病理学课件 血液循环障碍-2016 March-liugy

血液循环系统障碍

HemodynamicDisorders刘国元gyliu@《心血运动论》威廉·哈维AnAnatomicalStudyoftheMotionoftheHeartandoftheBloodinAnimals,1628ContainingHeart,artery,VeinGeneralcirculation&PulmonarycirculationFunctionsDeliveroxygenandnutrientsCarryawaymetabolicwastes健康的循环系统：

正常血容量（Normalbloodvolume）

血液稳态（Homeostasis）血液稳态

Normalhomeostasis

血管壁完整性vesselwallintegrity

静水压intravascularpressure

胶渗压osmolarity

正常凝血normalhemostasisEdema水肿Hyperemia&congestion

充血和淤血Thrombosis&Embolism

血栓形成和栓塞Infarction梗死Hemorrhage出血Shock休克ThreeMajorCausesofmorbidityandmortality

Myocardialinfarction心肌梗死

Pulmonaryembolism肺栓塞

Cerebralvascularaccident脑血管意外，中风CirculationDisturbanceGeneral(全身性)Someseveresituationaffectingalloverthebody:cardiacdysfunction心功能不全

shockLocal（局部性）Abnormalbloodvolumeandthevelocityofbloodflow:hyperemia&ischemiaAbnormalityofvascularintegrityandpermeability:edema&hemorrhage

Occlusionofthevessellumen:thrombosis,embolism&infarction

12WordsandVocabulariescyanosisedemasclerosisheartfailurecellbrownindurationnutmeglivermixedthrombushyalinethromusorganizationrecanalizationphlebolith&arteriolithcrossedembolismorparadoxicalembolismretrogradeembolismthromboembolismcaissondiseasedecompressionsicknessamnioticfluidembolismsepticinfarctEDEMA

(水肿)组织间隙(interstitialtissuespaces)液体含量增加General&localPathogenesisVascularhydrostaticpressurePlasmacolloidosmoticpressureLymphaticdrainageEDEMAIncreasedhydrostaticpressure(心功能不全致心源性水肿，cardiacedema)Reducedplasmaosmoticpressure(nephrotic,hepatic,malnutrientedema,etc.)Lymphaticobstruction(丝虫病感染—橡皮肿，乳癌扩大根治术后)Sodiumandwaterretention水钠潴留(急性肾衰)MinimalChangeDiseaseelephantiasisPittingedemaEDEMAMostcommontypesSubcutaneousedemaPulmonaryedemaEdemaofthebrainMorphologyLightMicroscope（LM）:ClearingandseparationoftheextracellularmatrixelementsCellswelling特殊类型Hydrothorax胸腔积液hydropericardium心包腔积液hydroperitoneum(ascites)腹腔积液Anasarca全身性水肿EDEMAClinicalcorrelationfromannoyingtofatalindicatesubtlediseasebenefitorharmfulHYPEREMIA&CONGESTION

充血和淤血局部组织血管内血液含量的增多Arterialhyperemia(hyperemia，充血)局部器官或组织由于动脉血输入量增多而发生的充血

anaugmentedbloodflowinducingarteriolarandcapillarydilationVenoushyperemia(congestion，淤血)局部器官或组织由于静脉血液回流受阻，血液淤积于小静脉和毛细血管内accumulationofbloodinsmallveinsandcapillariesresultfromdrainagedifficultyofveinsHyperemia:activeprocess主动过程;red,raisedtemperature,increasedvolume（红热肿）enhancedfunction功能增强;Congestion:

passiveprocess被动过程;generalorlocal;reddishbluecolor(cyanosis发绀),lowtemperature,increasedvolume,edema（紫冷肿）decreasedfunction功能低下机制：

血管舒张神经兴奋性↑

血管收缩神经兴奋性↓类型：

生理性：

如害羞时，运动时，进餐后

病理性：炎性充血，减压后充血

利弊：

－plentysupplyofO2,functionalenhancement,nutritionsubstance

－headache,hemorrhage,stroke

HYPEREMIA充血Pathologicchanges

Gross—Floridincolor

－Raisedtemperature

－Enlargedvolumeoforganortissue

LM－DilationofarterioleandcapillarystuffingwithRBCCauses:

全身性:体循环淤血，肺循环淤血

cardiacdysfunction(rightorleft)局灶性:局部静脉受压或阻塞

externalcompression---tumor,bandage occlusionoflumen---thrombosis,embolism thickeningofvenouswall paralysisofneurogenicmodulation---burn,frostbite

CONGESTION淤血CONGESTIONChroniccongestionraisedvenouspressure

AnoxiaMetaboliteaccumulationEnlargedinterendothelialgapBasemembranedegeneration

Parenchymal

InterstitialfibrosisAtrophyReticularfibercollapsedIncreasedpermeabilityDegenerationCollagenincreasedNecrosisFibroblastproliferationMicroscopicscarring

Edema&Hemorrhage

CongestivesclerosisCONGESTION

淤血

静脉压升高

缺氧及代谢产物堆积

毛细血管内皮间隙增宽

基底膜变性

实质细胞萎缩、变性和坏死间质纤维组织增生

血管通透性增加

淤血性水肿

淤血性出血

淤血性硬化Morphology大体镜下小血管内富含红细胞

CONGESTION肺急性肺淤血acutepulmonarycongestionGross:肺饱满肿胀，胸膜光亮，切面流出泡沫状红色水肿液体(edematousfluid)

LM:肺泡壁毛细血管高度扩张充血——串珠样、玫瑰样肺泡腔“虚实不一”，充满嗜酸性水肿液临床病理联系

气促、发绀、粉红色泡沫痰

foamypinkysputum慢性肺淤血chronicpulmonarycongestion多由风湿性心瓣膜病伴心功能不全引起Gross:质地较硬，棕褐色，散在分布有棕色小点

——褐色硬化(BrownInduration)LM:肺泡壁(septa)增厚纤维化心衰细胞(heartfailurecells)

——吞噬红细胞并将血红蛋白分解形成棕黄色的含铁血黄素（hemosiderin）的巨噬细胞

—hemosiderin-ladenmacrophage临床病理联系：

咳嗽，咳铁锈色痰，呼吸困难肝急性肝淤血acutehepaticcongestion大体：肝脏体积增大，呈暗红色镜下：

小叶中央静脉和肝窦(sinusoid)扩张，充满红细胞

严重时可有小叶中央肝细胞萎缩、坏死

慢性肝淤血chronichepaticcongestion槟榔肝NutmegLiver

Gross：肝小叶中央区因严重淤血而呈暗红色，肝小叶周边部肝组织因脂肪变性而呈黄色，红(淤血区)黄(肝脂肪变区)相间，状似槟榔切面。LM：肝小叶中央区淤血乃至出血，肝细胞萎缩，甚至坏死、崩解消失，肝小叶周边部肝细胞脂肪变性。长期严重的肝淤血

纤维组织增生，肝脏表面细小颗粒状“猪皮”

“淤血性肝硬化”（心源性肝纤维化）hepaticfibrosis(cardiaccirrhosis).nutmegliver

Centrilobularnecrosis慢性肝淤血Spleencongestion

Cause:livercirrhosis,cardiacfailurePathologicchange:

tobacconodulesGandy-Gammanodules

含铁小结/烟草小结

Hemorrhage（出血）Causes血管破裂(破裂性出血）Trauma Pepticulcer,aneurism,atherosclerosis出血倾向(漏出性出血）Enlargedinterendothelialgap(basementmembraneinjury).Theintegrityofthevesselsremainsintact

Injurytovascularwall:severeinfection,anoxia,toxinsChangeinnumberandqualityofplateletsuremia,leukemia,idiopathic

Disturbanceofcoagulationmechanismcongenitaldisease,DIC,deficiencyofVit.KHemorrhage瘀点petechiae紫癜purpuras瘀斑ecchymoses血肿hematoma胸腔积血hemothorax心包腔积血hemopericardium腹腔积血hemoperitoneum关节腔积血hemoarthrosis临床意义取决于出血的类型、出血量、出血速度和出血部位严重后果：

HemorrhagicshockStroke

NormalhemostasisMaintainbloodinafluid,clot-freestateLocalizedhemostaticplug止血栓血栓形成在活体的心脏和血管内，血液发生凝固或血液中某些有形成分凝集形成固体质块的过程称为血栓形成(thrombosis)；所形成的固体质块称为血栓(thrombus)。Hemostasis&thrombosis

（止血和血栓形成）凝血系统纤维蛋白溶解系统（抗凝血系统）Vasoconstriction血管挛缩Primaryhemostasis一期（初步）止血Hemostasis

止血过程Secondaryhemostasis二期止血antithromboticcounter-regulation抗血栓形成反向调节

Dependenton—Thevascularwall—Platelets—ThecoagulationcascadeHemostasisandthrombosis三个参与止血的主要成分

血管壁

血小板

凝血级联反应凝血途径CoagulationPathway内源性凝血途径；外源性凝血途径凝血因子Ⅰ~ⅩⅢ,Ca2+，血小板磷脂FⅢ：组织因子；FⅡ：凝血酶原；FⅠ：纤维蛋白原“a”代表水解激活后状态

Coagulationcascade凝血级联反应

Fibrinolyticsystem抗凝特性Antithrombotic（内皮完整时）屏障抗血小板antiplatelet抗凝anticoagulant纤溶fibrinolytic促凝特性Prothrombotic（内皮受损时）辅助血小板黏附激活外源性凝血途径抑制纤维蛋白溶解

Endothelium血管内皮细胞

黏附反应AdhesiontoECMvWF释放反应

(releasereaction/secretion)Ca++,ADP,TXA2黏集反应(aggregation)凝血级联反应

Platelets血小板ThrombosisPathogenesis心血管内皮细胞损伤血流状态异常血液凝固性增加

魏尔啸三角VirchowTriangle1心血管内皮细胞的损伤血栓形成的主要影响因素对心脏和动脉内血栓的形成尤为重要心肌梗死、心瓣膜炎严重动脉粥样硬化时有溃疡形成的斑块创伤/炎症性血管损伤损伤因素创伤、缺氧、化学物质、感染、免疫反应…高胆固醇血症、高血压、高胱氨酸尿、放射线…2血流缓慢、涡流形成静脉系血栓形成的主要原因血流缓慢——

心力衰竭、手术后及久卧床者涡流形成——动脉粥样硬化溃疡性斑块 动脉瘤 风湿性心瓣膜病二尖瓣狭窄ThemajorfactorinthedevelopmentofvenousthrombiIncidenceofthrombosisV:A=4:1Veinsofupperlimb:lowerlimb=1:33血液凝固性增强凝血系统纤维蛋白溶解系统遗传性高凝状态第Ⅴ因子基因突变、抗凝血酶Ⅲ以及C蛋白、S蛋白先天性缺乏…

继发性高凝状态严重创伤、手术或产后大面积烧伤、晚期肿瘤、肾病综合症…endothelialintegrity—singlemostimportantfactorindependentorcombinedimportantinheart/arterialthrombosismajorfactorinvenousthrombosis

HypercoagulableStatesPrimary(Genetic)Common

MutationinfactorVgene(factorVLeiden)

Mutationinprothrombingene

MutationinmethyltetrahydrofolategeneRare

AntithrombinIIIdeficiency

ProteinCdeficiency

ProteinSdeficiencyVeryrare

FibrinolysisdefectsSecondary(Acquired)Highriskforthrombosis

Prolongedbedrestorimmobilization

Myocardialinfarction

Atrialfibrillation

Tissuedamage(surgery,fracture,burns)

Cancer

Prostheticcardiacvalves

Disseminatedintravascularcoagulation

Heparin-inducedthrombocytopenia

Antiphospholipidantibodysyndrome(lupusanticoagulantsyndrome)Lowerriskforthrombosis

Cardiomyopathy

Nephroticsyndrome

Hyperestrogenicstates(pregnancy)

Oralcontraceptiveuse

Sicklecellanemia

SmokingThrombosisMorphology动脉血栓originatefrominjurysites静脉血栓

(phlebothrombus)originatefromthesitesofstasis bothextendtotheheart血栓形成2个阶段——血小板的沉积与凝集 血液的凝固

内皮损伤---血小板小丘、小梁---白细胞粘附---纤维蛋白网架---红细胞---阻塞管腔---红色血栓血栓头（白色血栓）混合血栓（血栓体）血栓尾（红色血栓）1.血栓头（白色血栓）与血管壁紧密粘着,血小板+少量纤维蛋白构成2.混合血栓（血栓体）Zahn线，灰白色与暗褐色相间的条纹状结构

paleplateletandfibrinlayers darkerythrocyte-richlayers

3.血栓尾（红色血栓）RBC血栓的结构LinesofZahnThrombosisLM:plateletstrabeculae+neutrophil fibrin+redcellsThrombosisTypes

MuralthrombusOcclusivethrombusGlobularthrombusVegetation细菌性血栓

肿瘤性血栓

PalethrombusMixedthrombusRedthrombusHyalinethrombus血栓的部位血栓的结构血栓的内容

白色血栓PaleThrombus血小板&纤维蛋白静脉性/延续性血栓头部

多见于心瓣膜、心腔或主动脉eg.赘生物vegetation：发生在心瓣膜上的附壁血栓Thrombosis

混合血栓Mixedthrombus

血小板小梁（trabaculaes）和富红细胞区域交替存在静脉性/延续性血栓体部eg.附壁血栓muralthrombus：黏附于心脏房室和血管（如动脉瘤）内膜面的的混合血栓附壁血栓muralthrombus球形血栓globularthrombus

红色血栓RedThrombus红细胞静脉性/延续性血栓尾部

透明血栓(微血栓)Hyalinethrombus(microthrombus)纤维蛋白与弥散性血管内凝血(DIC)有关毛细血管内肿瘤性血栓tumorthrombus细菌性血栓bacterialthrombusThrombosis闭塞性血栓(血管管腔完全阻塞)occlusivethrombus球形血栓globularthrombusThrombosisThrombosisDifferencebetweenthrombusandpostmortemclot

Thrombus

Postmortumclots干drywetandgelatinous“chickenfat”supernatant糙roughsurfacesmoothsurface硬hardsoft脆fragilegelatinous层LinesofZahnhomogenous紧firmlyattachednoattachment裂slitduetocontraction,fragmentation,generateembolusnoslit血栓死后血凝块Thrombosis转归与结局

延伸与阻塞Propagationandobstruction溶解与吸收Dissolutionandabsorption形成栓塞Embolization机化与再通Organizationandrecanalization钙化Calcification

静脉石或动脉石Phlebolith&arteriolithOrganization(机化)Recanalization(再通)临床联系静脉血栓形成

(phlebothrombosis)Varicosities静脉曲张DVT(DeepVeinThrombosis),trauma,surgery,postpartum产后心脏与动脉血栓形成(Cardiacandarterialthrombosis)muralthrombus(MI,AS)rheumaticheartdisease,valvediseaseEmbolizeperipherally,brain,kidney,spleen,etc毛细血管血栓形成弥散性血管内凝血

(Disseminatedintravascularcoagulation，DIC)

通常见于许多严重疾病

严重细菌或病毒感染，过敏性疾病，缺氧，创伤，休克，恶性肿瘤等血液凝固系统被激活

微血栓广泛形成，累及各种器官

Platelets+Fibrin

(lung,brain,kidney,liver,GItract,adrenalgland,etc.)

凝血物质大量消耗，纤溶系统被激活

临床表现：出血倾向，多器官功能衰竭（multiorgandysfunction，MOD）

consumptioncoagulopathy/defibrinationsyndrome

消耗性凝血病/去纤维蛋白综合征血栓对机体的影响

利——止血，有助于创口愈合， 局限感染区域，防止感染扩散 弊——血管阻塞和栓塞 多种因素影响其后果（部位、大小、形成速度、释放脱落以及侧支循环等）局部缺血----变性、坏死静脉血栓----组织淤血、水肿栓塞---组织缺血、梗死赘生物机化---心瓣膜变形弥散性血管内凝血----后果严重Embolism

（栓塞）Occlusionofcardiovascularsystembysomeinsolublemass.

ThemassistermedasEMBOLUS

在循环血液中出现的不溶于血液的异常物质，随血流运行阻塞血管腔的现象称为栓塞(embolism)。阻塞血管腔的异常物质称为栓子(embolus)。

Thromboembolism99%solid,liquid,gaseousmassfat,air,amnioticfluid,tumorfragments,bitsofbonemarrow,etc.Embolism栓子的运行途径

动脉栓塞——leadtosystemicembolism静脉栓塞——leadtopulmonaryembolism门静脉栓塞——leadtohepaticembolism交叉性栓塞（反常性栓塞）Paradoxicalembolism,crossedembolism

Embolifromveinsofthegeneralcirculationpassthroughanatrialorventricularseptaldefect,enteringarteriesofthegeneralcirculation.逆行性栓塞Retrogradeemboli动脉栓塞栓子来源

80%—Intracardiacmuralthrombi

2/3—Leftventricularwallinfarcts

1/3—Dilatedleftatria

20%—Ulceratedatheroscleroticplaques

Aorticaneurysms,valvularvegetation

栓塞部位 下肢(75%)脑(10%)

肾、脾、肠静脉栓塞栓子来源 右心和体循环静脉的栓子

95%—Deeplegvein栓塞部位 肺动脉主干、分支门静脉栓塞栓子来源——门静脉系的栓子栓塞部位——门静脉各级分支异常性/交叉性栓塞（paradoxical/crossedembolism）静脉系栓子房室间隔缺损动脉系逆行性栓塞(retrogradeembolism)大静脉栓子小静脉右心、下腔静脉肝、肾、股静脉胸、腰、盆腔静脉椎静脉系脊髓、脑Embolism

Canyouanswerthesequestions:Wheredotheycomefrom?Wheredotheylodge?Whatarethefeaturesoftheirimpairment?血栓栓塞Thromboembolism99%

—Pulmonary—Arterial非血栓栓塞Non-thromboticembolism

脂肪栓塞Fatembolism

气体栓塞Gasembolism

羊水栓塞Amnioticfluidembolism

Incidence:20-25/100,000hospitalizedpatientsSource:>95%fromDVTabovetheknee肺动脉栓塞PulmonaryThromboembolism后果:取决于血栓的大小、数量以及患者有无心肺疾患

绝大多数栓子（60%-80%）较小，临床上亦无症状Fewsmallemboli—Clinicalsilent(60-80%)NumerousSmallEmboli（>60%肺循环量)—PulmonaryhypertensionwithrightventricularfailureMediumSizeEmboli—出血，通常无梗死

—梗死？(withinsufficientcollateralcirculation)Largeemboli（saddleembolus骑跨在左右肺动脉主干)

猝死>60%circulationobstructed肺动脉栓塞引起死亡机制：

肺循环机械性阻塞

N反射支气管A、肺A痉挛5-HT冠状A、肺A、

支气管A痉挛

肺循环衰竭、心肌缺血Embolism来源:80%来自心内附壁血栓; MI,aorticaneurysms,ulceratedASplaques,vegetations栓塞部位: lowerextremities(75%),brain(10%),intestines,kidney,spleen结局:INFARCTION体循环动脉血栓栓塞

SystemicThromboembolismFatEmbolism脂肪栓塞releasedfromthebonemarrowandsofttissueduetosevereinjury由于严重创伤从骨髓和软组织释放Longbonefracture长骨骨折

softtissuetraumaorburns软组织挫伤或烧伤

squeezeofthefattychangedliver脂肪肝挤压Mainlyoccursinthelungand

thebrain大多数无症状，仅10%严重骨骼损伤有临床表现FatEmbolism后果取决于脂滴的大小以及数量

ф>20μm,引起肺栓塞

ф<20

μm,

引起脑栓塞和其他器官栓塞

特殊染色显示脂滴苏丹III染色锇酸染色FattyEmbolusintheVascularLumenPathogenesis损伤机制

阻塞&游离脂肪酸的损伤毒性

——内皮受损，血小板黏附和黏集反应，启动凝血途径Symptom症状

tachypnea,dyspnea,tachycardia呼吸急促、困难，心动过速；

irritability,restlessness,deliriumorcoma易激惹，烦躁，谵妄，昏迷；

anemiaandthrombocytopenia贫血，血小板减少

diffusepetechialrash广泛瘀点性皮疹(占20-50%)FatEmbolismGASEmbolism

气体栓塞来源:airorN2bubblesExogenic：输液transfusion

颈部或胸部手术或创伤

人工气胸、气腹

Endogenic:decompressionsickness减压病caissondisease沉箱病结局：

少量气体可被吸收

大量气体可占据心脏，因心脏博动产生血气泡，阻断血流，并导致死亡

造成心脑等多器官气体栓塞症状：

疼痛,猝死治疗:

高压舱治疗RecompressionGASEmbolismAmnioticFluidEmbolism羊水栓塞

Lowincidence低发病率(1/40,000)

HighMotality高致死率

(70%~80%)Source：Sinusoidswhichplacentaattached

胎盘附着处血窦

Torncervicalvessels撕裂的宫颈管ComponentsofAmnioticFluid:squamousepithelialcells,lanugohair,fat,fetalfeces,mucinandTXA2鳞状上皮,胎毛,胎脂,胎粪,黏蛋白及血栓紧张素等SquamouscellsandKeratinizationsubstances症状:

突发严重呼吸困难

紫绀

休克死因:

多发性栓塞;

肺栓塞;

反射性血管痉挛;

过敏性休克AllergicShock;DICAlcianBluePASstainingAmnioticFluidEmbolismINFARCTION

（梗死形成）

器官或局部组织由于血流中断导致的缺血性坏死，称为梗死(infarction)。梗死多由于动脉阻塞引起，但静脉回流中断，使局部血流停滞组织缺氧，也可引起梗死。发生坏死的病变区域称梗死灶。TheformationofalocalizedareaofischemicnecrosiswithinatissueororganduetoimpairedarterialsupplyorthevenousdrainageThenecrosisareaiscalled“infarct”.

Anextremelyimportantcauseofclinicalillness:

myocardiacinfarction，MI心肌梗死 cerebralinfarction脑梗死原因动脉阻塞或静脉回流不畅

Occlusionofarterialsupplyorvenousdrainage

Thrombosis,embolism,athermanousplaques,externalcompression功能性细动脉痉挛

Functionalspasmofarteriole类型Whiteinfarcts(anemicinfarcts)白色梗死（贫血性梗死）Redinfarcts(hemorrhagicinfarcts)红色梗死(出血性梗死)Septicinfarcts败血性梗死INFARCTIONINFARCTIONFactorsthatinfluencedevelopmentofaninfarct影响梗死形成和发展的要素NatureofthevascularsupplyRateofdevelopmentofocclusionVulnerabilitytohypoxiaOxygencontentofbloodanemicinfarct贫血性梗死WhiteinfarctionArterialocclusion动脉阻塞Solid,compactorgans质实组织或脏器Fewcollateralcirculation缺乏侧支循环spleen,kidney,heart,brain,etc.Morphology

GrossDullpale,dry,wedge-shapednecroticlesion,withahemorrhagiczonesurrounding灰白，干燥，大致呈楔形，尖端指向门部，底部紧邻包膜；病灶周围可见充血出血带。新鲜时病灶肿胀，略隆起于脏器表面，浆膜外可见絮状纤维蛋白性渗出；陈旧时病灶收缩，质实。LM Ischemiccoagulativenecrosis（kidney）NecroticcoreInflammatoryandgranulationtissue.HyperemicandhemorrhagiczoneMostundergoorganizationandscarringintheend.SpleenInfarctionCardiacInfarctionBrainInfarction(liquefiednecrosis)出血性梗死hemorrhagicinfarctRedinfarction♦Arterialocclusion动脉阻塞♦Venousocclusion静脉阻塞/淤滞（如卵巢扭转、大脑深静脉血栓形成）♦Loosetissue组织疏松,有利于血液积聚于梗死区♦Dualcirculations:lung,smallintestine

双重血供previouslycongestedre-establishedbloodflowtoasiteofpreviousarterialocclusionandnecrosis先前有动脉闭塞或组织坏死部位有血液再灌流Hemorrhagicinfar