2009年临床医学五年制教学课件4.局部血液循环障碍

局部血液循环障碍（Hemodynamicdisorders）四川大学华西临床医学院病理学教研室张文燕表现形式局部循环血量的异常

充血（淤血）、缺血心脏和血管壁完整性破坏或血管壁通透性增高

出血、水肿血管内出现异常物质

血栓形成、栓塞、梗死充血（hyperemia）定义

局部组织或器官的血管内血液含量增多分类

动脉性充血静脉性充血（淤血）

动脉性充血（arterialhyperemia）

（主动性充血、充血）原因：生理性

病理性（炎症性、减压后、侧支性）机理：舒血管神经兴奋性↑缩血管神经兴奋性↓局部血管活性物质增多特点主动性多为生理性神经、体液因素快而短类型生理性充血

生理代谢增强所致病理性充血

炎症反应的初始减压后充血

局部组织长期受压后突然解除压力静脉性充血（venoushyperemia）

（被动性充血、淤血congestion）原因

静脉受压静脉腔阻塞心力衰竭特点被动性病理性静脉受压、阻塞、心衰所致持续时间长对机体的影响大后果淤血性水肿漏出性出血实质细胞萎缩和变性间质细胞增生侧支循环建立淤血的原因及其后果

静脉性充血器官、组织萎缩，硬化静脉受压静脉腔阻塞心力衰竭流体静压升高水肿、体腔积液代偿侧支循环开放慢性肺淤血慢性肺淤血（肺褐色硬化）含铁血黄素(hemosiderin)心衰细胞（heartfailurecells）普鲁士蓝染色chroniccongestionofliver()槟榔肝（nutmegliver）

chroniccongestionofliver淤血性肝硬化congestivecirrhosis心源性肝硬化淤血性脾肿大（Congestivesplenomagely）Portosystemicvenousshunts“CaputMedusae”Portosystemicvenousshuntscausesandresults

venousobstructionheartfailure

congestion

increasedcompensationhydrostaticpressurebypasscirculationedemaopened

atrophynecrosissclerosis出血（hemmorhage）定义血液流出心脏或血管外类型内出血外出血

病因和发病机制破裂性出血（心脏和血管壁破裂）机械性损伤病变被周围病变侵蚀静脉破裂毛细血管破裂病因和发病机制漏出性出血（毛细血管和毛细血管后静脉通透性↑）血管壁损害血小板减少或功能障碍凝血因子缺乏病变积血（hematocele）血肿（hematoma）淤点（petechia，直径1-2mm）淤斑（echymosis，直径1-2cm）紫癜（purpura，直径3-5mm

）

petechiaonmucosaofintestine急性肺淤血,肺水肿主动脉壁动脉瘤Marfan’ssyndrome--myxomatousdegenerationofaortawall蛛网膜下腔出血皮下出血血栓形成（thrombosis）活体未破裂的心脏或血管腔内血液发生凝集或凝固形成固体团块的过程所形成的固体团块称为血栓（thrombus）生理状态

血小板凝血因子止血、凝血系统抗凝血系统

抗血小板粘附完整内皮细胞抗凝血纤溶作用（t-PA）正常血流状态

纤溶系统单核巨噬细胞系统

按国际命名法编号的凝血因子编号名称因子I纤维蛋白原因子II凝血酶原因子III组织因子因子IVCa2＋因子V前加速素因子VII前转变素按国际命名法编号的凝血因子编号名称因子VIII抗血友病因子(AHF)因子IX血浆凝血激酶(PTC)因子XStuart-Prower因子因子XI血浆凝血激酶前质(PTA)因子XII接触因子或Hageman因子因子XIII纤维蛋白稳定因子血液凝固过程的连锁反应（coagulationcascade）一系列酶促反应凝血酶原激活物凝血酶纤维蛋白形成

血液凝固系统（内源性）血管内皮损伤→内皮下胶原及微纤维暴露→激活血小板

XII→XIIa→XIIf

内源性凝血系统激活纤维蛋白原

凝血酶原凝血酶

纤维蛋白

血液凝固系统（外源性）

组织损伤组织因子

VIICa2+

外源凝血系统激活纤维蛋白原

凝血酶原凝血酶

纤维蛋白纤维蛋白溶解系统

激肽释放酶原

XIIaXIIf

激肽释放酶

纤溶酶原纤溶酶

纤维蛋白纤维蛋白降解产物正常情况下血液凝固的过程动脉血管的收缩神经反射性初级血液凝固血小板的作用（可逆性）次级血液凝固凝血系统启动（不可逆性）纤维蛋白溶解系统被激活限制血凝块的大小血管内膜（endothelium)

正常情况下，具有抗血栓形成和促血栓形成的双重作用。正常情况下内膜的抗血栓形成：

屏障血小板,凝血因子

内皮细胞合成前列环素(PGI2)和NO→抗血小板聚集

内膜上的肝素样分子+抗凝血酶→失活凝血因子

内膜上的凝血酶调节蛋白+凝血酶→活化蛋白C→活化纤溶系统

内皮细胞合成组织型纤溶酶原活化因子→降解纤维蛋白正常情况下内膜的促血栓形成：

内皮损伤→激活外源性凝血系统

释放vonWillebrand因子→促使血小板与内膜的粘集

分泌PAIs→抑制纤维蛋白降解图解血管内皮细胞的促凝作用和抗凝作用血小板电镜观血小板(platelet)颗粒颗粒（致密颗粒）纤维蛋白原 ADP纤维连接蛋白Ca2+血小板IV因子肾上腺素血小板源性生长因子（PDGF）组胺凝血酶敏感蛋白5-HT血小板的活化过程⑴粘附反应(adhesion)

内皮损伤→胶原暴露⑵释放反应(secretion)颗粒、颗粒（致密颗粒）⑶粘集反应(aggregation)ADP、血栓素A2血小板的活化在触发凝血的过程中起核心作用冯威勒布兰特病

巨血小板综合征格兰兹曼血小板功能不全血小板黏附和粘集血栓形成的条件

⑴心血管内膜的损伤

（endothelialinjury）

⑵血流状态的改变

（alterationsinnormalbloodflow）

⑶血液凝固性增加（hypercoagulabilityofblood）

心血管内膜的损伤血流缓慢血流的改变

血流的改变

涡流(tubulence)：主动脉和心脏内血栓形成

血流停滞(stasis)：静脉血栓形成血液的高凝状态原发性（遗传性）继发性（获得性）ⅴ因子基因突变高危因素：凝血酶原基因突变

长期卧床或不活动抗凝血酶III缺陷

心肌梗塞蛋白C或S缺陷

组织损伤

癌症

心瓣膜修补DIC等

血流状态改变血液的高凝状态内膜损伤血栓形成血栓形成的Virchow三联血栓形成的过程及血栓形态

血栓可发生于心血管系统的任何部位（心腔内、瓣膜上、动脉、静脉、毛细血管内）

动脉和心脏内血栓的形成

——多有内膜损伤和涡流

静脉血栓的形成

——常有血流停滞

静脉血栓的延伸常顺血流而行至心图解止血过程血管收缩图解止血过程原发性止血继发性止血图解止血过程血栓和抗血栓图解止血过程早期-血小板黏附后期-纤维蛋白沉着

机理：1、丧失原有抗凝作用

（一）内皮细胞损伤2、启动内外凝血途径3、合成vonWillibrand因子4、抑制纤溶原因：动脉粥样硬化血管炎

心内膜炎心肌梗死

创伤其他损伤

机理：1、破坏边流2、不能稀释活化的凝血因子3、抗凝因子难以补充4、内皮细胞损伤（二）血流状态改变：减慢、涡流原因：长期卧床心肌梗死

二尖瓣狭窄心衰

动脉瘤血管内膜溃疡

血液粘性增强：烧伤、红细胞增

多症、高脂血症

（三）血液凝固性增高凝血因子增多：严重创伤、肿瘤、肾病综合征、口服避孕药血小板增多：大失血后

其它：老年人、吸烟

（一）血小板的粘附与粘集

血小板粘附、变形

血小板释放反应

血小板粘集

二、血栓形成过程（二）血小板小梁间血液凝固

白色血栓（palethrombus）

三、血栓类型及形态红色血栓（redthrombus）

混合血栓（mixedthrombus）

透明血栓（hyalinethrombus）

赘生物（vegetation）

附壁血栓（muralthrombus）

阻塞性血栓（occlusivethrombus）

延续性血栓

3、钙化：静脉石（phlebolith）

四、血栓的结局1、软化、溶解、吸收2、机化、再通（recanalization）

4、出血

五、血栓对机体的影响1、阻塞血管2、栓塞3、心瓣膜变形

六、弥漫性血管内凝血

（DisseminatedIntravascularCoagulationDIC）

循环血液中出现的异常物质团块，随血液流动，阻塞血管腔的现象称为栓塞。阻塞血管腔的异常物质团块称为栓子（embolus）。

栓塞（embolism）

4、逆行栓塞

一、栓子的运行途径和栓塞部位1、来自左心和体循环动脉的栓子→体循环动脉分支2、来自右心和体循环静脉的栓子→肺动脉分支3、交叉/奇异栓塞（crossed/paradoxicalembolism）

二、栓塞的类型和对机体的影响

小栓子：大量→急性右心衰

长期反复小量→肺动脉

高压

（一）血栓栓塞（thromboembolism）

1、肺动脉栓塞大栓子→急死

中等大栓子→梗死

（二）脂肪栓塞（fatembolism）

2、体循环动脉栓塞→梗死

大于20μm脂滴→肺栓塞小于20μm脂滴→全身器官栓塞

1、空气栓塞（airembolism）

大量（100-150ml）→猝死

（三）气体栓塞

氮气栓塞（nitrogenembolism）→组织

缺血、梗死

2、减压病或沉箱病（pression

sicknessorcaissondisease）

肺动脉分支栓塞

过敏性休克

DIC

（四）羊水栓塞（amnioticfluidembolism）（五）其他栓塞

梗死（infarct）一、梗死的原因

1、动脉腔阻塞：血栓形成、栓塞2、动脉被压闭3、动脉持续痉挛动脉血流中断所致的组织坏死称为梗死。

4、组织代谢旺盛

梗死发生的有关因素

1、无有效侧支循环

2、阻塞速度快3、组织对缺血敏感

1、贫血性梗死（anemicinfarct）

二、梗死的病变和类型

2、出血性梗死（hemorrhagicinfarct）败血性梗死（septicinfarct）、单纯性梗死

影响决定于梗死的部位和大小

三、梗死的影响和结局

5、肾素-血管肾张素-醛固酮系统作用

水肿（edema）

组织间隙或体腔内过量体液潴留称为水肿。体腔内体液增多又称积水（hydrops）。

一、水肿的原因和机制1、血浆胶体渗透压降低

2、毛细血管内流体静压升高3、毛细血管壁通透性增高4、淋巴回流受阻

二、水肿的病变HemostasisandthrombosisNormalhemostasismaintainbloodinfluidstateinnormalvesselsrapidformationofhemostaticplugatthesiteofvascularinjuryThreeimportantcontributors

thevascularwall(endothelium;subendothelialconnectivetissue)plateletscoagulationsystem

coagulationcascade

aseriesofconversionofinactiveproenzymestoactivatedenzymesthrombinformationfibrinogentofibrinbloodclots

COAGULATIONFACTORS

FACTORNAMEIFibrinogenIIProthrombinIIITissuefactor(Thromboplastin)IVCalcium

VProaccelerin;labilefactorVIIProconvertin;SPCA;stablefactorVIIIAntihemophilicfactor(AHF)IXPlasmathromboplsticcomponent(PTC)XStuart-ProwerfactorXIPlasmathromboplastinantecedent(PTA)XIIHagemanfactor(contactfactor)XIIIFibrin-stabilizingfactorNormalhemostasis1.Arteriolarvasoconstrictionatribulabletoreflexneurogenicmechanisms2.Primaryhemostasis(reversible)plateletsplayanimportantrole3.Secondaryhemostasis(inreversible)

coagulationsystemworking

4.Fibrinolyticsystemisactivated

bytissueplasminogenactivator(t-PA)tolimitthesizeofthehemostaticplug

theprocessofnormalhemostasisEndotheliumdoublefunctionsofendotheliumforantithromboticandprothromboticpropertiesantithromboticantiplateleteffectsanticoagulantpropertiesfibrinolyticpropertiesProthromboticpropertiesafterendotheliuminjury

tosecretetissuefactorextrinsicsystemactivatedwillebrandfactor(vWF)secretionstoppedtoproduceinhibitorsofplasminogenactivator(PAIs)whichdepressfibrinolysis

Platelet

debrisofcytoplasmofmegakaryocyte

-granulesgranulesfibrinogen ADP/ATPfibronectin Ca++factorsVandVIII epinephrineplateletfactor4 histaminePDGF 5-HT(serotonin)TGFPlateletactivation1.Adhesionandshapechangeendotheliuminjuryexplosionofsubendotheliumcollagen2.Secretion(releasereaction)-granules,-granules3.AggregationADP,thromboxaneA2PlateletactivationplaysacentralroleinbothhemostasisandthrombosisPlateletadhesionandaggregation

coagulationcascade

aseriesofconversionofinactiveproenzymestoactivatedenzymesthrombinformationfibrinogentofibrinbloodclotsFibrinolyticsystemillustratingthevariousplasminogenactivatorsandinhibitorsthrombosisconceptionthrombosisisapathologicprocess,withformationofaclottedmassofbloodwithintheuninterruptedvascularsystem

Pathogenesisofthrombosisthreeprimaryinfluencespredisposetothrombusformation(Virchow’striad)1.endothelialinjury2.Alterationofbloodflow

(stasisorturbulence)3.bloodhypercoagulabilityEventsinthrombusformationEndotheliuminjuryanimportantfactorwhichcouldcausethrombosisdirectlyAlterationsinnormalbloodflowtubulence:thrombosisofaortaandheartstasis:thrombosisofveinsstasisHypercoagulabilityanmonandpoorlyunderstoodcausesofthrombosisconditionsassociatedwithanincreasedriskofthrombosisprimary(congenital)mutationsinfactorVgeneantithrombinIIIdeficiencyproteinCorSdeficiencyfibrinolysisdefectsSecondary(acquired)prolongedbedrestorimmobilizationmyocardialinfarctiontissuedamage(surgery/fracture/burns)cancercardiacfailureDIC

endothelialinjury

thrombosisabnormalbloodflow

hypercoagulability

Payattentionto

thrombimayformanywhereinthecardio-vascularsystematsitesoforigin,allthrombigenerallyarefirmlyattached

directionofpropagationofthrombus

arterialthrombitendtogrowinaretrogradedirection

venousthrombiextendinthedirectionofbloodflow

morphologyofthrombiAtypicalthrombus

headbodytail

Typesofthrombiwhite/palethrombusmixedthrombus(linesofZahn)redthrombushyalinethrombi(microthrombiincapillaries)muralthrombus(incardiacchambersoraorta)thethrombusattachtothevesselwall

thrombusincervicalvein

redthrombusinfemoralvein

white/palethrombusincardiacvalveWhitethrombusoncardiacvalvewhitethrombusonaorticvalve

infectiousthrombioncardiacvalveinpatientwithSBE

infectiousthrombioncardiacvalveinpatientwithSBEInfectiousthrombusofcardiacvalve(aspergillosis)Infectiousthrombusofcardiacvalve(aspergillosis)muralthrombusofleftcardiacventriclethrombusincoronaryartery

thrombusincoronaryarteryThrombusiniliacvein

Thrombusinrenalvein

histologyofthrombus

DisseminatedIntarvascularCoagulation

conception

acomplicationbutadiseasedysfunctionofdiffusemicrocirculationmechanism:hypercoagulabilityandthrombosishistology:micro-thrombi(hyalinethrombi)formationincapillariesclinicalmanifestations:hemorrhage,shock,multi-organdysfunctionanddeath

hyalinethrombiincapillariesofglomerulushyalinethrombusincapillaryofthelung(A12-98)

Fateofthrombus

ThelumenofthevesselisobstructedbythethrombusAtherosclerosisofthearterywiththrombusOrganizationofthrombusThrombuswasorganizedandincorporatedintothewall

OrganizationofthrombusOrganizationofthrombus

organizationandrecanalizationofthrombus

organizationandrecanalizationofthrombusCalcificationandphlebolith

hyalinethrombusincapillaryofthelung(A12-98)thromboembolusastridethebifurcationofthepulmonaryartery(saddleemboli)embolism

conception

adetachedintravascularsolid,liquidandgaseousmassthatiscarriedbythebloodtoasitedistantfromitspointoforigin(RobbinsBasicPathology)occlusionofavesselbyamassofmaterialthatistransportedinthebloodstream(Pathology)

Keypointsforembolismembolus:adetachedintravascularsolid,liquidandgaseousmasstransportedthroughthebloodstream(samedirectionwithbloodflow)causingvesselocclusion

TypesofemboliandtheiroriginTypesofembolism

1.thromboembolismpulmonaryembolism,PEsystemicembolism2.fatembolism3.airembolism4.amnioticfluidembolism5.tumorembolism6.Others:microorganism,parasites

Pulmonarythromboenbolism

Crossedembolismretrogradeembolismthromboembolism99%ofembolismsarethromboembolism

pulmonaryembolism(PE)emboliarisinginveinsusuallyimpactinthelungandover95%ofPEariseindeepveinsoflegsocclusionsofpulmonaryarteriesarealmostalwaysembolicbutinsituthrombosispotentialconsequencesarerelatedtosites,sizesandnumbersoftheemboli

pulmonaryembolism1.Largeemboli(about5%)impactinginthemajorpulmonaryarteryorastridethebifurcationofthepulmonaryartery(saddleemboli)suddendeathacutecorpulmonale(rightheartfailure)hemodynamiccompromisethromboembolusastridethebifurcationofthepulmonaryartery(saddleembolus)

valves2.smallemboli（60－80％)impactinginsmallpulmonaryartery

clinicallysilent

cardiacfailure(morethan60%ofpulmonarycirculationisoccluded)3.mediumsizedemboli(10-15%)occludingmoderate-sizedperipheralpulmonarybranchespulmonaryhemorrhageClinicalsignificancediagnosisofPEisoftendifficult2/3ofPEarenotdiagnosedbeforedeath

Systemicembolism(SE)

originsofarterialembolithrombiwithintheheart,secondarytomyocardialinfarction(80-85%)auricularthrombi,usuallyassociatedwithrheumaticheartdisease(5-10%)thrombiinthedilatedcardiacchambersofmyocarditisorcardiomyopathy

othersSitesoflodgmentemboliarisingonthearterialsideofcirculation,usuallyimpactinthelegs,brain,andvisceraandoftencauseinfarction

legs(70-75%)brain (10%)viscera(10%)arms (5%)

systemicembolism

Fatembolismthesecondcommonformofembolismoriginsofintravascularglobulesoffat:-fracturesoflonebonethathavefatmarrow-extensivetraumaoffattytissue-somediseases--diabetes,sicklecellanemia,pancreatitisonset：1to3daysaftertraumaClinicalsignificancefatemboliarepresentin90%ofpatientsfollowinglargefracture,inonly1to2%isitclinicallysignificantdependingonthenumberandsizeofthemicroglobulesoffatpresentedincirculationtobenoted:themerepresenceofintra-vascularfatglobulesisnotequaltofatembolismWhenlargenumberoffatglobules(about9to20grams)presentincirculationbloodandcause75%decreasingofpulmonarycirculation,acuterightheartfailure(acutecorpulmonale)mayoccurFatembolismsyndromeclinicalmanifestationspulmonaryinsufficiencyneurologicsymptomsanemiathrombocytopeniadeath(about10%)pathologicdiagnosisSudanIIIoroil-redOstaining(frozensection)

bonemarrowembolusinpulmonaryvesselbonemarrowembolusinpulmonaryvessel

SudanIIIstainingforfatglobulesonfrozensection

SudanIIIstainingforfatglobulesonfrozensectionairembolismWhenbubblesofairorgaswithinthecirculationobstructbloodflow,theresultantinjuryisreferredtoairembolismabout100mlofairorgasarenecessarytoeclinicallysignificantcaissondiseaseorpressionsickness--specialformofgasembolismair/gasmaygainaccesstothecirculation:

deliveryorabortion-ruptureduterinevenoussinusesperformanceofpneumothorax-largevesselsrupturedaccidentallywhentheinjurytothelungorchestwallopensalargeveinandpermitsentranceofairduringnegativepressurephaseofinspirationAnimalexperimentforairembolism

airembolipathogenesisofairembolismthebubblesactlikephysicalobstructionsandmaycoalescetoformfrothymassestooccludemajorvessels

acuteheartfailureistheresult

Amnioticfluidembolism

incidence1/50000deathrate80%amnioticfluidembolismTumorcellembolusTumorcellembolusinfemoralarteriesPLAPEffects1.occludingthebloodvessel

veins

congestion,edemaandhemorrhage

arteries

ischemicnecrosis(infarct)bypasscirculationopened

2.Disseminationofinfectionsandtumors

infarctionconceptionalocalizedareaofischemicnecrosiscausedbyocclusionofeitherthearterialsupplyorthevenousdrainageinaparticulartissue

causes

arteryobstruction97％

thrombosisarterialembolismarterialspasm

extrinsiccompressionofavessel

Factorsthatinfluencedevelopmentofaninfarct

natureofvascularsupply

organswithdualbloodsupply:lungliverorganswithendarterial:kidneyspleen

rateofdevelopmentofocclusion

susceptibilityofatissuetohypoxianeuron3-4min;myocardialcells20-30min

oxygencontentofbloodClassification1.withorwithouthemorrhagehemorrhagicinfarct(redinfarct)anemicinfarct(whiteorpaleinfarct)2.Infectionrelatedornot

septicinfarctbland

Grossappearanceshape--patternofvascularsupplycharacter--histologictypeofnecrosiscoagulationnecrosis:harderliquefactionnecrosis:softercolor--withorwithouthemorrhagehistology

sameasthatofnecrosis

anemicinfarct

structuredense

bloodsupplyend-arterial poorbypasscirculation

causearterialocclusionwithoutobstructionofvenousdrainage

organs

heart brain kidney spleen limbshemorrhagicinfarctstructureloosebloodsupplydualcirculationplentyofbypasscirculationcausearterialocclusionwithcongestionorganslung liver uterus

gastrointestinaltract(GIT)

myocardialinfarct(paleinfarct)myocardialinfarct(paleinfarct)

coagulationnecrosisofmyocardiumcoagulationnecrosisofmyocardium

anemic(pale)infarctofthespleenanemic(pale)infarctofthespleenAnemicinfarctofthekidney

CoagulationnecrosisofthekidneyCerebralinfarctEncephalomalaciaEncephalomalacia

encephalomalaciaHemorrhagicinfarctofthelungHemorrhagi