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INFANTILEDIARRHEACHCUMSDIVISIONOFINFECTIOUSDISEASEANDGASTROENTEROLOGYINFANTILEDIARRHEA.1INFANTILEDIARRHEAINFANTILEDIBackground

Diarrheaisaclinicalsyndromeofdiverseetiologyassociatedwithmanyinfluencingfactors.Itisthemostfrequentchildhooddiseasesecondonlytotherespiratoryinfection.Themajorcauseofdeathamongworld’schildrenandthenumberonekillerofchildrenunderfiveinmanydevelopingcountries..2BackgroundDiarrheaisaclinDiseaseBurden

Worldwide

3-5billionepisodes/year

4-5milliondeaths/year

Childrenarethepredominantpopulations.

3.2billionepisodes/yearin<5ychildren

1.3milliondeaths/yearin<5ychildren

InChina

836millionepisodesofdiarrheaeveryyear

1/4-1/3ofalloutdoorpatientsandalargeamountofhospitalizationsofchildrenareduetodiarrhea.3DiseaseBurdenWorldwide.3

FluidityVolumeNumberInpediatrics,diarrheaisdefinedasanincreaseintherelativetotheusualhabitsofeachindividualofstoolsDefinition.4FluidityInpediatrics,diarrhNormalStoolofChildrenBreastfedbabies:

passstools3-4timesadayyellowloose(softtorunny)buttexturedsweet-smellingBottlefedbabies:

onceadaypaleyelloworyellowish-brownbulkierandmoreformedprettypungentBabiesonsolids:

thickenanddarkenslightlyhaveastrongerodor.5NormalStoolofChildrenBreastDehydrationMalnutritionMortalityWhydiarrheaismoredangerousforchildren?.6DehydrationMalnutritionMoMalnutritionandChildMortality.7MalnutritionandChildMortaliIf:Diarrhea+MalnutritionThe

RISK

of

DEATH

is

4fold

higherthan

thatofwellnourishedchildren.8If:Diarrhea+MalnutritionTheWhychildrenarehighlyvulnerabletodiarrhea?

ImmaturedigestivesystemMorenutritiondemandWeaknessofdefensesystemThenormalintestinalflorahavenotbuiltupwell

Bottlefeeding.9WhychildrenarehighlyEtiologyofDiarrhea.10EtiologyofDiarrhea.10EtiologyofDiarrheaInfectiveNoninfectiveVirusesBacteriaParasitesFungi

Allergic

Symptomatic

Inappropriate

feeding

Food

intolerance

Climate.11EtiologyofDiarrheaInfectiveNViralEnteropathogensViralenteropathogenscausemostillnessesinpediatricpopulation.

Rotavirus

(mornthan50%acutediarrhea)

AstrovirusNorwalkvirusCoronavirusCalicivirusEntericadenovirus(serotypes40and41).12ViralEnteropathogensViralentRotavirus.13Rotavirus.13Themostcommoncauseofchildhooddiarrheasecondonlytotheviralenteropathogens

Escherichiacoli

EPEC;ETEC;EITC;EHEC;EAEC

Campylobacterjejuni

ShigellaspeciesSalmonellatyphimuriumYersiniaenterocoliticaStaphylococcusaureusClostridiumdifficileVibriocholeraeBacterialEnteropathogens.14ThemostcommoncauseofchildRareetiologicpathogenofdiarrhea

CryptosporidiumparvumEntamoebahistolyticGiardialambliaParasitesPathogens.15RareetiologicpathogenofdiaRareetiologicpathogenofdiarrhea

CandidaalbicansAspergillusMucor

FungousPathogens.16RareetiologicpathogenofdiaThemostimportantinfectivecausesofacutediarrheaindevelopingcountriesinchildrenare:RotavirusEnterotoxigenicescherichiacoliShigellaCampylobacterjejuniSalmonellatyphimurium.17ThemostimportantinfectivecEtiologyofDiarrheaInfectiveNoninfectiveVirusesBacteriaParasitesFungi

Allergic

Symptomatic

Inappropriate

feeding

lactose

intolerance

Climate.18EtiologyofDiarrheaInfectiveNOverfeedingIndigestibledietSuddenchangeofformula

Inappropriatefeedingforamilk-fedbabyshiftingintosolidfood(toomuch,tooearly,toorapid…)

DietaryDiarrheaInappropriatefeeding:.19OverfeedingDietaryDiarrheaAllergicDiarrheaPrimaryfoodhypersensitivity:

3monthsafterbirth

Secondfoodhypersensitivity:

Infection→injuryandhyperpermeabilityofintestinalmucosa→

largemolecularproteinenteringbloodstream→

allergicstateCow'smilkproteinSoybeanproteinEggwhite

peanuts,meat,andfishetc..20AllergicDiarrheaPrimaryfood

SymptomaticDiarrheaDiarrheaisonlyoneofthesymptomsofprimarydisease.Problemisnotoriginallylocatedinintestinaltract.RespiratorytractinfectionOtitismediaSomeinfectiousdiseases,etc.Alwaysbemild,andrecoverwiththeprimarydiseasegettingbetterTheyoungerthechildren,themorechancetogetasymptomaticdiarrheaaccompaniedbyotherdiseases..21SymptomaticDiarrheaDiar

LackofDisaccharidaseLactose

IntolerancePrimaryDisaccharidaseDeficiencyisararedisease(congenitaldefectsofcarbohydratehydrolysis).SecondDiaccharidaseDeficiency

:Rotavirusinfection

→Injurestheenterocytesofvilli→Transientdisaccharidasedeficiency→Malabsorptionoflactoseinthemilk→

Typicallooseandwaterystools.22LackofDisaccharidaseLactos

ClimateSeasonalvariation

affectsthedigestivefunctionofsmallchildren:incidenceofdiarrheaishighestduringtheearlyraninyseasonColdweather

causesincreasingofenterokinesiaHotweather

causesdecreasingofdigestiveenzymeandmalfunctionofdigestivetract

…….23Climate.23PathophysiologicalMechanismsofDiarrhea.24PathophysiologicalMechanismsVirusDiarrhea-RotavirusEnterotoxigenicEnteritis–ETEC,VibrioCholeraeEntero-InvasiveOrganisms–ShigellaSpecies,EIECDietaryDiarrheaPathophysiologicalMechanismsofDiarrhea.25VirusDiarrhea-RotavirusPathPathogenesisofVirusDiarrheaVirusinvadestheabsorptiveenterocytesofvillibutsparescryptcellsThevirusesreplicatesandinfectedenterocytesaredestroyedRotavirus.26PathogenesisofVirusDiarrheaPathogenesisofVirusDiarrhea1-Infectedabsorptiveenterocytesarekilledcausingpatchyepithelialcelldestructionandvillousshortening2-Destroyedabsorptivecellsarerapidlyreplacedbycellsthatmigratefromthecrypts.Villibecomecoveredwithimmaturenon-absorptivesecretorycellshaving:-nobrushborder-nobrushborderenzymesOsmotic

Diarrhea.27PathogenesisofVirusDiarrheaPathogenesisofVirusDiarrhea

(OsmoticDiarrhea)RotavirusesattachandreplicateinthematureenterocytesatthetipsofsmallintestinalvilliDestroyvillustipcells,variabledegreesofvillusbluntingmononuclearinflammatoryinfiltrateinthelaminapropriaImpairmentofdigestivefunctionsdiscreasinghydrolysisofdisaccharidesImpairmentofabsorptivefunctionsthetransportofwaterandelectrolytesviaglucoseandaminoacidco-transportersAnimbalanceintheratioofintestinalfluidabsorptiontosecretionMalabsorptionofcomplexcarbohydrates,particularlylactoseOtherthandegestedintomonosaccharide,lactosebelysisintoorganicacid,hyperosmosis

Waterystool.28PathogenesisofVirusDiarrheaVirusDiarrhea-RotavirusEnterotoxigenicenteritis–

ETEC,VibrioCholeraeEntero-InvasiveOrganisms–ShigellaSpecies,EIECDietarydiarrheaPathophysiologicalMechanismsofDiarrhea.29VirusDiarrhea-RotavirusPathPathogenesisofEnterotoxigenic

Diarrhea

Pathogens:

Vibriocholerae(cholera)ETECStaphylococcusaureusClostridiumdifficile.30PathogenesisofEnterotoxigeni

enterotoxigenicorganismsIngestionsmallbowelmucosaandproliferate

activatescellular

guanylatecyclase

Heat-stableenterotoxinpromotethenetsecretionofwaterandchlorideincreasedintracellularconcentrationsofcAMP

activatescellularadenylcyclasebindstoreceptorsofepithelialcellsHeat-labileenterotoxindecreaseabsorptionofsodiumandchloridebyvillouscellsincreasedintracellularconcentrationsofcGMP

Secretory

diarrheaPathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

.31enterotoxigenicorganismsIngePathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

1-EnterotoxigenicBacteriasecreteEnterotoxins2-ToxinstimulatestheproductionofC-AMPIncreasedC-AMPleadsto:3-InhibitionofabsorptionofNaandClfromthecellsofvilli4-StimulationofsecretionofClfromcryptcells+++---12341234.32PathogenesisofEnterotoxigeniPathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

Themucosaisnotdestroyedduringthisprocess.33PathogenesisofEnterotoxigeniAnimbalanceintheratioofintestinalfluidabsorptiontosecretion,sowaterystoolmayoccurinclinicalobservationPathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

.34AnimbalanceintheratioofiEnterotoxigenic

Diarrhea

Clinicalfinding:Waterydiarrheaandvomitingdevelopafteranincubationperiodof6hr-5days(2-3days,average)Low-gradefeveroccursinsomechildrenProfuse,painless,waterydiarrhea,sometimeswithflecksofmucusbutnobloodFluidandelectrolytelosses,tachycardia,tachypnea,asunkenanteriorfontanel,progresstocirculatorycollapse.35EnterotoxigenicDiarrheaCliniVirusDiarrhea-RotavirusEnterotoxigenicenteritis–ETEC,VibrioCholeraeEntero-InvasiveOrganisms–

ShigellaSpecies,EIECDietarydiarrheaPathophysiologicalMechanismsofDiarrhea.36VirusDiarrhea-RotavirusPathInvasiveDiarrheaEntero-InvasiveOrganisms:

ShigellaspeciesEIEC(enteroinvasiveE.coli)CampylobacterjejuniSalmonellatyphimuriumYersiniaenterocoliticaThecentraleventinpathogenesisisinvasionofcolonicmucosa.37InvasiveDiarrheaEntero-InvasiPathogenesisofInvasiveDiarrheaInvasiveenteropathogenIngestionGutlumenColonandrectummucousmembraneproper

ExtensivedestructionoftheepitheliallayerInflammation:Hyperemia,swelling,heavyneutrophilinfiltration,inflammatoryexudateThedesquamation,ulceration,andformationofmicroabscessesinthecolonicmucosainhibitabsorptionofwaterstoolsthatarefrequentandscantyandthatcontainblood

inflammatorycellsandmucus.38PathogenesisofInvasiveDiarrPathogenesisofInvasiveDiarrhea.39PathogenesisofInvasiveDiarrInvasiveDiarrheaClinicalfinding:Stoolsthatarefrequentandscantyandthatcontainbloodinflammatorycells,andmucusStoolexamination:largeamountofWBC,puscell,andRBCDehydrationandelectrolytedisturbancesarelessfrequentbecauseoflesslossofdigestivefluid.40InvasiveDiarrheaClinicalfindVirusDiarrhea-RotavirusEnterotoxigenicenteritis–ETEC,VibrioCholeraeEntero-InvasiveOrganisms–ShigellaSpecies,EIECDietarydiarrheaPathophysiologicalMechanismsofDiarrhea.41VirusDiarrhea-RotavirusPathPathogenesisofDietaryDiarrheaInappropriatedietIrritatesthebowelPromotetheperistalsisWaterenteringthelumenDecomposedproductamineslacticacidaceticacid

AciditydecreasingGivethechancetothebacteriawhichlivedinlowerpartofbowelcomingupEndogenousinfectionAggravatetheintestinalfunctiondisturbanceIndigestedfoodaccumulateintheupperpartofintestineDyspepsia

Indigestedfood

fermentandputrescenceHyperosmosisDiarrhea.42PathogenesisofDietaryDiarrhMorphologyofIntestinalMucosa.43MorphologyofIntestinalMucosMorphologyofIntestinalMucosaVillicoveredmainly(90%)bytallcolumnarabsorptivecells

(Enterocytes)havingamicrevillarbrushborderCryptsoflieberkuhnCoveredmainlybyshortcolumnarsecretorycellsGobletcellswithoutbrushborder.44MorphologyofIntestinalMucosDefenseBarriersoftheEnterocytes1.Physicalbarrier:mucus2.Bacteriological(flora)3.Immunological:SecretoryIgA123.45DefenseBarriersoftheEnteroNormalFloraBreast-fed:AGram-positivepopulation:BifidobacteriaandLactobacilli

Bottle-fed:AGram-negativeflora:Enterobacteriaceae.46NormalFloraBreast-fed:AGramClinicalManifestations.47ClinicalManifestations.47ClinicalmanifestationsGastrointestinalsymptomSystemicsymptomDehydrationandelectrolytedisturbances.48ClinicalmanifestationsGastrAssessmentofachildwithdehydration&electrolytedisturbances

.49AssessmentofachildwithdehDehydrationExcessivelossofwater,especiallylossofextracellularfluid..50DehydrationExcessivelossofw.2.53.53AssessmentofaDehydrationMildModerateSevereDehydration5%5-10%10-15%50ml/Kg50-100ml/Kg100-120ml/KgMentalStateNormalRestless,irritableProstration/ComaFontanelNormalSunkenDeeplySunkenTearNormalDecreaseAbsenceBucalMucosaMoistDryVeryDryTissueTurgorNormalAbsentAbsentUrineFlowDecreaseSlightlyDecreaseAnuriaShockAbsentAbsentPresent.54AssessmentofaDehydrationMilTypeofdehydrationHypotonic<280mOsm/LIsotonic280~300mOsm/Lhypertonic>300mOsm/LSerumsodium<130mmol/L130-150mmol/L<150mmol/LSkincolorSkintemperatureSkinturgorPaleColdAbsentPaleColdNormalFlush-NormalDurationofvomitinganddiarrheaVerylongLongShortThirstyNoNoYesMucousmembraneMoistMoistDryNSsyndromsLethargyNormalIrritableDisturbanceofperipheralcirculationYesNoNo.55TypeofdehydrationHypotonicIs

serumpotassium<3.5mmol/LEtiologyExcessiveoflossInsufficientintakeDistributionaldisturbanceofextracelluarandintracelluarpotassiumHypopotassaemia.56serumpotassium<3.5mmo(二)低鉀血癥Manifestations(1)lownervousandmuscularexcitability

nervousexcitability:downcast,lethargy

muscularexcitability:weakness、byporesalexiaoftendonjerk,paralysis

GIsmoothmuscleexcitability

:paralyticileus(2)cardiovascularsystem:cardiacdysrhythmia,lowheartsound,electrocardiographicabnormalityHypopotassaemia

serumpotassium<3.5mmol/L.57(二)低鉀血癥ManifestationsHypopot

serumcalcium<1.88mmol/L

HighnervousandmuscularexcitabilityHypocalcemia.58serumcalcium<1.88mmol/LHypoc

1etiology

(1)lossofalkalinesubstancefromGItrack(2)acidsubstanceaccumulationinbodyH+排除↓

2manifestations:

hyperpnoea、increasedheartrate、seriselip、consciousdisturbancefortheseverecases

H+產(chǎn)生↑MetabolicAcidosis.591etiologyH+MetabolicAcidoClassificationofDiarrheabasedon……SeverityDurationEtiology.60ClassificationofDiarrheabasClassificationofDiarrhea1.Milddiarrhea:

Mostofthecasesarenon-infectiousdiarrheaFrequencyofstooloftenlessthan10times/dayYellowishloosestool,soursmellwithafewofmucusfatdropinmicroscopicexamGeneralconditionisgood,self-limitedonseveraldays2.Moderatediarrhea:3.Severediarrhea:

Mostofthecasesareinfectiousdiarrhea(rotavirus,shigella)Frequencyofstooloftenmorethan10times/dayWaterystool,plentyofmucus.Generalconditionispoor,usuallyaccompanywithvomitingandfever,dehydrationandelectrolytedisturbance.61ClassificationofDiarrhea1.MAcutestage:thecourseofthediseaseslessthan2weeksPersistingtype:thecourseofdiseasemorethan2weeksbutlessthan2monthsChronicstage:thecourseofdiseasemorethan2monthsClassificationofDiarrhea.62Acutestage:thecourseofthePersistingandChronicDiarrheaComplicatereasons:Persistinginfection,Allergicstate,Lackofdisaccharidase,Immunodeficience,Broadspectrumantibioticusage,Malnutrition,Malabsorption,etc.

PathogenesisisnotclearGreatdangerous:MalnutritionandgrowthretardationMortalityishighTroublesometobecontrolled:AdequatecaloriesReestablishthenormalflora

.63PersistingandChronicDiarrheRotavirusesInfection.64RotavirusesInfection.64RotavirusesinfectionHistory:Firstrecognizedinhumansin1973byAustralianScientistBishop,withahubbedwheelappearanceunderelectronmicroscope,givingtheirname

Virology:Double-strandedRNAvirusVP6:A-Ggroup,groupAisthemostimportantgroupinchildhoodinfection.65RotavirusesinfectionHistory:RotavirusesinfectionPeakseason:Deepfallandwinter(October-February)Causingsharplyincreasingofoutdoorpatients

inautumnandwinter,alsonamedautumndiarrheaPeakage:6m-2y,rarelyhappeninchildrenabove4yDiseaseburden:80%infectiousdiarrheainpediatricclinicinautumnandwinterAbout1/4to1/3(morethan800cases)hospitalizeddiarrheachildrenarecausedbyrotavirusinourwardeveryyear.66RotavirusesinfectionPeakseaRotavirusesinfectionClinicalmanifestations:Onsetofsuddenfever,respiratorytractsymptoms

Vomiting,wateryorsoftstoolthatlackgrossbloodormucusSeveredehydrationthaninfectionbyotherviralpathogensComplicationsandfatalitiesarerelatedalmostexclusivelytotheadverseeffectsofdehydration,electrolyteimbalance,andacidosisMalnutritionisariskfactorforsevereconsequences

DisaccharidesIntolerance

Laboratoryfindings:SpecificantigensinstoolspecimenrecommendedbyWHO.67RotavirusesinfectionClinicalDiagnosis.68Diagnosis.68Diarrhea?

Watery,loosestoolswithoutoronlyaminuteamountofWBCEpidemicdataStoolcultureSerousassayStoolcultureSerousassayShigellaspeciesEIECCampylobacterjejuniSalmonellatyphimuriumYersiniaenterocoliticaVirusDiarrheaETEC,EPECLotsofWBCandRBC,mucusinstoolsAcutestagePersistingorchronicdiarrheaAntibioticassociatediarrheaInfectiveNon-infective

Allergicstate?

Symptomaticdiarrhea?Inappropriatefeeding?foodintoleranceLackofdisaccharidase?Immunodeficience?Malnutrition?Malabsorption?etc.Persistinginfection?EntamoebahistolyticGiardialambliaCryptosporidiumStaphylococcusClostridiumdifficileCandidaalbicans.69Diarrhea?Watery,loosestoolsTreatment.70Treatment.70MainlinesofmanagementFeedingFluidtherapyDrugs.71MainlinesofmanagementFeedin

1.Feedingduringdiarrhea

ContinuefeedingthechildGiveasmuchasthechildwantGivesmallfrequentfeedsEncourageanorexicchildtoeat.72

1.Feedingduringdiarrhea

Forbreast-fedContinuebreastfeedingasusualduringandafterdiarrheaandrehydrationtherapy.

1.Feedingduringdiarrhea

.73Forbreast-fedContinueb

Forformula-fed

Lowlactoseoflactose-freeformulaonlyincaseoflactoseintolerancechildren(rotavirus)

1.Feedingduringdiarrhea

.74Forformula-fed

ChildrenonMixedDietContinuenormalfeedingasusualGiverepeatedsmallfrequentfeedsAvoidtoosweetenedoroilyfoodsAvoidfoodscontainingahighfibercontent

1.Feedingduringdiarrhea

.75ChildrenonMixedDiet

1.Fe2.Fluidtherapy.762.Fluidtherapy.763.Drugsinthe

managementof

Diarrhea.773.Drugsinthe

managementofCommonlyuseddrugsindiarrheaAntimicrobialagentsAntiparasiticsProbiotics:lactobacilli,BifidobacteriaAntidiarrhealagents:adsorbantsandmucousmembraneprotectors:SMECTA.78CommonlyuseddrugsindiarrheAntimicrobialagentsAntimicrobialagentsarenotrecommendedforviraldiarrheainvasivepathogenandtoxicpathogeninfectionshouldchooseeffectiveantimicrobialagentsantibioticsshouldbestoppedorchangedfortheantibioticassociatediarrhea.79AntimicrobialagentsAntimicroFunctionsofNormalFloraDigestionProductionofvitaminsStimulationofhostimmuneresponseInhibitionofpathogenattachmentProductionofpathogeninhibitorysubstances.80FunctionsofNormalFloraDigesFluidTherapy.81FluidTherapy.81ORSTherapyinmildtomoderatedehydrationORSisthepreferredtreatmentforfluidandelectrolytelossescausedbydiarrhoeainchildrenwhohavemildtomoderatedehydration50-100ml/kgORStobegivenovera4-hourperiodWHOrecommendedORS

Highsodiumcontent90mmol/l.82ORSTherapyinmildtomoderatIntravenous

fluid

therapySeverelydehydratedorwhoareinastateofshockmustreceiveimmediateandaggressiveintravenousfluidtherapy

CompletecorrectingofthedeficitReplacingongoinglossofwaterandelectrolytesSupplythephysiologicalmaintenance.83IntravenousfluidtherapyCompPhaseI:Treatshock(0-30minutes)PhaseII:InitialRehydration(?-8hours)PhaseIII:ContinuedReplacement(8-24hours)10-20ml/kg0.9%NaClReassessImprovedNoChangeMeasureplasmaelectrolytesCalculatefluiddeficitandmaintenanceReviewplasmaelectrol

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