妊娠期高血壓疾病課件

HypertensiveDisorders

inPregnancyTengYinChengShanghaiJiaotongUniversityAffiliatedSixthPeople'sHospital,DeptofObs&GynContentsEtiology&PathogenesisClinicalfeaturesPhysiopathologyClassificationDiagnosisManagement234561IncidenceandRiskFactorsIncidenceCommonlyabout5percentMarkedlyinfluencedbyparityRelatedtoraceandethnicity—AgeneticpredispositionMainRiskFactorsNulliparous(初產(chǎn)婦)MultiplepregnancyHistoryofchronichypertensionMaternalageover35yearsObesityLowersocioeconomicstatus…EtiologyandPathogenesisNormal:vesselremodeling(血管重鑄)ofthedeciduaandmyometriumtransformingintolarge-capacitance,low-resistancevesselsPreeclampsia:incompleteremodelinglimitedtothe

superficialdeciduamyometrialsegmentsremain

narrowFaultyPlacentation(胎盤形成不良)---StageIPathogenesisofpreeclampsiaGeneticfactorsimmunologicalfactorsMaternalvasculardiseaseEnvironmentalfactorsReduceduteroplacentalperfusionFaultyplacentationEndothelialactivationSystemicvasculardysfunctionCapillaryleakvasospasmHypertensionCerebraledema(eclampsia)EdemaProteinuriaCoagulationabnormalities(HELLP)Fetalgrowthrestriction(FGR)Physiopathology

------sgageII

Basicchange:SystemVasospasm（全身小動脈痙攣）Hemorrhage,edema,hyperemia充血,thrombosis

Visualdisturbances:blurredvision,blindness,retinaldetachment（視網(wǎng)膜脫落）Reducedrenalperfusionandglomerularfiltration腎小球濾過率

Proteinuria;increaseduricacid;oliguriaIschemia,edema→elevatedserumtransaminases(ALT,AST,AKP..);jaundice（黃疸）Subcapsularhematoma(肝包膜下出血)orhepaticrupturePhysiopathologyPeripheralvascularresistance↑,cardiacoutput↓(低排高阻),bloodpressure↑Cardiacfailure(心力衰竭),pulmonaryedema(肺水腫)

Bloodvolume↓,hematocrit↑(HCT,紅細(xì)胞壓積)

,bloodconcentration

Hypercoagulability(高凝),thrombocytopenia(血小板減少)PlacentalischemiaandhypoxiaHigh-resistancecircuitwithdecreasedbloodFetalgrowthrestriction,fetaldistress(胎兒窘迫)WHATLINKSSTAGE

1&2?Theoryexploration:Genetics/AbnormallipidmetabolismEndocrinedysfunctionInflammationNotallwomenwithreducedplacentalperfusiondeveloppreeclampsia…

Whatlinksstages1and2?Reducedplacentalperfusionmustinteractwithmaternalfactorstoresultinpreeclampsia.Stage1???Stage2Roberts,J.M.,GammillH.S.(2005)Diversemanifestationsarepossible:maternalandfetal/placentalfactorsmayvaryinproportion.

Inawomanwithmany

predisposingfactors,evenaminorreductioninplacentalperfusionissufficientforstage2todevelop.Inawomanwithfewpredisposingfactors,aprofoundreductioninplacentalperfusionmayberequiredforpreeclampsiatodevelop.

Roberts,J.M.,GammillH.S.(2005)PredisposingfactorsReducedplacentalperfusionMicrosoftOffice2000Whatdoweknow?Weknowthatabnormalitiesinlipidmetabolismhaveageneticbasis.Wehavelearnedthatpreeclampsiaischaracterizedbyprofoundlipidabnormalitiessuchashypertriglyceridemia…Gratacos,E.(2000)MicrosoftOffice2000Couldabnormallipidmetabolismbeageneticfactorlinkingthestagesofpreeclampsia?

Stage1Stage2AbnormallipidmetabolismPreeclampsiaischaracterizedbymetabolicabnormalitiessimilartothosepresentinatherosclerosis:HypertriglyceridemiaReducedHDLcholesterolPredominanceofsmall-denseLDLcholesterolwhichhaveanincreasedpotentialtocauseendothelialcelldamageascomparedtolarger,morebuoyantLDL’s.GratacosE.,2000.Mostofthesuggestedlinkagescouldcontributetoorbestimulatedbyoxidativestress.Oxidativestressisproposedasrelevanttomanydiseases.Evidencesupportsthepresenceofoxidativestressinpreeclampsia:ProteinproductsofoxidativestresspresentinmaternalandfetaltissuesAntibodiestooxidativelymodifiedLDL’spresentinmaternalandfetaltissuesConcentrationsofcertainantioxidantsreducedinpreeclampticwomen.

Roberts,J.M.,GammillH.S.(2005)Insummary:Hypertriglyceridemiaandpredominanceofsmall-denseLDL’spriortopregnancycouldbeonepredisposingfactorfordevelopingpreeclampsia.Oxidativestressandinflammation maytriggerthematernaldisease.GratacosE.,(2000)MicrosoftOffice2000CouldendocrinedysfunctionbeafactorlinkingStage1andStage2?Stage1Stage2EndocrinedysfunctionStudieshaverepeatedlydemonstratedthatmetabolicabnormalitiesprecedetheclinicalsignsofpreeclampsia:InsulinresistanceandassociatedhyperinsulinemiaGlucoseintoleranceHypertriglyceridemiaThissuggeststhatinsulinresistanceanddyslipidemiamaybefactorsinvolvedinthedevelopmentofpreeclampsia.Innes,etal.(2005)Similaritiesbetweentheriskfactorsforpreeclampsiaandcardiovasculardiseaseinclude:InsulinresistanceDyslipidemia-decreasedHDLlevelsand elevatedtriglyceridelevelsTheseriskfactorsarethoughttoplayacausalroleinthedevelopmentofendothelialdysfunction,acharacteristicfeatureofpreeclampsiaandcardiovasculardisease.Innes,etal.(2005)“Preeclampsiaisassociatedwithanexcessiveinflammatoryresponsecomparedwithnormalpregnancy.”InastudydonebyBraekke,et.al(2005)inflammatorymarkers(calprotectin,CRP)wereevaluatedinmaternalandfetalserumandamnioticfluid.Braekke,K.,Holthe,Ml,Harsem,N.,Fagerhol,M.,Staff,A.,2005InflammatoryMarkers:Calprotectin:IsaproteinreleasedbyactivatedneutrophilsC-reactiveprotein(CRP):IsaproteinproducedbytheliverProductionisstimulatedbyinflammatorycytokinesBraekke,K.et.al.(2005)MicrosoftOffice2000CalprotectinandC-reactiveprotein(CRP),markersofinflammation,areelevatedinpreeclampsia.Theconcentrationofcalprotectininthematernalplasmaofpreeclampticwomenwashigherthaninthecontrolgroup(normalpregnantwomen).NostatisticallysignificantdifferenceincalprotectinlevelswasnotedbetweenwomenwithmildandseverepreeclampsiaBraekke,K.etal.(2005)C-reactiveprotein:Hasbeenusedtoevaluatelow-gradeinflammationasacardiovascularriskfactor

Braekkeetal.2005MicrosoftOffice2000CRPlevelsinthematernalplasmaofpregnantwomen:Correspondtoalow-gradeinflammationinpreeclampsiaandinnormalpregnancy.

Braekkeetal.2005MicrosoftOffice2000Concentrationsofcalprotectininbotharterialandvenousumbilicalplasma,andamnioticfluidweremuchlowerthaninmaternalplasmaCRPlevelsinfetalcirculationwere1/100ofmaternalCRPlevels.Noinflammatoryresponsewasnotedinthefetalcirculation.Braekkeetal.2005Theoretically,“Calprotectinconcentrationscouldplayaroleinthepathophysiologyofpreeclampsiathroughaugmentedplacentalcelldeathorreducedtrophoblastinvasion(stage1)”Braekkeetal.2005Whatstimulatestheinflammatoryresponse(activatestheneutrophils)inpreeclampsia?Researchershavebeenunabletodeterminewhyorexactlywheretheneutrophilsbecomeactivated.Maternalorplacentafactorstriggeringmaternalinflammationdonotappeartobetransferredintothefetalcirculation.

Braekkeetal.2005Futureimplications:Furtherresearchisneededtoevaluatetheroleofcalprotectininpregnancyorpregnancycomplications.Willcalprotectinconcentrationsbeused topredictpreeclampsiabeforetheonsetofclinicalsymptomsorasamarkeroftheclinicallyestablisheddisease?

Braekkeetal.2005ClassificationGestationalHypertensionBP≥140/90

mmHgforfirsttimeduringpregnancyNoproteinuriaBPreturntonormal<12weeks’postpartumFinaldiagnosismadeonlypostpartum（產(chǎn)后）Preeclampsia

BP≥140/90mmHgafter20weeks’gestationProteinuria300mg/24hoursor≥1+dipstick

EclampsiaSeizuresthatcannotbeattributedtoothercausesinawomanwithpreeclampsiaClassificationPreeclampsiaSuperimposedonChronicHypertensionNew-onsetproteinuria≥300mg/24hoursinhypertensivewomenbutnoproteinuriabefore20weeks’gestationAsuddenincreaseinproteinuriaorbloodpressureorplateletcount<100×109/LChronicHypertensioninPregnancyBP≥140/90mmHgbeforepregnancyordiagnosedbefore20weeks’gestationOrHypertensionfirstdiagnosedafter20weeks’gestationandpersistentafter12weeks’postpartumDiagnosis

HistoryHypertensionProteinuriaEdemaAssistantexaminationDiagnosisofseverepreeclampsiaCentralnervoussystem:headache,visualchanges,comaSubcapsularhematomaorhepaticrupture:epigastricdiscomfortorpersistrightupperquadrantpainHepaticimpairment:elevatedhepaticenzymesSystolicpressure≥160mmHg,ordystolicpressure≥110mmHgThrombocytopenia:<100×109/LProteinuria:≥5g/24hoursOliguria:<500ml/24hours(少尿)CerebralvascularcomplicationsIntravascularhemolysis:anemia,jaundice,LDH↑(血管內(nèi)溶血)CoagulationdisordersFGR(胎兒生長受限)orOligohydramnion(羊水過少)ManagementPrinciplesSedation(鎮(zhèn)靜)Antihypertension(降壓)Antispasm(解痙)Diuresis(利尿)TerminationofpregnancyManagementGeneralmanagementBedrestFrequentfetalandmaternalmonitoringSedationDiazepam(地西泮，安定)Hibemation(冬眠藥物)pathidine派替啶,chlorpromazine氯丙嗪promethazine異丙嗪ManagementAntispasm(解痙)

：Topreventseizures

Magnesiumsulfate（硫酸鎂）MechanismDoseregimenloadingdose:5g,5-10minutescontinuousinfusion:20-25g,1-2g/hourtotaldailydose:25-30