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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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