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1、ARCHITECTURAL LIVER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCEHepatic cirrhosisHepatic CirrhosisHepatic Cirrhosis End stage of any chronic liver diseaseEnd stage of any chronic liver disease Characterized Characterized histologicallyhistologically by by regen
2、erative nodules surrounded by regenerative nodules surrounded by fibrous tissuefibrous tissue ClinicallyClinically there are two types of cirrhosis: there are two types of cirrhosis: CompensatedCompensated DecompensatedDecompensatedDEFINITION OF CIRRHOSISCirrhosisCirrhosisNormalNormalNodulesNodulesI
3、rregular surfaceIrregular surfaceGROSS IMAGE OF A NORMAL AND A CIRRHOTIC LIVERCirrhotic liverCirrhotic liverNodular, irregular surfaceNodular, irregular surfaceNodulesNodulesGROSS IMAGE OF A CIRRHOTIC LIVERCirrhosisCirrhosisNormalNormalNodules surrounded by Nodules surrounded by fibrous tissuefibrou
4、s tissueHISTOLOGICAL IMAGE OF A NORMAL AND A CIRRHOTIC LIVERHISTOLOGICAL IMAGE OF CIRRHOSISFibrosisFibrosisRegenerative Regenerative nodulenodulePATHOGENESIS OF LIVER FIBROSISHepatocytesHepatocytesSpace of DisseSpace of DisseSinusoidal Sinusoidal endothelial cellendothelial cellHepatic Hepatic stell
5、ate cellstellate cellFenestraeFenestraeNormal Hepatic SInusoidNormal Hepatic SInusoidRetinoid Retinoid dropletsdropletsPATHOGENESIS OF LIVER FIBROSISAlterations in Microvasculature in CirrhosisAlterations in Microvasculature in Cirrhosis Activation of stellate cellsActivation of stellate cells Colla
6、gen deposition in space of DisseCollagen deposition in space of Disse Constriction of sinusoidsConstriction of sinusoids Defenestration of sinusoidsDefenestration of sinusoidsCompensatedCompensatedcirrhosiscirrhosisDecompensatedDecompensatedcirrhosiscirrhosisDeathDeathChronic Chronic liver liver dis
7、easediseaseNatural History of Chronic Liver DiseaseDevelopment of Development of complications:complications: Variceal hemorrhageVariceal hemorrhage Ascites Ascites Encephalopathy Encephalopathy Jaundice JaundiceNATURAL HISTORY OF CHRONIC LIVER DISEASE606040408080100100120120140140160160004040606080
8、802020202000100100MonthsMonthsProbability of Probability of survivalsurvivalAll patients All patients with cirrhosiswith cirrhosisDecompensated Decompensated cirrhosiscirrhosis180180Decompensation Shortens SurvivalDecompensation Shortens SurvivalGines et. al., Hepatology 1987;7:122Gines et. al., Hep
9、atology 1987;7:122Median survivalMedian survival 9 years 9 yearsMedian survivalMedian survival 1.6 years 1.6 yearsSURVIVAL TIMES IN CIRRHOSIS10Liver Liver insufficiencyinsufficiencyVariceal hemorrhageVariceal hemorrhageComplications of Cirrhosis Result from Portal Complications of Cirrhosis Result f
10、rom Portal Hypertension or Liver InsufficiencyHypertension or Liver InsufficiencyCirrhosisCirrhosisAscitesAscitesEncephalopathyEncephalopathyJaundiceJaundicePortal Portal hypertensionhypertensionSpontaneous Spontaneous bacterial bacterial peritonitisperitonitisHepatorenal Hepatorenal syndromesyndrom
11、eCOMPLICATIONS OF CIRRHOSISCirrhosis - DiagnosisCirrhosis - Diagnosis Cirrhosis is a histological diagnosisCirrhosis is a histological diagnosis However, in patients with chronic However, in patients with chronic liver disease the presence of various liver disease the presence of various clinical fe
12、atures suggests cirrhosisclinical features suggests cirrhosis The presence of these clinical The presence of these clinical features can be followed by non-features can be followed by non-invasive testing, prior to liver biopsyinvasive testing, prior to liver biopsyDIAGNOSIS OF CIRRHOSISIn Whom Shou
13、ld We Suspect Cirrhosis?In Whom Should We Suspect Cirrhosis? Any patient with chronic liver diseaseAny patient with chronic liver disease Chronic abnormal aminotransferases and/or Chronic abnormal aminotransferases and/or alkaline phosphatasealkaline phosphatase Physical exam findingsPhysical exam f
14、indings Stigmata of chronic liver disease (muscle wasting, Stigmata of chronic liver disease (muscle wasting, vascular spiders, palmar erythema)vascular spiders, palmar erythema) Palpable left lobe of the liverPalpable left lobe of the liver Small liver spanSmall liver span SplenomegalySplenomegaly
15、Signs of decompensation (jaundice, ascites, Signs of decompensation (jaundice, ascites, asterixis)asterixis)DIAGNOSIS OF CIRRHOSIS CLINICAL FINDINGSLaboratoryLaboratory Liver insufficiencyLiver insufficiency Low albumin ( 3.8 g/dL)Low albumin ( 1.3)Prolonged prothrombin time (INR 1.3) High bilirubin
16、 ( 1.5 mg/dL)High bilirubin ( 1.5 mg/dL) Portal hypertensionPortal hypertension Low platelet count ( 175 x1000/Low platelet count ( 1AST / ALT ratio 1In Whom Should We Suspect Cirrhosis?In Whom Should We Suspect Cirrhosis?DIAGNOSIS OF CIRRHOSIS LABORATORY STUDIESCT Scan in CirrhosisCT Scan in Cirrho
17、sisLiver with an irregular surfaceLiver with an irregular surfaceSplenomegalySplenomegalyCollateralsCollateralsDIAGNOSIS OF CIRRHOSIS CAT SCANNoNoYesYesDiagnostic AlgorithmDiagnostic AlgorithmPatient with chronic liver disease and any of the following:Patient with chronic liver disease and any of th
18、e following:Variceal hemorrhageVariceal hemorrhageAscitesAscitesHepatic encephalopathyHepatic encephalopathyLiver biopsy not Liver biopsy not necessary for the necessary for the diagnosis of cirrhosisdiagnosis of cirrhosisPhysical findings:Physical findings:Enlarged left hepatic lobeEnlarged left he
19、patic lobeSplenomegalySplenomegalyStigmata of chronic liver diseaseStigmata of chronic liver diseaseLaboratory findings:Laboratory findings:ThrombocytopeniaThrombocytopeniaImpaired hepatic synthetic functionImpaired hepatic synthetic functionRadiological findings:Radiological findings:Small nodular
20、liverSmall nodular liverIntra-abdominal collateralsIntra-abdominal collateralsAscitesAscitesSplenomegalySplenomegalyColloid shift to spleen and/or bone marrowColloid shift to spleen and/or bone marrowYesYesNoNoYesYesNoNoLiver biopsyLiver biopsyDIAGNOSTIC ALGORITHMMechanisms of Portal HypertensionMec
21、hanisms of Portal Hypertension Pressure (P) results from the interaction Pressure (P) results from the interaction of resistance (R) and flow (F):of resistance (R) and flow (F):P = R x FP = R x F Portal hypertension can result from: Portal hypertension can result from: increase in resistanceincrease
22、 in resistance to portal flow to portal flow and/or and/or increase in portal venous inflowincrease in portal venous inflowMECHANISMS OF PORTAL HYPERTENSIONNormal Liver Hepatic Hepatic veinveinSinusoidSinusoidPortal Portal veinveinLiverLiverSplenic Splenic veinveinCoronary Coronary veinveinTHE NORMA
23、L LIVER OFFERS ALMOST NO RESISTANCE TO FLOWPortal Portal systemic systemic collateralscollateralsDistorted Distorted sinusoidal sinusoidal architecturearchitectureleads to leads to increased increased resistanceresistancePortal Portal veinveinCirrhotic Liver SplenomegalySplenomegalyARCHITECTURAL LIV
24、ER DISRUPTION IS THE MAIN MECHANISM THAT LEADS TO AN INCREASED INTRAHEPATIC RESISTANCEAN INCREASE IN PORTAL VENOUS INFLOW SUSTAINS PORTAL HYPERTENSIONMesenteric Mesenteric veinsveins FlowFlowSplanchnicSplanchnicvasodilatationvasodilatationDistorted Distorted sinusoidal sinusoidal architechurearchite
25、churePortal Portal veinveinAn Increase in Portal Venous Inflow Sustains An Increase in Portal Venous Inflow Sustains Portal HypertensionPortal Hypertension20Small varicesSmall varicesLarge varicesLarge varicesNo varicesNo varices7-8%/year7-8%/year7-8%/year7-8%/yearVarices Increase in Diameter Varice
26、s Increase in Diameter ProgressivelyProgressivelyMerli et al. J Hepatol 2003;38:266Merli et al. J Hepatol 2003;38:266VARICES INCREASE IN DIAMETER PROGRESSIVELYA Threshold Portal Pressure of 12 mmHg is A Threshold Portal Pressure of 12 mmHg is Necessary for Varices to Form Necessary for Varices to Fo
27、rm P0.01P 50 mEq/dayUrine Na excretion 50 mEq/dayDiureticsDiuretics Should be spironolactone-basedShould be spironolactone-based A progressive schedule (spironolactone A progressive schedule (spironolactone furosemide) requires fewer dose adjustments than furosemide) requires fewer dose adjustments
28、than a combined a combined therapy (spironolactone + furosemide)therapy (spironolactone + furosemide)MANAGEMENT OF UNCOMPLICATED ASCITESSodium RestrictionSodium Restriction 2 g (or 5.2 g of dietary salt) a day2 g (or 5.2 g of dietary salt) a day Fluid restriction is not necessary unless there is Flu
29、id restriction is not necessary unless there is hyponatremia (125 mmol/L)hyponatremia (125 mmol/L) Goal: negative sodium balanceGoal: negative sodium balance Side effect: unpalatability may compromise Side effect: unpalatability may compromise nutritional statusnutritional statusManagement of Uncomp
30、licated AscitesMANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION40Diuretic Diuretic TherapyTherapyDosageDosage Spironolactone 100-400 mg/day Spironolactone 100-400 mg/day Furosemide (40-160 mg/d) for inadequate weight loss or Furosemide (40-160 mg/d) for inadequate weight loss or if hyperkalem
31、ia developsif hyperkalemia develops Increase diuretics if weight loss Increase diuretics if weight loss 1 kg in the first week and 1 kg in the first week and 2 kg/week thereafter0.5 kg/day in patients Decrease diuretics if weight loss 0.5 kg/day in patients without edema and 1 kg/day in those with e
32、demawithout edema and 1 kg/day in those with edema Side effectsSide effects Renal dysfunction, hyponatremia, hyperkalemia, Renal dysfunction, hyponatremia, hyperkalemia, encephalopathy, gynecomastiaencephalopathy, gynecomastiaManagement of Uncomplicated AscitesMANAGEMENT OF UNCOMPLICATED ASCITES: DI
33、URETIC THERAPYDefinition and Types of Refractory AscitesDefinition and Types of Refractory AscitesOccurs in 10% of cirrhotic patientsOccurs in 10% of cirrhotic patients Diuretic-intractable ascitesDiuretic-intractable ascitesTherapeutic doses of diuretics cannot be achieved Therapeutic doses of diur
34、etics cannot be achieved because of diuretic-induced complicationsbecause of diuretic-induced complications Diuretic-resistant ascitesDiuretic-resistant ascitesNo response to maximal diuretic therapy (400 mg No response to maximal diuretic therapy (400 mg spironolactone + 160 mg furosemide/day)spiro
35、nolactone + 160 mg furosemide/day)20%20%80%80%Arroyo et al. Hepatology 1996; 23:164Arroyo et al. Hepatology 1996; 23:164DEFINITION AND TYPES OF REFRACTORY ASCITESPeritoneo-Venous Shunt (PVS) is Useful in the Treatment of Refractory AscitesUse of jugular Use of jugular vein will hinder vein will hind
36、er TIPS placement TIPS placement Intraabdominal Intraabdominal adhesions may adhesions may complicate liver complicate liver transplant surgerytransplant surgeryOne-way One-way valvevalvePERITONEO-VENOUS SHUNT (PVS) IS USEFUL IN THE TREATMENT OF REFRACTORY ASCITESTreatment of AscitesTreatment of Asc
37、itesHepatorenalHepatorenalSyndromeSyndromeRefractoryRefractoryAscitesAscitesUncomplicatedUncomplicatedAscitesAscitesPortal HypertensionPortal HypertensionNo AscitesNo Ascites1) LVP + albumin1) LVP + albumin2) TIPS2) TIPS3) PVS (in non-TIPS, non-transplant 3) PVS (in non-TIPS, non-transplant candidat
38、es)candidates)LVP = large volume paracentesisLVP = large volume paracentesisTIPS = transjugular intrahepatic portosystemic shuntTIPS = transjugular intrahepatic portosystemic shuntTREATMENT OF REFRACTORY ASCITES44Spontaneous Bacterial Peritonitis (SBP) Spontaneous Bacterial Peritonitis (SBP) Complic
39、ates Ascites and Can Lead to Renal Complicates Ascites and Can Lead to Renal Dysfunction Dysfunction SBPSBPHVPG 10 mmHgHVPG 10 mmHgExtreme VasodilationExtreme VasodilationHVPG 10 mmHgHVPG 10 mmHgSevere VasodilationSevere VasodilationHVPG 10 mmHgHVPG 10 mmHgModerate VasodilationModerate VasodilationH
40、VPG 10 mmHgHVPG 250/mmPMN count 250/mm33Rimola et al., J Hepatol 2000; 32:142Rimola et al., J Hepatol 2000; 32:142EARLY DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)TREATMENTINDICATEDDiagnosis and Management of Spontaneous Bacterial PeritonitisDiagnostic ParacentesisDiagnostic ParacentesisPMN
41、250?PMN250?Culture Positive?Culture Positive?TREATMENT NOT INDICATEDNORepeat ParacentesisRepeat ParacentesisYESPMN250?PMN250?Culture Positive?Culture Positive?NONOYESYESYESNOMANAGEMENT ALGORITHM IN SPONTANEOUS BACTERIAL PERITONITIS (SBP)Treatment of Treatment of Spontaneous Bacterial Spontaneous Bac
42、terial PeritonitisPeritonitis Recommended antibiotics for initial empiric Recommended antibiotics for initial empiric therapytherapy i.vi.v. cefotaxime, amoxicillin-clavulanic acid. cefotaxime, amoxicillin-clavulanic acid oral nofloxacin (uncomplicated SBP)oral nofloxacin (uncomplicated SBP) avoid a
43、minoglycosidesavoid aminoglycosides Minimum duration: 5 daysMinimum duration: 5 days Re-evaluation if ascitic fluid PMN count has not Re-evaluation if ascitic fluid PMN count has not decreased by at least 25% after 2 days of decreased by at least 25% after 2 days of treatmenttreatmentRimola et al.,
44、J Hepatol 2000; 32:142Rimola et al., J Hepatol 2000; 32:142TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)All SBPsAll SBPsSBP caused by gram-SBP caused by gram-negative bacterianegative bacteriaProbability Probability of SBP of SBP recurrencerecurrenceMonthsMonthsp=0.0063p=0.0063PlaceboPlaceboN
45、orfloxacinNorfloxacinPlaceboPlacebop=0.0013p=0.0013NorfloxacinNorfloxacin001.01.0.8.8.4.4.2.2.6.6448812122020001616004488121220201616MonthsMonthsNorfloxacin Reduces Recurrence of Norfloxacin Reduces Recurrence of Spontaneous Bacterial PeritonitisSpontaneous Bacterial PeritonitisGines et al., Hepatol
46、ogy 1990; 12:716Gines et al., Hepatology 1990; 12:716NORFLOXACIN REDUCES RECURRENCE OF SPONTANEOUS BACTERIAL PERITONITIS (SBP)Indications for Prophylactic Antibiotics to Indications for Prophylactic Antibiotics to Prevent Spontaneous Bacterial Peritonitis Prevent Spontaneous Bacterial Peritonitis Ci
47、rrhotic patients hospitalized with GI hemorrhage Cirrhotic patients hospitalized with GI hemorrhage (short-term)(short-term) Norfloxacin 400 mg p.o. BID x 7 daysNorfloxacin 400 mg p.o. BID x 7 days Patients who have recovered from SBP (long-term)Patients who have recovered from SBP (long-term) Norfl
48、oxacin 400 mg p.o. daily, indefinitelyNorfloxacin 400 mg p.o. daily, indefinitely Weekly quinolones Weekly quinolones notnot recommended (lower efficacy, recommended (lower efficacy, development of quinolone-resistance)development of quinolone-resistance)INDICATIONS FOR PROPHYLACTIC ANTIBIOTICS TO P
49、REVENT SPONTANEOUS BACTERIAL PERITONITIS (SBP)50Characteristics of Hepatorenal SyndromeCharacteristics of Hepatorenal Syndrome Renal failure in patients with cirrhosis, advanced liver Renal failure in patients with cirrhosis, advanced liver failure and severe sinusoidal portal hypertensionfailure an
50、d severe sinusoidal portal hypertension Absence of significant histological changes in the Absence of significant histological changes in the kidney (“functional” renal failure)kidney (“functional” renal failure) Marked arteriolar vasodilation in the extra-renal Marked arteriolar vasodilation in the
51、 extra-renal circulationcirculation Marked renal vasoconstriction leading to reduced Marked renal vasoconstriction leading to reduced glomerular filtration rateglomerular filtration rateCHARACTERISTICS OF HEPATORENAL SYNDROME (HRS)Two Types of Hepatorenal SyndromeTwo Types of Hepatorenal SyndromeTyp
52、e 1Type 1 Rapidly progressive renal failure (2 weeks)Rapidly progressive renal failure (2 weeks) Doubling of creatinine to 2.5 or Doubling of creatinine to 2.5 or halving of creatinine clearance (CrCl) to 20 halving of creatinine clearance (CrCl) to 1.5 mg/dL or CrCl 1.5 mg/dL or CrCl 1.5 mg/dL or c
53、reatinine clearance 1.5 mg/dL or creatinine clearance 40 ml/min Absence of shock, bacterial infection, or nephrotoxic drugsAbsence of shock, bacterial infection, or nephrotoxic drugs Absence of excessive gastrointestinal or renal fluid lossAbsence of excessive gastrointestinal or renal fluid loss No
54、 improvement in renal function after plasma volume No improvement in renal function after plasma volume expansion with 1.5 L of isotonic salineexpansion with 1.5 L of isotonic saline Urinary protein 500 mg/dL and normal renal ultrasoundUrinary protein 500 mg/dL and normal renal ultrasoundMajor Crite
55、ria in the Diagnosis of Major Criteria in the Diagnosis of Hepatorenal SyndromeHepatorenal SyndromeArroyo et al., Hepatology 1996; 23:164Arroyo et al., Hepatology 1996; 23:164MAJOR CRITERIA IN DIAGNOSING HEPATORENAL SYNDROMEUrine Sodium and Urine Volume are Minor Urine Sodium and Urine Volume are Mi
56、nor Criteria in the Diagnosis of HRSCriteria in the Diagnosis of HRSMinor criteriaMinor criteria Urine sodium 10 mEq/LUrine sodium plasma osmolalityUrine osmolality plasma osmolality Serum sodium 130 mEq/LSerum sodium 130 mEq/L Urine volume 500 ml/dayUrine volume 500 ml/day Urine RBCs 50/HPFUrine RB
57、Cs 50/HPFArroyo et al., Hepatology 1996; 23:164Arroyo et al., Hepatology 1996; 23:164URINE SODIUM AND URINE VOLUME ARE MINOR CRITERIA IN THE DIAGNOSIS OF HEPATORENAL SYNDROME (HRS)Activation of Activation of neurohumoral neurohumoral systemssystemsSite of Action of Different Therapies for HRSSite of
58、 Action of Different Therapies for HRSAdvanced Advanced CirrhosisCirrhosisIntrahepatic Intrahepatic resistanceresistanceArteriolar Arteriolar resistanceresistance(vasodilation)(vasodilation)Sinusoidal Sinusoidal pressurepressureHepatorenal Hepatorenal syndromesyndromeRenal Renal vasoconstrictionvaso
59、constrictionTIPSTIPSTIPSTIPSTransplantTransplantEffective Effective arterial blood arterial blood volumevolumeVaso-Vaso-constrictorsconstrictorsAlbuminAlbuminMECHANISM OF ACTION OF THE DIFFERENT THERAPIES FOR HEPATORENAL SYNDROME (HRS)Management of Hepatorenal SyndromeManagement of Hepatorenal Syndr
60、omeProven efficacyProven efficacy Liver transplantationLiver transplantationUnder investigationUnder investigation Vasoconstrictor + albuminVasoconstrictor + albumin Transjugular intrahepatic portosystemic shunt (TIPS)Transjugular intrahepatic portosystemic shunt (TIPS) Vasoconstrictor + TIPSVasocon
61、strictor + TIPS Extracorporeal albumin dialysis (ECAD)Extracorporeal albumin dialysis (ECAD)IneffectiveIneffective Renal vasodilators (prostaglandin, dopamine)Renal vasodilators (prostaglandin, dopamine) HemodialysisHemodialysisMANAGEMENT OF HEPATORENAL SYNDROMEHEPATIC ENCEPHALOPATHYHepatic Encephal
62、opathyHepatic Encephalopathy60Hepatic EncephalopathyHepatic EncephalopathyNomenclatureNomenclature Type AType AAssociated with Associated with A Acute liver failurecute liver failure Type BType BAssociated with porto-systemic Associated with porto-systemic B Bypass ypass without intrinsic hepatocell
63、ular diseasewithout intrinsic hepatocellular disease Type CType CAssociated with Associated with C Cirrhosis and porto-systemic irrhosis and porto-systemic shuntingshuntingFerenci et al., Hepatology 2002; 35:716Ferenci et al., Hepatology 2002; 35:716HEPATIC ENCEPHALOPATHY NOMENCLATURE Treatment: rar
64、ely effective Treatment: rarely effective short of liver transplantshort of liver transplantCharacteristics of Type A vs. Type C Characteristics of Type A vs. Type C Hepatic EncephalopathyHepatic Encephalopathy Gradual onsetGradual onset Rarely fatalRarely fatal Main cause: Main cause: shunting / to
65、xinshunting / toxin PrecipitantPrecipitant Treatment: usually Treatment: usually effectiveeffective Rapid onsetRapid onset Frequently fatalFrequently fatal Main cause:Main cause:cerebral edemacerebral edemaType AType AType CType CCHARACTERISTICS OF TYPE A VS. TYPE C ENCEPHALOPATHYType C Hepatic Ence
66、phalopathy is Type C Hepatic Encephalopathy is the Encephalopathy of Cirrhosis the Encephalopathy of Cirrhosis Neuropsychiatric complication of cirrhosisNeuropsychiatric complication of cirrhosis Results from spontaneous or surgical / Results from spontaneous or surgical / radiological portal-system
67、ic shunt + chronic radiological portal-systemic shunt + chronic liver failureliver failure Failure to metabolize neurotoxic substancesFailure to metabolize neurotoxic substances Alterations of astrocyte morphology and Alterations of astrocyte morphology and function (Alzheimer type II astrocytosis)f
68、unction (Alzheimer type II astrocytosis)TYPE C HEPATIC ENCEPHALOPATHY IS THE ENCEPHALOPATHY OF CIRRHOSISHepatic Encephalopathy PathogenesisHepatic Encephalopathy PathogenesisBacterial actionBacterial actionProtein loadProtein loadFailure to Failure to metabolize metabolize NHNH33NHNH33 ShuntingShunt
69、ingGABA-BD GABA-BD receptorsreceptorsToxinsToxinsPATHOPHYSIOLOGY OF HEPATIC ENCEPHALOPATHYHepatic Encephalopathy Is A Hepatic Encephalopathy Is A Clinical DiagnosisClinical Diagnosis Clinical findings and history importantClinical findings and history important Ammonia levels are unreliableAmmonia l
70、evels are unreliable Ammonia has poor correlation with Ammonia has poor correlation with diagnosisdiagnosis Measurement of ammonia Measurement of ammonia notnot necessary necessary Number connection testNumber connection test Slow dominant rhythm on EEGSlow dominant rhythm on EEGHEPATIC ENCEPHALOPAT
71、HY IS A CLINICAL DIAGNOSISStageStageMental stateMental stateNeurologic signsNeurologic signs1 1Mild confusion: limited attention Mild confusion: limited attention Incoordination, tremor,Incoordination, tremor,span, irritability, inverted sleep span, irritability, inverted sleep impaired handwritingi
72、mpaired handwritingpatternpattern22Drowsiness, personality changes,Drowsiness, personality changes,Asterixis, ataxia, dysarthriaAsterixis, ataxia, dysarthriaintermittent disorientationintermittent disorientation33Somnolent, gross disorientation,Somnolent, gross disorientation,Hyperreflexia, muscleHy
73、perreflexia, musclemarked confusion, slurred speechmarked confusion, slurred speechrigidity, Babinski signrigidity, Babinski sign44ComaComaNo response to pain, No response to pain, decerebrate posturedecerebrate postureStages of Hepatic EncephalopathyStages of Hepatic EncephalopathySTAGES OF HEPATIC
74、 ENCEPHALOPATHYSTAGES OF HEPATIC ENCEPHALOPATHYConfusionConfusionDrowsinessDrowsinessSomnolenceSomnolenceComaComa11223344StageStageStages of Hepatic EncephalopathyStages of Hepatic EncephalopathyAsterixisAsterixisASTERIXIS IS THE HALLMARK IN THE DIAGNOSIS OF HEPATIC ENCEPHALOPATHY1122334455667788991
75、010111112121313141415151616171718181919202021212222232324242525BeginBeginEndEndTime to complete_Time to complete_Number Connection Test (NCT)Number Connection Test (NCT)Sample handwritingSample handwritingDraw a starDraw a starNUMBER CONNECTION TEST70Electroencephalogram in Hepatic EncephalopathyELE
76、CTROENCEPHALOGRAM IN HEPATIC ENCEPHALOPATHYMinimal Hepatic Encephalopathy Occurs in 30-70% of cirrhotic patients Occurs in 30-70% of cirrhotic patients without overt hepatic encephalopathywithout overt hepatic encephalopathy Detected by psychometric and neuro-Detected by psychometric and neuro-psych
77、ological testingpsychological testing May improve with lactulose or synbiotics May improve with lactulose or synbiotics (probiotics and fermentable fiber)(probiotics and fermentable fiber)MINIMAL HEPATIC ENCEPHALOPATHYMinimal Hepatic EncephalopathyAbnormalities on testing Attention and cognitive def
78、icitsAttention and cognitive deficits Visual-spacial perception impairedVisual-spacial perception impaired Defects in visual constructive abilityDefects in visual constructive ability Impaired driving abilityImpaired driving ability Evoked potentials and spectral electro-Evoked potentials and spectr
79、al electro-encephalography abnormalencephalography abnormalMINIMAL HEPATIC ENCEPHALOPATHY ABNORMALITIES ON TESTINGTreatment of Hepatic EncephalopathyTreatment of Hepatic Encephalopathy Identify and treat precipitating factorIdentify and treat precipitating factor InfectionInfection GI hemorrhageGI h
80、emorrhage Prerenal azotemiaPrerenal azotemia SedativesSedatives ConstipationConstipation Lactulose (adjust to 2-3 bowel movements/day)Lactulose (adjust to 2-3 bowel movements/day) Protein restriction, short-term (if at all)Protein restriction, short-term (if at all)TREATMENT OF HEPATIC ENCEPHALOPATH
81、YHepatic Encephalopathy PrecipitantsHepatic Encephalopathy PrecipitantsGI bleedingGI bleedingExcess proteinExcess proteinSedatives / Sedatives / hypnoticshypnoticsTIPSTIPSDiureticsDiureticsSerum KSerum K+Plasma volume Plasma volume AzotemiaAzotemiaTempTempInfectionsInfectionsHEPATIC ENCEPHALOPATHY P
82、RECIPITANTSActions of LactuloseActions of LactuloseLactuloseLactuloseLactic acidLactic acidDecreased pHDecreased pHNHNH33Urease-producing Urease-producing bacteriabacteriaIncrease cathartic Increase cathartic effecteffectNHNH33NHNH44+ACTIONS OF LACTULOSEHepatic EncephalopathyHepatic EncephalopathyTr
83、eatment: SummaryTreatment: SummaryDecrease ammonia Decrease ammonia production in gut:production in gut: LactuloseLactulose AntibioticsAntibiotics Adjustment in Adjustment in dietary proteindietary proteinIncrease ammonia Increase ammonia fixation in liver:fixation in liver: Ornithine aspartateOrnithine aspartate BenzoateBenzoateShunt Shunt occlusion or occlusion or reductionreductionHEPATIC ENCEPHALOPATHY TREATMENT SUMMARYFlumazenil