NUTRITIONAL

IRONDEFICIENCYANEMIA

（缺鐵性貧血）JieYu

MD.ProfessorTheDepartmentofPediatricsHematology/Oncology,Children’sHospitalCasestudyBoy,9monthsPalefor9months,cough3daysPretermtwins,birthweight2.7kg;BreastfeedinguntilnowHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALdateWBCNLRBCHbMCVMCHMCHCPLTRet4.2424.280.750.254.055661.513.82257794.25260.530.423.955561132277350.0224.26160.240.714.31686315276240.022Hypochromic

microcyticanemia

？CasestudyHypochromic

microcyticanemiaHbF1.40,HbA21.80%,血紅蛋白電泳（-），SI6.15(11-30)umol/L,TIBC85(50-70)umol/L,TS7.2%.4.25CR:雙肺紋理增多、紊亂、模糊、中內(nèi)帶見(jiàn)片絮影，雙肺充氣過(guò)度，心影胸腺部分重疊。肺炎。

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALWhatkindofAnemiaisthis?Classification-Etiology

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL造血減少所致貧血Reducedcapacitytoproduceredbloodcells--deficiencysyndrome溶血性貧血：Hemolysis失血性貧血：BloodLossIronandHemoglobinTheimpactofIDACONTENTSINDUCTIONIRONMETABOLISMETIOLOGY/PATHOGENESISMANIFESTATIONSLABORATORYFINDINGSDIAGNOSIS&DIFFERENTIALPREVENTION&TREATMENTINTRODUCTIONDefinitionoftheirondeficiencyanemia(IDA)由于體內(nèi)鐵缺乏最終導(dǎo)致儲(chǔ)存鐵減少血紅蛋白合成減少所致的貧血N-IDA:Theanemiacausedbyinsufficientdietaryironuptake,inwhichtheironstorageandhemoglobinsynthesisdecreased.HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALClinicalcharacteristics(臨床特征）貧血：hemoglobinconcentration,microcytic

hypochromicanemia,鐵生化：

serumferritin(SF),serumiron(SI),transferrinsaturation(TS)治療反應(yīng)：goodresponsetoirontherapy.年齡：6moto3yrs.Incidence

INTRODUCTIONHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTheprevalence:

InChina(2004)，aninvestigationfrom9118childrenin15provincesand26citiesreveledthattheprevalenceis30.1%vs16.8%forthechildrenwith7～12mosand15.5%vs4.4%forthechildrenwith13～36mosIntheUSItisabout9%of1-2yr-oldsareirondeficient;3%haveanemia.Ofadolescentgirls,9%areirondeficientand2%haveanemia.INTRODUCTIONINTRODUCTIONHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALIRONMETABOLISMCOMPARTMENTHemoglobin64%Storageiron30%Ferritin-SFhemosiderinMyloglobin

3%Enzymeiron0.4%Serumiron0.4%HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCONTENTSNewborn75mg/kgChildren35-70mg/kgAdultsM50mg/kgF35mg/kgIronsourcesHemoglobinironDietaryironHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALIRONMETABOLISMIronsources:Hemoglobiniron+DietaryironHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALIRONMETABOLISMironBMBMIRON-SIIRON-HbSPLEENIronDietaryironHighinironRedmeat/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’SHOSPITALIRONMETABOLISMFe 動(dòng)物食品 非動(dòng)物食品 (血紅蛋白/肌紅蛋白)（膠狀氫氧化高鐵）

胃酸胃蛋白酶 蛋白酶游離鹽酸

血紅素 三價(jià)鐵

血紅素分解酶

*VitC

腸： 二價(jià)鐵

十二指腸空腸上 三價(jià)鐵 腸黏膜細(xì)胞

轉(zhuǎn)運(yùn)鐵蛋白* 入血

脫落入腸道

肝脾儲(chǔ)存 骨髓造血

（圖1）IronabsorptionandtransportationFIGURE12-2

Duodenalirontransfer.Ironistakenupbyenterocytesliningtheduodenalvilli.Theseabsorptivecellsstartoutasundifferentiatedprecursorsintheintestinalcrypts.Cryptcellsappeartobeprogrammedforanironabsorption“set-point”thatisdeterminedinresponsetoironneeds.Asthecellsdifferentiate,theymigrateupthevilliandbegintoexpressirontransporterproteins.Accordingtocurrentmodels,nonhemeironuptakeoccursinmatureenterocytesthroughtheenzymaticreductionofiron,transmembraneimportintothecellbyDMT1,transmembraneexportfromthecellbyferroportin,andenzymaticoxidationbyhephaestinbeforeloadingontoapotransferrintoproducediferric

transferrin(HOLO-TF).

NatRevGenet.2000;1:208-217.)鐵吸收的調(diào)節(jié)

REGULATIONTfR腸黏膜細(xì)胞↑鐵吸收利用缺鐵

Ironstoresandutilizing食物鐵血紅素鐵SIliverspleenBonemarrowHb合成肌紅蛋白含鐵酶IRONMETABOLISMRequirementandexcretion

demand

excretion

adults 1mg/d1mg/d 4mo-3yr 1mg//kg(15ug/kg/d) premature 2mg/kgHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALSummaryandkeypointsIroncompartmentorfunctionHbStores(SF-hemosiderin)MyloglobinEnzymeSerumironIronsourcesIronabsorptionandtransportationSF/SI/TIBCIrondailyrequirementandexcretionIRONMETABOLISMHEMATOLOGY/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

(肺含鐵…）ulcer,gastritis(潰瘍、胃炎）hemangioma,meckel

diverticulum.

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先天儲(chǔ)鐵不足B.poorironintake鐵攝入量不足C.overdevelopment生長(zhǎng)發(fā)育過(guò)快D.problemwithironabsorptionE.ironloose鐵丟失過(guò)多HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALPathogenesisiron

+protoporphyrin

IDAheme+globinshemoglobinHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGY&PATHOGENESISID.Irondeficiency（鐵減少期）decreasedironstore-SFIDE.Irondeficiencyerythropoiesis

（紅細(xì)胞生成鐵減少期）decreasedironstore-SFIncreaseFEPIDA.Irondeficiencyanemia（缺鐵性貧血期）decreasedironstore-SFIncreasedFEPSI,TIBC,TSHypochromic/microcyticanemiaETIOLOGY&PATHOGENESISPathogenesisHypochromic/microcyticanemiaID.IrondeficiencyIDE.IrondeficiencyerythropoiesisIDA.IrondeficiencyanemiaEnzymesImmunefunctionSkin/mucosalHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALETIOLOGY&PATHOGENESISFeatures特點(diǎn)Age:6mo~3yrsTheonsetoftheIDAThedegreeofanemiaHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATIONSPallor蒼白Extramedullary

hematopoiesis

髓外造血Theslightsplenomegalyisfoundin10-15%ofthecasesHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATIONSModerate/SevereconditionDigestivesystem食欲減低、惡心嘔吐、腹瀉、舌炎、胃炎Cardiacfunctiontachycardia,cardiacdilatationandsystolicmurmursareoftenpresentNeurology/intellectual神萎或煩躁、頭暈、耳鳴、注意力不集中、反應(yīng)遲鈍、學(xué)習(xí)能力和智力ImmunefunctionHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALCLINICALMANIFESTATIONSHemoglobin:belowtheacceptablelevelforageRedcellindices:MCV<80fl,MCH<26ug,MCHC<0.31,highRDWBloodsmear:Hypochromicsandmicrocyticwithanisocytosisandpoikilocytosis

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALLABORATORYFINDINGSReticulocytecount:isusuallynormalbutinsevereIDAassociatedwithbleeding,areticulocytecountof3-4%mayoccurPlateletcountItvariesfromthrombocytopeniatothrombocytosis.ThrombocytopeniaismorecommoninsevereIDA;thrombocytosisispresentwhenthereisassociatedbleedingfromthegut.FreeerythrocyteprotoporphyrinFEPelevationoccursassonasthebodystresofironaredepleted,before

microcyticanemiadevelops.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月生產(chǎn)史、喂養(yǎng)史小細(xì)胞低色素性貧血Diagnosis：biochemicalchangeSF減低；FEP升高；SI減低，TIBC升高，TS降低ProvenbytherapyHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALDIAGNOSIS&DIFFERENTIALTypicalpictureHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTable3-8DiagnosticTestsforIron-deficiencyAnemiaBloodsmearHypochromic

microcyticredcells,confirmedbyRBCincices:MCVlessthannromalrangeofageMCHlessthan27.0pgMCHClessthan30%RDWgreaterthan14.5%Freeerythrocyteprotoporphyrin:elevatedSerumferritin:decreasedSerumironandironbingdingcapacityDecreasedserumironIncreasedironbindingcapacityDecreasedironsaturation(16%orless)Serumtransferrinreceptorlevel：elevatedBonemarrowDealyed

cytoplasmicmaturationDecreasedorabsentstainalbeiron

TherpeuticresponsestooralironReticulocytosiswithpeak5-10daysafterinstitutionoftherapyFollowingpeakreticulocytosis

Hblevelrisesonanverageby0.25-0.4g/dl/dyorhematocritrises1%/dayDifferential地中海貧血alassemiaChronic&inflammatorydiseases肺含鐵血黃素沉著癥Pulmonaryhemosiderosis鐵粒幼細(xì)胞貧血SiderblasticanemiaHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALDIAGNOSIS&DIFFERENTIALDifferential—Thalassemia是血紅蛋白珠蛋白肽鏈合成障礙引起的一組遺傳性溶血性貧血。地區(qū)性明顯，有家族史；輕型臨床上難以區(qū)別，重型常有特殊面容，肝脾腫大明顯；外周血涂片可見(jiàn)靶形紅細(xì)胞和有核紅細(xì)胞血紅蛋白檢查顯示胎兒血紅蛋白水平異常增高或血紅蛋白電泳出現(xiàn)異常成分區(qū)帶；血清鐵增高，骨髓鐵粒幼細(xì)胞增多HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALDIAGNOSIS&DIFFERENTIALGeneralcareEradicatethecauses*Ironsupplementation*TransfusionHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL原則去除病因補(bǔ)充鐵劑

PREVENTION&TREATMENT預(yù)防和治療(Treatment)QA哪些因素或病因是可以預(yù)防的？哪些因素或病因是可以去除的？預(yù)防(Prevention)NutritionalCounseling喂養(yǎng)指導(dǎo)Maintainbreastfeedingforatleast6moUseaniron–fortifiedinfantformulauntil1yearageUseiron–fortifiedcerealfrom6mo-1yearFacilitatorsofironabsorptionsuchasVC-richfoods,meat,fishandpoutryshouldbeincludedinthedietandinhibitorsofironabsorptionsuchtea,phosphateandphytatescommoninvegetariandietsshouldelinminated預(yù)防(Prevention)Preterm早產(chǎn)兒whoisfedhumanmilkshouldreceiveasupplementofelementalironat2mg/kgperday,by1mo-12moWhoisfedastandardformulawillreceiveapproximately2mg/kgperdayofiron預(yù)防(Prevention)Term,BreastfedInfantsTherefore,at4monthsofage,breastfedinfantsshouldbesupplementedwith1mg/kgperdayoforalironuntilappropriateiron-containingcomplementaryfoodsareintroducedinthedietTerm,formula-fedinfantstheironneedsforthefirst12monthsoflifecanbemetbyastandardinfantformulaandtheintroductionofiron-containingcomplementaryfoodsafter4to6monthsofage,includingiron-fortifiedcereals.Wholemilkshouldnotbeusedbefore12completedmonthsofage.Ironsupplementation（補(bǔ)鐵）Elementaliron：4-6mg/kg/dOralironmedicationTypes-ferrousformAdministrationBetweenmealsVitaminCCourse:6-8weeksafterHbnormalization

HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

TREATMENTFerrousSalts4mg/kg/dFerroussulfate（20%）(硫酸亞鐵）20mg/kg/dferrousfumarate

(30%）（富馬酸亞鐵）13mg/kg/dFerrousgluconate（11%）（葡萄糖酸亞鐵）40mg/kg/dHEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITALTable:FerroussaltsanttheironcontentsIronsupplementation（補(bǔ)鐵）Parenteraliron（胃腸外注射鐵）

Indication:intoleranttooralironorabsorptionproblemtypes：HEMATOLOGY/ONCOLOGY,CHILDREN’SHOSPITAL

TREATMENT

IRONTHERAPYRESPONSE（fromNelson）timeresponse12-24hrReplacementofironenzymes,subjectiveimprovement36-48hrInitialmarrowresponse:erythroidhyperplasia48-72hrReticulocytespeaking5-7d