白蛋白与肝硬化ppt课件.pptx

人血白蛋白在肝硬化治疗领域中的应用,概要,人血白蛋白简介肝硬化概述人血白蛋白在肝硬化并发症治疗中应用,人血白蛋白制品,是从健康人血浆中提纯的一类特殊药品。目前国内外临床需求量最大、使用最多、最安全的一种血浆蛋白制品。与血浆相比，最大优势是经过病毒灭活处理，无传播病毒性传染病可能。,白蛋白分子特性,白蛋白含量最多，占52-58%。610个AA组成的多肽，不含糖，仅少量脂肪酸。分子量小，67KD。健康人血浆半衰期17-21天，危重患者则仅9天。水溶性好，粘度低，25%的白蛋白粘度与全血相当。,白蛋白的生理功能,维持和调节胶体渗透压占血浆总胶体渗透压80%。运输转运各种离子、激素、胆红素、药物等。解毒如汞中毒。营养供给合成组织蛋白、氧化供能、氮源为组织提供营养。促进肝细胞修复和再生。,适应症,低蛋白血症（营养不良、合成障碍、丢失过多）大面积烧伤（补晶体液、补蛋白、维持血容量）血浆置换（丢失蛋白要及时补充，尤其有肝肾疾患者）扩容、维持胶体渗透压体外循环（用白蛋白和晶体液做底液，比血液安全，减少肾衰危险）新生儿溶血病（结合游离胆红素，避免胆红素脑病）脑水肿（提高胶渗压，减轻脑水肿）,不良反应与血浆相比要低得多,偶有寒战、发热、头痛症状，需对症处理。快速输注可引起循环超负荷导致肺水肿。极少发生低血压、呼吸困难、甚至休克等严重过敏性变态反应。输注被污染的白蛋白，会出现菌血症、休克甚至败血症。,禁忌症,对白蛋白有严重过敏者病情难以承受血容量迅速增加，如心衰或心功能低下、高血压患者、肺功能不全严重贫血患者肾功能不全者脱水状态尚未补足液体,小结,适应症广泛、副反应极少。提高胶体渗透压功能更强，时间更持久。制品纯度高，副作用小，无需考虑血型相合问题。浓缩制品体积小，最高浓度可达25%，质量稳定。使用和储存方便，便于运输。,概要,人血白蛋白简介肝硬化概述人血白蛋白在肝硬化并发症治疗中应用,肝硬化概念,是一个病理解剖学概念多种原因引起的慢性、进行性、弥漫性肝病肝细胞弥漫性变性、坏死、凋亡残存肝细胞再生、结节结缔组织增生形成纤维隔正常小叶结构破坏代之硬化结节或假小叶,Normalliverhistology,Cirrhoticliverhistology,病因,病毒感染乙、丙肝最常见、丁型、日本血吸虫病。药物与毒物酒精、甲氨蝶呤、CCl4。代谢性肝豆状核变性、血色病。心血管疾病慢性右心衰竭、布-加综合征等等。其他可能原因自身免疫性肝炎、空回肠短路术后营养不良。,肝硬化病理生理与主要并发症,门静脉高压症侧支循环建立与扩大腹水形成肝肾综合征自发性细菌性腹膜炎肝性脑病肝肺综合征原发性肝癌严重感染,Slightdecreaseineffectivearterialbloodvolume,Increasedblood/plasmavolume,Portalhypertension,CIRRHOSIS,Circulatoryfunctioninearlycirrhosis,RAA,renin-angiotensin-aldosterone;ADH,antidiuretichormone,Renalretentionofsodiumandwater,Increasedcardiacoutput,Releaseofvasodilatorse.g.nitricoxide,PRIMARYPATHOPHYSIOLOGICALEVENT,Decreasedsystemicvascularresistance;poolingofintravascularvolumeatsplanchniclevel,TransientactivationoflowandhighpressurebaroreceptorsandRAAS,releaseofADHandanti-natriureticfactors,Moderatesplanchnicarterialvasodilatation,MAINTENANCEOFEFFECTIVEBLOODVOLUME,RAA,renin-angiotensin-aldosterone;ADH,antidiuretichormone,Markeddecreaseineffectivearterialbloodvolume血容量明显下降,Increasedblood/plasmavolume血容量增加,Portalhypertension门脉高压,CIRRHOSIS,Circulatoryfunctioninadvancedcirrhosis,Avidrenalretentionofsodiumandwater钠水潴留,Increasedcardiacoutput,Releaseofvasodilatorse.g.nitricoxide,PRIMARYPATHOPHYSIOLOGICALEVENT,Decreasedsystemicvascularresistance;poolingofintravascularvolumeatsplanchniclevel,Pronouncedsplanchnicarterialvasodilatation,ChronicactivationofbaroreceptorsandRAAsystem,releaseofADHandanti-natriureticfactors,INADEQUATEMAINTENANCEOFEFFECTIVEBLOODVOLUME有效循环血容量不能充分维护,Prognosticscoringofcirrhosis肝硬化预后评分,PT,prothrombintime;MELD,ModelforEnd-stageLiverDisease;INR,internationalnormalisedratio1Pughetal.BrJSurg1973;60:646649;2Kamathetal.Hepatology2001;33:464470,概要,人血白蛋白简介肝硬化概述人血白蛋白在肝硬化并发症治疗中应用,白蛋白在肝硬化并发症的治疗,难治性腹水大容量穿刺后循环功能障碍的防治自发性细菌性腹膜炎治疗中肾损伤的预防肝肾综合征治疗中血管收缩的辅助用药,Ascites,LVP,large-volumeparacentesisGins53:397417,腹水指过多的液体在腹腔内积聚是肝硬化最常见的并发症病史10年以上肝硬化患者腹水发生近50%传统治疗方案低钠饮食利尿剂应用LVP穿刺,JamesHeilman,MD/CC-BY-SA-3.0,RAA,renin-angiotensinaldosterone;ADH,antidiuretichormone,Decreaseineffectivearterialbloodvolume,Increasedblood/plasmavolume,Portalhypertension,CIRRHOSIS,Pathophysiologyofascites,Renalretentionofsodiumandwater,Increasedhydrostaticpressureinliversinusoids,Increasedhepaticlymphproductionandtransudationinperitoneum,PRIMARYPATHOPHYSIOLOGICALEVENT,Releaseofvasodilatorse.g.nitricoxide,Decreasedsystemicvascularresistance;poolingofintravascularvolumeatsplanchniclevel,Splanchnicarterialvasodilatation,ChronicactivationofbaroreceptorsandRAAsystem,releaseofADHandanti-natriureticfactors,ASCITES,Gradingofascites腹水分级,EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenalsyndromeincirrhosis.JHepatol2010;53:397417,轻、中度腹水治疗,轻度(grade1)不需治疗，根据欧洲肝病研究学会指南，尚无轻度腹水进展到中、重度腹水的相关资料。中度腹水(grade2):诱导负钠平衡，抵消肾钠潴留。限钠4-6g/d，10%-20%患者有效。利尿首选醛固酮拮抗剂初始100mg/d，无效，增加100mg/7d直至400mg/d。最大剂量仍无效，加用呋塞米40mg/d，最大160mg/d。联合治疗是复发性腹水最合适的治疗方案。,补充白蛋白对利尿剂效果的影响(RCT),Gentilinietal.JHepatol1999;30:639645,Results1:白蛋白增加了利尿剂的治疗效果！,p5L:albuminmustbeused;otherplasmaexpandersarelesseffectiveatpreventingPPCDLVP5Lasciticfluidareremovedalbumindose8g/Loffluidremoved,TheunderlyingcauseofascitesshouldbeaddressedLVPshouldbefollowedbydietaryrestrictionanddiuretictherapytoreversesodiumretentionandpreventfluidre-accumulation,Hometreatmentofasciteswithalbumin,TreatmentofasciteswithalbumincanbeprolongedADelphistudysoughtconsensusonseveralissuessurroundingtheuseofalbumin,includingitsuseathomefollowingdischargefromhospitalItwasagreedthatbenefitsofdomiciliaryalbumincouldincludereducedrateofascitesrelapseimprovedresponsetodiureticsenhancedqualityoflifedecreasedneedforhospitalisation,Gentilinietal.DigLiverDis2004;36:539346,小结,腹水的形成提示预后不良。LVP是3级腹水的一线治疗。LVP后同时应用血浆扩容剂对预防PPCD至关重要。,白蛋白在肝硬化并发症的治疗,难治性腹水大容量穿刺后循环功能障碍的防治自发性细菌性腹膜炎治疗中肾损伤的预防肝肾综合征治疗中血管收缩的辅助用药,自发性细菌性腹膜炎(SBP),SBP又称原发性或特发性腹膜炎，指在腹腔内或邻近组织内没有感染源（如腹腔脓肿、急性胰腺炎、胆囊炎、肠穿孔等）情况下发生的腹膜急性弥漫性细菌感染。肝硬化是发生SBP最常见的基础疾病。也可发生于急性肝衰竭及肾病综合征或晚期肿瘤伴大量腹水的患者。,自发性细菌性腹膜炎(SBP),SBP是肝硬化腹水常见而严重的并发症，发生率高达10%-25%，国际腹水俱乐部的统计资料是10%-30%。重型肝炎SBP发生率17.7%-47%，预后较肝硬化SBP更差。临床表现可为典型的腹膜炎，也可完全无症状。易漏诊，预后差，病死率高。,自发性细菌性腹膜炎(SBP),诊断主要依靠诊断性腹腔穿刺后腹水多形核细胞计数和腹水培养。腹水培养阳性率低，国外报道40%，国内更低腹水PMN计数最敏感的临界值(0.25x109/L)最特异的临界值0.5x109/L推荐对肝硬化腹水患者进行诊断性腹腔穿刺进行筛查。,SBP肾损害,1/3的SBP患者发生肾功能损害。肾功能的恶化与RAAS激活，肾脏血管收缩，有效灌注不足有关。因此扩容治疗可能获益。,1Folloetal.Hepatology1994;20:14951501;2Navasaetal.Hepatology1998;27:12271232;3Sortetal.NEnglJMed1999;341:403409,EffectsofalbumininfusiononrenalimpairmentinSBP,Sortetal.NEnglJMed1999;341:403409,Results:白蛋白联合抗生素（头孢噻肟）有效预防了SBP肾损害！降低了在院以及3个月死亡率！,Sortetal.NEnglJMed1999;341:403409,Patients(%),p=0.002,p=0.01,p=0.03,21/63,6/63,18/63,6/63,14/63,26/63,AlbumininfusioninSBP,SBP,spontaneousbacterialperitonitis;RCTs,randomisedcontrolledtrialsSalernoetal.ClinGastroenterolHepatol2013;11:123130,Results:AlbumininfusioninSBP,SBP,spontaneousbacterialperitonitis;RCT,randomisedcontrolledtrials;AASLD,AmericanAssociationfortheStudyofLiverDiseasesSalernoetal.ClinGastroenterolHepatol2013;11:123130,Thismeta-analysisprovidesthebasisforaLevelArecommendationthatpatientswithSBPshouldbetreatedwithalbumin,AlbumininfusiondecreasedtheincidenceofrenalimpairmentandmortalityinpatientswithSBP,EuropeanguidelinesrecommendallpatientswithSBPshouldreceivealbumininfusionuntilfurtherevidenceisavailable2,小结,肝硬化腹水住院患者中，SBP发生率10%。肾损害是SBP的常见并发症。白蛋白输注预防SBP患者肾衰竭的发生。推荐白蛋白作为SBP治疗中广谱抗生素的辅助用药。,白蛋白在肝硬化并发症的治疗,难治性腹水大容量穿刺后循环功能障碍的防治自发性细菌性腹膜炎治疗中肾损伤的预防肝肾综合征治疗中血管收缩的辅助用药,肝肾综合征,Hepatorenalsyndrome,是严重肝脏病变时发生的无肾脏器质性病变的一种功能性肾衰竭。是终末期肝病的严重并发症。腹水患者中，1year:18%;at5years:39%2病情顽固、预后凶险。平均中位生存期3月功能性肾衰持续可导致急性肾衰。,肝肾综合征的病理生理机制,门脉高压时内脏血管扩张导致有效循环血量减少、平均动脉压的下降。为了恢复有效循环血量和动脉压，血管收缩机制启动。RAAS激活以及其他血管收缩介质释放SNA激活结果肾血管收缩，肾灌注不足，肾功能损害。,RAA,renin-angiotensin-aldosteroneGinsetal.Lancet2003;362:18191827;EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenalsyndromeincirrhosis.JHepatol2010;53:397417,Markeddecreaseineffectivearterialbloodvolume,Increasedblood/plasmavolume,Portalhypertension,CIRRHOSIS,Circulatoryandrenalfunctioninadvancedcirrhosis,Avidrenalretentionofsodiumandwater,Increasedcardiacoutput,RAA,renin-aldosterone-angiotensin;ADH,antidiuretichormone,Releaseofvasodilatorse.g.nitricoxide,PRIMARYPATHOPHYSIOLOGICALEVENT,Decreasedsystemicvascularresistance;poolingofintravascularvolumeatsplanchniclevel,Pronouncedsplanchnicarterialvasodilatation,MAINTENANCEOFRENALPERFUSION,ActivationoflowandhighpressurebaroreceptorsandRAAsystem,releaseofADHandanti-natriureticfactors,Pathogenesisofhepatorenalsyndrome,Markeddecreaseineffectivearterialbloodvolume,Increasedblood/plasmavolume,Portalhypertension,CIRRHOSIS,RAA,reninaldosteroneangiotensin;ADH,antidiuretichormone,Renalretentionofsodiumandwater,Insufficientincreaseincardiacoutput,Releaseofvasodilatorse.g.nitricoxide,PRIMARYPATHOPHYSIOLOGICALEVENT,Decreasedsystemicvascularresistance;poolingofintravascularvolumeatsplanchniclevel,Pronouncedsplanchnicarterialvasodilatation,ActivationoflowandhighpressurebaroreceptorsandRAAsystem,releaseofADHandanti-natriureticfactors,Cardiacdysfunction,Impairedactivityofrenalvasodilatorsystems,HEPATORENALSYNDROME,HRS,hepatorenalsyndromeGinsetal.Lancet2003;362:18191827;Lameireetal.Lancet2005;385:417430,Diagnosisofhepatorenalsyndrome,RENALFAILURE(Serumcreatinine1.5mg/dL),Nephrotoxicdrugs,Volumedepletion,Shock,Biochemicalparameters,Abnormalrenalultrasonography,Signsofinfection,Proteinuriaand/orhaematuria,Clinicalsigns,Renalultrasonography,HRS,PRERENALFAILURE,ACUTETUBULARNECROSIS,INFECTION-INDUCEDRENALFAILURE,NEPHROTOXICITY,PARENCHYMALNEPHROPATHY,Classificationofhepatorenalsyndrome:Type1,SBP,spontaneousbacterialperitonitisSalernoetal.Gut2007;56:13101318;EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenalsyndromeincirrhosis.JHepatol2010;53:397417,Rapidlyprogressiveacuterenalfailure急进性肾衰竭Definedbydoublingofinitialserumcreatinineto226mol/L(2.5mg/dL)within2weeksOftendevelopsfollowingaprecipitatingevent(e.g.SBP)butmayoccurspontaneouslyAssociatedwithacutedeteriorationofcirculatoryfunction(arterialhypotensionandactivationoftheendogenousvasoconstrictorsystems)rapidimpairmentinliverfunctionandencephalopathyVerypoorprognosismeansurvivalapproximately1monthifuntreated,Classificationofhepatorenalsyndrome:Type2,HRS,hepatorenalsyndrome;SBP,spontaneousbacterialperitonitisSalernoetal.Gut2007;56:13101318;EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenalsyndromeincirrhosis.JHepatol2010;53:397417,Slowlyprogressivemoderaterenalfailure缓慢进展中度Definedbyserumcreatinine1.5mg/dLor133mol/LOftendevelopsspontaneouslyUsuallyassociatedwithrefractoryascitesMayprogresstoType1HRSeitherspontaneouslyorprecipitatedbyanevent(e.g.SBP)Decreasedsurvivalcomparedwithasciticpatientswithoutrenalfailure(mediansurvivalapproximately6months),肝肾综合征对肝移植结局的影响,HRS,hepatorenalsyndromeGonwaetal.Transplantation1995;59:361365,HRS患者肝移植后结局更差!,肝肾综合征治疗史对移植后结局的影响,前瞻性研究比较有HRS治疗的患者与无HRS患者肝移植后结局,移植前经历HRS治疗的患者与无HRS患者，在肝移植后结局无明显差异！,Initialmanagementofhepatorenalsyndrome:achecklist,Admissiontohospital(generalward/intensivecareunit*)CentrallineplacementishelpfulbutnotmandatoryCompletebloodtestsAbdominalultrasoundtoexaminetheliverandkidneys24-hoururinecollectionurineNa+/K+urinevolumeurinesediment/proteinDiagnosticparacentesistoexcludeongoinginfectionalbumin,cellcount,fluidcultureinbloodculturebottlesPlasmaexpansionwithalbumintoruleoutprerenalfailureNutritionistconsultationtomanagemalnutritionEvaluationfororthotopiclivertransplantation,AdaptedfromCardenasetal.ClinLiverDis2006:10:371385,TreatmentofHRSwithalbuminandterlipressin,Martn-Llahetal.Gastroenterology2008;134:13521359,Results:albumininassociationwithterlipressinimprovesrenalfunctioninpatientswithHRS,Martn-Llahetal.Gastroenterology2008;134:13521359,白蛋白+特利加压素治疗HRS，肾功能改善显著高于单用白蛋白组！,p=0.017,10/23,2/23,TreatmentofHRSwithterlipressinandalbumin,GFR,glomerularfiltrationrate;MAP,meanarterialpressure;PRA,plasmareninactivityOrtegaetal.Hepatology2002;36:941948,*p0.05withrespecttobaseline,白蛋白是HRS治疗有效的独立预测因素！,TreatmentofHRSwithalbuminandterlipressin:survival,Ortegaetal.Hepatology2002;36:941948,HRS,hepatorenalsyndrome,白蛋白的应用是生存的独立预测因素！,Europeanguidelinesforthemanagementofhepatorenalsyndrome,EASLclinicalpracticeguidelinesonthemanagementofascites,spontaneousbacterialperitonitis,andhepatorenalsyndromeincirrhosis.JHepatol2010;53:397417,Monitorcarefully,screenforsepsis,ConsiderLVPwithalbuminifindicated,Suspenddiureticsduringdiagnosisandevaluation,Albuminwithterlipressinisfirst-linedrugtherapy,LivertransplantationistheoptimaltreatmentHRSshouldbetreatedbeforethepr