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INFANTILEDIARRHEACHCUMSDIVISIONOFINFECTIOUSDISEASEANDGASTROENTEROLOGYINFANTILEDIARRHEA1Background

Diarrheaisaclinicalsyndromeofdiverseetiologyassociatedwithmanyinfluencingfactors.Itisthemostfrequentchildhooddiseasesecondonlytotherespiratoryinfection.Themajorcauseofdeathamongworld’schildrenandthenumberonekillerofchildrenunderfiveinmanydevelopingcountries.2DiseaseBurden

Worldwide

3-5billionepisodes/year

4-5milliondeaths/year

Childrenarethepredominantpopulations.

3.2billionepisodes/yearin<5ychildren

1.3milliondeaths/yearin<5ychildren

InChina

836millionepisodesofdiarrheaeveryyear

1/4-1/3ofalloutdoorpatientsandalargeamountofhospitalizationsofchildrenareduetodiarrhea3

FluidityVolumeNumberInpediatrics,diarrheaisdefinedasanincreaseintherelativetotheusualhabitsofeachindividualofstoolsDefinition4NormalStoolofChildrenBreastfedbabies:

passstools3-4timesadayyellowloose(softtorunny)buttexturedsweet-smellingBottlefedbabies:

onceadaypaleyelloworyellowish-brownbulkierandmoreformedprettypungentBabiesonsolids:

thickenanddarkenslightlyhaveastrongerodor5DehydrationMalnutritionMortalityWhydiarrheaismoredangerousforchildren?6MalnutritionandChildMortality7If:Diarrhea+MalnutritionThe

RISK

of

DEATH

is

4fold

higherthan

thatofwellnourishedchildren8Whychildrenarehighlyvulnerabletodiarrhea?

ImmaturedigestivesystemMorenutritiondemandWeaknessofdefensesystemThenormalintestinalflorahavenotbuiltupwell

Bottlefeeding9EtiologyofDiarrhea10EtiologyofDiarrheaInfectiveNoninfectiveVirusesBacteriaParasitesFungi

Allergic

Symptomatic

Inappropriate

feeding

Food

intolerance

Climate11ViralEnteropathogensViralenteropathogenscausemostillnessesinpediatricpopulation.

Rotavirus

(mornthan50%acutediarrhea)

AstrovirusNorwalkvirus

Coronavirus

CalicivirusEntericadenovirus(serotypes40and41)12Rotavirus13Themostmoncauseofchildhooddiarrheasecondonlytotheviralenteropathogens

Escherichiacoli

EPEC;ETEC;EITC;EHEC;EAEC

Campylobacterjejuni

ShigellaspeciesSalmonellatyphimurium

Yersinia

enterocoliticaStaphylococcusaureus

Clostridiumdifficile

Vibrio

choleraeBacterialEnteropathogens14Rareetiologicpathogenofdiarrhea

Cryptosporidiumparvum

Entamoebahistolytic

Giardia

lamblia

ParasitesPathogens15Rareetiologicpathogenofdiarrhea

Candidaalbicans

Aspergillus

Mucor

FungousPathogens16Themostimportantinfectivecausesofacutediarrheaindevelopingcountriesinchildrenare:Rotavirus

Enterotoxigenic

escherichiacoli

ShigellaCampylobacterjejuniSalmonellatyphimurium17EtiologyofDiarrheaInfectiveNoninfectiveVirusesBacteriaParasitesFungi

Allergic

Symptomatic

Inappropriate

feeding

lactose

intolerance

Climate18OverfeedingIndigestibledietSuddenchangeofformula

Inappropriatefeedingforamilk-fedbabyshiftingintosolidfood(toomuch,tooearly,toorapid…)

DietaryDiarrheaInappropriatefeeding:19AllergicDiarrheaPrimaryfoodhypersensitivity:

3monthsafterbirth

Secondfoodhypersensitivity:

Infection→injuryandhyperpermeabilityofintestinalmucosa→

largemolecularproteinenteringbloodstream→

allergicstateCow'smilkproteinSoybeanproteinEggwhite

peanuts,meat,andfishetc.20

SymptomaticDiarrheaDiarrheaisonlyoneofthesymptomsofprimarydisease.Problemisnotoriginallylocatedinintestinaltract.Respiratorytractinfection

OtitismediaSomeinfectiousdiseases,etc.Alwaysbemild,andrecoverwiththeprimarydiseasegettingbetterTheyoungerthechildren,themorechancetogetasymptomaticdiarrheaacpaniedbyotherdiseases.21

LackofDisaccharidaseLactose

IntolerancePrimaryDisaccharidaseDeficiencyisararedisease(congenitaldefectsofcarbohydratehydrolysis).SecondDiaccharidaseDeficiency

:Rotavirusinfection

→Injurestheenterocytesofvilli

→Transientdisaccharidasedeficiency→Malabsorptionoflactoseinthemilk→

Typicallooseandwaterystools22

ClimateSeasonalvariation

affectsthedigestivefunctionofsmallchildren:incidenceofdiarrheaishighestduringtheearlyraninyseasonColdweather

causesincreasingofenterokinesiaHotweather

causesdecreasingofdigestiveenzymeandmalfunctionofdigestivetract

……23PathophysiologicalMechanismsofDiarrhea24VirusDiarrhea-Rotavirus

EnterotoxigenicEnteritis–ETEC,Vibrio

Cholerae

Entero-InvasiveOrganisms–

ShigellaSpecies,EIECDietaryDiarrheaPathophysiologicalMechanismsofDiarrhea25PathogenesisofVirusDiarrheaVirusinvadestheabsorptiveenterocytesofvillibutsparescryptcellsThevirusesreplicatesandinfectedenterocytesaredestroyedRotavirus26PathogenesisofVirusDiarrhea1-Infectedabsorptiveenterocytesarekilledcausingpatchyepithelialcelldestructionandvillousshortening2-Destroyedabsorptivecellsarerapidlyreplacedbycellsthatmigratefromthecrypts.Villi

beecoveredwithimmaturenon-absorptivesecretorycellshaving:-nobrushborder-nobrushborderenzymesOsmotic

Diarrhea27PathogenesisofVirusDiarrhea

(OsmoticDiarrhea)Rotavirusesattachandreplicateinthematureenterocytesatthetipsofsmallintestinalvilli

Destroyvillustipcells,variabledegreesofvillusbluntingmononuclearinflammatoryinfiltrateinthelaminapropria

ImpairmentofdigestivefunctionsdiscreasinghydrolysisofdisaccharidesImpairmentofabsorptivefunctionsthetransportofwaterandelectrolytesviaglucoseandaminoacidco-transportersAnimbalanceintheratioofintestinalfluidabsorptiontosecretionMalabsorptionofplexcarbohydrates,particularlylactoseOtherthandegestedintomonosaccharide,lactosebelysisintoorganicacid,hyperosmosis

Waterystool28VirusDiarrhea-Rotavirus

Enterotoxigenicenteritis–

ETEC,Vibrio

Cholerae

Entero-InvasiveOrganisms–

ShigellaSpecies,EIECDietarydiarrheaPathophysiologicalMechanismsofDiarrhea29PathogenesisofEnterotoxigenic

DiarrheaPathogens:

Vibrio

cholerae(cholera)ETECStaphylococcusaureusClostridiumdifficile30enterotoxigenicorganismsIngestionsmallbowelmucosaandproliferate

activatescellular

guanylatecyclase

Heat-stableenterotoxin

increasedintracellularconcentrationsofcAMP

activatescellularadenylcyclase

bindstoreceptorsofepithelialcellsHeat-labileenterotoxin

decreaseabsorptionofsodiumandchloridebyvillouscellsincreasedintracellularconcentrationsofcGMP

Secretory

diarrheaPathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

31PathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

1-EnterotoxigenicBacteriasecreteEnterotoxins2-ToxinstimulatestheproductionofC-AMPIncreasedC-AMPleadsto:3-InhibitionofabsorptionofNaandClfromthecellsofvilli4-StimulationofsecretionofClfromcryptcells+++---1234123432PathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

Themucosaisnotdestroyedduringthisprocess33Animbalanceintheratioofintestinalfluidabsorptiontosecretion,sowaterystoolmayoccurinclinicalobservationPathogenesisofEnterotoxigenicDiarrhea(SecretoryDiarrhea)

34Enterotoxigenic

DiarrheaClinicalfinding:Waterydiarrheaandvomitingdevelopafteranincubationperiodof6hr-5days(2-3days,average)Low-gradefeveroccursinsomechildrenProfuse,painless,waterydiarrhea,sometimeswithflecksofmucusbutnobloodFluidandelectrolytelosses,tachycardia,tachypnea,asunkenanteriorfontanel,progresstocirculatorycollapse35VirusDiarrhea-Rotavirus

Enterotoxigenicenteritis–ETEC,Vibrio

Cholerae

Entero-InvasiveOrganisms–

ShigellaSpecies,EIECDietarydiarrheaPathophysiologicalMechanismsofDiarrhea36InvasiveDiarrheaEntero-InvasiveOrganisms:

ShigellaspeciesEIEC(enteroinvasiveE.coli)CampylobacterjejuniSalmonellatyphimurium

Yersinia

enterocoliticaThecentraleventinpathogenesisisinvasionofcolonicmucosa37PathogenesisofInvasiveDiarrheaInvasiveenteropathogenIngestionGutlumenColonandrectummucousmembraneproper

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

inflammatorycellsandmucus38PathogenesisofInvasiveDiarrhea39InvasiveDiarrheaClinicalfinding:Stoolsthatarefrequentandscantyandthatcontainbloodinflammatorycells,andmucusStoolexamination:largeamountofWBC,puscell,andRBCDehydrationandelectrolytedisturbancesarelessfrequentbecauseoflesslossofdigestivefluid40VirusDiarrhea-Rotavirus

Enterotoxigenicenteritis–ETEC,Vibrio

Cholerae

Entero-InvasiveOrganisms–

ShigellaSpecies,EIECDietarydiarrheaPathophysiologicalMechanismsofDiarrhea41PathogenesisofDietaryDiarrheaInappropriatedietIrritatesthebowelPromotetheperistalsisWaterenteringthelumenDeposedproductamineslactic

acidaceticacid

AciditydecreasingGivethechancetothebacteriawhichlivedinlowerpartofbowelingupEndogenousinfectionAggravatetheintestinalfunctiondisturbanceIndigestedfoodaccumulateintheupperpartofintestineDyspepsia

Indigestedfood

fermentandputrescenceHyperosmosisDiarrhea42MorphologyofIntestinalMucosa43MorphologyofIntestinalMucosaVillicoveredmainly(90%)bytallcolumnarabsorptivecells

(Enterocytes)havingamicrevillarbrushborderCryptsoflieberkuhnCoveredmainlybyshortcolumnarsecretorycellsGobletcellswithoutbrushborder44DefenseBarriersoftheEnterocytes1.Physicalbarrier:mucus2.Bacteriological(flora)3.Immunological:Secretory

IgA12345NormalFloraBreast-fed:AGram-positivepopulation:BifidobacteriaandLactobacilli

Bottle-fed:AGram-negativeflora:Enterobacteriaceae46ClinicalManifestations47ClinicalmanifestationsGastrointestinalsymptomSystemicsymptomDehydrationandelectrolytedisturbances48Assessmentofachildwithdehydration&electrolytedisturbances

49DehydrationExcessivelossofwater,especiallylossofextracellularfluid.50515253AssessmentofaDehydration54Typeofdehydration55

serumpotassium<3.5mmol/LEtiologyExcessiveoflossInsufficientintakeDistributionaldisturbanceofextracelluarandintracelluarpotassiumHypopotassaemia56(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/L57

serumcalcium<1.88mmol/L

HighnervousandmuscularexcitabilityHypocalcemia

58

1etiology

(1)lossofalkalinesubstancefromGItrack(2)acidsubstanceaccumulationinbodyH+排除↓

2manifestations:

hyperpnoea、increasedheartrate、seriselip、consciousdisturbancefortheseverecases

H+產(chǎn)生↑MetabolicAcidosis59ClassificationofDiarrheabasedon……SeverityDurationEtiology60ClassificationofDiarrhea1.Milddiarrhea:

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

Mostofthecasesareinfectiousdiarrhea(rotavirus,shigella)Frequencyofstooloftenmorethan10times/dayWaterystool,plentyofmucus.Generalconditionispoor,usuallyacpanywithvomitingandfever,dehydrationandelectrolytedisturbance61Acutestage:thecourseofthediseaseslessthan2weeksPersistingtype:thecourseofdiseasemorethan2weeksbutlessthan2monthsChronicstage:thecourseofdiseasemorethan2monthsClassificationofDiarrhea62PersistingandChronicDiarrhea

plicatereasons:Persistinginfection,Allergicstate,Lackofdisaccharidase,Immunodeficience,Broadspectrumantibioticusage,Malnutrition,Malabsorption,etc.

PathogenesisisnotclearGreatdangerous:MalnutritionandgrowthretardationMortalityishighTroublesometobecontrolled:AdequatecaloriesReestablishthenormalflora

63RotavirusesInfection64RotavirusesinfectionHistory:Firstrecognizedinhumansin1973byAustralianScientistBishop,withahubbedwheelappearanceunderelectronmicroscope,givingtheirname

Virology:Double-strandedRNAvirusVP6:A-Ggroup,groupAisthemostimportantgroupinchildhoodinfection65RotavirusesinfectionPeakseason:Deepfallandwinter(October-February)Causingsharplyincreasingofoutdoorpatients

inautumnandwinter,alsonamedautumndiarrheaPeakage:6m-2y,rarelyhappeninchildrenabove4yDiseaseburden:80%infectiousdiarrheainpediatricclinicinautumnandwinterAbout1/4to1/3(morethan800cases)hospitalizeddiarrheachildrenarecausedbyrotavirusinourwardeveryyear66RotavirusesinfectionClinicalmanifestations:Onsetofsuddenfever,respiratorytractsymptoms

Vomiting,wateryorsoftstoolthatlackgrossbloodormucusSeveredehydrationthaninfectionbyotherviralpathogens

plicationsandfatalitiesarerelatedalmostexclusivelytotheadverseeffectsofdehydration,electrolyteimbalance,andacidosisMalnutritionisariskfactorforsevereconsequences

DisaccharidesIntolerance

Laboratoryfindings:SpecificantigensinstoolspecimenremendedbyWHO67Diagnosis68Diarrhea?

Watery,loosestoolswithoutoronlyaminuteamountofWBCEpidemicdataStoolcultureSerousassayStoolcultureSerousassayShigellaspeciesEIECCampylobacterjejuniSalmonellatyphimurium

Yersinia

enterocoliticaVirusDiarrheaETEC,EPECLotsofWBCandRBC,mucusinstoolsAcutestagePersistingorchronicdiarrheaAntibioticassociatediarrheaInfectiveNon-infective

Allergicstate?

Symptomaticdiarrhea?Inappropriatefeeding?foodintoleranceLackofdisaccharidase?

Immunodeficience?Malnutrition?Malabsorption

?etc.Persistinginfection?Entamoebahistolytic

Giardia

lamblia

CryptosporidiumStaphylococcusClostridiumdifficileCandidaalbicans

69Treatment70MainlinesofmanagementFeedingFluidtherapyDrugs71

1.Feedingduringdiarrhea

ContinuefeedingthechildGiveasmuchasthechildwantGivesmallfrequentfeedsEncourageanorexicchildtoeat72

Forbreast-fedContinuebreastfeedingasusualduringandafterdiarrheaandrehydrationtherapy.

1.Feedingduringdiarrhea

73

Forformula-fed

Lowlactoseoflactose-freeformulaonlyincaseoflactoseintolerancechildren(rotavirus)

1.Feedingduringdiarrhea

74

ChildrenonMixedDietContinuenormalfeedingasusualGiverepeatedsmallfrequentfeedsAvoidtoosweetenedoroilyfoodsAvoidfoodscontainingahighfibercontent

1.Feedingduringdiarrhea

752.Fluidtherapy763.Drugsinthe

managementof

Diarrhea77monlyuseddrugsindiarrheaAntimicrobialagents

Antiparasitics

Probiotics:lactobacilli,

Bifidobacteria

Antidiarrhealagents:adsorbantsandmucousmembraneprotectors:SMECTA78AntimicrobialagentsAntimicrobialagentsarenotremendedforviraldiarrheainvasivepathogenandtoxicpathogeninfectionshouldchooseeffectiveantimicrobialagentsantibioticsshouldbestoppedorchangedfortheantibioticassociatediarrhea79FunctionsofNormalFloraDigestionProductionofvitaminsStimulationofhostimmuneresponseInhibitionofpathogenattachmentProductionofpathogeninhibitorysubstances80FluidTherapy81ORSTherapyinmildtomoderatedehydrationORSisthepreferredtreatmentforfluidandelectrolytelossescausedbydiarrhoeainchildrenwhohavemildtomoderatedehydration50-100ml/kgORStobegivenovera4-hourperiodWHOremendedORS

Highsodiumcontent90mmol/l82Intravenous

fluid

therapySeverelydehydratedorwhoareinastateofshockmustreceiveimmediateandaggressiveintravenousfluidtherapy

pletecorrectingofthedeficitReplacingongoinglossofwaterandelectrolytesSupplythephysiologicalmaintenance83PhaseI:Treatshock(0-30minutes)PhaseII:InitialRehydration(?-8hours)PhaseIII:ContinuedReplacement(8-24hours)10-20ml/kg0.9%NaClReassessImprovedNoChangeMeasureplasmaelectrolytesCalculatefluiddeficitandma

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