肝功能損害與sepsis管向東

1、重癥病人肝臟功能狀態(tài)的判斷,管向東,,肝臟功能?,肝臟的生理功能,,肝臟的生理功能,（一）代謝功能糖類：肝糖原貯存、分解、糖異生脂類：脂肪、膽固醇及磷脂蛋白質：血清總蛋白、白蛋白血漿凝血因子幾乎全部在肝臟合成,肝臟的生理功能,（二）分泌和排泄功能（三）生物轉化：解毒作用（四）免疫防御,肝功能狀態(tài)的判斷,Hepatic Failure,Definition: Loss of functional liver cell mass

2、 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, death,Andres T. Ble

3、i.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.,Hepatic Failure,Production of Endogenous Toxins & Drug metabolic FailureBile Acids, Bilirubin, Pro

4、stacyclins, 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 vascular tone,An

5、dres T. Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.,ICU內如何迅速判斷重癥病人肝臟功能?,（一）意識狀態(tài),清醒？譫妄？昏睡、昏迷？原因：肝性腦病腦水腫其他,腦水腫機制,滲透性異常 血氨、谷氨酰胺腦

6、血流減慢 血管舒張、腦代謝減慢,Andres T. Blei.Pathophysiology of Brain Edema in Fulminant Hepatic Failure, Revisited.Metabolic Brain Disease, 2001;16: Nos. 1/2.,,,肝性腦病發(fā)病機制,氨中毒學說GABA/苯二氮卓類受體復合物學說支鏈氨基酸和假神經遞質學說5-羥色胺學說鋅/錳學說

7、,W.J. Cash,P. Mcconville,et al.Current concepts in the assessment and treatment of Hepatic Encephalopathy.Q J Med 2010; 103:9–16.,其他原因,內環(huán)境異常------由肝功能異常導致:組織灌注不足：局部/系統(tǒng)血流動力學異常代謝紊亂：電解質/酸堿平衡紊亂,（二）凝血功能障礙,凝血因子產生減少血漿凝血因子幾

8、乎全部在肝臟合成,Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006, 10:222,凝血因子減少,Marcel Levi,Steven M Opal.Critical Care 2006, 10:222,血小板減少,Marcel Levi,Steven M Opal.Coagulation a

9、bnormalities in critically ill patients.Critical Care 2006, 10:222,（三）乳酸,主要在肝臟代謝（>90%）糖酵解產物,Nicolaos F. Madias.Lactic acidosis.Kidney International, Vol. 29 (1986), 752-774.,Daniel De Backer.Lactic acidosis.Intensi

10、ve Care Med (2003) 29:699–702,乳酸水平升高的原因,氧需求增加組織缺氧肝衰竭藥物毒物特殊疾病:糖尿病,Nicolaos F. Madias.Lactic acidosis.Kidney International, Vol. 29 (1986), 752-774.,乳酸&膿毒癥,乳酸清除率—早期提示組織缺氧程度并與死亡率相關（severe sepsis and septic shock）,H

11、. 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; 32:1637–1642,乳酸&急性肝臟衰竭,William Bernal, Nora Donaldson,et al

12、.Blood lactate as an early predictor of outcome in paracetamolinduced acute liver failure: a cohort study.Lancet 2002; 359: 558–63,乳酸&預后,William Bernal, Nora Donaldson,et al.Blood lactate as an early predictor of out

13、come in paracetamolinduced acute liver failure: a cohort study.Lancet 2002; 359: 558–63,乳酸&發(fā)病率、死亡率(肝葉切除術后),預測發(fā)病率和死亡率,Izuru Watanabe, Toshihiko Mayumi,et al. Hyperlactemia can predict the prognosis of liver resection.

14、 Shock. 2007 Jul;28(1):35-8,乳酸與ICU住院時間,Izuru Watanabe, Toshihiko Mayumi,et al. Hyperlactemia can predict the prognosis of liver resection. Shock. 2007 Jul;28(1):35-8,（四）酸堿平衡,酸中毒: 乳酸 堿中毒: 低白蛋白血癥（堿化血漿）,,Georg-Christian Fu

15、nk, Daniel Doberer1,er al.Equilibrium of acidifying and alkalinizing metabolic acid–base disorders in cirrhosis.Liver International 2005: 25: 505–512,（五）糖代謝,高血糖：胰島素耐受（與肝臟疾病嚴重程度相關）低血糖：肝臟利用糖原障礙，糖酵解受損,Aparajita Dey,Karthi

16、keyan Chandrasekaran .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

17、,26:214–221,肝功能狀態(tài)的判斷,糖代謝：嚴重高血糖與手術部位(Surgical site infection )感染密切相關高血糖增加術后移植物排斥風險,Chulsoo Park,Chehao Hsu,et al. Severe Intraoperative Hyperglycemia Is Independently Associated With Surgical Site Infection After Liver

18、Transplantation. Transplantation 2009;87: 1031–1036,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）

19、肝酶學,,Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.,（六）肝酶學,Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.,肝酶學,肝酶升高程度與肝細胞損傷程度成正相關（限于急性肝損傷）慢性肝損傷、肝癌和肝衰竭患者的轉氨酶不能真實反映其肝臟損害的程度。 （滯后性）,Edoardo G. Giannin

20、i, Roberto Testa, Vincenzo Savarino. CMAJ 2005;172(3):367-79,Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.,蛋白質,蛋白質代謝：血清總蛋白：90%在肝臟合成白蛋白：全部在肝臟合成急性肝損害、局灶性肝損害: 二者多正?！哺未鷥斈芰?、清蛋白半衰期長(17-21天）〕延遲性肝損害:二者均下降（反映

21、肝實質細胞儲備功能）,血氨,血氨,Alison S. Clay, Bryan E. Hainline. Hyperammonemia in the ICU. CHEST 2007; 132:1368–1378,（七）序貫臟器損傷,腎臟功能障礙呼吸功能障礙血流動力學異常感染,Anne M. Larson.Diagnosis and management of acute liver failure.Current Opinion i

22、n Gastroenterology 2010,26:214–221.,1、肝腎綜合征－發(fā)病機制,Andres Cardenas.Hepatorenal Syndrome:A Dreaded Complication of End-Stage Liver Disease.Am J Gastroenterol 2005;100:460-467,肝腎綜合征－實驗室檢查,Elaine M. Fisher,Diane K. Brown.Hepa

23、torenal Syndrome.AACN Advanced Critical Care 2010; 21: 2, 165–184,2、肝肺綜合征－發(fā)病機制,Roberto Rodríguez-Roisin,Michael J. Krowka.Hepatopulmonary Syndrome — A Liver-Induced Lung Vascular Disorder.N Engl J Med 2008;358:2378-

24、87.,Normal alveolar ventilation and pulmonary blood f low,肝肺綜合征－發(fā)病機制,毛細血管擴張通氣/血流失調肺內分流,Roberto Rodríguez-Roisin,Michael J. Krowka.Hepatopulmonary Syndrome — A Liver-Induced Lung Vascular Disorder.N Engl J Med 2008

25、;358:2378-87.,肝肺綜合征診斷參考,alveolar–arterial oxygen gradient liver disease and/or portal hypertensionintrapulmonary vascular dilatation,Ulf Hempricha, Peter J. Papadakosa,Burkhard LachmannCurrent Opinion in Anaesthesiolog

26、y 2010, 23:133–138,3、血流動力學改變－發(fā)病機制,血管舒張因子釋放,Søren Møller, Jens H Henriksen.Cardiopulmonary complications in chronic liver disease.World J Gastroenterol 2006 January 28; 12(4): 526-538,血流動力學改變－循環(huán)系統(tǒng)表現(xiàn),Søren

27、Møller, Jens H Henriksen.Cardiopulmonary complications in chronic liver disease.World J Gastroenterol 2006 January 28; 12(4): 526-538,4、感染,免疫功能受損 感染風險增加病原菌：細菌，真菌，合并感染感染部位：肺47%，血26%，尿23%,,Anne M. Larson.Cu

28、rrent Opinion in Gastroenterology 2010,26:214–221,Javier Vaquero, Julie Polson,et al.Infection and the Progression of Hepatic Encephalopathy in Acute Liver Failure.Gastroenterology 2003;125:755–764,4.其他判斷方法,代謝呼吸試驗影像學檢查,

29、代謝呼吸試驗,13C-phenylalanine breath tests-苯丙氨酸羥化酶活性13C-galactose breath tests-半乳糖激酶活性上述兩種可判斷肝硬化程度并與Child–Turcotte–Pugh評分密切相關13C-methionine breath test-肝臟線粒體氧化功能13C-caffeine breath test-HBV相關性纖維變性以及長期拉米夫定治療后肝功能的改善13C-met

30、hacetin breath test-急\慢性肝臟損害,Y. ILAN. Review article: the assessment of liver function using breath Tests. Aliment Pharmacol Ther 2007:26, 1293–1302,影像學檢查,B超、CT、MR核素：Hepatobiliary Scintigraphy－評估術后肝衰，尤肝實質剩余量不明時99MTc-G

31、SA Scintigraphy－術前肝臟儲備，術后肝臟再生其它：1H NMR spectroscopic study－移植術后肝功能評估,Wilmar de Graaf, Roelof J. Bennink,et al.J Nucl Med 2010; 51:742–752,Wilmar de Graaf, Krijn P. van Lienden,et al. J Gastrointest Surg 2010;14:369–378,

32、Pratima Tripathi, Lakshmi Bala,et al. J Gastrointestin Liver Dis September 2009;18;3, 329-336,,評分系統(tǒng),Child-Pugh-TurcotteMELDBioCliM score,（一）評分系統(tǒng)-CTP,,Juan F. Gallegos-Orozco, Hugo E. Vargas. Liver Transplantation:From

33、 Child to MELD. Med Clin N Am 93 (2009) 931–950,（二）評分系統(tǒng)-MELD,,評分系統(tǒng)-MELD,,Shahid M. Malik, Jawad Ahmad. Med Clin N Am 93 (2009) 917–929,Silvina E. Yantorno, Walter K. Kremers.et al. Liver Transpl 13:822-828, 2007.,（三）評分

34、系統(tǒng)- Biochemical and Clinical Model (BioCliM score),,評分系統(tǒng)-BioCliM score,The risk scores for individual patients were calculated using the following equation: [1.370 × loge (creatinine mmol/L) + 0.349 × loge (b

35、ilirubin mmol/L) + 2.310× (ascites: 0 if absent or medically controlled and 1 if uncontrolled) + 0.909 × (encephalopathy: 0 if absent or medically controlled and 1 if uncontrolled) + 1.195× (bleeding esoph

36、ageal varices: 0 if absent or present without relapses and 1 if present with relapses).,總結,重癥病人肝功能狀態(tài)的迅速判斷的重點:意識狀態(tài)凝血功能乳酸水平內環(huán)境其他臟器損傷綜合考慮，排除其它因素,,在同時使用萬古+二性霉素B條件下，CRRT第28天小便出現(xiàn)、腎功能逐漸恢復正常，第34天停呼吸機。三個月后痊愈出院。,1.報公安部特批一等功臣