內(nèi)科學(xué) 肝硬化張順財(cái)

內(nèi)科學(xué)肝硬化張順財(cái)?shù)?頁，課件共67頁，創(chuàng)作于2023年2月Cirrhosis---definition

chronic,progressed,diffuse

hepatocellularinjury

fibrosis

nodularregenerationIncidence:17/100000/yAge:20-50yr.第2頁，課件共67頁，創(chuàng)作于2023年2月Hepaticcirrhosis》EtiologyLiverfunctionInjury,PortalhypertensionDiffuse,chronicliverinjuryHepato-cellularnecrosis,collapseofhepaticlobulesregenerativenodules

formationFormationofdiffusefibrousseptaComplations:UpperGIBleeding,Hepaticcoma,infections,primarylivercancer,Functionalrenalfailure第3頁，課件共67頁，創(chuàng)作于2023年2月1.Chronicviralhepatitis(慢性病毒性肝炎):[HBV,HCV,HBV+HDV]2.Long-termalcoholism(慢性酒精中毒)[80g/d,10yr.]3.Prolongedcholestasis(長期膽汁郁積),intra-andextra-hepatic:[primarybiliarycirrhosis,PBC]/[secondarybiliarycirrhosis]4.Drugsandtoxins(藥物和毒物)[toxichepatitis---chronicactivehepatitis---cirrhosis]5.Nonalcoholicsteatohepatitis(NASH)(非酒精性脂肪性肝炎)Etiologyofcirrhosis(I)第4頁，課件共67頁，創(chuàng)作于2023年2月Etiologyofcirrhosis(II)6.Hepaticvenousoutflowobstruction(肝血液循環(huán)障礙)

veno-occlusivedisease,Budd-Chiarisyndrome,constrictivepericarditis7.Metabolicdisorders

(遺傳代謝性疾病)

hemochromatosis(血色病);Wilson‘sdisease(肝豆?fàn)詈俗冃?;8.Autoimmunehepatitis(AIH)(自身免疫性肝炎)9.Schistosomiasis(血吸蟲病)10.Cryptogenic

(隱原性)11.Mixed:alcohol+virus,HBV+HCV,HBV+schistosomiasis第5頁，課件共67頁，創(chuàng)作于2023年2月Hepaticstellatecellactivation第6頁，課件共67頁，創(chuàng)作于2023年2月Liverfibrosisaccumulationofextracellularmatrixinliver

synthesisofmatrixproteinsdegradationofmatrixproteinsCollagenstypeIandIIIconstitutemorethan95%ofthetotalcontentofincreasedcollageninfibroticliver

第7頁，課件共67頁，創(chuàng)作于2023年2月第8頁，課件共67頁，創(chuàng)作于2023年2月第9頁，課件共67頁，創(chuàng)作于2023年2月Pathogenesis:chronic,progressed,diffuseHepatocyteinjuryleadingtonecrosis.Chronicinflammation-(hepatitis).Capillarization(肝竇毛細(xì)血管化)ofthespaceofDisseisakeyevent.Bridgingfibrosis.Regenerationofremaininghepatocytesproliferateasroundnodulessurroundedbyfibroussepta.Lossofvasculararrangementresultsinregeneratinghepatocytesineffective.Cirrhosismayleadtoliverfailure,portalhypertension,ordevelopmentofhepatocellularcarcinoma

第10頁，課件共67頁，創(chuàng)作于2023年2月Histopathologic

classificationmicronodular

uniformlysmallnodules(<3mmindiameter)andregularbandsofconnectivetissuemacronodular

nodulesthatvaryinsize(3mmto5cmindiameter)mixedmacroandmicronodular

(incompleteseptalcirrhosis)combineselementsofmicronodularandmacronodularcirrhosis.

第11頁，課件共67頁，創(chuàng)作于2023年2月第12頁，課件共67頁，創(chuàng)作于2023年2月第13頁，課件共67頁，創(chuàng)作于2023年2月Consequencesofportalhypertension[I]1.Splenomegaly(脾腫大)2.Formationandopenofportal-systemiccollateral’s(門體側(cè)支循環(huán)開放)

--Esophageal/gastricvarices

(食管/胃靜脈曲張)

(shortgastric/coronaryveins)

--Rectalcollateral‘s(痔靜脈叢)

(Suphemorrhoidal/middle&inf.hemorrhoidal)

--Caputmedusae(水母頭)(

umbilical/epigastric)

--abdominalwallvarices(腹壁靜脈曲張)

--Portalsystemandleftrenal第14頁，課件共67頁，創(chuàng)作于2023年2月第15頁，課件共67頁，創(chuàng)作于2023年2月Consequencesofportalhypertension[II]3.Ascites(腹水)

Theoriesofascitesformation

Underfillingtheory(灌注不足假說）

Overflowtheory(泛溢假說)Arterialvasodilationtheory(動脈擴(kuò)張假說)第16頁，課件共67頁，創(chuàng)作于2023年2月第17頁，課件共67頁，創(chuàng)作于2023年2月AscitesSodiumretention

---Reninangiotensionaldosteronesystem(RAAS)---sympatheticnervesystem,norepinephrine---Intrarenalfactors:Kallikrein-kininsystem,Adenosine.Waterretention

---Antidiuretichormone(ADH)

---ImpairedrenalsynthesisofPGs(PGE2)Renalvasoconstriction

---RAAS,AngiotensionII---SNS---ADH---ET第18頁，課件共67頁，創(chuàng)作于2023年2月Endocrinesystemgynecomastia(男性乳房發(fā)育),telangiectases(毛細(xì)血管擴(kuò)張癥),spidernevi(蜘蛛痣),palmarerythema(肝掌)

testicularatrophy(睪丸萎縮)menstrualirregularities(月經(jīng)失調(diào))第19頁，課件共67頁，創(chuàng)作于2023年2月PulmonarymanifestationsHepatichydrothorax

(肝性胸水)Hepatopulmonarysyndrome(HPS,肝肺綜合征)HRSischaracterizedclinicallybythetriadofpulmonaryvasculardilatationcausingarterialhypoxemiainthesettingofadvancedliverdisease.

第20頁，課件共67頁，創(chuàng)作于2023年2月HRS(Hepatorenalsyndrome,肝腎綜合征)

Occurredinthesettingof:---chronicliverdisease---advancedhepaticfailure---portalhypertensioncharacterizedby:

---impairedrenalfunction---markedabnormalitiesinarterialcirculation---activationofendogenousvasoactivesystemClassifiedinto2differenttypes:

---TypeI:Rapidlyprogressive---TypeII:Notrapidlyprogressive.Oftenresultsinmildrenalinsufficiencycausingdiureticresistantascites第21頁，課件共67頁，創(chuàng)作于2023年2月MechanismsofHRS[II]第22頁，課件共67頁，創(chuàng)作于2023年2月Clinicalfeatures[I]Compensatedcirrhosis(代償期)

Manypeopleexperiencefewsymptomsattheonsetofcirrhosis,symptomsaretypicallyvagueandnonspecific.

---Fatigueandlossofenergy.---Lossofappetiteandnausea.---Spiderangiomas---liverfunctionisnormalDecompensatedcirrhosis(失代償)

Symptomscausedbylossoffunctioninglivercells

---System：fatigue,weakness,weightloss,malnutrition---DigestiveSystem:Lossofappetite,nausea,diarrhea.第23頁，課件共67頁，創(chuàng)作于2023年2月Clinicalfeatures[II]

---Tendencytohemorrhage(出血傾向)andanaemia(貧血):Duetoreducedsynthesisofcoagulationfactors(II,V,VII,IX,X),hypersplenism(脾亢),lowplateletcount,poorabsorption，gastrointestinalbleeding.---Hormonalabnormalities

gynecomastia(男性乳房發(fā)育),telangiectases(毛細(xì)血管擴(kuò)張癥),spidernevi(蜘蛛痣),palmarerythema(肝掌)

---Jaundice(黃疸)第24頁，課件共67頁，創(chuàng)作于2023年2月Clinicalfeatures[III]Portalhypertension(門靜脈高壓)1.Splenomegaly:anemia,leukopenia,thrombocytopeniaduetohypersplenism

2.developmentandopenofcollateralvesselsinportalhypertension

a.

Esophagealvarices

b.Rectalcollateral's

c.Caputmedusae

d.Abdominalwallvarices

e.Portalsystemandleftrenal

3.Ascites、hepatichydrothorax

第25頁，課件共67頁，創(chuàng)作于2023年2月第26頁，課件共67頁，創(chuàng)作于2023年2月第27頁，課件共67頁，創(chuàng)作于2023年2月Clinicalfeatures[IV]

Palpationofliverfirm,hard,irregular,enlargementroundedorsharpedgebelowtherightlowerribs.

Thespleenisoftenpalpable,andmaybeverylarge.第28頁，課件共67頁，創(chuàng)作于2023年2月Theclinicalmanifestationsfoundincirrhosis

、第29頁，課件共67頁，創(chuàng)作于2023年2月Complications[I]Uppergastrointestinalbleeding(上消化道出血):

Hematemesis(嘔血)/melena(黑糞).Esophageal/gastricvaricealbleeding(食管/胃靜脈出血);portalhypertensivegastropathy(門脈高壓性胃病);pepticulcer(消化性潰瘍)第30頁，課件共67頁，創(chuàng)作于2023年2月Infections:spontaneousbacterialperitonitis(自發(fā)性細(xì)菌性腹膜炎)(4-8%)：Fever,worseningjaundiceorrenaldysfunction,abdominalpain(occurringonlyin50%ofpatients),andencephalopathyarethemostcommonclinicalfindingsinSBP.However,thepatientisfrequentlyasymptomatic.BecausecultureofascitesfluidisnegativeinalargenumberofpatientswithSBP,diagnosisshouldbebasedonthepresenceof>250neutrophils/mm3.第31頁，課件共67頁，創(chuàng)作于2023年2月Complications[II]Hepatocellularcarcinoma(肝細(xì)胞肝癌)Hepaticencephalopathy

(肝性腦病)Asterixis(撲翼樣振顫)Disoriented(定向障礙)Coma(昏迷)

第32頁，課件共67頁，創(chuàng)作于2023年2月Complications[III]

Hepatorenalsyndrome(HRS):

Oliguria(少尿),azotemia(氮質(zhì)血癥),hypotension(低血壓),

dilutionalhyponatremia(稀釋性低鈉血癥),lowurinarysodium(低鈉尿)第33頁，課件共67頁，創(chuàng)作于2023年2月Complications[IV]Electrolyteandacid-baseimbalance(電介質(zhì)酸鹼平衡失調(diào))

hyponatremia,hypokalemiaAndhypochloremicalkalosis

第34頁，課件共67頁，創(chuàng)作于2023年2月Laboratoryfindings[I]BloodandurineroutinesLiverfunctiontests

---toestimatetheseverityofliverdysfunction：ALT,AST,AKP,GGT,serumtotalbilirubin,serumalbumin,prothrombintime,globulin,cholesterol.---todifferentialdiagnosis:Alcoholic:AST/ALT>=2;PBC:AKP,GGT>>ALT,AST

---torefecthepaticfibrosis:PIIIP、HA、laminin---toquanlityliverfunction第35頁，課件共67頁，創(chuàng)作于2023年2月Immunology

Cellularimmune,hormonalimmuneautoimmuneliverdisease:IgG,globulinANA(+),SMA(+)PBC:IgM,AMA(+)MarkerofvirusAFP第36頁，課件共67頁，創(chuàng)作于2023年2月Laboratoryfindings[II]Ascitesparacentesis:

routine,culture,ADA,LDH,SAAG(serumascitesalbumingradient)

(血清腹水白蛋白梯度)>11g/LUltrasonography,CTscanning：

biliaryobstruction,livermasses,splenomegaly,ascites.

Endoscopy:

thenumber,appearance,andsizeofanyesophageal/gastricvarix,portalhypertensivegastropathy(PHG)第37頁，課件共67頁，創(chuàng)作于2023年2月Laboratoryfindings[III]

Radionuclide:99mTC-MIBI,H/Lliverbiopsy:toconfirmthediagnosisLaparoscopyHVPG(hepaticveinpressuregradient)(肝靜脈壓力梯度)(wedged-free)hepaticvenouspressureNormal:5-6mmHg,>10mmHg:varices;>12mmHg:rupture

第38頁，課件共67頁，創(chuàng)作于2023年2月第39頁，課件共67頁，創(chuàng)作于2023年2月第40頁，課件共67頁，創(chuàng)作于2023年2月第41頁，課件共67頁，創(chuàng)作于2023年2月第42頁，課件共67頁，創(chuàng)作于2023年2月Diagnosis[I]

EtiologyofcirrhosisPathologyofcirrhosisEvaluatingofliverfunction:Child-PughclassificationSearchingforcomplications第43頁，課件共67頁，創(chuàng)作于2023年2月Diagnosis[II]

thehistoryofdiseasecontributestoidentifyingthecauseofcirrhosis.

historyofviralhepatitis,bloodtransfusions,medicationuse,alcoholuse,sexualpracticesshouldbecarefullyreviewed.

signsandsymptomsconfirmtoexistenceofportalhypertensionandimparedliverfunction.

liverfunctiontests:hypoalbuminemia,hyperbilirubinemia，theprolongedprothrombintimesuggesthepaticdecompensation.

Imagingstudy:UltrasoundandCTreadilyidentifythelesion,buthavenocharacteristicfindings.第44頁，課件共67頁，創(chuàng)作于2023年2月

Child-Pughclassification

Scorea

variable

123Encephalopathy(degree)NilSlight-ModerateModerate-SevereAscites(degree)NilSlightModerate-SevereBilirubin(umol/L)<3434-51>51Albumin(g/L)3528-34<28ProthrombinIndex(%)>7040-70<40ProthrombinTime(s)<1415-17>18ProthrombinTime(INR)

<1.31.3～1.5>1.5*PBC:SB(μmol/L)17～6868～170>170

aScoresaresummedtodetermineChild’sclass:classA=5-6classB=7-9classC=10-15Diagnosis[III]第45頁，課件共67頁，創(chuàng)作于2023年2月DifferentialDiagnosis

Otherconditionofhepatomegalyorsplenomegaly：

chronicvirushepatitis,Gaucher’sdisease,lymphomasandleukaemias,congestivesplenomegalyDifferebtialdiagnosisofcirrhoticascitesandothertypesofascites：

malignantascites,constrictivepericarditis,tuberculousperitonitis,etal.Portalhypertension:第46頁，課件共67頁，創(chuàng)作于2023年2月Treatmentofcirrhosis[I]specifictreatmentfortheunderlyingetiologyoftheliverdisease

antivirustherapy--viralhepatitisabstinencefromalcohol--alcoholicUrsodeoxycholicacid(UDCA)(熊去氧膽酸)--PBCPenicillamine(青霉胺)—Wilson’sdisease

GeneralTreatments:

Highcalories(40kcal/kg·d)、adequateprotein(1-1.5g/kg·d)、vitamin、Herbalcompounds.第47頁，課件共67頁，創(chuàng)作于2023年2月TreatmentofAscitesa.Bedrest,sodium

andwaterrestriction.

1.Fluidintake:800-1000ml/d(hyponatremia,serumsodium<130meq/L)2.Dietarysodiumintake

：88mmol/d(2.0gNacl)Mildpatients：restonbed，withdietarysaltrestriction,lossofascitesoccursin10%to15%ofpatients.第48頁，課件共67頁，創(chuàng)作于2023年2月TreatmentofAscites[II]

b.Increasingrenalsodiumandwaterexcretion:

--Diuretics:

urinarysodium/urinarypotassium>1Spironolactone(安體舒通)+furosemide(速尿)urinarysodium/urinarypotassium<1higherdosesspironolactone，

第49頁，課件共67頁，創(chuàng)作于2023年2月TreatmentofAscites(III)c.Large-volumeparacentesis

associatedwithplasmavolumeexpansiond.Ascitesultrafiltrationandre-infusione.Peritoneo-venous(LeVeen)shuntsf.

TIPS(transjugularintrahepaticporto-systemicstent)(經(jīng)頸靜脈門體分流術(shù))

g.Livertransplantation(肝移植)第50頁，課件共67頁，創(chuàng)作于2023年2月第51頁，課件共67頁，創(chuàng)作于2023年2月TIPS---stentpositionedbetweenthehepaticandportalveins第52頁，課件共67頁，創(chuàng)作于2023年2月Treatmentofcirrhosis[IV]surgicaltreatmentofportalhypertension

portacavalshuntsurgery：

portacavalmesocaval

distalsplenorenalshunts

Choiceofpatients：

Child-Pugh:A,Bbleedingfromgastroesophagealvarices,hypersplenism.第53頁，課件共67頁，創(chuàng)作于2023年2月Treatmentofcirrhosis[V]TreatmentcomplationsTreatmentofacutevaricealhaemorrhage：

----Generalmanagement:abstainfood,intensivecare,volumeandbloodreplacement,specificmeasurestostopthebleeding

----Pharmacologicaltherapy:

vasopressin(垂體后葉素)somatostatin(生長抑素)

Octreotide(奧曲肽)第54頁，課件共67頁，創(chuàng)作于2023年2月Treatmentofacutevaricealhaemorrhage：

___Emergentendoscopy:afterPatient’shemodynamicstatusstabilized(usuallywithin2-12hours)

----Balloontubetamponade(ifbleedingcontinues)

----Endoscopicvaricealsclerotherapyandbandligation

----Prophylactictherapytopreventrebleeding:Beta-adrenergicantagonists(普奈洛爾),endoscopicsclerotherapy(硬化劑)/banding(套扎)(usually3-6sessions),portacavalshunting,TIPS第55頁，課件共67頁，創(chuàng)作于2023年2月第56頁，課件共67頁，創(chuàng)作于2023年2月第57頁，課件共67頁，創(chuàng)作于2023年2月第58頁，課件共67頁，創(chuàng)作于2023年2月第59頁，課件共67頁，創(chuàng)作于2023年2月第60頁，課件共67頁，創(chuàng)作于2023年2月TIPS---stentpositionedbetweenthehepaticandportalveins第61頁，課件共67頁，創(chuàng)作于2023年2月Treatmentportalhypertension(<12mmHg)EradicatevaricesLivertransplantationShuntSurgicalshuntsTIPSPharmacotherapyQ

Endoscopy:EVS,EVLDevascularizationR第62頁，課件共67頁，創(chuàng)作于2023年2月TreatmentofSBP1.AscitesPMN>250/mm3:antibiotictherapyshouldbeinitiated.2.AscitesPMN<250/mm3andasciticfluidculturecontinuestobepositive:initiationofantibiotictreatment.3.Follow-updiagnosticparacentesisperformed48hoursafterstartingtherapyallowsassessmentofresponsetotreatmentandtheneedtomodifyantibioticcoverage.4.Long-termprophylaxis---Patientswho