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1、Organ Transplantation2Transplantationistheprocessoftakingagraftcells,tissues,ororgansfromoneindividualthedonor,andplacingitintoanotherindividualtherecipient,orhost.31.HistoricalOverviewThedreamofcuringillnessandinjurybytransplantingtissuesorentireorgansisprobablyasoldasthehistoryofhealingitself.Writ
2、tenaccountsfromEgypt,ChinaandIndiadatingbackmanycenturiesdescribemanifoldexperimentationsingrafting(SharmaandUnruh2004).4Thekidneywasthefirstvitalorgantobesuccessfullytransplanted.AlexisCarrelsuccessfullytransplantedkidneysandotherorgansinanimalsanddevelopedtechniquesofmodernvascularsurgerythatresul
3、tedinbeingawardedaNobelPrizein1912.5In1933,theRussiansurgeonVeronoffperformedthefirsthumanallograft(kidneyfrommothertoson)withoutthebenefitoftissuetyping.Intheearly1950s,Medawarandcolleaguesdescribedrejectionanditspreventioninmice(NobelPrize,1960),whichstimulatedsurgeonstoresumehumanrenaltransplanta
4、tion.6In 1954, Joseph Murray achieved the first In 1954, Joseph Murray achieved the first successful kidney transplantation from one successful kidney transplantation from one identical twin to another without using anti-identical twin to another without using anti-rejection drugs.rejection drugs.7I
5、n1962thefirstcadaverickidneytransplantwasperformed(Transweb2000).Theorganfunctionedfor21months.Thiswasmadepossiblethanksto6-mercaptopurine,thefirstusefulimunosuppressivedrug.Rejectionofthetransplantremainedamajorobstacleuntilthelate1970s.8OtherorgantransplantationsfollowedIn1963JamesHardytransplante
6、dthefirstlung.In1966therewasthefirstsimultaneouspancreas/kidneytransplantationand1yearlaterthefirstsuccessfullivertransplantationfollowed.9Thefirstsuccessfulhumanhearttransplantationwasperformedon3December1967byChristianBarnard.Therecipientinitiallyrecoveredbutsubsequentlydiedofpseudomonaspneumonia1
7、8dayslater.10Progressinhistocompatibilitytyping,immunosuppressivetherapy,andorganpreservationandaccumulationofclinicalexperiencegraduallyresultedinfurtherimprovementintransplantationthatallowedsuccessfulreplacementofnotonlyfailingkidneysbutothervitalorgansaswell.1112132.DefinitionTransplantationcanb
8、echaracterizedaccordingtoeitherthegeneticrelationshipbetweenthedonorandrecipientortheanatomicalsiteoftheimplantation.14Thegeneticrelationshipischaracterizedinto4classesAutograft:thedonorandrecipientisthesameindividual.Isotransplantation(Isogrant):thedonorandrecipientaregeneticallyidentical(eg,monozy
9、gotictwins).15Allotransplantation(Allogrant):thedonorandrecipientaregeneticallyunrelatedbutbelongtothesamespecies.,suchastransplantationofanorganfromonehumantoanotherhumanorfromonedogtoanotherdog.Xenotransplantation(Xenogrant):thedonorandrecipientbelongtodifferentspecies.16Basedonthesiteofimplantati
10、onOrthotopictransplantationreferstodonortissueimplantedintheanatomicallycorrectpositionintherecipient;Heterotopictransplantationreferstotherelocationoftheimplantintherecipientatasitedifferentfromthenormalanatomy.173.TRANSPLANTIMMUNOLOGYANDIMMUNOSUPPRESSIONNofieldofmedicinehasbeensointimatelyrelatedt
11、oscientificadvancesastransplantation.Thefailurehasbeenbroadlytermedrejection,anditsstudyhasfueledmostofthemajordiscoveriesinimmunology.18Thedegreetowhichanallograftsharesregulatorymoleculesoftheimmunesystemwiththerecipientisreferredtoasthehistocompatibilityofthegraft.Thisisadescriptionofthesimilarit
12、yofaclusterofgenesonchromosome6knownasthemajorhistocompatibilitycomplex(MHC,knownashumanleukocyteantigenHLAinhumanbeings).19InthecurrentdefinitionofHLAassixlocionchromosome6,encodingtworelatedcellsurfacemolecules:classI(HLA-A,B,andC)andclassII(HLA-DR,DP,andDQ).Themostsignificantadvanceinimmunosuppre
13、ssionwasthediscoveryofcyclosporinebyBorelin1976.20Itisnowrareforanallografttobelosttoacuterejection.Futureadvancesmustfocusonthechronicdiseasesofagrowingtransplantpopulation.Ideally,theconceptofspecificimmunologicaltolerancefirstdescribed50yearsagowillsoonbeunderstoodandwillallowfortransplantationwi
14、thoutimmunosuppression.21BiologyofTransplantAntigenRecognitionandDestructionT-CellActivationT-CellAmplificationT-Cell-MediatedCytotoxicityB-CellActivationandClonalExpansionAntibody-MediatedCytotoxicity22ClinicalRejectionSyndromesRejectionhasbeenclassifiedashyperacute,acute,orchroniconthebasisofthege
15、neralpathophysiologyandeffectorarmoftheimmunesysteminvolved.Ofthese,onlyacuterejectioncanbesuccessfullyreversed.Thoughhyperacuterejectionisuntreatable,itismostlyapreventablephenomenon.Chronicrejectionremainsadifficultproblem.23HyperacuteRejectionHyperacuterejection(HAR)iscausedbyHyperacuterejection(
16、HAR)iscausedbypresensitizationoftherecipienttoanantigenpresensitizationoftherecipienttoanantigenexpressedbythedonor.Itdevelopsinthefirstexpressedbythedonor.Itdevelopsinthefirstminutestohoursfollowinggraftreperfusion.minutestohoursfollowinggraftreperfusion.Antibodiesincirculationpriortotransplantatio
17、n,Antibodiesincirculationpriortotransplantation,theresultofpriorexposuretodonor-typetheresultofpriorexposuretodonor-typealloantigensorABObloodgroupantigens,bindalloantigensorABObloodgroupantigens,bindtothedonortissue.Thisinitiatescomplement-tothedonortissue.Thisinitiatescomplement-mediatedlysisandin
18、ducesaprocoagulantmediatedlysisandinducesaprocoagulantstate,resultinginimmediategraftthrombosis.state,resultinginimmediategraftthrombosis.24PreoperativeverificationofproperABOmatchingandanegativecrossmatcheffectivelypreventshyperacuterejectionin99.5percentoftransplants.25AcuteRejectionAcuterejection
19、iscausedprimarilybyTcellsandAcuterejectioniscausedprimarilybyTcellsandevolvesoveraperiodofdaystoweeks.Itcanevolvesoveraperiodofdaystoweeks.Itcanoccuratanytimeafterthefirst5postoperativeoccuratanytimeafterthefirst5postoperativedays,butismostcommoninthefirst6months,days,butismostcommoninthefirst6month
20、s,andistheinevitableresultofanallotransplantandistheinevitableresultofanallotransplantunlessimmunosuppressiondirectedagainsttheunlessimmunosuppressiondirectedagainsttheTcellisused.Tcellisused.26TheincidenceofacuterejectiondeclineswithdecreasingMHCdisparity,butanymismatchputsthepatientatriskforT-cell
21、mediatedgraftdestructionandmandatesT-cellspecificimmunosuppression.27Treatmentleadstosuccessfulrestorationofgraftfunctionin90to95percentofcases,andfailuretotreatresultsalmostuniformlyingraftloss.Mostacuterejectionepisodesforpatientsonmodernimmunosuppressiontherapyareasymptomaticuntilthesecondaryeffe
22、ctsoforgandysfunctionoccur.28ChronicRejectionChronicrejection(CR)ispoorlyunderstood.Itsonsetisinsidious,occurringoveraperiodofmonthstoyears,andbecausethepathophysiologyisnotwelldefined,itisuntreatable.Heightenedimmunosuppressionisnoteffectiveinreversingorretardingtheprogressionofchronicrejection.29C
23、hronicrejectionrequiresretransplantation.30HLAmatchingandthecrossmatchMatchingforHLA,themajorhistocompatibilityMatchingforHLA,themajorhistocompatibilitycomplex(complex(MHCMHC)inman,presentsmajorlogistic)inman,presentsmajorlogisticproblemsincadavertransplantationbecauseofproblemsincadavertransplantat
24、ionbecauseofthegeneticcomplexityoftheHLAsystem.thegeneticcomplexityoftheHLAsystem.Formanyyears,followingtherecognitionofFormanyyears,followingtherecognitionofhyperacuterejectionofatransplantedkidneyinhyperacuterejectionofatransplantedkidneyinthepresenceofapositivecrossmatchbetweenthepresenceofaposit
25、ivecrossmatchbetweendonorandrecipient,apositivecrossmatchwasdonorandrecipient,apositivecrossmatchwasconsideredtobeanabsolutecontraindicationtoconsideredtobeanabsolutecontraindicationtorenaltransplantation.renaltransplantation.31ImmunosuppressionWithoutsomeattenuationoftheimmuneWithoutsomeattenuation
26、oftheimmunesystem,allallograftseventuallywouldbesystem,allallograftseventuallywouldbedestroyed.destroyed.MedicationsusedtopreventacuterejectionforMedicationsusedtopreventacuterejectionforthelifeofthepatientarecalledmaintenancethelifeofthepatientarecalledmaintenanceimmunosuppressants.Theseagentsarewe
27、llimmunosuppressants.Theseagentsarewelltoleratedifdosedappropriately.Allhavesidetoleratedifdosedappropriately.Allhavesideeffectsthatincreasetheriskofinfectionandeffectsthatincreasetheriskofinfectionandmalignancy.Immunosuppressantsusedtomalignancy.Immunosuppressantsusedtoreverseanacuterejectionepisod
28、earecalledreverseanacuterejectionepisodearecalledrescueagents.rescueagents.32CorticosteroidsCorticosteroids,inparticulartheglucocorticoidCorticosteroids,inparticulartheglucocorticoideffectofsteroidpreparations,remainacentraleffectofsteroidpreparations,remainacentraltoolinthepreventionandtreatmentofa
29、llografttoolinthepreventionandtreatmentofallograftrejection.rejection.Usedalone,theyareineffectiveinpreventingUsedalone,theyareineffectiveinpreventingallograftrejection,butincombinationwiththeallograftrejection,butincombinationwiththeotheragentsdescribedbelowtheysignificantlyotheragentsdescribedbelo
30、wtheysignificantlyimprovegraftsurvival.improvegraftsurvival.33Theadverseeffectsofsteroidtherapyarenumerous.Theseeventsusuallycanbeamelioratedbytaperingthesteroiddose.34AntiproliferativeAgentsAzathioprineMycophenolateMofetil35CalcineurinInhibitorsCyclosporineItsuseresultedindramaticimprovementsinther
31、esultsofallorgantransplants,butparticularlyinhepaticandcardiactransplantation.Ithasremainedamainstayimmunosuppressantinmostmaintenanceregimens.36TacrolimusTacrolimus,likecyclosporine,blockstheeffectsofNF-AT,preventscytokinetranscription,andarrestsT-cellactivation.Tacrolimusis100timesmorepotentinbloc
32、kingIL-2andIFN-gproductionthancyclosporine.37AntilymphocytePreparationsAntilymphocyteGlobulinOKT3TheonlycommerciallyavailablepreparationofmonoclonalantibodiesforuseinorgantransplantationisthemurinemonoclonalantibodytothesignaltransductionsubunitonhumanTcells(CD3),knownasOrthocloneOKT3.38TransplantOr
33、ganProcurementI. Donor SelectionI. Donor Selection ThegreatestobstacletoorgantransplantationisThegreatestobstacletoorgantransplantationisthelackofsuitabledonororgans.Livedonationthelackofsuitabledonororgans.Livedonationhasprovidedanimportantsourceoforgans,hasprovidedanimportantsourceoforgans,withann
34、uallivingkidneydonorssurpassingwithannuallivingkidneydonorssurpassingdeceaseddonors.Lessfrequently,livedonationdeceaseddonors.Lessfrequently,livedonationisbeingutilizedinliverandlungtransplantation.isbeingutilizedinliverandlungtransplantation.ThepatientswaitingfororgansoutnumbertheThepatientswaiting
35、fororgansoutnumbertheavailableorgans,andthewaitinglistfororganavailableorgans,andthewaitinglistfororgantransplantsgrowseachyear.transplantsgrowseachyear.39II. Deceased Donors (formerly known as brain-dead or cadaveric donors)Strictcriteriaforestablishingbraindeathincludethepresenceofirreversiblecoma
36、andtheabsenceofbrainstemreflexes(i.e.,pupillary,corneal,vestibulo-ocular,orgagreflexes).40Consentisrequiredfromthefamily,andinquiriesintothedonorsmedicalhistoryaremade.Ideally,thedonorshouldhavestablehemodynamics,althoughtheuseofvasopressorsiscommon.Allpatientsmeetingbraindeathcriteriashouldbeconsid
37、eredaspotentialdonors.41SurgicalTechniqueoftheAbdominalOrganProcurementOrganprocurementisthelifebloodoforgantransplantation.Itisanessentialpartoftheorgantransplantationandcontributesforatleast50%toitssuccessorfailure.424344454647484950515253Livingdonornephrectomy545556575859Renal/Kidneytransplantati
38、on60IntroductionTransplantationofthekidneyhasbecomethetreatmentofchoiceforendstagerenalfailureinmostagegroupswithperhapstheexceptionoftheveryyoungandtheveryold.Thatthishashappenedoverthepast40yearsrepresentsoneofthemostsignificantdevelopmentsinmedicineinthiscentury.61Indicationsforrenaltransplantati
39、onGlomerulonephritisGlomerulonephritisIdiopathicandpostinfectiousIdiopathicandpostinfectiouscrescenticMembranousMesangiocapillary(typeI)crescenticMembranousMesangiocapillary(typeI)Mesangiocapillary(typeII)(densedepositdisease)IgAMesangiocapillary(typeII)(densedepositdisease)IgAnephropathyAnti-GBMFoc
40、alglomerulosclerosisnephropathyAnti-GBMFocalglomerulosclerosisHenochSchnleinHenochSchnleinChronicpyelonephritisChronicpyelonephritis(refluxnephropathy)(refluxnephropathy)HereditaryHereditaryPolycystickidneysNephronophthisisPolycystickidneysNephronophthisis(medullarycysticdisease)Nephritis(includingA
41、lports(medullarycysticdisease)Nephritis(includingAlportssyndrome)syndrome)MetabolicMetabolicDiabetesmellitusOxalosisCystinosisDiabetesmellitusOxalosisCystinosisFabrysdiseaseAmyloidGoutFabrysdiseaseAmyloidGout62ObstructiveuropathyObstructiveuropathyToxicToxicAnalgesicnephropathyOpiateabuseAnalgesicne
42、phropathyOpiateabuseMultisystemdiseasesMultisystemdiseasesSystemiclupuserythematosusSystemiclupuserythematosusVasculitisProgressivesystemicsclerosisVasculitisProgressivesystemicsclerosisHaemolyticuraemicsyndromeHaemolyticuraemicsyndromeTumoursTumoursWilmstumourRenalcellcarcinomaWilmstumourRenalcellc
43、arcinomaIncidentalcarcinomaMyelomaIncidentalcarcinomaMyelomaCongenitalHypoplasiaCongenitalHypoplasiaHorseshoekidneyHorseshoekidneyIrreversibleacuterenalfailureIrreversibleacuterenalfailureCorticalnecrosisAcuteCorticalnecrosisAcutetubularnecrosistubularnecrosisTraumaTrauma6364656667Surgicalsteps686970717273747576 777879808182ComplicationsTechnicalcomplicationsImmunologicalcomplicationsCardiovascularcomplications8384858687888990919293姓名：克拉什尼奇（IvanKlasnic）国籍：克罗地亚场上位置：前锋出生日期：1980年1月29日身高：182cm体重：76kg现效力俱乐部：不莱梅曾效力俱乐部：圣保利94Livertransplantation9596979899谢谢！
