病理學(xué)課件：5-心血管系統(tǒng)

1、Diseases of Cardiovascular System心血管系統(tǒng)Key points for studying systemic pathology1. MorphologyMarcopathologic changes:Microscopic pathologic changes: histopathology2. Clinical course or featuresFunctional alterations of tissues and organsSymptoms, signslaboratory analysisComplicationsOutcome and sequ

2、ences3. Etiology: pathogenic agents, risk or associated factorsCategories of Cardiovascular DiseasesInflammatory diseases： infectious: endocarditis, myocarditis, pericarditis non-infectious: rheumatic fever, vasculitis2. Arteriosclerosis動(dòng)脈硬化: atherosclerosis動(dòng)脈粥樣硬化, Medial calcific sclerosis動(dòng)脈中層鈣化, a

3、rteriolosclerosis細(xì)動(dòng)脈硬化癥 (hypertension)3. Valvular diseases: congenital or acquired4. Cardiomyopathy: primary cardiomyopathy5. Congenital heart diseases:6. Cor pulmonale （肺心病）: 7. Cardiac tumor:Cardiovascular diseases and age distributionChildren, youth: Congenital heart diseases Inflammatory disease

4、s: rheumatic fever, myocarditisAdults: valvular diseases, cardiomyopathy, vasculitisElderly: arteriosclerosis, cor pulmonaleDiseases in discussionArteriosclerosis:Atherosclerosis: coronary heart diseaseHypertension: hypertensive heart diseaseRheumatic disease：rheumatic heart diseaseInfectious endoca

5、rditisValvular diseasesmyocarditisCardiomyopathy Histological structure Blood vessel HeartIntima: endothelium Endocardium: endothelium Media: internal elastic lamina, elastin, SMC Myocardia: myocyte Adventitia: external elastic lamina Adventitia: CT, neurofiber Atherosclerosis 動(dòng)脈粥樣硬化DefinitionEpidem

6、iologyBasic pathologic changesSecondary changesLesions involved organs and manifestations Atherosclerosis 動(dòng)脈粥樣硬化 Definition 廣泛累及大 、中動(dòng)脈，以脂質(zhì) (主要是膽固醇) 在動(dòng)脈內(nèi)膜沉積、平滑肌細(xì)胞和膠原纖維增生，繼發(fā)壞死，形成粥樣斑塊，常造成血管腔不同程度狹窄及血管壁硬化的疾病，相應(yīng)器官可出現(xiàn)缺血性改變。1. Systemic involvement of large, medium-sized arteries(aorta, coronary, cerebral, r

7、enal 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 arterial lumen and loss of elasticity.3. Ischemia of organs: atrophy, fibrosis, infarction Epidemiologypopulat

8、ion：elderlymale femaleIndustrialized: developed countries or regionsurban ruralBasic pathologic changes: 3 stagesPreferable sites: aorta and its main branchesAbdominal aorta, coronary, carotid, renal and iliac branch ostia, protruding surface of curve1. Fatty streak（脂紋）: lipids deposit Gross：yellow

9、streaks or spots flatten or slightly elevatedCautions: 1. Reversible lesion 2. Progress to fibro-plaque in only some patientsfatty streaks formationFatty streak: foam cells aggregate and thickening of intimaL/M： deposited lipids and aggregated foam cells Sudan III staining of lipids Foam cells: smal

10、l nuclei and vacuous cytoplasmfoam cells deriving from: macrophages of bloodSMC migrate from mediaTrans-differentiation of SMC and collagen production: fibrosisEarlier fibrous plaqueIntima L/M: superficial fibrous cap: SMCs and extracellular matrix(collagen, elastin, proteoglicans, external lipids).

11、 Underlying proliferated SMCs, macophages, foam cells, free lipids and extracellular matrix.2. Fibrous plaque （纖維斑塊） Gross：elevated, gray-yellow plaques3. Atheromatous plaque (atheroma) 粥樣斑塊（粥瘤）Gross： marked elevated, gray-yellow plaques.Eccentric plaque and narrowing of lumenAtheromatous plaque: fi

12、brosis, necrosis(clefts of cholesterol) and narrowing of lumenL/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.Atheromatous plaque: media

13、 atrophyAtheromatous plaque: necrosis, cholesterol crystals, foam cellssecondary changes Hemorrhage: intraplaque hemorrhage, hematoma（血腫） secondary changes Focal rupture, ulceration: embolism: cholesterol emboli, Thrombosis：infarction Calcification：mineral deposition in cap, necrotic area leading to

14、 hardening, rigidity, fragility of arterial wall Aneurysm(動(dòng)脈瘤）: segmental dilation in saccular or fusiform due to media atrophy. True aneurysm: segmental dilation in saccular or fusiform due to media atrophy. Dissecting aneurysm(夾層動(dòng)脈瘤）: dissection of media, accumulation of blood coming from rupture

15、of cap or vasa vasorumsecondary changesAneurysm1-4：true aneurysm5：dissecting aneurysm（夾層動(dòng)脈瘤）6：false aneurysmdissecting aneurysm of abdominal aortaLesions involved organs and manifestations1. Narrowing of lumen ischemic atrophy2. Obstruction of lumen infarctionhemorrhage of intra-plaque thrombosis3.

16、Media atrophy aneurysmatherosclerosis of aortas with ulceration蘇丹III染色1. Aorta:1. Aorta:aneurysm: abdominal aorta, fatal hemorrhageDissecting aneurysm of aorta: thrombus, double lumen and atherosclerosis2. Atherosclerosis of coronary arteriesAtherosclerosis of coronary arteries ischemia of myocardia

17、 coronary heart diseaseAngina pectorisMyocardial infarctionChronic ischemic heart diseaseSudden cardiac death3. Atherosclerosis of cerebral arteriesPreferable sites: carotid, basilar artery, circles of Willis, middle cerebral arteryInternal carotid: carotid artery - one middle cerebral artery and on

18、e anterior cerebral arteryVertebral: two vertebral arteries - one basilar artery - two posterior cerebral arteries.20% of cardiac output goes to the brain, and 80% of carotid flow goes to the ipsilateral middle cerebral artery. Anatomy of cerebral circulation Atherosclerosis of cerebral arteriesChro

19、nic ischemia cerebral atrophydementia, 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 infarction4. Atherosclerosis of renal arteriesSegment: renal artery and main branche

20、sChronic ischemia-repeated infarction and scaring- atrophy and fibrosisGross: atherosclerotic atrophy of kidney: bilateral, asymmetric, de-conformation.atherosclerotic atrophy of kidney動(dòng)脈粥樣硬化固縮腎5. Atherosclerotic arteries of extremitiesSites：iliac arteriesLower extremities： atrophy of muscles stumbl

21、e: gangrene: ischemic infarctionAtherosclerosis and affection on various organsPathogenesisPathogenic agents: risk factorsPathogenesis:Hard risk factors (Large contribution to incidence; potentially avoidable or treatable)1. Hyperlipidemia: Particularly hypercholesterolemia LDL , VLDL , HDL , apo-A1

22、 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 critical event in pathogenesis of ASHard risk factors2. Hypertension: e

23、specially 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 hypercholesterolemiaAge : age-related disease, incidence of severe dise

24、ase rises with each decade. degeneration of arterial wall: decline in potential of lipids-cleaningSex : estrogen level-related. before menopause: malefemale; menopause: male= femaleGenetics: Some families have increased mutation in genes of LDL receptor, apoprotein, lipoprotein esterase multiple gen

25、es: predispositionConstitutional risk factorsSoft risk factors (Small contribution to incidence in statistical studies)Lack of regular exerciseObesityStressful lifestyleHigh carbohydrate intakeHardened unsaturated fat intakePathogenesis hypothesis1. Lipid hypothesis脂源性學(xué)說(shuō)2. Injury and response hypoth

26、esis損傷應(yīng)答學(xué)說(shuō)Endothelial dysfunction3. SMC proliferation or Mutagenesis hypothesis4. Chronic inflammation hypothesis5. Macrophage effect hypothesisMedicine, Volume 42, Issue 9, September 2014, Pages 480-484Monocytes and macrophagesT cellsMediators of InlammationVolume 2013Key process1. Endothelia injur

27、y and lipids deposition2. Endothelia dysfunction3. Macrophage infiltration4. Emigration and proliferation of SMC5. Fibrosis and necrosisCoronary Heart Disease冠心病 冠狀動(dòng)脈狹窄引起心肌缺血、缺氧，造成缺血性心臟病 (Ischemic Heart Disease，IHD)。 The narrowing of coronary artery results in hypoperfusion, hypoxia (ischemia) of my

28、ocardium. PathogenesisAtherosclerosis of coronary arteries：95% the initial and proximal segments, main branches of left or right coronary artery, especially left anterior descending branchseverity: I75%thrombosis, rupture, intraplaque hemorrhage2. Coronary artery vasospasm（冠狀動(dòng)脈痙攣）：3. Inflammatory di

29、seases of coronary artery: syphilis, some of arteritisTypes and features1. Angina pectoris 心絞痛2. Myocardial infarction 心肌梗死3. Chronic ischemic heart disease 慢性缺血性心臟病4. Sudden cardiac death 急性心源性死亡Angina pectoris 心絞痛This is a symptom complex. Symptoms caused by transient myocardial ischaemia that fal

30、ls short of inducing the cellular necrosis that defines myocardial infarction. Intermittent chest pain, transient, reversible myocardial squeezing, crushing substernal sensation, radiating to left arm Mechanism: ischemiamyocytes injury, metabolic products accumulation nerve systemAngina PectorisSubt

31、ypes and features1. Stable： Most common form. 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：Uncommon pattern, occurs at r

32、est; unrelated to physical activity, heart rate or blood pressure; generally responds to vasodilators. cause: vasospasmMyocardial infarction: 心肌梗死Persistent and complete ischemia of local myocardiumnecrosis of myocytesPathogenesis:1. Thrombosis2. Spasm3. Hypoperfusion - increasing demandTypes: left-

33、side heart1. Transmural:2. Subendocardial: Subendocardial MI 心內(nèi)膜下心肌梗死Features:1. Inner 1/3 of myocardium, including 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 la

34、rge parts of arteries4. Vasospasm related Regional myocardial (or transmural) infarction MI 區(qū)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 interventricu

35、lar septum, right ventricle Others：left circumflex: lateral left ventricle Morphology Coagulative necrosisinflammatory responsefibrous healingGross: post-infarctionIrregular shaped areas of infarcts6 hr: pallor 8-9 hr： yellow, dry, firm3-7 d： yellow, soft, hyperemic and hemorrhage border10 d: softer

36、, obvious hemorrhage border 2-3 wk： red: granulation tissue, 5 wk： gray, firm, shrunk: scaring (organization) Infarct in left anterior wallInfarct in left anterior, interventricular septumL/M: coagulative necrosis: No changes in early phase1-2 hr: wavy fiber change9 hr： neutrophils appear18-24 hr: c

37、ytoplasmic condensation (increasing 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 surrounding2-8 wk: scaring (organization)

38、Wavy fiber changeCytoplasmic: condensation(increasing eosinophilia)Nuclear change: pyknosis karyorrhexisCytoplasmic condensation (increasing eosinophilia, contraction bands), karyorrhexis, hyperemiaCytoplasmic condensation (increasing eosinophilia), karyorrhexis, infiltrating neutrophilsInfiltrating

39、 neutrophils, myocytolysisMacrophages: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 myofibroblas

40、tAngiogenesisExtracellular matrix proteinStem cell transplantationEmbryonic stem cellsSomatic stem cells: bone marrow mesenchymal neonatal cardiomyocytes other sourcesiPS: induced pluripotent cell Biochemical detectionProtein: Myohemoglobulin（肌紅蛋白）Enzymes： Creatine kinase(CK)肌酸激酶: 2-4 hr, 24h peak,

41、72h normal LDH (乳酸脫氫酶）: LDH1,LDH2 95% patients LDH1/LDH2 1 Troponins（肌鈣蛋白）: 2-4 hr, 24 peak, last 4- 7 d indicator of myocyte injury心內(nèi)膜下心肌梗死透壁性心肌梗死深度累及心室壁內(nèi)側(cè)1/3的心肌，波及肉柱及乳頭肌。累及心室壁全層或達(dá)室壁2/3范圍多發(fā)性、小灶性壞死，分布不規(guī)則。嚴(yán)重者引起環(huán)狀梗死梗死部位與冠狀動(dòng)脈分支供血區(qū)一致,病灶大,最大直徑在2.5厘米以上原因嚴(yán)重、彌漫的冠狀動(dòng)脈AS性狹窄 + 誘因一支冠狀動(dòng)脈病變突出,并常附有動(dòng)脈痙攣或血栓形成Complica

42、tions and sequelae1. rupture ：within 1-2 weeksapical: 1/3tamponade（心包填塞）septum: heart failure papillary musclesmitral insufficiency left heart failureAm J Cardiol. 2015 Jan 1;115(1):125-1402. Ventricular aneurysm：acute or healing phase apical heart failure, mural thrombosisLeft ventricular aneurysm3

43、. Mural thrombi：infarct or Ventricular aneurysm4. Pericarditis：fibrins exudates 5. Cardiogenic shock The infarct area of left ventricle40%，output shock6. Cardiac arrhythmias：involve conduct system7. Scar formation Organization：small：2 weekslarge：4-6 weeksMyocardial fibrosis (心肌纖維化）Sudden cardiac dea

44、th (心源性猝死）Chronic ischemic heart disease (慢性缺血性心臟?。?Hypertension高血壓病Essential or primary hypertension: idiopathic， arteriolosclerosis Type：benign or malignant(accelerate)Secondary hypertension: as a part of diseases(kidney, endocrine tumor）Benign hypertension良性高血壓病 onset at middle or elderly，progres

45、s slowly Clinical course：1. Functional deregulation: interval vasospasm of arteriole or small arteries，hypertension in fluctuation; asymptomatic2. Arteriolosclerosis: persistent hypertension3. Organs: compensatory（代償期）: hypertrophy of heart, nephrosclerosis, cerebral arteriosclerosis, decompensatory

46、（失代償期）: cardiac 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

47、 artery Pathology: 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

48、 arteries(muscular 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 dis

49、ease: left ventricle 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 dilatio

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

51、ophy and fibrosis 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).Benign nephro

52、sclerosis: characteristic granular appearanceMicroscopic features of benign nephrosclerosisRenal dysfunction and clinical manifestationsProteinuria, hematuria：glomeruli damageGlomerular filtration rate: atrophy of glomeruli and tubulesRenal failure：azotimia, uremia3) Brain：headache, nausea Cerebral

53、vessels：hyaline, or fibrinoid necrosis arterioles; atherosclerosis of small arteries, thrombosis, microaneurysms: infarction and hemorrhage.A. Arteriolosclerosis: hyaline wall thickening and mild lumen narrowing. B. Media mineralisationA. fibrinoid necrosis. B. fibrosis. C. thrombosed lesionLacunes:

54、 small foci of infarctsCerebral hemorrhage destruction of brain tissue, elevated Intracranial pressureherniation Basal ganglia area (Putamen): hemiparesis (paralysis of half the body), hemianopsia, or aphasia. Cerebral lobes: Thalamus: Cerebellum：nausea, vomiting, dizziness, ataxia. Pons：Hemorrhage

55、of basal ganglia area with midline shiftBasal ganglia hemorrhage involving ventriclePontine hemorrhage Subarachnoid hemorrhage and hyaline degeneration of small arteriesHypertensive encephalopathy（高血壓腦?。? blood pressure over the limits of cerebral autoregulation, dysfunction of central nerve system.

56、 hypertensive emergency（高血壓危象）: marked elevated blood pressure and multiple organs dysfunction.4) Hypertensive retinopathy:Sclerosis of central retinal artery: white, silvery papilledema retinal exudation: flame-shaped hemorrhage focal infarction: spot(soft cotton-wool) retinal detachmentEyes vessel

57、 changes could predict severe hypertension risk The eyes may be the window to the soul and future hypertensionThe most common findings: inter-retinal hemorrhages, both flame-shaped and dot and blot hemorrhagesMalignant hypertension惡性高血壓病 Primary, or benign hypertension deriving Elevated level of pla

58、sma reninClinical features： Severe hypertension: 230/130 mmHg Hypertensive encephalopathy Renal dysfunction: persistent proteinuria, hematuria Death within one year: uremia, cerebral hemorrhage, cardiac failurePathologic changes1. Arteriole：fibrinoid necrosis-necrotizing arteriolitis2. Smaller arter

59、ies： hyperplastic arteriosclerosis thickening intima: hyperplastic SMC，“onion-skin”3. kidney：malignant nephrosclerosis Necrotizing arteriolitis: Necrotizing glomerulolitis: micro-hemorrhages Thrombosis: micro-infarctions4. Brain：ischemia, infarction, hemorrhageFlea-bitten kidneyEtiology and Pathogen

60、esis Benign Hypertension Risk factors of hypertension1. Genetic: familial, genetic predisposition polygenetic2. Dietary habit: intakes: high sodium, low potassium and calcium3. Psychologic：stress4. Occupation:5. Obesity: PathogenesisKey process 1. Blood volume： Na+-fluids accumulation2. Peripheral r