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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
2、liver disease) 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 r
3、esults in poor vascular 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
4、in Fulminant Hepatic Failure, Revisited.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
5、：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 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 critical
6、ly ill patients.Critical Care 2006, 10:222,（三）乳酸,主要在肝脏代谢 （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
7、 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（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, N
8、ora 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&预后,William Bernal, Nora Donaldson,et al.Blood lactate as an early predictor of outcome in paracetamolinduced acute liver failure: a cohort study.Lan
9、cet 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 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
10、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.Equilibrium 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 Chandrasek
11、aran .Hyperglycemia 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,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,
12、Chehao Hsu,et al. Severe Intraoperative Hyperglycemia Is Independently Associated With Surgical Site Infection After Liver Transplantation. Transplantation 2009;87: 10311036,Wallia A,Parikh ND,Molitch ME.Posttransplant hyperglycemia is associated with increased risk of liver allograft rejection. Tra
13、nsplantation. 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,Dufour 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
14、 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: 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
15、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,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,Elaine M. Fisher,Diane K.
16、 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 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,毛细血管扩张 通气/血
17、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.,肝肺综合征诊断参考,alveolararterial oxygen gradient liver disease and/or portal hypertension intrapulmonary vascular dilatation,Ulf Hempricha, Peter J. Papadakosa,
18、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 chronic 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 complication
19、s 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 in Gastroenterology 2010,26:214221,Javier Vaquero, Julie Polson,et al.Infection and the Progression of Hepatic Encephalopathy in Acute
20、 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 brea
21、th 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 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.
22、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 September 2009;18;3, 329-336,评分系统,Child-Pugh-Turcotte MELD BioCliM score,（一）评分系统-CTP,Juan F. Gallegos-Orozco, Hugo
23、 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.et al. Liver Transpl 13:822-828, 2007.,（三）评分系统- Biochemical and Clinical Model (BioCliM scor
24、e),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 controlled and 1 if uncontrolled) + 0.909 (encephalopathy: 0 if absent or medically co
25、ntrolled 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!,