肝功能损害与Sepsis管向东

1、重症病人肝脏功能状态的判断管向东第一页，共五十二页。肝脏功能?第二页，共五十二页。肝脏的生理功能第三页，共五十二页。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第四页，共五十二页。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）免疫防御第五页，共五十二页。肝功能状态的判断第六页，共五十二页。Hepatic FailureDefinition: Loss of functional liver cell mass below a critical level results in liv

2、er failure (acute or complicating a chronic liver disease)Results in: hepatic encephalopathy & Coma, Jaundice, cholestasis, ascites, bleeding, renal failure, deathAndres T. Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.第七页，共五十二

3、页。Hepatic FailureProduction of Endogenous Toxins & Drug metabolic FailureBile Acids, Bilirubin, Prostacyclins, NO, Toxic fatty acids, Thiols, Indol-phenol metabolitesThese toxins cause further necrosis/apoptosis and a vicious cycleDetrimental to renal, brain and bone marrow function; results in poor

4、 vascular toneAndres T. Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.第八页，共五十二页。ICU内如何迅速判断重症病人肝脏功能?第九页，共五十二页。（一）意识状态清醒？谵妄？昏睡、昏迷？原因：肝性脑病脑水肿其他第十页，共五十二页。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 Ede

5、ma in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.第十一页，共五十二页。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.第十二页，共五十二页。其他原因内环境异常-

6、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/酸碱平衡紊乱第十三页，共五十二页。（二）凝血功能障碍凝血因子产生减少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第十四页，共五十二页。凝血因子减少Marcel Levi,Steven M Opal.Critical Care 2006, 10:222TEST RESULTSCAUSEPT延长，APTT正常VII因子缺乏轻度Vit

7、K缺乏少量VitK拮抗剂PT正常，APTT延长VII、IX、XI因子缺乏使用非小分子肝素抑制剂抗体和/或抗磷脂抗体XII因子和前激肽释放酶缺乏PT、APTT均延长X、V、II因子缺乏VitK严重缺乏VitK拮抗剂全部凝血因子缺乏第十五页，共五十二页。血小板减少Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006, 10:222第十六页，共五十二页。（三）乳酸主要在肝脏代谢（90%）糖酵解产物Nicolaos F. Madias.Lactic acidos

8、is.Kidney International, Vol. 29 (1986), 752-774.Daniel De Backer.Lactic acidosis.Intensive Care Med (2003) 29:699702第十七页，共五十二页。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.第十八页，共五十二页。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（severe sepsis and

9、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第十九页，共五十二页。乳酸&急性肝脏衰竭William Bernal, Nora Donaldson,et al.Blood lactate as an early predictor of outcome in paracetamol

10、induced acute liver failure: a cohort study.Lancet 2002; 359: 55863第二十页，共五十二页。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第二十一页，共五十二页。乳酸&发病率、死亡率(肝叶切除术后)预测发病率和死亡率Izuru Watanab

11、e, Toshihiko Mayumi,et al. Hyperlactemia can predict the prognosis of liver resection. Shock. 2007 Jul;28(1):35-8 第二十二页，共五十二页。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 第二十三页，共五十二页。（四）酸碱平衡酸中毒: 乳酸 碱中毒: 低白蛋白血

12、症（碱化血浆）Georg-Christian Funk, Daniel Doberer1,er al.Equilibrium of acidifying and alkalinizing metabolic acidbase disorders in cirrhosis.Liver International 2005: 25: 505512第二十四页，共五十二页。（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 Change

13、s in Liver: In vivo and In vitro Studies.Current Diabetes Reviews, 2009, 5, 67-78 Diagnosis and management of acute liver failure.Current Opinion in Gastroenterology 2010,26:214221第二十五页，共五十二页。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 In

14、traoperative Hyperglycemia Is Independently Associated With Surgical Site Infection After Liver Transplantation. Transplantation 2009;87: 10311036Wallia A,Parikh ND,Molitch ME.Posttransplant hyperglycemia is associated with increased risk of liver allograft rejection.Transplantation. 2010 Jan 27;89(

15、2):222-6. 第二十六页，共五十二页。（六）肝酶学 Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.第二十七页，共五十二页。分类标志物部位肝细胞完整性AST肝、心、骨骼肌、肾、脑、红细胞ALT肝胆汁淤滞碱性磷酸酶骨骼、小肠、肝、胎盘谷氨酰转移酶与碱性磷酸酶水平相关（六）肝酶学 Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.第二十八页，共五十二页。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

16、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.第二十九页，共五十二页。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: 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）第三十页，共五十二页。血氨血氨Alison S. Clay, Bryan E.

17、 Hainline. Hyperammonemia in the ICU. CHEST 2007; 132:13681378第三十一页，共五十二页。（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.第三十二页，共五十二页。1、肝肾综合征发病机制Andres Cardenas.Hepatorenal Syndrome:A Dreaded Complication

18、 of End-Stage Liver Disease.Am J Gastroenterol 2005;100:460-467第三十三页，共五十二页。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第三十四页，共五十二页。2、肝肺综合征发病机制Roberto Rodrguez-Roisin,Michael J. Krowka.Hepatopulmonary Syndrome A Liver-Induced Lung Vasc

19、ular Disorder.N Engl J Med 2008;358:2378-87.Normal alveolar ventilation and pulmonary blood f low第三十五页，共五十二页。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.第三十六页，共五十二页。肝肺综合征诊断参考 alveola

20、rarterial oxygen gradient liver disease and/or portal hypertensionintrapulmonary vascular dilatationUlf Hempricha, Peter J. Papadakosa,Burkhard LachmannCurrent Opinion in Anaesthesiology 2010, 23:133138第三十七页，共五十二页。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 chr

21、onic liver disease.World J Gastroenterol 2006 January 28; 12(4): 526-538 第三十八页，共五十二页。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 第三十九页，共五十二页。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%An

22、ne M. Larson.Current Opinion in Gastroenterology 2010,26:214221Javier Vaquero, Julie Polson,et al.Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure.Gastroenterology 2003;125:755764第四十页，共五十二页。4.其他判断方法代谢呼吸试验影像学检查第四十一页，共五十二页。代谢呼吸试验13C-phenylalanine breath tests-苯丙氨酸羟化酶活性13C

23、-galactose breath tests-半乳糖激酶活性上述两种可判断肝硬化程度并与ChildTurcottePugh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,

24、12931302第四十二页，共五十二页。影像学检查B超、CT、MR核素：Hepatobiliary Scintigraphy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; 51:742752Wilmar de Graaf, Krijn P. van Lienden,et al. J Gastrointest Surg 2010;14:369378Pr

25、atima Tripathi, Lakshmi Bala,et al. J Gastrointestin Liver Dis September 2009;18;3, 329-336, 第四十三页，共五十二页。评分系统Child-Pugh-TurcotteMELDBioCliM score第四十四页，共五十二页。（一）评分系统-CTPJuan F. Gallegos-Orozco, Hugo E. Vargas. Liver Transplantation:From Child to MELD. Med Clin N Am 93 (2009) 931950第四十五页，共五十二页。（二）评分系统-MELD第四十六页，共五十二页。评分系统-MELDShahid M. Ma