肝功能损害与Sepsis-管向东

1、重症病人肝脏功能状态的判断重症病人肝脏功能状态的判断管向东管向东肝脏功能肝脏功能?肝脏的生理功能肝脏的生理功能肝脏的生理功能肝脏的生理功能（一）代谢功能（一）代谢功能糖类：肝糖原贮存、分解、糖异生糖类：肝糖原贮存、分解、糖异生脂类：脂肪、胆固醇及磷脂脂类：脂肪、胆固醇及磷脂蛋白质：血清总蛋白、白蛋白蛋白质：血清总蛋白、白蛋白血浆凝血因子几乎全部在肝脏合成血浆凝血因子几乎全部在肝脏合成肝脏的生理功能肝脏的生理功能（二）分泌和排泄功能（二）分泌和排泄功能（三）生物转化：解毒作用（三）生物转化：解毒作用（四）免疫防御（四）免疫防御肝功能状态的判断肝功能状态的判断Hepatic FailureDefi

2、nition: Loss of functional liver cell mass below a critical level results in liver 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 Fulm

3、inant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.Hepatic FailureProduction of Endogenous Toxins & Drug metabolic Failure Bile Acids, Bilirubin, Prostacyclins, NO, Toxic fatty acids, Thiols, Indol-phenol metabolites These toxins cause further necrosis/apoptosis and a vi

4、cious cycleDetrimental to renal, brain and bone marrow function; results in poor vascular toneAndres T. Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.ICU内内如何迅速判断重症病人肝脏功能如何迅速判断重症病人肝脏功能?（一）意识状态（一）意识状态清醒？谵妄？昏睡、昏迷？清醒？谵妄？昏睡、昏迷？原因：原因

5、：肝性脑病肝性脑病脑水肿脑水肿其他其他脑水肿机制脑水肿机制渗透性异常渗透性异常 血氨、谷氨酰胺血氨、谷氨酰胺脑血流减慢脑血流减慢 血管舒张、脑代谢减慢血管舒张、脑代谢减慢Andres T. Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.肝性脑病发病机制肝性脑病发病机制氨中毒学说氨中毒学说GABA/苯二氮卓类受体复合物学说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支链氨基酸和假神经递质学说5-羟色胺

6、学说羟色胺学说锌锌/锰学说锰学说W.J. Cash,P. Mcconville,et al.Current concepts in the assessment and treatment of Hepatic Encephalopathy.Q J Med 2010; 103:916.其他原因其他原因内环境异常内环境异常-由肝功能异常导致由肝功能异常导致: 组织灌注不足：局部组织灌注不足：局部/系统血流动力学异常系统血流动力学异常 代谢紊乱：电解质代谢紊乱：电解质/酸碱平衡紊乱酸碱平衡紊乱（二）凝血功能障碍（二）凝血功能障碍凝血因子产生减少凝血因子产生减少 血浆凝血因子几乎全血浆凝血因子几乎全

7、部在肝脏合成部在肝脏合成Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006, 10:222凝凝血血因因子子减减少少Marcel Levi,Steven M Opal.Critical Care 2006, 10:222TEST RESULTSCAUSEPT延长，APTT正常VII因子缺乏轻度VitK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

8、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血小板减少血小板减少Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006, 10:222（三）乳酸（三）乳酸主要在肝脏代谢主要在肝脏代谢（90%）糖酵解产物糖酵解产物Nicolaos F. Madias.Lactic acidosis.Kidney International, Vol. 29 (1986), 752-774.Daniel De Backer.Lactic acidos

9、is.Intensive Care Med (2003) 29:699702乳酸水平升高的原因乳酸水平升高的原因氧需求增加氧需求增加组织缺氧组织缺氧肝衰竭肝衰竭药物毒物药物毒物特殊疾病特殊疾病:糖尿病糖尿病Nicolaos F. Madias.Lactic acidosis.Kidney International, Vol. 29 (1986), 752-774.乳酸乳酸&脓毒症脓毒症乳酸清除率乳酸清除率早期提示组织缺氧程度并与早期提示组织缺氧程度并与死亡率相关（死亡率相关（severe sepsis and septic shock）H. Bryant Nguyen, Emanue

10、l P. Rivers,et al. Early lactate clearance is associated with improved outcome in severe sepsis and septic shock. Crit Care Med 2004; 32:16371642乳酸乳酸&急性肝脏衰竭急性肝脏衰竭William Bernal, Nora Donaldson,et al.Blood lactate as an early predictor of outcome in paracetamolinduced acute liver failure: a cohor

11、t study.Lancet 2002; 359: 55863乳酸乳酸&预后预后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乳酸乳酸&发病率、死亡率发病率、死亡率(肝叶切除术后肝叶切除术后)预测发病率预测发病率和死亡率和死亡率Izuru Watanabe, Toshihiko Mayumi,et

12、al. Hyperlactemia can predict the prognosis of liver resection. Shock. 2007 Jul;28(1):35-8 乳酸与乳酸与ICU住院时间住院时间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（四）酸碱平衡酸中毒酸中毒: 乳酸乳酸 碱中毒碱中毒: 低白蛋白血症（碱化血浆）低白蛋白血症（碱化血浆）Georg-

13、Christian Funk, Daniel Doberer1,er al.Equilibrium of acidifying and alkalinizing metabolic acidbase disorders in cirrhosis.Liver International 2005: 25: 505512（五）糖代谢（五）糖代谢高血糖：胰岛素耐受（与肝脏疾病严重程高血糖：胰岛素耐受（与肝脏疾病严重程度相关）度相关）低血糖：肝脏利用糖原障碍，糖酵解受损低血糖：肝脏利用糖原障碍，糖酵解受损Aparajita Dey,Karthikeyan Chandrasekaran .Hypergl

14、ycemia Induced Changes 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肝功能状态的判断肝功能状态的判断糖代谢：糖代谢：严重高血糖与手术部位严重高血糖与手术部位( (Surgical site infection ) )感染密切相关感染密切相关高血糖增加术后移植物排斥风

15、险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 Infection After Liver Transplantation. Transplantation 2009;87: 10311036Wallia A,Parikh ND,Molitch ME.Posttransplant hyperglycemia is associated with increased risk of liv

16、er allograft rejection.Transplantation. 2010 Jan 27;89(2):222-6. （六）肝酶学（六）肝酶学 Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.分类分类标志物标志物部位部位肝细胞完整性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（六）肝酶学 Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.肝酶学肝酶学肝酶升高程度与肝细胞损伤

17、程度成正相关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）（限于急性肝损伤）慢性肝损伤、肝癌和肝衰竭患者的转氨酶慢性肝损伤、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。不能真实反映其肝脏损害的程度。 （滞后（滞后性）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.蛋白质蛋白质蛋白质代谢：蛋白质代谢：血清总蛋白：血清总蛋白：90%在肝脏合成在肝脏合成白蛋

18、白：全部在肝脏合成白蛋白：全部在肝脏合成急性肝损害、局灶性肝损害急性肝损害、局灶性肝损害: 二者多正常二者多正常肝代偿能力强、清蛋白半衰期长肝代偿能力强、清蛋白半衰期长(17-21天）天）延迟性肝损害延迟性肝损害:二者均下降二者均下降（反映肝实质细胞储备功能）（反映肝实质细胞储备功能）血氨血氨血氨血氨Alison S. Clay, Bryan E. Hainline. Hyperammonemia in the ICU. CHEST 2007; 132:13681378（七）序贯脏器损伤（七）序贯脏器损伤肾脏功能障碍肾脏功能障碍呼吸功能障碍呼吸功能障碍血流动力学异常血流动力学异常感染感染Ann

19、e 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、肝肾综合征发病机制Andres 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肝肾综合征实验室检查Elaine M. Fisher,Diane K.

20、Brown.Hepatorenal Syndrome.AACN Advanced Critical Care 2010; 21: 2, 1651842、肝肺综合征发病机制、肝肺综合征发病机制Roberto Rodrguez-Roisin,Michael J. Krowka.Hepatopulmonary Syndrome 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肝肺综合征发病

21、机制毛细血管扩张毛细血管扩张通气通气/血流失调血流失调肺内分流肺内分流Roberto Rodrguez-Roisin,Michael J. Krowka.Hepatopulmonary Syndrome A Liver-Induced Lung Vascular Disorder.N Engl J Med 2008;358:2378-87.肝肺综合征诊断参考肝肺综合征诊断参考 alveolararterial oxygen gradient liver disease and/or portal hypertensionintrapulmonary vascular dilatationUlf

22、 Hempricha, Peter J. Papadakosa,Burkhard LachmannCurrent Opinion in Anaesthesiology 2010, 23:1331383、血流动力学改变发病机制、血流动力学改变发病机制血管舒张因子释放血管舒张因子释放Sren Mller, Jens H Henriksen.Cardiopulmonary complications in chronic liver disease.World J Gastroenterol 2006 January 28; 12(4): 526-538 血流动力学改变血流动力学改变循环系统表现Sr

23、en Mller, Jens H Henriksen.Cardiopulmonary complications in chronic liver disease.World J Gastroenterol 2006 January 28; 12(4): 526-538 4、感染、感染免疫功能受损免疫功能受损 感染风险增加感染风险增加病原菌：细菌，真菌，合并感染病原菌：细菌，真菌，合并感染感染部位：肺感染部位：肺47%，血，血26%，尿，尿23%Anne M. Larson.Current Opinion in Gastroenterology 2010,26:214221Javier Vaq

24、uero, Julie Polson,et al.Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure.Gastroenterology 2003;125:7557644.其他判断方法其他判断方法代谢呼吸试验代谢呼吸试验影像学检查影像学检查代谢呼吸试验代谢呼吸试验13C-phenylalanine breath tests-苯丙氨酸羟化酶活性苯丙氨酸羟化酶活性13C-galactose breath tests-半乳糖激酶活性半乳糖激酶活性 上述两种可判断肝硬化程度并与上述两种可判断肝硬化程

25、度并与ChildTurcottePugh评分密切相关评分密切相关13C-methionine breath test-肝脏线粒体氧化功能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相关性纤维变性以及长期拉米夫定治疗后肝功能的改善疗后肝功能的改善13C-methacetin breath test-急急慢性肝脏损害慢性肝脏损害Y. ILAN. Review article: the assessment of liver function using breath Tests. Aliment Pharmacol Ther 2007:

26、26, 12931302影像学检查B超、超、CT、MR核素：核素：Hepatobiliary Scintigraphy评估术后肝衰，尤评估术后肝衰，尤肝实质剩余量不明时肝实质剩余量不明时99MTc-GSA Scintigraphy术前肝脏储备，术后肝术前肝脏储备，术后肝脏再生脏再生其它：其它：1H NMR spectroscopic study移植术移植术后肝功能评估后肝功能评估Wilmar de Graaf, Roelof J. Bennink,et al.J Nucl Med 2010; 51:742752Wilmar de Graaf, Krijn P. van Lienden,et a

27、l. J Gastrointest Surg 2010;14:369378Pratima Tripathi, Lakshmi Bala,et al. J Gastrointestin Liver Dis September 2009;18;3, 329-336, 评分系统评分系统Child-Pugh-TurcotteMELDBioCliM score（一）评分系统（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（二）评分系统（二）评分系统-MELD评分系统评分系统-MELDShahid M. Mali