PepticUlcerDisease

(PUD)BingqiangZhang

DepartmentofGastroenterology,theFirstAffiliatedHospitalofChongqingMedicalUniversityDefinition

epidemiology

3.Etiologyandpathogenesis4.Clinicalpresentations5.Diagnosis6.Complications7.TreatmentMainContents1.DefenitionofPUDPUDisUlcerationofgastrointestinalmucosaresultingfromauto-digestionofgastricacidandpepsin.Stomach(gastriculcer,GU)Duodenum(deodenalucler,DU)esophagusGastro-jejunalanastomosis(postsubtotalgastrectomy)Terminalileumdiverticulum（回腸末段憩室）

(Meckel’sdiverticulum，heterotopicgastricmucosa)SitesofpepticulcerSitesofpepticulcerAnastomoticulcerSitesofpepticulcerSitesofpepticulcerDifferenceofulceranderosionUlcerisamucosaldefectthatpenetratesthemuscularismucosa（粘膜肌層）Erosionisasmall,superficialmucosalbreakthatnomorethanthemuscularismucosa（粘膜肌層）2.EpidemiologyPrevalencerateabout10%overalllifetimeTheincidenceofDUwashigherthanGUTheincidenceofwasmalehigherthanfemaleThepredominantageofDUisbetween20and50yearsold,whereasGUoccursinpatientsmorethan40yearsoldThediseaseismorecommoninsmokers3.EtiologyandpathogenesisGastricMucosa&SecretionsTheinsideofthestomachisbathedinabout2litersofgastricjuiceeverydayGastricjuiceiscomposedofdigestiveenzymes&concentratedhydrochloricacid,whichcaneasilytearapartthetoughestfoodormicroorganism12pathogenesisofPUD

protectiveordefensivefactors

damagingoraggressivefactorsAggressivefactorsincreasingorthedefensivefactorsdecreasingwillresultinmucosaldamage,thenleadtoulceration.PathogenesisofUlcersAggressiveFactorsH.pylori

NSAIDsGastricacid,pepsinBilesaltsPancreatinSmokingandalcoholothers

DefensiveFactorsMucus-bicarbonatelayer

（粘液-碳酸氫鹽）Mucosa（粘膜）Bloodflow,cellrenewalProstaglandinsGrowthfactorsDefensivefacors:

1)Mucus-bicarbonatelayer（粘液-HCO3-屏障）:

MucosalcellssecretedmucusandHCO3-,whichmixedandformedgel-likelayeronmucosalsurface.（粘膜細(xì)胞分泌的粘液和HCO3-，混合在一起覆蓋于粘膜的表面形

成凝膠狀的不流動(dòng)層）

2)mucosalbarrier（粘膜屏障）

Formedbytightjunctionsbetweenmucosalepithelialcells.

（粘膜上皮頂部的細(xì)胞膜及其細(xì)胞之間的緊密連接，稱為粘膜屏障）

3)mucosalbloodflow（粘膜血流）ProvideoxygenandnutrientstoMucosaandsubmucosaltissues（給予粘膜和粘膜下組織供應(yīng)氧和營(yíng)養(yǎng)物質(zhì)）CarryoffH+andmetaboliteintissues

（帶走組織中的H+和代謝產(chǎn)物）Transportbicarbonatetomucosalsurfaceforpreventingexcessiveacidificationofmucosalcells.（向粘膜表面細(xì)胞輸送HCO3-

，防止細(xì)胞過(guò)度酸化）16Mucus-bicarbonatelayermucosalbarriermucosalbloodflow4)ProstaglandinE(PGE)Promotemucosalbloodcirculationpromotethesecretionofbicarbonate(HCO3-)PromoteDNAsynthesisofmucosalcells5)cellfactors:EGF(EpidermalGrowthFactor)FGF(fibroblastGrowthFactor)TGF(transformingGrowthFactor)importantregulatoryeffectonmucosalwoundrepairEtiology(AggressiveFactors)Helicobacterpylori(H.pylori)NSAIDs(non-steroidalanti-inflammatorydrugs)AcidandpepsinOtherriskfactors:

geneticpredisposition,smoking,alcohol,stress,diet,virusinfectionEtiology

H.pyloriinfectionSpiralshaped,flagellated,gram-negativebacillus

（螺旋狀，帶有鞭毛，革蘭氏陰性桿菌）

H.Pylori:ColonizinginhumanstomachTransmittedfrompersontopersonbyoral–oralorfeco-oralspreadNobelPrize2005“fortheirdiscoveryofthebacteriumHelicobacterpylorianditsroleingastritisandpepticulcerdisease"BarryJ.Marshall

J.RobinWarrenMostpepticulcersassociatedwithH.pyloriinfection90-100%ofDUand80-90%ofGUareassociatedwithH.PyloriinfectionClinicalSurveyProvement2.riskfordevelopmenttopepticulcersinpatientswithH.pyloriinfectionisincreasedForthepatientswithH.pyloripositive,about15to20%willdeveloptopepticulcersin10yearsClinicalSurveyProvementEradicationofH.pyloriisassociatedwithhigherhealingratesthehealingrateofpepticulcerOnlyeradicationofH.pylorivshigheffectiveacidsuppressivetherapyAftereradicationofH.pylori,refractoryulcercanbehealedClinicalSurveyEvidence4.Eradicationof

H.pyloriisassociatedwithlowerulcerrecurrencerate

therecurrencerateofpepticulcer(peryear):ClinicalSurveyProvementnotreatmentofH.pylori

H.pylorieradication50-70%＜5%WhyH.pyloriisoneofthe

maincausesofPUD?1.MostpepticulcersassociatedwithH.pyloriinfection2.riskfordevelopmenttopepticulcersinpatientswithH.pyloriinfectionisincreased3.EradicationofH.pyloriisassociatedwithhigherhealingrates4.Eradicationof

H.pyloriis

associatedwithlowerulcerrecurrencerate

Question:Thehighacidityofthestomachkillsmanymicroorganisms.ButhowcanH.pylorisurviveinhighacidenvironment?WhyHpcansurviveinthestomach(Hp在胃內(nèi)存活的原因)1）UreasesecretedbyH.pyloricanhydrolysisureatoformammoniaand“ammoniaclouds”aroundH.pylori,whichneutralizeorbuffergastricacidandprotectH.pylori.

（Hp產(chǎn)生的尿素酶水解尿素產(chǎn)生的氨在Hp周?chē)纬伞鞍痹啤保?/p>

中和周?chē)杆?，從而保護(hù)Hp）2）Theflagellum（鞭毛）makeitmotile,allowingittolivedeepbeneaththemucuslayer

（Hp菌體呈螺旋形，一端有鞭毛，提供運(yùn)動(dòng)動(dòng)力，使

其能寄居于最適部位）3)H.pyloricanexcreteadhesivefactor,whichmakeH.pyloriadheretogastricepithelium,thenfacilitatethetoxinstodamagegastricepithelialcells.

(Hp存在粘附因子，它使Hp特異地粘附于胃粘膜，其

毒素作用上皮細(xì)胞)

2.HpdamagedDefenseandrepairmechanismofgastricmucosaHp損害粘膜的防御修復(fù)機(jī)制

1)Vacuolatingcytotoxin(VacA):thecellsvacuoles空泡毒素（VacA）蛋白：使細(xì)胞產(chǎn)生空泡2)Urease:damagemucosaldirectlyorindirectly尿素酶：直接或間接破壞粘膜屏障

3)Mucusenzyme:degradatemucus,andpromoteH+dispersion粘液酶：降解粘液，促進(jìn)H+反彌散

4)Lipopolysaccharide,esterase,andphospholipase:destructionofmucosalintegrity.脂多糖、酯酶、磷脂酶：破壞粘膜的完整性3.H.pyloristimulatesexcesssecretionofgastrinhormone,whichelevatesacidsecretionandthusincreasesaggressivefactors.EtiologyNon-SteroidalAnti-inflammatoryDrugs(NSAIDS)Aspirin,Ibuprofen,Naproxen…Riskfactor:age,dose,durationoftherapyPU:10~30%GUismorethanDUcomplicationsarehigherthangeneralpopulationComplication:1~5%NSAIDsinhibitprostaglandinsynthesis

byblockingcyclooxygenase(COX)PathogenesisofNSAIDSCOX-2selectiveinhibitor(celecoxib)preferentiallyinhibitCOX-2,anddecreasetheriskofNSAID-relatedulceration.NSAIDsAttention:BothNSAIDsandHelicobacterpylori

aretheindependentriskfactorsofpepticulcer.（NSAIDs和幽門(mén)螺桿菌是引起消化性潰瘍的兩個(gè)獨(dú)立因素

）EtiologyGastricacidandpepsin

Pepsinisthedirectfactorwhichcandamagegastricmucosa,

butpepsincanbeactivatedonlywhenPHvaluelessthan4

instomachPUonlyoccursinpositionwhichcontactwithgastricacidInhibitionacidsecretioncanhealulcerGastrinomaproducemultiple,atypical,refractoryulcersPUwon’toccurwhenacidiscompletelylacking

Noacid,noulcerEtiologygeneticpredispositionGeneticsusceptibilityorintrafamilialH.pyloriinfectionTheconcordanceofpepticulcerincidenceindizygotictwinshigherthanenzygotictwinsEtiology

Otherriskfactors:

smoking,alcohol,stress,diet,virus

infectionSummaryPepticulcerisamultiplefactorsdiseaseBothHelicobacterpyloriandNSAIDsaremaincausesImbalancebetweenMucosalaggressivefactorsanddefensivefactorsNoacid,noulceremphasisonthepathogenesisofGUandDUisdifferencePathology

（病理）Location:DUisalwayslocatedintheanteriorwallofduodenum,GUisalwaysbefoundonthegastricangleand

lessercurvatureofgastricantrum

（部位:DU多在球部前壁，GU多在胃角和胃竇小彎）Numbers:singleormultipleSize:DU<15mm,GU<20mm

Giantulcer(diameter>20mm)Shape:round,oval,linear,irregularClinicalManifestationsMainsymptoms:abdominalpain

Properties:dull,burning,swelling,sharp

Position:vagueOtherdyspepticsymptoms:anorexia（厭食）,nausea,vomiting,bloating,belching…Characteristicsofabdominalpain:

1.Chronic,recurrentattacks（慢性過(guò)程，反復(fù)發(fā)作）

2.periodic,remissionphaseisalternatingwithattacks.

（發(fā)作呈周期性，與緩解期相互交替）

3.seasonal,occurswhenautumnturnsintowinterorwinterturnsintospring（季節(jié)性，多在秋冬、冬春之交）4.rhythmicity（發(fā)作時(shí)上腹痛呈節(jié)律性）5.acidsuppressiontherapyiseffective（抑酸治療有效）ClinicalManifestationsRhythmicity

GU:meal-pain-remissionaccentuatedbyeating

DU:pain-meal-remissionhungerpain:manifestsmostlybeforethemeal,relievedbyfoodnocturnalpain:wakesuppatientatmidnightSigns:Activepepticulcer:fixedandlimitedtendernessAlleviatedpepticulcer:noobvioussignsPhysicalExaminationSpecialTypesofPUDPostbulbarduodenalulcer（球后潰瘍）Silenceulcer（無(wú)癥狀性潰瘍）Pyloricchannelulcer（幽門(mén)管潰瘍）Ulcerinelderly（老年人潰瘍）Complexulcers（復(fù)合潰瘍）：GU+DURefractoryulcer（難治性潰瘍）DiagnosisofPUDHistoryEndoscopyandbiospyBariumRadiologyUpperEndoscopythemostaccuratetestforPUDUpperEndoscopyRoutinebiopsycanbeusedforexcludegastriccarcinomaUpperEndoscopyEnsureifthereisornoulcer,siteandstageofulcer,themisseddiagnosisrateisbelow5~10%BiopsycanbeusedfordistinguishbenignandmalignantulcerMorereliablethantheBariumRadiologyforfindinggastricbodyposteriorwallulcer（胃體后壁潰瘍）

andduodenalulcer.Endoscopichemostasis（止血）EvaluationoftherapeuticeffectBariumRadiologyDirectsigns:niche（龕影）forestablishingulcerniche

isoutsidestomachandduodenumBariumcontourinBenignulcer

niche

isinsidestomachandduodenumBariumcontourinmalignantulcer

Indirectsigns:justindicateulcerLocaltenderness（局部壓痛）incisuraleadingbyspasmingastricgreatercurvature（胃大彎痙攣切跡）bulbardeformity（球部變形）52BariumRadiologyAdvantages:nopainDisadvantages:

(1)Noulcerinbariumradiologycannotruledoutulcercompletely(2)CannotbeusedforHpdetection

(3)Distinguishingbetweenbenignandmalignantulcer

isnotreliableSelectionprinciple:

(1)Nocontraindication,preferredendoscopy

(2)Ifpatientscan’tafford,bariumradiologyisrecommendBariumRadiologyDiagnosisofH.pyloriInfectionNon-invasiveC13orC14UreaBreathTestStoolantigentestH.pyloriIgGtiter(serology)Invasivetest(endoscopy)RapidureasetestHistologicalexaminationMicrobialcultureDiagnosisofH.pylori:non-invasive1.C13orC14UreaBreathTestThebestnon-invasivetestforH.pyloriinfectionThepreferredmethodforre-evaluationDiagnosisofH.pylori:non-invasive2.SerologyTestSerumAntibodies(IgG)toH.pyloriNotforactiveinfection3.StoolantigentestFecalantigenofH.pyloripossiblealternativetoureatestDiagnosisofH.pylori:invasive1.RapidureasetestConsideredtheendoscopicdiagnostictestofchoiceGastricbiopsyspecimensareplacedinthetestkit.IfHpyloriarepresent,bacterialureaseconvertsureatoammonia,whichchangespHandproducesaCOLORchangeDiagnosisofH.pylori:invasive2.HistologicalexaminationH.PyloriongastricepithelialcellsDiagnosisofH.pylori:invasive3.Microbialculture-UsedinresearchstudiesandisnotavailableroutinelyforclinicaluseDifferentialDiagnosisofPUDFunctionaldyspepsia-endoscopyBiliaryorpancreaticdiseases-ultrosonography,-MRCP,ERCPGastriccancerGastrinomas(ZollingerEllisonsyndrome)DifferentialDiagnosis:Benigngastriculcer

-smooth,regular,roundededges,

-flat,smoothulcerbaseGastriccancer

-ulceratedmass

-nodular,clubbed,

-fusedsurroundingfolds

-irregularorthickenedmarginsMultiplebiopsiesoptimalnumberofbiopsiesfirstbiopsy-correctdiagnosisin70%fourbiopsy>95%Sevenbiopsy>98%Follow-upendoscopyDifferentiation:gastriculcervs.cancerDifferentialDiagnosis:Gastrinomas(Zollinger-Ellisonsyndrome)non-betaisletcelltumorofthepancreasleadingtomassiveproductionofgastrinandexcessivesecretionofgastricacidmultiple&refractoryulcersinunusuallocationsoftencompaniedwithdiarrheaGastricsecretorytest-Basicacidoutput>15mEq/hourFastingserumgastrin>500pg/mlUltrosonography,CTGastrinomas(Zollinger-Ellisonsyndrome)ComplicationsofPUDCommon:HemorrhagePerforationoutletStenosisorpyloricobstructionMalignantTransformation1.HemorrhagethemostcommoncomplicationItoccurswhentheulcererodesoneofthebloodvesselsclinicalfeaturesmayappearashematemesisorbloodyvomitus,orthebloodmayappearinstools,whereitgivesthestoolsadark,tarryappearance,whichisreferredtoasmelenaSeverehemorrhagemayleadtoshockhematemesistreatment-Routinemedicaltherapy-Emergencyendoscopytostopbleeding-Surgery69

Forresttypingofpepticulcerbleeding（消化性潰瘍出血的Forrest分型）

type

characteristics

rateofbleedingagain

treatment(類(lèi)型）（特點(diǎn)）（再出血率%）

（治療策略）

Ⅰactivebleeding

（活動(dòng)性動(dòng)脈出血）90PPI+endoscopy+PPI

ⅡaNakedbloodvesselswithobviousErrhysis

（裸漏血管伴明顯滲血）50PPI+endoscopy+PPI

Ⅱbbloodclot

（血凝塊）25-30PPI,endoscopy

ⅢaafewErrhysis

（少量滲血）10PPI

Ⅲb(onlyulcer,noblood)

僅有潰瘍，無(wú)血跡3PPI2.Perforation:Anulcercanbreakthroughtheentiregastro-intestinalwallBacteriaandpartiallydigestedfoolspillintoperitoneum=peritonitisclinicalfeaturesThefirstsignisoftensuddenintenseabdominalpainSignsofacuteperitonitisBoardlikerigidityofabdomenX-ray

mayrevealfreegasunderthediaphragmtreatmentSurgeryisrequiredimmediately3.StenosisScarringandswellingduetoulcerscausesnarrowingintheduodenumandgastricoutletobstructionGastricoutletobstructionclinicalfeaturesRecurrent,large-volumevomiting,unpleasantinnature,totallylackinginbile,containingfoodstufftakenseveraldayspreviously4.MalignantTransformation:DUgenerallybenignGUwithpossibilityofmalignancyBiopsyisveryimportantTreatmentLifestylechangesMedicationsSurgicalintervention1.Life-styleModificationRegularlifestyle,

rest,relaxationDiet:Regularmealsblanddiet（清淡飲食）:avoidspices,coffee,alcohol,ordietsrichinmilkandcream

SmokingcessationNSAIDsdiscontinuationifpossible2.MedicationsAcidsuppressionEradicationofH.pyloriMucosalProtectantsAcidSuppression1.Protonpumpinhibitors(PPIs)2.H2-recptorantagonists(H2RAs)

Noacid,noulcer!ProtonPumpInhibitors(PPIs)MechanismofactionUncompetitiveandirreversibleinhibitionofprotonpump(H+/

K+-ATPase)thatisresponsibleforfinalstepingastricacidsecretionfromtheparietalcell.Mosteffectivedrugsinacidsuppression,inhibitingover90%

of24-houracidsecretionPPIsinclude:

Omeprazole,Lansoprazole,PantoprazoleRabeprazole,EsomeprazoleMechanismofactionCompetitivelyandreversiblyblocktohistamineH2receptorsontheparietalcellsthusreducegastricsecretionLesspotentthanPPIsH2RAsinclude:Cimetidine,Ranitidine,Famotidine,NizatidineH2-recptorAntagonists(H2RAs)EradicationofH.pylori:H.pylori

issensitivetothefollowingantibiotics:Amoxicillin（阿莫西林）Tetracyclin（四環(huán)素）Clarithromycin（克拉霉素）Metronidazole（甲硝唑）TherapywithoneortwodrugsisineffectiveCombinedtherapyisusuallyused

-EradicationofH.pyloriThestandardfirst-linetherapyis"tripletherapy”-PPIorbismuth+twoantibioticsquadrupletherapy:PPI+bismuth+twoantibioticscourseoftreatmentis10or14daysEradicateH.pyloriinfectionPPIandBismuth

TwoAntibiotics

+Clarithromycin500mgbidAmoxicillin1000mgbid(Tetracycline)750mgbidMetronidazole400mgbidFurazolidone100mgbidQuadrupletherapy,for10or14daysOmeprazole20mgbidLansoprazole30mgbidPantoprazole40mgbidRabeprazole10mgbidEsomeprazole20mgbidTreatmentcourseofpepticulcer

TotalcouseforGU:6-8weeks

TotalcourseforDU：4-6weeksAttention:treatmentcourseforPU≠courseforeradicatingHPMucosalProtectiveAgentsSucralfate（硫糖鋁）Misoprostol（米索前列醇）ColloidalBismuthcompounds（膠體鉍化合物）Sucralfate:CoatsulceratlowpH,thuspromotinghealingThemainsideeffectisconstipationColloidalBismuthcompoundsItformsaprecipitatewithmucouscovertheulcerwithaprotectivecoatthatpreventeffectofHClPromotehealingofulcerBactericidaleffectagainstH.pyloriMisoprostolProstaglandinanalogsShouldbeparticularlyeffectiveathealingNSAIDinducedulcersFrequentlycausesdiarrheaanduterinecontraction（子宮收縮）GeneralStrategyDeterminetheetiologyofulcerEradicateH.pyloriinfectionDiscontinueNSAIDsuseifpossibleSmokingcessationshouldbeencouragedUseAcidsuppressivetherapyTreatcomplications3.SurgicalTreatmentIndications:itisdifficulttocontrolthebleedingofdigestivetractwithconservativetreatmentacuteperforationandfollowingacutediffuseperitonitiscicatricialpyloricobstruction（瘢痕性幽門(mén)梗阻）Malignantulcer

CasestudyCase1:

A27-year-oldmanhasa3-monthhistoryofintermittentburningepigastricpainthatismadeworsebyfa