內(nèi)科學(xué)課件 3、Pepticulcer消化性潰瘍

PepticUlcer

IntroductionDefinition:PUisulcerationwhichmayoccuratanysiteinthegastrointestinaltractthatisexposedtoacid-pepsinsecretion.(“noacid,noulcer.”)Defectsinthegastrointestinalmucosaextendingthroughthe

muscularismucosaeintothesubmucosaormuscularis

muscularismucosaeserosamuscularissubmucosa

mucosaHistologyofstomachwall

epithelium

laminapropria

ErosionAcuteulcerChroniculcerIntroductionTypicalulcers:Gastriculcer(GU),Duodenalulcer(DU)

IntroductionTwomajorcauses:Hp(helicobacterpylori)NSAIDs(nonsteroidalanti-inflammatorydrugs)Mainmechanism:ImbalancebetweenaggressivefactorsandmucosaldefensesEpidemiologyPepticulcers(PU)occurinupto10~15%ofthepopulationatsometime,andaremorecommoninmen.Duodenalulcers(DU)aremorecommonthangastriculcers(GU).InDUandGU,men:women=4.4~6.8:1and3.6~4.7:1respectively.PUoccuratdifferentage.DUareabout10timesmorecommonthanGUinyoungpatients,butintheolderagegroupsthefrequencyisaboutequal.EtiologyandPathophysiology1.Howulcershappen:Whenrepairandhealingmechanismsfail.(GU)Impairedhealingofmucosalinjuriesdifferentiatesulcerpatientsfromnon-ulceronesexposedtosameriskfactors.WhendefensemechanismsarecompromisedbyHp-inducedinflammationandNSAID-inducedreductionofprostaglandinsynthesis,andsoon.(DU)EtiologyandPathophysiology2.

NormalmucosaldefenseandhealingRegulationofacid-pepsinsecretion:balancebetweenneural,endocrine,paracrine,andautocrinepathwaysinvolvesbothstimulatoryandinhibitorymechanismsNormalgastroduodenalmucosahasaremarkableabilitytodefendandrepairitselfMucosaldefensesExogenousfactorsAcidandpepsinEndogenousfactorsMucosalrepairandhealingEtiologyandPathophysiology3.

H.PyloriandPepticUlcer(1)HelicobacterPylori(HP)

-Foundin1983byMarshallandWarren.-Livedundermicro-oxygenandacidiccondition.-MaincauseofchronicgastrtisandPU.-Secretionofsomeinflammatoryfactors:

urease,vacuolatingcytotoxin,lipopolysaccharideendotoxin,proteinase,lipaseandphospholipaseA2.BarryJ.Marshall

J.RobinWarren

3.

H.PyloriandPepticUlcer(2)TwolinesofevidenceestablishedHPasacrucialcausalfactorfordevelopmentofbothDUandGU:(i)thelargemajorityofDU(＞90%)andGU(＞75%)areassociatedwithHP.(ii)Severalwell

designed,controlledstudiesandnumerousotherlessrigoroustrialshaveconsistentlyindicatedthatsuccessfullycuringtheHPinfectionpredictsamarkedlyreducedrateofulcerrecurrence.3.

H.PyloriandPepticUlcer(3)Hpinfectiondestroythebalancebetweentheaggressivefactorsanddefensive/repairingfactors.Hp→inflamation&immuneresponse→damagethemechanismofmucosaldefenceandrepair.Hp→gastrin↑,acid↑.EtiologyandPathophysiology4.NSAIDsandPepticUlcer(1)Mechanism:①Damagedirectlygastricmucosalbarrier.②

Inhibittheproductionofendogenouspostaglandin(PG).NSAIDssystemicallyinhibitgastricCOXReducesmucosalprostaglandinproductionLimitstheabilityofthemucosatodefenditselfagainstinjuryfromsuperimposedfactors4.NSAIDsandPepticUlcer(2)

RiskfactorsforNSAIDulcersAge:elderlyindividuals,above60PrevioushistoryofulcersorcomlicationsDurationoftherapyDoseanddurationofactionanduseofmultipleNSAIDsDyspepsiaCotherapywithcorticosteroids

Others:Hpinfection,smoking,etc.EtiologyandPathophysiology5.Acid-pepsinandpepticulcer(1)Pepticulcersformationarefinallydependentupontheacid-pepticactivityingastricjuice(2)PepticactivityiscloselylinkedtogastricpHPrecursorpepsinogenisconvertedintoactiveproteaseatlowpH.PepsinisinactivatedwhenpHiselevatedabove4,accountsforthehealingofrefractoryulcerswhenthepHiselevatedabove4.EtiologyandPathophysiology5.Acid-pepsinandpepticulcer(3)AdequateacidsecretionisnecessaryforDU,GUmayoccurinlowacidconcentrationsInhibitingacidsecretionpromoteshealingDUandGUAveragemaximalacidsecretorytostimulationisgreaterinmostofulcersSpeciallyinmostGU,maximalgastricacidoutput(MAO)andbasalgastricacidoutput(BAO)arenormalorlessthannormal.5.Acid-pepsinandpepticulcer(4)CausesofexcessofgastricacidsecretioninDUpatientsAmountofparietalcells↑

mormal:10hundredmillionDU:19hundredmillionSusceptibilityofparietalcellstostimulators↑e.g.:foods,five-peptidegastrin.(4)CausesofexcessofgastricacidsecretioninDUpatientsNormalfeedbackinhibitory

Mechanismofgastricacidsecretionhassomeshortcomings.Tensionofvagalnerve↑

acid↑,gastrin↑

6.OtherfactorsandPU(1)Disturbanceofgastricemptyingandbilereflux.(2)Geneticfactors

Pre-Hpera:polygenicinheritance(3)InfectionsotherthanHpHerpessimplexvirustype1(HSV-1)Cytomegalovirus(CMV)(4)StressandPsychologicalfactorssecretion,motilityandmucosalcirculationofGItract.RegulationEtiologyandPathophysiologyVagalnerveStress,Psychologicalfactors(5)DrugexposuresAnumberofdrugsbesidesNSAIDs:Platelet-activeagentsSteroidsAnticoagulantsSirolimus:patientsundergoingtransplantationAlendronate:prescribedtotreatosteoporosis(6)CigarettesmokingImpairsulcerhealing,promotesrecurrences,increasestheriskofcomplicationsIncreasedduodenalacidloadbyincreasinggastricsecretionandimpairingduodenalandpancreaticbicarbonatesecretion.(7)AlcoholDamagethegastricmucosalbarrierStimulatesacidsecretionEtiologyandPathophysiology7.Comorbidulcers:Chronicobstructivepulmonarydisease(COPD)Pepticulcersoccurinupto30%ofCOPDpatientsCirrhosisPrevalenceranging10-49%incirrhosispatientsRenalfailureOrgantransplantationPathologySiteGU:Lessercurvature(antrum,incisuraangularis

)DU:Theanteriorwallofduodenalbulb.Number:mostlysolitarySizeGU:lessthan2.0cmindiameterDU:＜1.5cm

DepthExtendingthroughthemuscularismucosaintothesubmucosaormuscularis

ClinicalManifestations1.SymptomAbdominalpain

Characteristicsofpain:①Chronic:

◆recurrence;◆weeks,months,years.②Periodically:

◆Clustersofpainlastingafewdaysorweeksormonths,followedbypain-freeperiodsofweeksormonthsCharacteristicsofpain:③RhythmicallyDU:hunger(2-3hoursaftermeals):whenacidissecretedintheabsenceoffoodbufferAtnight(11pm-2am)/nocturnalpain:whenthecircadianstimulationofacidsecretionismaximalRelievedwhenintakingalkali,food,antisecretoryagentsGU:LesslikelytoberelievedbyfoodorantiacidsMorelikelytodisplayfoodprovocation(within1houraftermeals)Characteristicsofpain:④Locatedatepigastricportion⑤Character:dullpain,hungrilypain,gnawing,etc.⑥D(zhuǎn)egree:mild,moderate,severe⑦Frequency:paroxysmal,persistent⑧relieve/enhancefactorsClinicalManifestations(2).Otherdyspepsiasymptomsandcomplication’ssymptoms:acidreflux,belching,heartburn,epigastricfullnessanddiscomfort,bloating,earlysatiety,nauseaandvomiting,hematemesis,melena,weightloss,anorexia,etc.ClinicalManifestations2.Signs

Mild,localizedepigastrictenderness,oftenunremarkable.Signsofulcercomplications:ComplicationsBleeding(hemorrhage)①mostcommoncauseofUGIbleeding②Themostcommoncauseofulcer-relateddeath③symptom&signComplications2.Perforation①Secondmostcommoncomplicationofpepticulcer②Typicalclinicalpresentation:Acuteonsetofsevere,intolerableabdominalpainUnremitting&exacerbatedbyanymovementPreciselyidentificationofexacttimethepainbeganPeritonealirritationsign

Tenderness;Reboundtenderness;MuscleguardingBowelsound↓Freeairunderneaththediaphragm(abdominalX-ray)2.Perforation①Secondmostcommoncomplicationofpepticulcer②Typicalclinicalpresentation:Acuteonsetofsevere,intolerableabdominalpainUnremitting&exacerbatedbyanymovementPreciselyidentificationofexacttimethepainbeganPeritonealirritationsignTenderness;Reboundtenderness;MuscleguardingBowelsound↓Freeairunderneaththediaphragm(abdominalX-ray)Complications3.ObstructionAcuteulcers?obstructionduetoedema±m(xù)otordysfunction(functionalobstruction)Chroniculcer?obstructionoccursecondarytoscarringofanulcerinpyloricchannelorduodenum(organicobstruction)

Presentationgastricretention→frequentvomiting→succussionsplashComplications4.CancerationGU1%-2%ofGUptsAlertsignals:

ChronicGUhistoryAbove45ysRecurrentulcersContinuingoccultbloodtest(OB)pisitiveDUNocancerationtendencySpecialtypesofPUSilenceulcer:asymptomaticulcer,

morecommominelderlyTheagedulcer:atypical,GU≥DUComplexulcer:combinedgastricandduodenalulcers

Pyloricchannelulcer:acid↑,vomit,obstructionPostbulbarulcer:5%ofDU,nightpain,backpain,bleeding.Giantulcers:DU>2cm,GU>3cmRefractoryulcer:chronic,repeatedly

Stressulcer:Cushing’s,Curling’sKissingulcer:theanteriorwallandbackwallofduodenalbulb.

Pyloricchannelulcer

KissingulcerAssistant

test1.DiagnostictestsforHP⑴Noninvasive:·Serology:Anti-HpIgGantibodies

·Carbon13or14ureabreathtest(UBT)

·Stoolantigentest1.DiagnostictestsforHP⑵Invasive(endoscopicbiopsyrequired):Rapidureasetest(RUT)：SimplestmethodwhenendoscopyisnecessarySimple;rapid;sensitivity:80to95%;specificity:95to100%Invasive;false-negativespossibleiftestingisdonetoosoonaftertreatmentwithPPI,antimicrobialsorbismuthcompounds

HistologyCultureAssistant

test2.Fastingserumgastrinlevel:Gastrinoma3.Gastricjuiceanalysis:Gastrinoma4.

X-raybarium-Contrastmealdirectsign：nicheindirectsignGenerallyroundorovalandmaybesurroundedbyasmoothmoundofedemaSecondarychangesincludefoldsradiatingtothecrater,anddeformitiesintheregionsecondarytospasm,edema,andscarringAlthoughendoscopyhasreplacedradiology,radiologycanoccasionallybeuseful

LateralFrontAssistant

test5.EndoscopyandmucosalbiopsyProvidesasensitive,specific,andsafemethodfordiagnosingPUDAllowingdirectinspectionandbiopsy(goldstandardfordeterminingbenignormalignant)Benignulcers：smooth,regular,androundededges;aflatandsmoothulcerbaseoftenfilledwithexudateMalignantulcers:anulceratedmassthatprotrudesintothelumen,surroundingfoldsthatarenodular,clubbed,fused,orstopshortoftheulcermargin,ormarginsthatareoverhanging,irregular,orthickened

Biopsyshouldbeperformedforallgastriculcers,asbenign-appearingulcersmayharbormalignancy.benignMalignantMalignantDiagnosisClinicalfeature(history,symptoms,signs)X-raybarium-ContrastmealEndoscopyandmucosalbiopsyDifferentialDiagnosisFunctionaldyspepsiaChronicCholecystitisandCholecystolithiasisGastriccancerGastrinomaTreatment1.GeneralmeasureDietEmotionRegularlifestyleTreatment2.DrugtherapyEradicationofH.pylori①PPI–basedtripletherapy/Bismuth-basedtripletherapyDoublestandardamountofPPI(bismuthsubsalicylate)+twoantibioticsAntibioticsinclude:Clarithromycin500mgbid,Amoxicillin1gbid,Metronidazole400mgbid,Tetracycline500mgbid,Furazolidone100mgbid7-14days,14dayswasthepreferredtime(1)EradicationofH.pylori②Quadruple-therapyWhenTriple-therapyfailedTriple-therapy+PPI/Bismuthsubsalicylate③ConfirmationofHpcureItisimportanttowaitasufficienttimeafterstoppingantibioticstoavoidfalse-negativeresult4wkshiatusispreferableforhistology,culture,orureabreathtests;8wksisrequiredforstoolantigentestPPIsshouldbestoppedfor1wkatleast2.Drugtherapy(2)Antisecrerotydrugs:H2receptorantagonists(H2RAs)Protonpumpinhibitors(PPIs)AnticholinergicsRestingparietalcellwithcollapsedsecretorycanaliculicytoplasmictubulovesiclesexpressingH+,K+-ATPaseStimulatedparietalcellwithformedsecretorycanaliculiexpressingactiveH+,K+-ATPasepumps.Functionaltransformationofsecretingparietalcell(acetylcholine)(2)Antisecrerotydrugs:Availabledrugs:Cimetidine800mg/d4-6w(DU)6-8w(GU)Ranitidine300mg/d4-6w(DU)6-8w(GU)Famotidine40mg/d4-6w(DU)6-8w(GU)Nizatidine300mg/d4-6w(DU)6-8w(GU)Availabledrugs:standardamountOmeprazole20mg/d4-6w(DU)6-8w(GU)Lansoprazole30mg/d4-6w(DU)6-8w(GU)Pantoprazole40mg/d4-6w(DU)6-8w(GU)Rabeprazole10-20mg/d4-6w(DU)6-8w(GU)Esomeprazole20mg/d4-6w(DU)6-8w(GU)2.Drugtherapy(3)AntacidsNeutralizegastricacid，increasesgastroduodenalpH,rapidlyreleaseulcerpainordiscomfortHavealonghistoryinthetherapyofpepticulcer,butinconvenient,requiringmultipledosesperdayBeoutmodedforPUDAvailabledrugsCalciumcarbonateantacidsMagnesium-containingantacidsAluminum-containingantacids2.Drugtherapy(4)Enhancementofmucosaldefenses:SucralfateBismuthProstaglandinE1analogue(Misoprostol)2.Drugtherapy(5)

TreatmentofNSAIDulcersCriticalstepsintreatingNSAIDulcersWheneverpossiblediscontinueoratleastreducetheNSAIDdoseSearchforandcureHpinfectionAppropriatecourseofstandardulcertherapyAntiulcerdrugs:PPIsarepreferedforulcerhealinginthepresenceofongoingNSAIDsProstaglandinsaregenerallynotgoodalternativeforthehealingofNSAIDulcers,onlybeusedforpreventionH2RAs,sucralfateandantacidsareinadequatefortreatmentofNSAIDulcers,especiallycontinuingNSAIDuse(5)TreatmentofNSAIDulcersPreventionofNSAIDulcersProstaglandinsMisoprostol:200mg,fourtimesdailyPPIsThelowestdoseoftheleastexpensivePPIisprobablysufficientNotH2RAStandarddosesdonotpreventNSAID-inducedulcers2.Drugtherapy(6)RefractoryandrecurrentulcersMostPUDrespondtoantimicrobialtherapyforHporwithdrawalofNSAIDs,orhealwithusualdosesofpotentantisecretorydrugs.Occasionalulcersareeitherrefractorytotreatmentorrecurfollowinginitialhealing.Ulcersareconsideredrefractoryifunhealedafter8-12wksoftreatmentCausesofrefractoryandrecurrentulcers(6)RefractoryandrecurrentulcersTreatmentofrefractoryulcersReconsiderthediagnosisandmanagementConfirm:thepatientiscompliantwithanadequatePPIregimenE