肝功能損害與Sepsis-管向東

1、重癥病人肝臟功能狀態(tài)的判斷重癥病人肝臟功能狀態(tài)的判斷管向東管向東肝臟功能肝臟功能?肝臟的生理功能肝臟的生理功能肝臟的生理功能肝臟的生理功能（一）代謝功能（一）代謝功能糖類：肝糖原貯存、分解、糖異生糖類：肝糖原貯存、分解、糖異生脂類：脂肪、膽固醇及磷脂脂類：脂肪、膽固醇及磷脂蛋白質(zhì)：血清總蛋白、白蛋白蛋白質(zhì)：血清總蛋白、白蛋白血漿凝血因子幾乎全部在肝臟合成血漿凝血因子幾乎全部在肝臟合成肝臟的生理功能肝臟的生理功能（二）分泌和排泄功能（二）分泌和排泄功能（三）生物轉(zhuǎn)化：解毒作用（三）生物轉(zhuǎn)化：解毒作用（四）免疫防御（四）免疫防御肝功能狀態(tài)的判斷肝功能狀態(tài)的判斷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內(nèi)內(nèi)如何迅速判斷重癥病人肝臟功能如何迅速判斷重癥病人肝臟功能?（一）意識(shí)狀態(tài)（一）意識(shí)狀態(tài)清醒？譫妄？昏睡、昏迷？清醒？譫妄？昏睡、昏迷？原因：原因

5、：肝性腦病肝性腦病腦水腫腦水腫其他其他腦水腫機(jī)制腦水腫機(jī)制滲透性異常滲透性異常 血氨、谷氨酰胺血氨、谷氨酰胺腦血流減慢腦血流減慢 血管舒張、腦代謝減慢血管舒張、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(jī)制肝性腦病發(fā)病機(jī)制氨中毒學(xué)說氨中毒學(xué)說GABA/苯二氮卓類受體復(fù)合物學(xué)說苯二氮卓類受體復(fù)合物學(xué)說支鏈氨基酸和假神經(jīng)遞質(zhì)學(xué)說支鏈氨基酸和假神經(jīng)遞質(zhì)學(xué)說5-羥色胺

6、學(xué)說羥色胺學(xué)說鋅鋅/錳學(xué)說錳學(xué)說W.J. Cash,P. Mcconville,et al.Current concepts in the assessment and treatment of Hepatic Encephalopathy.Q J Med 2010; 103:916.其他原因其他原因內(nèi)環(huán)境異常內(nèi)環(huán)境異常-由肝功能異常導(dǎo)致由肝功能異常導(dǎo)致: 組織灌注不足：局部組織灌注不足：局部/系統(tǒng)血流動(dòng)力學(xué)異常系統(tǒng)血流動(dòng)力學(xué)異常 代謝紊亂：電解質(zhì)代謝紊亂：電解質(zhì)/酸堿平衡紊亂酸堿平衡紊亂（二）凝血功能障礙（二）凝血功能障礙凝血因子產(chǎn)生減少凝血因子產(chǎn)生減少 血漿凝血因子幾乎全血漿凝血因子幾乎全

7、部在肝臟合成部在肝臟合成Marcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006, 10:222凝凝血血因因子子減減少少M(fèi)arcel Levi,Steven M Opal.Critical Care 2006, 10:222TEST RESULTSCAUSEPT延長(zhǎng)，APTT正常VII因子缺乏輕度VitK缺乏少量VitK拮抗劑PT正常，APTT延長(zhǎng)VII、IX、XI因子缺乏使用非小分子肝素抑制劑抗體和/或抗磷脂抗體XII因子和前激肽釋放酶缺乏PT、APTT均

8、延長(zhǎng)X、V、II因子缺乏VitK嚴(yán)重缺乏VitK拮抗劑全部凝血因子缺乏血小板減少血小板減少M(fèi)arcel Levi,Steven M Opal.Coagulation abnormalities in critically ill patients.Critical Care 2006, 10:222（三）乳酸（三）乳酸主要在肝臟代謝主要在肝臟代謝（90%）糖酵解產(chǎn)物糖酵解產(chǎn)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組織缺氧組織缺氧肝衰竭肝衰竭藥物毒物藥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&膿毒癥膿毒癥乳酸清除率乳酸清除率早期提示組織缺氧程度并與早期提示組織缺氧程度并與死亡率相關(guān)（死亡率相關(guān)（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&急性肝臟衰竭急性肝臟衰竭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&預(yù)后預(yù)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&發(fā)病率、死亡率發(fā)病率、死亡率(肝葉切除術(shù)后肝葉切除術(shù)后)預(yù)測(cè)發(fā)病率預(yù)測(cè)發(fā)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 乳酸與乳酸與ICU住院時(shí)間住院時(shí)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（四）酸堿平衡酸中毒酸中毒: 乳酸乳酸 堿中毒堿中毒: 低白蛋白血癥（堿化血漿）低白蛋白血癥（堿化血漿）Georg-

13、Christian Funk, Daniel Doberer1,er al.Equilibrium of acidifying and alkalinizing metabolic acidbase disorders in cirrhosis.Liver International 2005: 25: 505512（五）糖代謝（五）糖代謝高血糖：胰島素耐受（與肝臟疾病嚴(yán)重程高血糖：胰島素耐受（與肝臟疾病嚴(yán)重程度相關(guān)）度相關(guān)）低血糖：肝臟利用糖原障礙，糖酵解受損低血糖：肝臟利用糖原障礙，糖酵解受損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肝功能狀態(tài)的判斷肝功能狀態(tài)的判斷糖代謝：糖代謝：嚴(yán)重高血糖與手術(shù)部位嚴(yán)重高血糖與手術(shù)部位( (Surgical site infection ) )感染密切相關(guān)感染密切相關(guān)高血糖增加術(shù)后移植物排斥風(fēng)

15、險(xiǎn)高血糖增加術(shù)后移植物排斥風(fēng)險(xiǎn)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）肝酶學(xué)（六）肝酶學(xué) Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.分類分類標(biāo)志物標(biāo)志物部位部位肝細(xì)胞完整性AST肝、心、骨骼肌、腎、腦、紅細(xì)胞ALT肝膽汁淤滯堿性磷酸酶骨骼、小腸、肝、胎盤谷氨酰轉(zhuǎn)移酶與堿性磷酸酶水平相關(guān)（六）肝酶學(xué)（六）肝酶學(xué) Dufour DR, Lott JA, et al. Clin Chem 2000;46(12):2027-49.肝酶學(xué)肝酶學(xué)肝酶升高程度與肝細(xì)胞損傷

17、程度成正相關(guān)肝酶升高程度與肝細(xì)胞損傷程度成正相關(guān)（限于急性肝損傷）（限于急性肝損傷）慢性肝損傷、肝癌和肝衰竭患者的轉(zhuǎn)氨酶慢性肝損傷、肝癌和肝衰竭患者的轉(zhuǎn)氨酶不能真實(shí)反映其肝臟損害的程度。不能真實(shí)反映其肝臟損害的程度。 （滯后（滯后性）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.蛋白質(zhì)蛋白質(zhì)蛋白質(zhì)代謝：蛋白質(zhì)代謝：血清總蛋白：血清總蛋白：90%在肝臟合成在肝臟合成白蛋

18、白：全部在肝臟合成白蛋白：全部在肝臟合成急性肝損害、局灶性肝損害急性肝損害、局灶性肝損害: 二者多正常二者多正常肝代償能力強(qiáng)、清蛋白半衰期長(zhǎng)肝代償能力強(qiáng)、清蛋白半衰期長(zhǎng)(17-21天）天）延遲性肝損害延遲性肝損害:二者均下降二者均下降（反映肝實(shí)質(zhì)細(xì)胞儲(chǔ)備功能）（反映肝實(shí)質(zhì)細(xì)胞儲(chǔ)備功能）血氨血氨血氨血氨Alison S. Clay, Bryan E. Hainline. Hyperammonemia in the ICU. CHEST 2007; 132:13681378（七）序貫臟器損傷（七）序貫臟器損傷腎臟功能障礙腎臟功能障礙呼吸功能障礙呼吸功能障礙血流動(dòng)力學(xué)異常血流動(dòng)力學(xué)異常感染感染Ann

19、e M. Larson.Diagnosis and management of acute liver failure.Current Opinion in Gastroenterology 2010,26:214221.1、肝腎綜合征發(fā)病機(jī)制、肝腎綜合征發(fā)病機(jī)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(shí)驗(yàn)室檢查肝腎綜合征實(shí)驗(yàn)室檢查Elaine M. Fisher,Diane K.

20、Brown.Hepatorenal Syndrome.AACN Advanced Critical Care 2010; 21: 2, 1651842、肝肺綜合征發(fā)病機(jī)制、肝肺綜合征發(fā)病機(jī)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肝肺綜合征發(fā)病機(jī)制肝肺綜合征發(fā)病

21、機(jī)制毛細(xì)血管擴(kuò)張毛細(xì)血管擴(kuò)張通氣通氣/血流失調(diào)血流失調(diào)肺內(nèi)分流肺內(nèi)分流Roberto Rodrguez-Roisin,Michael J. Krowka.Hepatopulmonary Syndrome A Liver-Induced Lung Vascular Disorder.N Engl J Med 2008;358:2378-87.肝肺綜合征診斷參考肝肺綜合征診斷參考 alveolararterial oxygen gradient liver disease and/or portal hypertensionintrapulmonary vascular dilatationUlf

22、 Hempricha, Peter J. Papadakosa,Burkhard LachmannCurrent Opinion in Anaesthesiology 2010, 23:1331383、血流動(dòng)力學(xué)改變發(fā)病機(jī)制、血流動(dòng)力學(xué)改變發(fā)病機(jī)制血管舒張因子釋放血管舒張因子釋放Sren Mller, Jens H Henriksen.Cardiopulmonary complications in chronic liver disease.World J Gastroenterol 2006 January 28; 12(4): 526-538 血流動(dòng)力學(xué)改變血流動(dòng)力學(xué)改變循環(huán)系統(tǒng)表現(xiàn)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、感染免疫功能受損免疫功能受損 感染風(fēng)險(xiǎn)增加感染風(fēng)險(xiǎn)增加病原菌：細(xì)菌，真菌，合并感染病原菌：細(xì)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.其他判斷方法其他判斷方法代謝呼吸試驗(yàn)代謝呼吸試驗(yàn)影像學(xué)檢查影像學(xué)檢查代謝呼吸試驗(yàn)代謝呼吸試驗(yàn)13C-phenylalanine breath tests-苯丙氨酸羥化酶活性苯丙氨酸羥化酶活性13C-galactose breath tests-半乳糖激酶活性半乳糖激酶活性 上述兩種可判斷肝硬化程度并與上述兩種可判斷肝硬化程

25、度并與ChildTurcottePugh評(píng)分密切相關(guān)評(píng)分密切相關(guān)13C-methionine breath test-肝臟線粒體氧化功能肝臟線粒體氧化功能13C-caffeine breath test-HBV相關(guān)性纖維變性以及長(zhǎng)期拉米夫定治相關(guān)性纖維變性以及長(zhǎng)期拉米夫定治療后肝功能的改善療后肝功能的改善13C-methacetin breath test-急急慢性肝臟損害慢性肝臟損害Y. ILAN. Review article: the assessment of liver function using breath Tests. Aliment Pharmacol Ther 2007:

26、26, 12931302影像學(xué)檢查B超、超、CT、MR核素：核素：Hepatobiliary Scintigraphy評(píng)估術(shù)后肝衰，尤評(píng)估術(shù)后肝衰，尤肝實(shí)質(zhì)剩余量不明時(shí)肝實(shí)質(zhì)剩余量不明時(shí)99MTc-GSA Scintigraphy術(shù)前肝臟儲(chǔ)備，術(shù)后肝術(shù)前肝臟儲(chǔ)備，術(shù)后肝臟再生臟再生其它：其它：1H NMR spectroscopic study移植術(shù)移植術(shù)后肝功能評(píng)估后肝功能評(píng)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, 評(píng)分系統(tǒng)評(píng)分系統(tǒng)Child-Pugh-TurcotteMELDBioCliM score（一）評(píng)分系統(tǒng)（一）評(píng)分系統(tǒng)-CTPJuan F. Gallegos-Orozco, Hugo E. Vargas. Liver Transplantation:From Child to MELD. Med Clin N Am 93 (2009) 931950（二）評(píng)分系統(tǒng)（二）評(píng)分系統(tǒng)-MELD評(píng)分系統(tǒng)評(píng)分系統(tǒng)-MELDShahid M. Mali