醫(yī)技學(xué)院（華盛頓醫(yī)療手冊(cè)培訓(xùn)器官移植）ppt課件

SolidOrganTransplantMedicine Dr BaiXue liTheDepartmentofHBPSurgeryandLiverTransplantation Contents In1954 Prof JosephMurrayachievedthefirstsuccessfulkidneytransplantationfromoneidenticaltwintoanotherwithoutusinganti rejectiondrugsThefirstsuccessfulkidneytransplantation Thefirstlivingorgantransplantation Thefirstrelativekidneytransplantation Thefirstorgantransplantationbetweenidenticaltwins 1990 History History Dr ThomasE Starzl1963firstlivertransplantation Prof ChristiaanBarnard1967firsthearttransplantation Dr JamesD Hardy1963firstlungtransplantation GeneralPrinciplesAsurgicaloperationwhereafailingordamagedorganinthehumanbodyisremovedandreplacedwithanewoneAtreatment notacure forend stageorganfailureofthekidney liver pancreas heartandlung SolidOrganTransplantBasics AllorgansremaininshortsupplywithincreasingwaitingtimesforpotentialrecipientsLiving donortransplantsareconsideredasapartialsolutiontoorganshortageXenotransplantationisnotaviableoptioninthenearfuture GeneralPrinciples ImmunologicconsiderationspriortothetransplantmustbefullyevaluatedIncludingABOcompatibility HLAtyping andsomedegreeofimmuneresponsetestingtotheproposeddonor GeneralPrinciples Evaluationoftherecipient CauseoforganfailureTreatmentfororganfailurepriortotransplantationTypeanddateoftransplantCMVstatusofdonorandrecipientInitialimmunosuppression particularlyuseofantibody basedinductiontherapy Evaluationoftherecipient Initialandcurrentfunctionoftransplant nadircreatinine FEV1 ejectionfraction syntheticfunctionandtransaminases etc Complicationsoftransplantation surgicalproblems acuterejection infections chronicorgandysfunction etc Currentimmunosuppressionregimenandrecentdruglevels Treatment Immunosuppressionpromoteacceptanceofagraft inductiontherapy preventrejection maintenancetherapy reverseepisodesofacuterejection rejectiontherapy Complicationsinfectionmalignancynonimmunetoxicity nephrotoxicity diabetesmellitus bonedisease gout hyperlipidemia cardiovasculardisease orneurotoxicity Immunosuppressiveagents 1 Glucocorticoids methylprednisolonemechanismsimmunosuppressiveandanti inflammatoryinhibitionofcytokinetranscriptioninductionoflymphocyteapoptosisdownregulationofadhesionmoleculeandMHCexpressionsideeffectsdiabetesmellitusCushingsyndromeosteoporosisPepticulcer 2 Antiproliferativeagents Azathioprine MPAAzathioprinemechanisms metabolizedto6 mercaptopurineinhibitsthesynthesisofDNA suppressestheproliferationofactivatedlymphocytesadverseeffects myelosuppressionMPA MPA MMFmechanisms inhibitstherate limitingstepindenovopurinesynthesis selectivelyinhibitslymphocytesproliferationadverseeffects gastrointestinaldisturbances hematologicdisturbances 3 Calcineurininhibitors CNI Cyclosporine CsA TacrolimusCsAmechanisms blockadeofinterleukin 2andothercytokinetranscription inhibitionofT lymphocyteactivationandproliferationsideeffect nephrotoxicity 30 hirsutism hypertension glucoseintolerance hyperlipidemiaFK506 firstchoiceforlivertranspl mechanisms blockadeofinterleukin 2transcription inhibitionofT lymphocyteactivationandproliferationsideeffect nephrotoxicity neurotoxicanddiabetogenic morethanCsA hypertension 4 Sirolimusmechanisms inhibitstheactivationofaregulatorykinase mammaliantargetofrapamycin mTOR prohibitsT cellprogressionfromtheG1totheSphaseofthecell Anti HCCsideeffect Nonephrotoxicityandneurotoxicitygastrointestinalsymptomshyperlipidemiaanemia 5 Polyclonalantibodies Antithymocyteglobulin ATG Antilymphocyteglobulin ALG 6 Monoclonalantibodies OKT3 Anti interleukin 2receptormonoclonalantibodies Daclizumab Basiliximab mechanisms competitivelyinhibitCD25andtherebyinhibitactivationofTcells Preventinginfection Trimethoprim sulfamethoxazole preventsurinarytractinfections Pneumocystisjirovecipneumonia andNocardiainfectionsAcyclovir preventsHSVandvaricella zoster ineffectiveinCMVprophylaxisGanciclovirorvalganciclovir preventsreactivationofCMVinfectionFluconazoleorketoconazole systemicfungalinfectionsorrecurrentlocalizedfungalinfections GraftRejection HyperacuteRejection GraftRejection ChronicRejection AcuteRejection GraftRejection Hyperacuterejection occurswithin24hoursaftertransplantationmediatedbypre existingantibodiesspecificforgraftantigensmassiverecruitmentofneutrophilsoccursfollowedbyrapidinflammationABOincompatibility GraftRejection Acuterejection occursinthefirstfewdaystomonthsaftertransplantation 80 90 inthefirstmonthMediatedbyTcellsimmuneresponseMassiveinfiltrationbymacrophagesandlymphocytes GraftRejection Chronicrejection occursinmonthstoyearsaftertransplantationmediatedbyhumoralandcellresponseschronicvascularrejectionandvascularendothelialinjury organdegenerationanddysfunctionnotinducedbyimmuneresponse AcuteRejection Kidney occurinthe1styearaftertransplantation inonly10 ofpatients ifdonotreceiveinductiontherapy 20 30 Reasons inadequatedruglevels noncompliance orlesscommonformsofrejection suchasantibody mediatedrejectionorplasmacellrejection mediatedbythecellularimmunesystemandTlymphocytesspecificpathologicchanges lymphocyticinterstitialinfiltrates tubulitis andarteritis AcuteRejection Kidney Diagnosis percutaneousrenalbiopsy excludingcalcineurininhibitornephrotoxicity troughand orpeaklevelsandassociatedsigns infection urinalysisandculture andobstruction renalultrasound Manifestations elevatedserumcreatinine initialsymptom decreasedurineoutput increasededema orworseninghypertension Constitutionalsymptoms fever malaise arthralgia painfulorswollenallograft areuncommon AcuteRejection Lung Ofthesolidorgantransplants thelungisthemostimmunogenicorgan Themajorityofpatientshaveatleastoneepisodeofacuterejection developmentofchronicrejection bronchiolitisobliteranssyndrome occursfrequentlyandmostcommonlyinthefirstfewmonthsaftertransplantationDiagnosis fiberopticbronchoscopywithbronchoalveolarlavageandtransbronchialbiopsies AcuteRejection Lung Manifestations nonspecific fever dyspnea andanonproductivecough chestradiographisusuallyunchanged Changeinpulmonaryfunctiontestingisnotspecificforrejection buta10 orgreaterdeclineinforcedvitalcapacityorforcedexpiratoryvolumein1second orboth isusuallyclinicallysignificantmustdistinguishrejectionfrominfection Toughsymptomsaresimilar treatmentsaremarkedlydifferent AcuteRejection Heart twotothreeepisodesofacuterejectioninthefirstyearaftertransplantation 50 to80 atleastonerejectionepisode mostcommonlyinthefirst6months Diagnosis endomyocardialbiopsyperformedduringroutinesurveillanceoraspromptedbysymptoms irreplaceable repeatedendomyocardialbiopsies severetricuspidregurgitationManifestations symptomsandsignsofleftventriculardysfunction dyspnea paroxysmalnocturnaldyspnea orthopnea syncope palpitations newgallops andelevatedjugularvenouspressureManypatientsareasymptomatic AcuteRejection Liver occurswithinthefirst3monthsaftertransplantandofteninthefirst2weeksaftertheoperationgenerallyreversibleanddoesnotportendapotentiallyseriousadverseoutcomeasinotherorganscommonlyexperienceacuteallograftrejection withatleast60 havingoneepisode AcuteRejection Liver Diagnosis liverbiopsyManifestations mild onlyaslightelevationintransaminases severe developtoliverfailure fever malaise anorexia abdominalpain ascites decreasedbileoutput elevatedbilirubin andelevatedtransaminases Differentialdiagnosis primarygraftnonfunction preservationinjury vascularthrombosis biliaryanastomoticleak orstenosis 肝匯管區(qū)內(nèi)大量以淋巴細(xì)胞為主的炎性細(xì)胞浸潤(rùn) 并可見(jiàn)小葉間膽管上皮炎性細(xì)胞浸潤(rùn)形成導(dǎo)管上皮炎損傷 肝小葉間靜脈血管內(nèi)皮炎 內(nèi)皮層有淋巴細(xì)胞浸潤(rùn)并呈內(nèi)皮水腫 ChronicAllograftDysfunction accountsforthevastmajorityoflategraftlosses mediatedbyimmuneandnonimmunefactorsslowlyprogressive insidious majorobstacletolong termgraftsurvivalPathologiccharacterization gradualvascularandductalobliteration parenchymalatrophy andinterstitialfibrosisDiagnosis oftendifficultandgenerallyrequiresabiopsyTreatment ifestablished noeffectivetherapy requireasecondsolidorgantransplant aimedatprevention CompanyLogo GraftRejection GeneralPrinciples Diagnosis Manifestations Treatment ChronicAllograftDysfunction Accountsforthevastmajorityoflategraftlossesandisthemajorobstacletolong termgraftsurvival Difficult Requireabiopsy Mediatedbyimmuneandnonimmunefactors Unique Noeffectivetherapy Asecondsolidorgantransplant Prevention Complications Skincancer LipCancer LymphoproliferativeDisease BronchogenicCarcinoma KaposiSarcoma Uterine CervicalCarcinoma RenalCellCarcinoma AnogenitalNeoplasms CompanyLogo Complications Infections Treatment Treatment Valganciclovir 450to900mgPObid Ganciclovir 2 5to5 0mg kgbidIVadjustedforRenalFunction CMV Hyperimmuneglobulin Ganciclovir OrganInvolvement Foscarnet Cidofovir GanciclovirResistant Complications Infections HepatitisB HepatitisC OralFluconazole Playaroleinthedevelopmentofposttransplantlymphoproliferativedisease Immunosuppression OralFluconazole Complications Infections EBV Fungus Parasite CompanyLogo TimingandEtiologyofPosttransplantInfections CompanyLogo Complications RenaldiseaseTheleadingcauseofallograftlossinrenaltransplantrecipientsCalcineurininhibitor CsA Tacrolimus NephrotoxicityChronicrenalinsufficiencyEnd stagerenaldisease ESRD CompanyLogo Complications MalignancyThree tofourfoldhigherthangeneralpopulationSkinandlipcancers 40 50 intransplantrecipients Riskfactors immunosuppression UVradiation HPV Developatyoungerage Recommend protectiveclothing sunscreensavoidsunexposure Diagnosis examinationoftheskin CompanyLogo Complications MalignancyPosttransplantlymphoproliferativedisease 1 5ofallmalignanciesaftertransplantation Riskfactors antilymphocytetherapy Majority large cellnon HodgkinlymphomasoftheB celltype Presentation atypical Diagnosis requiresahighindexofsuspicionfollowedbyatissuebiopsy Treatment reductionorwithdrawalofimmunosuppressionchemotherapy CompanyLogo SpecialConsiderations DrugInteractionsImportantdruginteractionsarealwaysaconcerngiventhepolypharmacyassociatedwithtransplantpatients prescribinganewmedicationtoatransplantrecipient alwaysinvestigatedrug