles over 2 cm in thickness concentric hypertrophy : without chamber dilation (compensation) eccentric hypertrophy：chamber dilationcardiac fai

54、lure (decompensation)L/M: hypertrophic muscle fibers Normalconcentric hypertrophyThickening of left ventricle wall 2 cm NormalConcentric hypertrophyNormalEccentric hypertrophyDilated chamber2) kidney: benign nephrosclerosismechanism：afferent arteriole hyalinosis and luminal narrowing-atrophy and fib

55、rosis of nephron accompanying compensatory hypertrophy of nephron.Pathologic changes：symmetric, granular atrophyHyaline arteriosclerosis and small artery sclerosisdiffuse atrophy of nephrons, interstitial fibrosis. Hypertrophy of glomeruli and dilated tubules (compensation).Renal dysfunction and cli

56、nical manifestationsProteinuria, hematuria：glomeruli damageGlomerular filtration rate: atrophy of glomeruli and tubulesRenal failure：azotimia, uremiaBenign nephrosclerosis: characteristic granular appearanceMicroscopic features of benign nephrosclerosis3) Brain：headache, nausea Cerebral vessels：hyal

57、ine, or fibrinoid necrosis arterioles; atherosclerosis of small arteries, thrombosis, microaneurysms: infarction and hemorrhage. Lacunes: small foci of infarcts, thrombosis. Cerebral hemorrhage：destruction of brain tissue, elevated Intracranial pressureherniation Basal ganglia area (Putamen): hemipa

58、resis (paralysis of half the body), hemianopsia, or aphasia. Cerebral lobes: Thalamus: Cerebellum：nausea, vomiting, dizziness, ataxia. Pons：Hypertensive encephalopathy: blood pressure over the limits of cerebral autoregulation, dysfunction of central nerve system. hypertensive emergency: marked elev

59、ated blood pressure and multiple organs dysfunction. Arteriolosclerosis A. Arteriolosclerosis: hyaline wall thickening and mild lumen narrowing. B. Media mineralisation Arteriolosclerosis A. fibrinoid necrosis. B. fibrosis. C. thrombosed lesion.Small vessel atherosclerosis Lacunes: small foci of inf

60、arctsHemorrhage of basal ganglia area with midline shiftBasal ganglia hemorrhage involving ventriclePontine hemorrhage Subarachnoid hemorrhage and hyaline degeneration of small arteries4) Hypertensive retinopathy:Sclerosis of central retinal artery: white, silvery papilledema retinal exudation: flam