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1、重症病人肝脏功能状态的判断,管向东,肝脏功能?,肝脏的生理功能,肝脏的生理功能,（一）代谢功能糖类：肝糖原贮存、分解、糖异生脂类：脂肪、胆固醇及磷脂蛋白质：血清总蛋白、白蛋白血浆凝血因子几乎全部在肝脏合成,肝脏的生理功能,（二）分泌和排泄功能（三）生物转化：解毒作用（四）免疫防御,肝功能状态的判断,Hepatic Failure,Definition:Loss of functional liver cell mass below a critical level results in liver failure(acute or complicating a chronic liver di
2、sease)Results in:hepatic encephalopathy&Coma,Jaundice,cholestasis,ascites,bleeding,renal failure,death,Andres T.Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure,Revisited.Metabolic Brain Disease,2001;16:Nos.1/2.,Hepatic Failure,Production of Endogenous Toxins results in poor vascular
3、 tone,Andres T.Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure,Revisited.Metabolic Brain Disease,2001;16:Nos.1/2.,ICU内如何迅速判断重症病人肝脏功能?,（一）意识状态,清醒？谵妄？昏睡、昏迷？原因：肝性脑病脑水肿其他,脑水肿机制,渗透性异常 血氨、谷氨酰胺脑血流减慢 血管舒张、脑代谢减慢,Andres T.Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure,Revisi
4、ted.Metabolic Brain Disease,2001;16:Nos.1/2.,肝性脑病发病机制,氨中毒学说GABA/苯二氮卓类受体复合物学说支链氨基酸和假神经递质学说5-羟色胺学说锌/锰学说,W.J.Cash,P.Mcconville,et al.Current concepts in the assessment and treatment of Hepatic Encephalopathy.Q J Med 2010;103:916.,其他原因,内环境异常-由肝功能异常导致:组织灌注不足：局部/系统血流动力学异常代谢紊乱：电解质/酸碱平衡紊乱,（二）凝血功能障碍,凝血因子产生减少
5、血浆凝血因子几乎全部在肝脏合成,Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006,10:222,凝血因子减少,Marcel Levi,Steven M Opal.Critical Care 2006,10:222,血小板减少,Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006,10:222,（三）乳酸,主要在
6、肝脏代谢（90%）糖酵解产物,Nicolaos F.Madias.Lactic acidosis.Kidney International,Vol.29(1986),752-774.,Daniel De Backer.Lactic acidosis.Intensive Care Med(2003)29:699702,乳酸水平升高的原因,氧需求增加组织缺氧肝衰竭药物毒物特殊疾病:糖尿病,Nicolaos F.Madias.Lactic acidosis.Kidney International,Vol.29(1986),752-774.,乳酸&脓毒症,乳酸清除率早期提示组织缺氧程度并与死亡率相关
7、（severe sepsis and septic shock）,H.Bryant Nguyen,Emanuel P.Rivers,et al.Early lactate clearance is associated with improved outcome in severe sepsis and septic shock.Crit Care Med 2004;32:16371642,乳酸&急性肝脏衰竭,William Bernal,Nora Donaldson,et al.Blood lactate as an early predictor of outcome in paracet
8、amolinduced acute liver failure:a cohort study.Lancet 2002;359:55863,乳酸&预后,William Bernal,Nora Donaldson,et al.Blood lactate as an early predictor of outcome in paracetamolinduced acute liver failure:a cohort study.Lancet 2002;359:55863,乳酸&发病率、死亡率(肝叶切除术后),预测发病率和死亡率,Izuru Watanabe,Toshihiko Mayumi,et
9、 al.Hyperlactemia can predict the prognosis of liver resection.Shock.2007 Jul;28(1):35-8,乳酸与ICU住院时间,Izuru Watanabe,Toshihiko Mayumi,et al.Hyperlactemia can predict the prognosis of liver resection.Shock.2007 Jul;28(1):35-8,（四）酸碱平衡,酸中毒:乳酸 碱中毒:低白蛋白血症（碱化血浆）,Georg-Christian Funk,Daniel Doberer1,er al.Eq
10、uilibrium of acidifying and alkalinizing metabolic acidbase disorders in cirrhosis.Liver International 2005:25:505512,（五）糖代谢,高血糖：胰岛素耐受（与肝脏疾病严重程度相关）低血糖：肝脏利用糖原障碍，糖酵解受损,Aparajita Dey,Karthikeyan Chandrasekaran.Hyperglycemia Induced Changes in Liver:In vivo and In vitro Studies.Current Diabetes Reviews,
11、2009,5,67-78,Diagnosis and management of acute liver failure.Current Opinion in Gastroenterology 2010,26:214221,肝功能状态的判断,糖代谢：严重高血糖与手术部位(Surgical site infection)感染密切相关高血糖增加术后移植物排斥风险,Chulsoo Park,Chehao Hsu,et al.Severe Intraoperative Hyperglycemia Is Independently Associated With Surgical Site Infect
12、ion After Liver Transplantation.Transplantation 2009;87:10311036,Wallia A,Parikh ND,Molitch ME.Posttransplant hyperglycemia is associated with increased risk of liver allograft rejection.Transplantation.2010 Jan 27;89(2):222-6.,（六）肝酶学,Dufour DR,Lott JA,et al.Clin Chem 2000;46(12):2027-49.,（六）肝酶学,Duf
13、our DR,Lott JA,et al.Clin Chem 2000;46(12):2027-49.,肝酶学,肝酶升高程度与肝细胞损伤程度成正相关（限于急性肝损伤）慢性肝损伤、肝癌和肝衰竭患者的转氨酶不能真实反映其肝脏损害的程度。（滞后性）,Edoardo G.Giannini,Roberto Testa,Vincenzo Savarino.CMAJ 2005;172(3):367-79,Dufour DR,Lott JA,et al.Clin Chem 2000;46(12):2027-49.,蛋白质,蛋白质代谢：血清总蛋白：90%在肝脏合成白蛋白：全部在肝脏合成急性肝损害、局灶性肝损害:
14、二者多正常肝代偿能力强、清蛋白半衰期长(17-21天）延迟性肝损害:二者均下降（反映肝实质细胞储备功能）,血氨,血氨,Alison S.Clay,Bryan E.Hainline.Hyperammonemia in the ICU.CHEST 2007;132:13681378,（七）序贯脏器损伤,肾脏功能障碍呼吸功能障碍血流动力学异常感染,Anne M.Larson.Diagnosis and management of acute liver failure.Current Opinion in Gastroenterology 2010,26:214221.,1、肝肾综合征发病机制,An
15、dres Cardenas.Hepatorenal Syndrome:A Dreaded Complication of End-Stage Liver Disease.Am J Gastroenterol 2005;100:460-467,肝肾综合征实验室检查,Elaine M.Fisher,Diane K.Brown.Hepatorenal Syndrome.AACN Advanced Critical Care 2010;21:2,165184,2、肝肺综合征发病机制,Roberto Rodrguez-Roisin,Michael J.Krowka.Hepatopulmonary Syn
16、drome A Liver-Induced Lung Vascular Disorder.N Engl J Med 2008;358:2378-87.,Normal alveolar ventilation and pulmonary blood f low,肝肺综合征发病机制,毛细血管扩张通气/血流失调肺内分流,Roberto Rodrguez-Roisin,Michael J.Krowka.Hepatopulmonary Syndrome A Liver-Induced Lung Vascular Disorder.N Engl J Med 2008;358:2378-87.,肝肺综合征诊
17、断参考,alveolararterial oxygen gradient liver disease and/or portal hypertensionintrapulmonary vascular dilatation,Ulf Hempricha,Peter J.Papadakosa,Burkhard LachmannCurrent Opinion in Anaesthesiology 2010,23:133138,3、血流动力学改变发病机制,血管舒张因子释放,Sren Mller,Jens H Henriksen.Cardiopulmonary complications in chro
18、nic liver disease.World J Gastroenterol 2006 January 28;12(4):526-538,血流动力学改变循环系统表现,Sren Mller,Jens H Henriksen.Cardiopulmonary complications in chronic liver disease.World J Gastroenterol 2006 January 28;12(4):526-538,4、感染,免疫功能受损 感染风险增加病原菌：细菌，真菌，合并感染感染部位：肺47%，血26%，尿23%,Anne M.Larson.Current Opinion
19、 in Gastroenterology 2010,26:214221,Javier Vaquero,Julie Polson,et al.Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure.Gastroenterology 2003;125:755764,4.其他判断方法,代谢呼吸试验影像学检查,代谢呼吸试验,13C-phenylalanine breath tests-苯丙氨酸羟化酶活性13C-galactose breath tests-半乳糖激酶活性上述两种可判断肝硬化程度并与Ch
20、ildTurcottePugh评分密切相关13C-methionine breath test-肝脏线粒体氧化功能13C-caffeine breath test-HBV相关性纤维变性以及长期拉米夫定治疗后肝功能的改善13C-methacetin breath test-急慢性肝脏损害,Y.ILAN.Review article:the assessment of liver function using breath Tests.Aliment Pharmacol Ther 2007:26,12931302,影像学检查,B超、CT、MR核素：Hepatobiliary Scintigraph
21、y评估术后肝衰，尤肝实质剩余量不明时99MTc-GSA Scintigraphy术前肝脏储备，术后肝脏再生其它：1H NMR spectroscopic study移植术后肝功能评估,Wilmar de Graaf,Roelof J.Bennink,et al.J Nucl Med 2010;51:742752,Wilmar de Graaf,Krijn P.van Lienden,et al.J Gastrointest Surg 2010;14:369378,Pratima Tripathi,Lakshmi Bala,et al.J Gastrointestin Liver Dis Sep
22、tember 2009;18;3,329-336,评分系统,Child-Pugh-TurcotteMELDBioCliM score,（一）评分系统-CTP,Juan F.Gallegos-Orozco,Hugo E.Vargas.Liver Transplantation:From Child to MELD.Med Clin N Am 93(2009)931950,（二）评分系统-MELD,评分系统-MELD,Shahid M.Malik,Jawad Ahmad.Med Clin N Am 93(2009)917929,Silvina E.Yantorno,Walter K.Kremers
23、.et al.Liver Transpl 13:822-828,2007.,（三）评分系统-Biochemical and Clinical Model(BioCliM score),评分系统-BioCliM score,The risk scores for individual patients were calculated using the following equation:1.370 loge(creatinine mmol/L)+0.349 loge(bilirubin mmol/L)+2.310(ascites:0 if absent or medically contro
24、lled and 1 if uncontrolled)+0.909(encephalopathy:0 if absent or medically controlled and 1 if uncontrolled)+1.195(bleeding esophageal varices:0 if absent or present without relapses and 1 if present with relapses).,总结,重症病人肝功能状态的迅速判断的重点:意识状态凝血功能乳酸水平内环境其他脏器损伤综合考虑，排除其它因素,在同时使用万古+二性霉素B条件下，CRRT第28天小便出现、肾功能逐渐恢复正常，第34天停呼吸机。三个月后痊愈出院。,1.报公安部特批一等功臣。2.升职为科长。3.出院一年，生儿子一个！,谢谢!,
