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DiarrheaDisease

ThefirstaffiliatedhospitalSUNYAT-SENuniversity

Prof.WangHuishen

王慧深DiarrheaDiseasMajorcauseofchildren’s(﹤5y)deathindevelopingcountriesin2002ARIdiarrheaMalariameaslesAIDSDiseaseinperinatalstageothers18%25%23%4%5%10%15%WHO/UNICEF.ClinicalmanagementofacutediarrheaSources:Theworldhealthreport2003,WHO,Geneva.Majorcauseofchildren’s(﹤5y)diarrhea(嬰兒腹瀉英文)后修課件GeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContent

GeneralintroductionConceptcommondiseaseinchildhoodfrequencyandcharactersofstoolAges6m~2y50%<1ySeasonsviralorigins—lateautumnandspringbeginning

bacterialorigins—summernoninfectiousdiarrhea—everyseasonMultiplesourcesandfactors

GeneralintroductionConceptGeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentCausesCourseDegreeInfectiousdiarrhea:virus,bacterium,fungi,parasitesNoninfectiousdiarrhea:diet,weather,othersAcute:<2wpersistent:2w2mchronic:>2mMild:thetimesofstoolandcharacterchangeSevere:accompanydehydration,electrolytesabnormalityandgeneraltoxicitysymptomsClassificationCausesCourseDegreeInfectiousdGeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentGastricacidsecretion,secretionandactivityofenzyme,qualityandquantityofdietchangequickly.Watermetabolism,toleranceofhydropenia,easytobodyfluiddisorder.Nerves,endocrine,circulation,liverandrenalfunction:notmature,easytodigestivetractfunctiondisorder.

Predisposingfactor-1Developmentofinfancydigestivesystem:notmatureGastricacidsecretion,secPredisposingfactor-2Defensesystem:notmatureThreedefensesystem():microflora,epithelium,immunityPredisposingfactor-2DefensesGrowanddevelop,demandfornutrients,burdenofthestomachandintestines,easytoindigestion.Artificalfeeding:enteritismorbility10timeshigherthanbreastfeeding.milk:nutritionalingredientdestroyedmilktool:disinfection.Predisposingfactor-3&4

3

4Thelowerlevelofserumimmunoglobulin,especiallyserumIgAlocatedingastrointestinaltractissmallerthanothers.Disordermicrobialpopulationofdigestivetractresultingfromusingantibacterialdrugsforalongtimeornormalmicrobialpopulationhavenotbeenestablishedinneonates.

Growanddevelop,demandfoRelationbetweenfeedingandinfectionininfants(﹤3m)Purebreastmilkn=95Partialbreastmilkn=126Laboratorymilkn=257pGastrointestinalinfection2.9%5.1%15.7%<0.001Respiratoryinfection25.6%24.2%37.0%<0.05(Howieetal1990)

Artificialfeeding:easytointestinalinfectionRelationbetweenfeedingandiBreastfeedingDays%oftotalfaecalmicro-organismsArtificialfeedingDays0102030405060708090100%oftotalfaecalmicro-organismsBacillusbifidusBacilluscoliBacillusfaecalis510152001020304050607080901000101520255010152025AccordingtoHarmsenetal.,2000

Artificialfeeding:easytodisordermicrobialpopulationBreastfeedingDays%oftotalfGeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentInfectiousanimalInfectioushumanwaterSusceptiblepopulationfoodfecal

-oral

wayEtiology-1:intraentericinfectionInfectiousanimalInfectioushuFromKapikianAZ,ChanockRM.Rotaviruses.In:FieldsVirology3rded.Philadelphia,PA:Lippincott-Raven;1996:1659.DevelopedcountryBacteriumUncertainreasonRotavirusCalicivirusRotavirusBacilluscoliParasiteOtherbacteriumAdenovirusCalicivirusAstrovirus

AdenovirusAstrovirusUncertainreasonDevelopingcountryDistributionofetiologicalagentIntraentericinfectionFromKapikianAZ,ChanockRM.RotavirusAstrovirusCalicivirus:Norwalkvirus,sapovirusEnterovirus:Coxsackievirus,echovirus,entericadenovirusCoronavirus:torovirusIntraentericinfection---virusVirus80%infantilediarrheaincoldmonths.RotavirusIntraentericinfeDeathforrotavirusinfectioninchildren﹤5y(‰)0.0-0.10.6-0.91.0-1.92.0-3.40.2-0.5Intraentericinfection---rotavirusDeathforrotavirusinfectionIntraentericinfection---rotavirus20-sidebody(65-75nm)Nucleus:45-50nmShape:wheelLife:7mBearacid-20℃:keeplongIntraentericinfection---roPhotoCredit:F.P.Williams,U.S.EnvironmentalProtectionAgency;AdaptedfromParasharetal,EmergInftDis199814(4)561–570RotavirusinstoolbyelectronmicroscopIntraentericinfection---rotavirusPhotoCredit:F.P.Williams,Bacilluscoli

enteropathogenicE.coli………EPEC

enterotoxigenicE.coli…………ETEC

enteroinvasiveE.coli…………..EIEC

enterhemorrhagicE.coli………EHEC

enteroadherentaggregativeE.coli……………EAECCampylobacterjejuni,Yersiniaenterocolitica,othersFungi

:blastomycesalbicansProtozoa(parasite)

:giardialamblia,amebicprotozoa

Intraentericinfection---bacteriumetc.Bacilluscoli

enteropathogDisorderintestinalfunctionInfectintestinaltractdirectlyIrritationofrectum(eg.bladderinfection)alterationofintestinalfloraMuchantibioticsusedtransportofcarbohydratelactase

Etiology-2:extraentericinfectionPneumonia,URI,USI,otitismedia,skininfection,etc.DisorderintestinalfunctionDietaryfactorsqualityandquantityoffood(feedingstarchandfattooearly)Allergicdiarrhea:milkorbeanPrimaryandsecondarydisaccharidasedeficiencyEtiology-3:noninfectiouscausesWeatherfactorsCoolenterokinesiaHotsecretionofdigestivejuiceandgastrictakemilkbecauseofthirstyDietaryfactorsEtiology-3:GeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentOsmoticdiarrhea:muchpoorlyabsorbedandhyperosmoticsoluteSecretorydiarrhea:electrolyteshypersecretionExudativediarrhea:inflammatorystatescausingliquorexudationMotilitydisturbance:dynamicabnormalityofintestineNoninfectiousdiarrhea:feedingfactorsPathogenesisUsuallycombinationofseveralmechanismsOsmoticdiarrhea:muchpoorlyPathogenesis-1:enterotoxinAdenylatecyclaseIntestinaljuicesecretionLabiletoxin(LT)CAMPH2O,Na+,Cl-transferintoentericcavityStabletoxin(ST)GuanylatecyclaseGTPCGMPATPactivateactivateVolumeofintestinaljuicediarrheaPathogenesis-1:enterotoxin產(chǎn)毒性大腸桿菌附著到小腸粘膜上進(jìn)行繁殖在小腸上部,通過菌毛上的粘附因子腸毒素不耐熱腸毒素

Labiletoxin,LT

耐熱腸毒素

stabletoxin,ST

腺苷酸環(huán)化酶鳥苷酸環(huán)化酶

細(xì)胞內(nèi)ATPcAMP

GTPcGMP

抑制小腸絨毛上皮細(xì)胞吸收Na+、Cl-和水,并促進(jìn)Cl-分泌

腸液中Na+、Cl-和水總量增多,超過結(jié)腸吸收限度

大量水樣腹瀉

激活激活腸毒素引起的腸炎發(fā)病機(jī)理——以產(chǎn)毒性大腸桿菌為例

產(chǎn)毒性大腸桿菌附著到小腸粘膜上進(jìn)行繁殖在小腸上部,通過腸Pathogenesis-2:bacteriuminvadesenteroninvadeSmallintestinecolonEnteronwall

mucosa:congestion,edema,effusion,ulserandhemorrhagePoorlyabsorptionofH2OandelectrolytediarrheaPathogenesis-2:bacteriuminva侵襲性細(xì)菌

在腸粘膜侵襲和繁殖

炎癥改變

(充血、腫脹、炎性細(xì)胞浸潤(rùn)、滲出和潰瘍)

水和電解質(zhì)不能完全吸收

腹瀉

便中WBC,RBC大量增加嚴(yán)重中毒癥狀

侵襲性腸炎發(fā)病機(jī)制侵襲性細(xì)菌

在腸粘膜侵襲和繁殖

炎癥改變

(充VirusinvasionPathogenesis-3:virusinfectionrecrementDisacchridePoorlydecomposedlactoseOsmoticdiarrheaNa+transportblock

H2OelectrolytedisaccharidaseVirusPathogenesis-3:virusin病毒性腸炎發(fā)病機(jī)理病毒侵入小腸粘膜絨毛上皮細(xì)胞并復(fù)制粘膜受累,絨毛被破壞

絨毛縮短微絨毛腫脹,紊亂并脫落線粒體、內(nèi)質(zhì)網(wǎng)膨脹雙糖酶活性下降載體減少消化吸收面積減少雙糖(乳糖)吸收減少

葡萄糖鈉與載體結(jié)合偶聯(lián)轉(zhuǎn)運(yùn)吸收障礙營(yíng)養(yǎng)物質(zhì)吸收減少部分乳糖分解為小分子的乳酸滲透壓增加水樣腹瀉

病毒性腸炎發(fā)病機(jī)理病毒侵入小腸粘膜絨毛上皮細(xì)胞并復(fù)制粘膜受Pathogenesis-4:noninfectiousdiarrheaFoodfermnmydesisEntericosmoticpressureDigestivefunctiondisorderOsmoticdiarrheaOver-feeding,NoproperdietaryPathogenesis-4:noninfectious食物質(zhì)、量不當(dāng)食物消化吸收障礙而積滯在上消化道胃酸度下降腸道下部細(xì)菌上移并繁殖內(nèi)源性感染發(fā)酵、腐敗有機(jī)酸(乳酸、乙酸)胺類

腸腔內(nèi)滲透壓增高腸蠕動(dòng)增強(qiáng)

腹瀉、脫水、電解質(zhì)紊亂、酸中毒分解食物中毒癥狀

肝解毒功能不全毒素進(jìn)入血循環(huán)飲食不當(dāng)引起腹瀉發(fā)生機(jī)理食物質(zhì)、量不當(dāng)食物消化吸收障礙而積滯在上消化道胃酸度TheRViscomposedby11gemesegments,NSP4(非結(jié)構(gòu)蛋白4)istheclosenessofPathogenesisThestudyprogressionbyRVcausediarrhea

TheRViscomposedby11gemeA組RV病毒基因組功能基因片段:123469

編碼結(jié)構(gòu)蛋白:VP1VP2VP3VP4VP6VP7(核心)(核心)(核心)(外殼)(內(nèi)殼)(外殼區(qū)分G血清型1-14)

裂解抗原區(qū)分(A-G組)

VP5VP8A組為Ⅰ,Ⅱ亞群(P血清型1-44)基因片段:5781011

編碼非結(jié)構(gòu)蛋白:NS53NS34NS35NS28NS26(NSP1NSP2NSP3NSP4NSP5)A組RV病毒基因組功能基因片段:12GeneralintroductionclassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentDigestivetractsymptomWater,electrolytesandacid-basedisorderDehydrationMetabolicacidosisElectrolytesdisorderDiarrheavomitAbdominalpainClinicalmanifestationDigestivetractWater,electrolMildandseverediarrheaMild:thetimesofstoolandcharacterchange

——stool:frequency,loose,liquid,color:yelloworgreenyellow,smell:sourflavor,shape:eggsoup

——vomiting:seldom——generalpoisoningsymptom:

without

——dehydration,electrolytes

abnormalityandgeneraltoxicitysymptoms':

noneMildandseverediarrheaSevere:accompanydehydration,electrolytesabnormalityandgeneraltoxicitysymptoms

—digestivetractsymptom:

diarrheaserious,mucusbloodsamplestool,anorexia,nausea,abdominalpainandabdominaldistention

—general

poisoningsymptom:

lethargy,dysphoria,unconsciousnessandcoma

—dehydration,electrolytesabnormality,acidbaseimbalance

MildandseverediarrheaSevere:accompanydehydration,Degree

Quality

mildmoderateHypotonicdehydration.Na+﹤130mmol/LHypertonicdehydration.Na+﹥150mmol/L

Clinicalmanifestation-1:dehydrationsevereIsotonicdehydration.Na+:130~150mmol/LDegreeQualitymildmoderateHyp

SeverityclinicalsignsofdehydrationmildmoderatesevereWaterlossByweightSpiritSkinMucousAnteriorfontanelandeyeballTearthirstUrineoutputPeripheralcirculation<50ml/kg<5%SlightlydispiritedslightlyagitatedSlightlydrySlightlydrySlightlydepressedNormalslightlydecreasednormal50~100ml/kg5%~10%DispiritedAgitatedDry,paleVerydrydepressedReducedincreasedLittleornoLittlecool100~120ml/kg>10%Extremelydispiritedapathy,hypnody,comaGraymottledParcheddepressedgreatlyNoGreatlyincreasedNourineoutputCool,weakpulse,shockDehydrationSeverityclinicalsignsAnuriatachypneaAnteriorfontanelandeyeballDepressedNoTearCool,weakpulse,shockDry,pale,Graymottledapathy,dispiritedSkinandMocousdryWeightdecreaseAnuriatachypneaAnteriorfontanEyesocketdepressed,rimaoculinotclosedEyesocketdepressed,rimaocuXerocheilia,chapXerocheilia,chapDehydrationSameproportionlossPIFCPIFCElectrolytelossmorePhypotonic,IF+ChypertonicCellexpansionSevereEasytoshockP:plasma,IF:interstitialfluid,C:cellIsotonicPIFCWaterlossmorePhypertonicIF+ChypotonicCellhydrationMildThirsty

AcutediarrheaaftervomitinggreatlyHypotonic

Hypertonic

DehydrationSameproportionVomitinganddiarrhea:AlkalinityintestinaljuicelostEat

:calorie,malabsorptionlipoclasisketo-bodiesHypovolemiapachemiabloodflowslowlyhypoxiaanaerobicglycolysislacticaciddehydrationbloodflowexcludingacid

acidmetabolicproductClinicalmanifestation-2:metabolicacidosisCauses:Vomitinganddiarrhea:AlkalinDispirited,dysphoria,drowsiness,comaHypernea(Kussmaulsbreathing),exhalationcoolExpiratorygassmellsketoneCherrylipsNausea,vomitMetabolicacidosis--clinicalmanifestationMild:breathfrequencyslightlySevere:occur:Dispirited,dysphoria,drowsinK+(potassium)<3.5mmol/L(normal:3.5~5.5mmol/L)causes:

Excessivelosses:vomit,diarrhea.Inadequateintake.Renalfunctionofkeepingkalium,itcontinuesexcludingkaliumwhenwithhypokalemia.Clinicalmanifestation-3:electrolytedisorderHypokalemiaK+(potassium)<3.5mmol/L(nordepressedTensionofskeletalmuscle,tendonreflex,

evenrespiratorymuscleweaknessTensionofsmoothmuscle,abdominaldistention

intestinalsoundordisappearMyocardiumexcitability,arrhythmia,ECG:T-waveisloworinversion,U-waveoccurs,prolongedP-RintervalandQ-Tinterval,STsectiondescending.BaseosishypokalemiaClinicalmanifestation:nerveandmuscularexcitabilitydepressedhypokalemiaCliniCa2+﹤1.75mmol/L(7mg/dl);Mg2+﹤0.6mmol/L(1.5mg/dl).Symptomsusuallyoccurafterdehydrationandacidosisresolved,orfluidreplacement.Clinicalmanifestation:thrill,tetany,convulsion.Ifconvulsionhasn’trelievedaftersupplementcalcium,payattentiontohypomagnesemia.hypocalcemia&hypomagnesemiaCa2+﹤1.75mmol/L(7mg/dl);GeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentSeveralcommonenteritis-1:Season:coolmonths(autumnandwinter)Age:6m~2ySymptom:fever,vomit,mildgeneraltoxicitysymptoms.Stool:frequency,amount,water;yellow-wateroreggsoup-like;asmallamountofmucus.Dehydration:mild/moderate,isotonic/hypertonicComplication:convulsion,myocardiumdamaged.Prognosis:self-limited,course:3~8d.Viralantigendetection:fromstool.Rotavirusenteritis

→humanrotavirus(HRV)Severalcommonenteritis-

Severalcommonenteritis-2:ETECenteritis

產(chǎn)毒性細(xì)菌Season:summerSymptom:vomitanddiarrhea,noobviousgeneraltoxicitysymptoms.Stool:water-likeoreggsoup-like,withoutmucus,bloodorpus,noWBC(testundermicroscope).Dehydration:dehydration,electrolyteandacid-basedisorderusuallyoccur.Prognosis:self-limited,course:3~7d.ETECenteritisSeveralcommonenteritis-2:Severalcommonenteritis-3:EIECenteritis

侵襲性細(xì)菌Similarwithbacillarydysentery.Symptom:diarrheawithfever,nausea,vomit,abdominalpain,tenesmus.Severegeneraltoxicitysymptoms,e.g.ardentfever,consciousnesschange,evensepticshock.Stool:withmucus,bloodandpus,smelloffish,withWBC(testundermicroscope).Stoolculture:pathogenicbacterium.EIECenteritisSeveralcommonenteritis-3:E

Severalcommonenteritis-4:fungalenteritisPathogen:usuallyBlastomycesalbicans.Age:﹤2y.Complicationbyotherinfection,orafterusingantibioticsforlongtime.Persistentcourse,usuallythrushcompanion.Stool:yellowthinstool,morefoamwithmucus,sometimestofukasu-like.testundermicroscope:fungalsporeandhypha.fungalenteritisSeveralcommonenteritis-4:GeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentGastricmucosaanalosisbacteriumandyeastfungusIntestinalmucosathinnerindigestionandmalabsorptionBacteriuminuppersmallintestineenterocytedamagedDynamicabnormalityofintestine.Usingantibioticsforlongtime.ImmunefunctiondefectliabilitytoagentsPersistentdiarrhea

acutediarrheawithoutproperorthoroughtreatment.

Causes:GastricmucosaanalosisbactmalnutritiondiarrheaviciouscycleDiarrhea+malnutrition:mortality4timeshigherthannormalchildrenmalnutritiondiarrheaviciouscyGeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentDiagnosisNotdifficultAccordingtoclinicalmanifestation,laboratorytestsandcharacterofstool.++InfectiousOrNoninfectious

DehydrationDegreeandquality

ElectrolytedisturbancesAndDisturbanceofacid-basebalanceDiagnosisNotdifficult++InfGeneralintroductionClassificationPredisposingfactorEtiologyPathogenesisClinicalmanifestationsClinicalfeaturesofseveralcommonenteritisPersistentdiarrheaDiagnosisDifferentialDiagnosisTreatmentContentGeneralintroductionContentDifferentialdiagnosis-1:physiologicaldiarrheaUsually﹤6m,bloating,breast-feeding.Usuallywitheczema.Normalappetite,growthanddeveloped.Aftercofoodaddition,stoolturnstonormal.AspecialtypeoflactoseintoleranceDifferentialdiagnosis-1:ph

Differentialdiagnosis-2:dysentery

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