2009年臨床醫(yī)學(xué)五年制教學(xué)課件4.局部血液循環(huán)障礙

局部血液循環(huán)障礙（Hemodynamicdisorders）四川大學(xué)華西臨床醫(yī)學(xué)院病理學(xué)教研室張文燕表現(xiàn)形式局部循環(huán)血量的異常

充血（淤血）、缺血心臟和血管壁完整性破壞或血管壁通透性增高

出血、水腫血管內(nèi)出現(xiàn)異常物質(zhì)

血栓形成、栓塞、梗死充血（hyperemia）定義

局部組織或器官的血管內(nèi)血液含量增多分類

動脈性充血靜脈性充血（淤血）

動脈性充血（arterialhyperemia）

（主動性充血、充血）原因：生理性

病理性（炎癥性、減壓后、側(cè)支性）機理：舒血管神經(jīng)興奮性↑縮血管神經(jīng)興奮性↓局部血管活性物質(zhì)增多特點主動性多為生理性神經(jīng)、體液因素快而短類型生理性充血

生理代謝增強所致病理性充血

炎癥反應(yīng)的初始減壓后充血

局部組織長期受壓后突然解除壓力靜脈性充血（venoushyperemia）

（被動性充血、淤血congestion）原因

靜脈受壓靜脈腔阻塞心力衰竭特點被動性病理性靜脈受壓、阻塞、心衰所致持續(xù)時間長對機體的影響大后果淤血性水腫漏出性出血實質(zhì)細胞萎縮和變性間質(zhì)細胞增生側(cè)支循環(huán)建立淤血的原因及其后果

靜脈性充血器官、組織萎縮，硬化靜脈受壓靜脈腔阻塞心力衰竭流體靜壓升高水腫、體腔積液代償側(cè)支循環(huán)開放慢性肺淤血慢性肺淤血（肺褐色硬化）含鐵血黃素(hemosiderin)心衰細胞（heartfailurecells）普魯士藍染色chroniccongestionofliver()檳榔肝（nutmegliver）

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

venousobstructionheartfailure

congestion

increasedcompensationhydrostaticpressurebypasscirculationedemaopened

atrophynecrosissclerosis出血（hemmorhage）定義血液流出心臟或血管外類型內(nèi)出血外出血

病因和發(fā)病機制破裂性出血（心臟和血管壁破裂）機械性損傷病變被周圍病變侵蝕靜脈破裂毛細血管破裂病因和發(fā)病機制漏出性出血（毛細血管和毛細血管后靜脈通透性↑）血管壁損害血小板減少或功能障礙凝血因子缺乏病變積血（hematocele）血腫（hematoma）淤點（petechia，直徑1-2mm）淤斑（echymosis，直徑1-2cm）紫癜（purpura，直徑3-5mm

）

petechiaonmucosaofintestine急性肺淤血,肺水腫主動脈壁動脈瘤Marfan’ssyndrome--myxomatousdegenerationofaortawall蛛網(wǎng)膜下腔出血皮下出血血栓形成（thrombosis）活體未破裂的心臟或血管腔內(nèi)血液發(fā)生凝集或凝固形成固體團塊的過程所形成的固體團塊稱為血栓（thrombus）生理狀態(tài)

血小板凝血因子止血、凝血系統(tǒng)抗凝血系統(tǒng)

抗血小板粘附完整內(nèi)皮細胞抗凝血纖溶作用（t-PA）正常血流狀態(tài)

纖溶系統(tǒng)單核巨噬細胞系統(tǒng)

按國際命名法編號的凝血因子編號名稱因子I纖維蛋白原因子II凝血酶原因子III組織因子因子IVCa2＋因子V前加速素因子VII前轉(zhuǎn)變素按國際命名法編號的凝血因子編號名稱因子VIII抗血友病因子(AHF)因子IX血漿凝血激酶(PTC)因子XStuart-Prower因子因子XI血漿凝血激酶前質(zhì)(PTA)因子XII接觸因子或Hageman因子因子XIII纖維蛋白穩(wěn)定因子血液凝固過程的連鎖反應(yīng)（coagulationcascade）一系列酶促反應(yīng)凝血酶原激活物凝血酶纖維蛋白形成

血液凝固系統(tǒng)（內(nèi)源性）血管內(nèi)皮損傷→內(nèi)皮下膠原及微纖維暴露→激活血小板

XII→XIIa→XIIf

內(nèi)源性凝血系統(tǒng)激活纖維蛋白原

凝血酶原凝血酶

纖維蛋白

血液凝固系統(tǒng)（外源性）

組織損傷組織因子

VIICa2+

外源凝血系統(tǒng)激活纖維蛋白原

凝血酶原凝血酶

纖維蛋白纖維蛋白溶解系統(tǒng)

激肽釋放酶原

XIIaXIIf

激肽釋放酶

纖溶酶原纖溶酶

纖維蛋白纖維蛋白降解產(chǎn)物正常情況下血液凝固的過程動脈血管的收縮神經(jīng)反射性初級血液凝固血小板的作用（可逆性）次級血液凝固凝血系統(tǒng)啟動（不可逆性）纖維蛋白溶解系統(tǒng)被激活限制血凝塊的大小血管內(nèi)膜（endothelium)

正常情況下，具有抗血栓形成和促血栓形成的雙重作用。正常情況下內(nèi)膜的抗血栓形成：

屏障血小板,凝血因子

內(nèi)皮細胞合成前列環(huán)素(PGI2)和NO→抗血小板聚集

內(nèi)膜上的肝素樣分子+抗凝血酶→失活凝血因子

內(nèi)膜上的凝血酶調(diào)節(jié)蛋白+凝血酶→活化蛋白C→活化纖溶系統(tǒng)

內(nèi)皮細胞合成組織型纖溶酶原活化因子→降解纖維蛋白正常情況下內(nèi)膜的促血栓形成：

內(nèi)皮損傷→激活外源性凝血系統(tǒng)

釋放vonWillebrand因子→促使血小板與內(nèi)膜的粘集

分泌PAIs→抑制纖維蛋白降解圖解血管內(nèi)皮細胞的促凝作用和抗凝作用血小板電鏡觀血小板(platelet)顆粒顆粒（致密顆粒）纖維蛋白原 ADP纖維連接蛋白Ca2+血小板IV因子腎上腺素血小板源性生長因子（PDGF）組胺凝血酶敏感蛋白5-HT血小板的活化過程⑴粘附反應(yīng)(adhesion)

內(nèi)皮損傷→膠原暴露⑵釋放反應(yīng)(secretion)顆粒、顆粒（致密顆粒）⑶粘集反應(yīng)(aggregation)ADP、血栓素A2血小板的活化在觸發(fā)凝血的過程中起核心作用馮威勒布蘭特病

巨血小板綜合征格蘭茲曼血小板功能不全血小板黏附和粘集血栓形成的條件

⑴心血管內(nèi)膜的損傷

（endothelialinjury）

⑵血流狀態(tài)的改變

（alterationsinnormalbloodflow）

⑶血液凝固性增加（hypercoagulabilityofblood）

心血管內(nèi)膜的損傷血流緩慢血流的改變

血流的改變

渦流(tubulence)：主動脈和心臟內(nèi)血栓形成

血流停滯(stasis)：靜脈血栓形成血液的高凝狀態(tài)原發(fā)性（遺傳性）繼發(fā)性（獲得性）ⅴ因子基因突變高危因素：凝血酶原基因突變

長期臥床或不活動抗凝血酶III缺陷

心肌梗塞蛋白C或S缺陷

組織損傷

癌癥

心瓣膜修補DIC等

血流狀態(tài)改變血液的高凝狀態(tài)內(nèi)膜損傷血栓形成血栓形成的Virchow三聯(lián)血栓形成的過程及血栓形態(tài)

血栓可發(fā)生于心血管系統(tǒng)的任何部位（心腔內(nèi)、瓣膜上、動脈、靜脈、毛細血管內(nèi)）

動脈和心臟內(nèi)血栓的形成

——多有內(nèi)膜損傷和渦流

靜脈血栓的形成

——常有血流停滯

靜脈血栓的延伸常順血流而行至心圖解止血過程血管收縮圖解止血過程原發(fā)性止血繼發(fā)性止血圖解止血過程血栓和抗血栓圖解止血過程早期-血小板黏附后期-纖維蛋白沉著

機理：1、喪失原有抗凝作用

（一）內(nèi)皮細胞損傷2、啟動內(nèi)外凝血途徑3、合成vonWillibrand因子4、抑制纖溶原因：動脈粥樣硬化血管炎

心內(nèi)膜炎心肌梗死

創(chuàng)傷其他損傷

機理：1、破壞邊流2、不能稀釋活化的凝血因子3、抗凝因子難以補充4、內(nèi)皮細胞損傷（二）血流狀態(tài)改變：減慢、渦流原因：長期臥床心肌梗死

二尖瓣狹窄心衰

動脈瘤血管內(nèi)膜潰瘍

血液粘性增強：燒傷、紅細胞增

多癥、高脂血癥

（三）血液凝固性增高凝血因子增多：嚴重創(chuàng)傷、腫瘤、腎病綜合征、口服避孕藥血小板增多：大失血后

其它：老年人、吸煙

（一）血小板的粘附與粘集

血小板粘附、變形

血小板釋放反應(yīng)

血小板粘集

二、血栓形成過程（二）血小板小梁間血液凝固

白色血栓（palethrombus）

三、血栓類型及形態(tài)紅色血栓（redthrombus）

混合血栓（mixedthrombus）

透明血栓（hyalinethrombus）

贅生物（vegetation）

附壁血栓（muralthrombus）

阻塞性血栓（occlusivethrombus）

延續(xù)性血栓

3、鈣化：靜脈石（phlebolith）

四、血栓的結(jié)局1、軟化、溶解、吸收2、機化、再通（recanalization）

4、出血

五、血栓對機體的影響1、阻塞血管2、栓塞3、心瓣膜變形

六、彌漫性血管內(nèi)凝血

（DisseminatedIntravascularCoagulationDIC）

循環(huán)血液中出現(xiàn)的異常物質(zhì)團塊，隨血液流動，阻塞血管腔的現(xiàn)象稱為栓塞。阻塞血管腔的異常物質(zhì)團塊稱為栓子（embolus）。

栓塞（embolism）

4、逆行栓塞

一、栓子的運行途徑和栓塞部位1、來自左心和體循環(huán)動脈的栓子→體循環(huán)動脈分支2、來自右心和體循環(huán)靜脈的栓子→肺動脈分支3、交叉/奇異栓塞（crossed/paradoxicalembolism）

二、栓塞的類型和對機體的影響

小栓子：大量→急性右心衰

長期反復(fù)小量→肺動脈

高壓

（一）血栓栓塞（thromboembolism）

1、肺動脈栓塞大栓子→急死

中等大栓子→梗死

（二）脂肪栓塞（fatembolism）

2、體循環(huán)動脈栓塞→梗死

大于20μm脂滴→肺栓塞小于20μm脂滴→全身器官栓塞

1、空氣栓塞（airembolism）

大量（100-150ml）→猝死

（三）氣體栓塞

氮氣栓塞（nitrogenembolism）→組織

缺血、梗死

2、減壓病或沉箱?。╬ression

sicknessorcaissondisease）

肺動脈分支栓塞

過敏性休克

DIC

（四）羊水栓塞（amnioticfluidembolism）（五）其他栓塞

梗死（infarct）一、梗死的原因

1、動脈腔阻塞：血栓形成、栓塞2、動脈被壓閉3、動脈持續(xù)痙攣動脈血流中斷所致的組織壞死稱為梗死。

4、組織代謝旺盛

梗死發(fā)生的有關(guān)因素

1、無有效側(cè)支循環(huán)

2、阻塞速度快3、組織對缺血敏感

1、貧血性梗死（anemicinfarct）

二、梗死的病變和類型

2、出血性梗死（hemorrhagicinfarct）敗血性梗死（septicinfarct）、單純性梗死

影響決定于梗死的部位和大小

三、梗死的影響和結(jié)局

5、腎素-血管腎張素-醛固酮系統(tǒng)作用

水腫（edema）

組織間隙或體腔內(nèi)過量體液潴留稱為水腫。體腔內(nèi)體液增多又稱積水（hydrops）。

一、水腫的原因和機制1、血漿膠體滲透壓降低

2、毛細血管內(nèi)流體靜壓升高3、毛細血管壁通透性增高4、淋巴回流受阻

二、水腫的病變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