儿科学教学课件：缺铁性贫血

NUTRITIONAL

IRONDEFICIENCYANEMIA

（缺铁性贫血）CasestudyBoy,9monthsPalefor9months,cough3daysPretermtwins,birthweight2.7kg;BreastfeedinguntilnowHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALdateWBCNLRBCHbMCVMCHMCHCPLTRet4.2424.280.750.254.055661.513.82257794.25260.530.423.955561132277350.0224.26160.240.714.31686315276240.022Hypochromicmicrocyticanemia

？CasestudyHypochromicmicrocyticanemiaHbF1.40,HbA21.80%,血红蛋白电泳（-），SI6.15(11-30)umol/L,TIBC85(50-70)umol/L,TS7.2%.4.25CR:双肺纹理增多、紊乱、模糊、中内带见片絮影，双肺充气过度，心影胸腺部分重叠。肺炎。

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALWhatkindofAnemiaisthis?Classification-Etiology

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL造血减少所致贫血Reducedcapacitytoproduceredbloodcells--deficiencysyndrome溶血性贫血：Hemolysis失血性贫血：BloodLossIronandHemoglobinTheimpactofIDACONTENTSINDUCTIONIRONMETABOLISMETIOLOGY/PATHOGENESISMANIFESTATIONSLABORATORYFINDINGSDIAGNOSIS&DIFFERENTIALPREVENTION&TREATMENTINTRODUCTIONDefinitionoftheirondeficiencyanemia(IDA)由于体内铁缺乏最终导致储存铁减少血红蛋白合成减少所致的贫血N-IDA:Theanemiacausedbyinsufficientdietaryironuptake,inwhichtheironstorageandhemoglobinsynthesisdecreased.HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALClinicalcharacteristics(临床特征）铁生化：

serumferritin(SF),serumiron(SI),transferrinsaturation(TS)贫血：hemoglobinconcentration,microcytichypochromicanemia,治疗反应：goodresponsetoirontherapy.年龄：6moto3yrs.Incidence

INTRODUCTIONHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTheincidence:

InChina(2004)，aninvestigationfrom9118childrenin15provincesand26citiesreveledthattheincidenceis30.1%vs16.8%forthechildrenwith7～12mosand15.5%vs4.4%forthechildrenwith13～36mosIntheUSItisabout9%of1-2yr-oldsareirondeficient;3%haveanemia.Ofadolescentgirls,9%areirondeficientand2%haveanemia.INTRODUCTIONIRONMETABOLISMCOMPARTMENTHemoglobin64%Storageiron30%Ferritin-SFhemosiderinMyloglobin3%Enzymeiron0.4%Serumiron0.4%HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCONTENTSNewborn75mg/kgChildren35-70mg/kgAdultsM50mg/kgF35mg/kgIronsourcesHemoglobinironDietaryironHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALIRONMETABOLISMDietaryironHighinironRedmeat/liverkidney/oilyfishAverageironBeans/fortifiedcereals/darkgreenvegetables/driedfruit/nutsandseedsPoorinironMilk(1.5vs0.5mg/L)HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALIRONMETABOLISMIronabsorption

generalabsorption 1-20%Meat/fish/chicken 10-25%Cereals/vegetables 1%Breast/cow’smilk 50%/10%HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALIRONMETABOLISM 动物食品 非动物食品 (血红蛋白/肌红蛋白)（胶状氢氧化高铁）

胃酸胃蛋白酶 蛋白酶游离盐酸

血红素 三价铁

血红素分解酶

*VitC

肠： 二价铁

十二指肠空肠上 三价铁 肠黏膜细胞

转运铁蛋白* 入血

脱落入肠道

肝脾储存 骨髓造血

（图1）Ironabsorptionandtransportation

Ironstoresandutilizing食物铁血红素铁SIliverspleenBonemarrowHb合成肌红蛋白含铁酶IRONMETABOLISMRequirementandexcretion

demand

excretion

adults 1mg/d1mg/d 4mo-3yr 1mg//kg(15ug/kg/d) premature 2mg/kgHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

ETIOLOGY&PATHOGENESISETIOLOGY病因PoorironstoresPoordietaryintakeofiron*

OverdevelopChronicbleedingAbsorptionproblemsPoorironstoresPrematurebirthMultiplebirth/LowweightbirthCordbloodMotherironreservePoordietaryintakeofiron*overdevelopBloodlossandirondepletionHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

ETIOLOGY&PATHOGENESISPoorironstoresPoordietaryintakeofiron*MilkandcerealsFactorsinfluencingabsorptionOverdevelopBloodlossandirondepletionHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

ETIOLOGY&PATHOGENESIS

ETIOLOGY&PATHOGENESISPoorironstoresPoordietaryintakeofiron*Overdevelop3-5mo/1yrPrematurebirthPubertyChronicbleedingHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALPoorironstoresPoordietaryintakeofiron*overdevelopChronicbleedingCow’smilkHookworminfectionMenstruatingOthers:idiopathicpulmonaryhemosiderosis(肺含铁…）ulcer,gastritis(溃疡、胃炎）hemangioma,meckeldiverticulum.

ETIOLOGY&PATHOGENESISHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

ETIOLOGY&PATHOGENESISPoorironstoresoverdevelopPoordietaryintakeofiron*ChronicbleedingAbsorptionproblemsDiarrhea/Infection

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

ETIOLOGY&PATHOGENESISQA：Girl，llmoths,paleforonemonth,developmentisgood，noblackstool,nodiseasehistory，breast-fedonly.Birthweight3kg,now10kg.Motherisinhealth.DiagnosisisIDA.Thepossiblereason?A.poorironstore先天储铁不足B.poorironintake铁摄入量不足C.overdevelopment生长发育过快D.problemwithironabsorptionE.ironloose铁丢失过多HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALPathogenesisiron

+protoporphyrin

IDAheme+globinshemoglobinHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGY&PATHOGENESISID.Irondeficiency（铁减少期）decreasedironstore-SFIDE.Irondeficiencyerythropoiesis（红细胞生成铁减少期）decreasedironstore-SFIncreaseFEPIDA.Irondeficiencyanemia（缺铁性贫血期）decreasedironstore-SFIncreasedFEPSI,TIBC,TSHypochromic/microcyticanemiaETIOLOGY&PATHOGENESISPathogenesisHypochromic/microcyticanemiaID.IrondeficiencyIDE.IrondeficiencyerythropoiesisIDA.IrondeficiencyanemiaEnzymesImmunefunctionSkin/mucosalHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGY&PATHOGENESISFeatures特点Age:6mo~3yrsTheonsetoftheIDAThedegreeofanemiaHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATIONSPallor苍白Extramedullaryhematopoiesis髓外造血Theslightsplenomegalyisfoundin10-15%ofthecasesHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATIONSModerate/SevereconditionDigestivesystem食欲减低、恶心呕吐、腹泻、舌炎、胃炎Cardiacfunctiontachycardia,cardiacdilatationandsystolicmurmursareoftenpresentNeurology/intellectual神萎或烦躁、头晕、耳鸣、注意力不集中、反应迟钝、学习能力和智力ImmunefunctionHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATIONSHemoglobin:belowtheacceptablelevelforageRedcellindices:MCV<80fl,MCH<26ug,MCHC<0.31,highRDWBloodsmear:HypochromicsandmicrocyticwithanisocytosisandpoikilocytosisHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALLABORATORYFINDINGSReticulocytecount:isusuallynormalbutinsevereIDAassociatedwithbleeding,areticulocytecountof3-4%mayoccurPlateletcountItvariesfromthrombocytopeniatothrombocytosis.ThrombocytopeniaismorecommoninsevereIDA;thrombocytosisispresentwhenthereisassociatedbleedingfromthegut.FreeerythrocyteprotoporphyrinFEPelevationoccursassonasthebodystresofironaredepleted,beforemicrocyticanemiadevelops.AnelevatedFEPlevelisthereforeanincicationforirontherapyevenwhenanemiaandmicrocytosishavenotyetdeveloped.HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALLABORATORYFINDINGSSerumferritinItreflectsthelevelofbodyironstores;itisquantitative,reproducible,specificandsensitive.Aconcentrationoflessthan12ng/mlisconsidereddiagnosisofirondeficiency.SerumironandironsaturationpercentageSI：<9-10.7umol/L(12.8-31.3umol/L) or<50-60ug/dl(75-175ug/dl）TIBC：>62.7umol/L(>350ug/dl)TS：<15%（30-50%）HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALLABORATORYFINDINGSSerumtransferrinreceptorlevels(STfR)ItssensitiveandcorrelateswithHbandotherLabparametersofironstatus.ItisincreasedininstancesofhyperplasiaoferythroidprecursorssuchasIDAandthalassemiaItisunaffectedbyinfectionandinflammationBonemarrow:Erythroidhyperplasia;StainableironHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALLABORATORYFINDINGSHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

NormalIDIDEIDAMarrowiron+++0SF(ug%)1006010-20FEP

SITIBCTS

HbMCVMCH

DiagnosisImpression6月-24月/36月生产史、喂养史小细胞低色素性贫血Diagnosis：biochemicalchangeSF减低；FEP升高；SI减低，TIBC升高，TS降低ProvenbytherapyHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALDIAGNOSIS&DIFFERENTIALTypicalpictureHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTable3-8DiagnosticTestsforIron-deficiencyAnemiaBloodsmearHypochromicmicrocyticredcells,confirmedbyRBCincices:MCVlessthannromalrangeofageMCHlessthan27.0pgMCHClessthan30%RDWgreaterthan14.5%Freeerythrocyteprotoporphyrin:elevatedSerumferritin:decreasedSerumironandironbingdingcapacityDecreasedserumironIncreasedironbindingcapacityDecreasedironsaturation(16%orless)Serumtransferrinreceptorlevel：elevatedBonemarrowDealyedcytoplasmicmaturationDecreasedorabsentstainalbeironTherpeuticresponsestooralironReticulocytosiswithpeak5-10daysafterinstitutionoftherapyFollowingpeakreticulocytosisHblevelrisesonanverageby0.25-0.4g/dl/dyorhematocritrises1%/dayDifferential地中海贫血alassemia慢性Chronic&inflammatorydiseases肺含铁血黄素沉着症Pulmonaryhemosiderosis铁粒幼细胞贫血SiderblasticanemiaHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALDIAGNOSIS&DIFFERENTIALDifferential—Thalassemia是血红蛋白珠蛋白肽链合成障碍引起的一组遗传性溶血性贫血。地区性明显，有家族史；轻型临床上难以区别，重型常有特殊面容，肝脾肿大明显；外周血涂片可见靶形红细胞和有核红细胞血红蛋白检查显示胎儿血红蛋白水平异常增高或血红蛋白电泳出现异常成分区带；血清铁增高，骨髓铁粒幼细胞增多HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALDIAGNOSIS&DIFFERENTIAL

TREATMENTGeneralcareEradicatethecauses*Ironsupplementation*TransfusionHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL原则去除病因补充铁剂

治疗

(Treatment)QA哪些因素或病因是可以预防的？哪些因素或病因是可以去除的？

治疗

(Treatment)NutritionalCounselingMaintainbreastfeedingforatleast6moUseaniron–fortifiedinfantformulauntil1yearageUseiron–fortifiedcerealfrom6mo-1yearProvidesupplementalironforlowbirthweightinfants:Infants1.5-2.0kg:2mg/kg/dsupplementalironInfants1.0-1.5kg:3mg/kg/dsupplementalironInfants<1.0kg:4mg/kg/dsupplementalironFacilitatorsofironabsorptionsuchasVC-richfoods,meat,fishandpoutryshouldbeincludedinthedietandinhibitorsofironabsorptionsuchtea,phosphateandphytatescommoninvegetariandietsshouldelinminatedIronsupplementation（补铁）Elementaliron：4-6mg/kg/dOralironmedicationTypes-ferrousformAdministrationBetweenmealsVitaminCCourse:6-8weeksafterHbnormalization

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

TREATMENTFerrousSalts4mg/kg/dFerroussulfate（20%）(硫酸亚铁）20mg/kg/dferrousfumarate

(30%）（富马酸亚铁）13mg/kg/dFerrousgluconate（11%）（葡萄糖酸亚铁）40mg/kg/dHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTable:FerroussaltsanttheironcontentsIronsupplementation（补铁）Parenteraliron（胃肠外注射铁）

Indication:intoleranttooralironorabsorptionproblemtypes：HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

TREATMENT

IRONTHERAPYRESPONSE（fromNelson）timeresponse12-24hrReplacementofironenzymes,subjectiveimprovement36-48hrInitialmarrowresponse:erythroidhyperplasia48-72hrReticulocytespeaking5-7d4-30daysHemoglobinlevel1-3moReplenishofstoresHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTREATMENTTransfusion（输血）IndicationsSevereanemiaInfectionPre-operationComponent：redbloodcellsVolume：Hb<30g/L,3-5ml/kg Hb30-60g/L,5-10ml/kgAttentionsHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALPREVENTION预防EducationForpregnantwomenFortermBreastmilk/cow’smilkIronrichsupplementaryfoodIron-fortifiedfoodForprematureinfantHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALMegaloblasticAnemia

(营养性巨幼细胞贫血)INTRODUCTIONDefinition:AkindofanemiawithlargerRBC,causedbythedeficiencyoffolicacidand/orvitaminB12Clinicalfeatures:macrocyticanemia,neuropsychiatricchanges,megaloblasticRBCinthebonemarrow,responsetovitaminB12andfolicacidwell.Theincidence:changingfromcommontorare

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGY

Inadequateintake

DecreasedabsorptionDruginducedabnormalitiesCongenitalabnormalitiesHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGYInadequateintake

AllweneedofB12andfolateisfromfood;Therequirement:forB12:1ug/d;forfolate:60-100ug/d(WHO)Underclinicalconditionswherethereareincreasedvitaminrequirements(pregnancy,growthininfancy,chronichemolysis).HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGYInadequateintakeFolatesabundantinmanyfoodsincludinggreenvegetables,fruits,andanimalorgans(liver,kidney).Humanbreastmilk,pasteurizedcow'smilk.andinfantformulasprovideadequateamountsoffolicacid.Goat'smilkisdeficient;folicacidsupplementationmustbegivenwhenitisthemainfood.Unlesssupplemented,powderedmilkmayalsobeapoorsourceoffolicacid.HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGYInadequateintakeVitaminB12VitaminB12(cobalamin)ispresentinmanyfoods,mostlyinanimalfoods,VitaminB12deficiencymayoccurinthecasesofextremedietaryrestriction(strictvegetariansorvegans)

occursinbreast-fedinfantswhosemothersarevegansorthemselveshaveperniciousanemiaHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGYDecreasedabsorptionChronicdiarrheaInflammatorydiseasesNeonatalnecrotizingenterocolitisSurgeryininterestine/terminalileumHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGYDruginducedabnormalitiesCertainanticonvulsantdrugs(e.g.,phenytoin,primidone,phenobarbital)canimpairabsorptionoffolicacid

Anumberofdrugshaveanti–folicacidactivity:MethotrexateHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGYCongenitalabnormalitiesCcongenitaldihydrofolatereductasedeficiencyLackofintrinsicfactor-CongenitalperniciousanemiaTranscobalaminII(TC-II)deficiency

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALPATHOGENESIS

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALVitamin12↓Folicacid↓FolicacidreductaseDNASynthesis↓

TetrahydrofolicacidNucleotidePATHOGENESISInfluenceonhematopoiesis(造血）MegaloblasticRBCDecreasedDNAsynthesisdelaysthematurationofthenucleusoferythrocytesNeutrophilandMegakaryocytehypersegmentedneutrophils(manyneutrophilswithmorethanfourtofivelobes).Ineffectiveerythropoiesis（无效造血）thatdescribesactiveerythropoiesiswithprematuredeathofcells,adecreasedoutputofRBCfromthemarrow,and,consequently,anemia.HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALPATHOGENESISInfluenceonneurological

systemVitaminB12playsimportantroleinkeepingtheintactofthenervefiberscontainingmyelinsheathThedeficientresultinneuropsychiatricchangesHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATION

General一般情况6～18moWeakness,fatigue,orirritability,failuretothrive,glossitis,vomiting,diarrheaHair:lessandyellowish.Anemia血液系统:Paleandpuffyicterus;PetechiaHepatomegaly/splenomeaglyHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATION

Neurologicalinvolvement（神经系统）developmentaldelay,developmentalregressionTrembles,seizuresparesthesias,sensorydeficits,hypotonianeuropsychiatricchanges.

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALNeurologicproblemsfromvitaminB12deficiencycanoccurintheabsenceofanyhematologicabnormalitiesLABFINDINGS

MacrocyticnormochromicanemiaNeutrophilsmay