Ironoccurrenceinhumanbody

• Totalbodycontent:25-30 gm• Occurrence :Liver,Bonemarrow,muscles

Blood(14.5gm %)

75%-Hemoglobin

5%-Myoglobin

15%Ferritin

DietaryRequirementofIron

ØDietaryRequirement of Iron :Individual Requirementof Iron

Indianadult 20mg

AdultfromWesterncountries 15mg(dietdosenotcontaininhibitors)

Child 20-30mg(dietsupplementedwithcereals)

Menstruatingwoman 18mg

Pregnantwoman 40mg/dl

Childisdependenton“Ironreserve“receivedfrommotherduringpregnancy(TRANSPLACENTALTRANSFER)

DietarysourcesofIron

q DietarySourcesofIron

Dietarysource Ironcontentper100gm

GreenLeafyvegetables 20mg

Cereals 10mg

Liver 50mg

meat 20mg

Milk,wheat,polishedricearepoorsourcesofIron.

Jaggery,Apple,pulses,cereals,molasses,fish,dryfruitsaregoodsourcesofIron.Meat,liver,Heart,kidneyarerichsources.CookinginIronutensilisbeneficial.

BiochemicalfunctionsofIron

qBiochemical functions :ironmainlyexertsitsfunctionthroughbiomoleculesinwhichitispresent.

q1.Hemoglobin &Myoglobin –transportofoxygen&CO₂q2.Cytochromes&certainnon-heme proteinsàelectrontransportchain&oxidativephosphorylation

q3.Peroxidase (lysosomalenzyme)–phagocytosis&killingofbacteriabyneutrophils.

q4.Ironassociatedwitheffectiveimmunecompetenceofhumanbody.

Factors affecting Ironabsorption1. Ferrous(Fe²⁺) absorbed,Ferric(Fe³⁺) notabsorbedinhumanbody’2. Acidity,HCl,vitaminC,Cysteine,SHgroupofproteinsfacilitates (Fe³⁺)à (Fe²⁺)

whichisabsorbedeasily.3. AdministrationAlkalidecreasesIronabsorption.4. Calcium,Copper,Zinc&LeadinhibitIronabsorption.5. Phyticacid(foundincereals)&oxalicacid(foundinleafyvegetables)forminsoluble

saltswithIronà Thereforedecrease(interfere)Ironabsorption.6. Smallpeptides,aminoacidfavorironuptake7. Deficiencyanemia- ironabsorptionincreased2-10timesthatofnormal8. HighphosphatedietarycontentdecreaseIronabsorption&lowphosphatepromotes.9. Ironabsorptionisdiminishedincopperdeficiency.10. Tea&eggsdecrease Ironabsorption.11. ImpairedIronabsorptioninMalabsorptionsyndromesuchsteatorrhoea.12. Inpatientswithpartial&totalsurgicalremovalofof stomatch &orintestineIron

absorptionimpaired.

Ironexcretionfromhumanbody

qIronisonewayelement.qHomeostasisatAbsorptionlevel.

menstrualcycleqBleeding

pregnancyq Bleedingulcers,piles

qUnabsorbedIronq30%intestinalcellsdesquamatedexcretionofIroninfaecesqLessions inurinarytractà excretionofIroninurine

IronMetabolism:Absorptionandtransport

IronMetabolism

IronMetabolism:heme andnon- heme absorption

Roleofcopperions inIronMetabolism

IronMetabolism

Ironisconservedbyhumanbody

RBCLysisacuteproteinininflammation↓↑LiverKuffer’scells

Hemoglobinà hemoglobinà Haptoglobin(α₂globin)à ironutilization↓

Globinremoved↓

Hemeà Heme–Hemoplexin (betaglobin)complex(takenbyhepatocytesIronutilized)

↓Porphyrinà Bilirubin

IronDeficiencyAnemiaNutritionaldeficiencydisease:PrevalenceinIndiaà 70%(Rajsthan 90%,AndhraPradesh-33%)

Maternalanemiaàincreasedperinatalmortality

Child’sanemia

Irreversibleimpairmentofchild‘slearningability

INDIANDIETcontainsinhibitorsofabsorptionthereforeIndiandevelopIrondeficiencyanemia

IronDeficiencyAnemiaqSign&symptomsofirondeficiencyanemia:1. Microcytichypochromicanemia(<10gm/dl)2. Lackofoxygen3. Apathy4. Sluggish(ATPsynthesisdecreaseasironisconstituentofcytochromesofETC)ØGastricepitheliumdeficiencyà leadingAchlorhydriaà lesserIronabsorptionà prolongedapathy

ØAtrophyofepitheliuminoralcavity&esophagusà DysplasiaØPlummer–Wilsonsyndrome(precancerouscondition)ØChronicirondeficiencyanemiaàimpairedattention,irritability.loweredmemory&poorscholasticperformance

ØAnemia&apathygohandinhand.vTreatmentofIrondeficiencyanemia:Adult:100mgIron+500μgFolicacid+Ascorbicacid+vitaminEChildren:50mgIron+100μgFolicacid+ Ascorbicacid+vitaminEAscorbicacid(Ferricà ferrousincreaseinIronabsorption)vitaminE(preventsfreeradicalformation–antioxidant)

IronDeficiencyAnemia1.Hookworminfestation:Lossofblood(0.3ml/day)Ruralareapoorsanitation,300worms/individualà lossof1%totalbody/day

2.NutritionaldeficiencyofIron

3.Repeatedpregnancy(loss1gmironloss/deliveryafterpregnancy

4.4.Nephrosisàkidneyglomerularmechanisminsufficiencyà proteinuria(Haptoglobin,Hemoplexin ,&transferrinlostinurine (Thusirondeficiencyanemiacommon innephritis )

5.Chronicbloodlossà pepticulcer,uterinehemorrhages,piles

6.Lackofabsorption:subtotalgastrectomy,Achlorhydria

7.Lead&absorptionopposeeachother:Leadtoxicityà Ironabsorptiondecreased,Hbsynthesisdecreasedà Irondeficiencyà Leadabsorptionincreased(viscouscyclee )

RegulationofIronAbsorptionSiteofabsorption:duodenum&jejunumHomeostasis:regulationatlevelofabsorptionandnotbyexcretion“MUCOSALBLOCK”OfregulationofIronabsorptiona. AdequatequantityofIronstoredà Ironabsorptiondecreasedb. Ironstoresdepletedà AbsorptionofIronincreasedc. Receptormediateduptakeismoreinirondeficientstated. Ironexcess:receptorsnotproduced

RegulationofIronAbsorption

RegulationofIronAbsorption

RegulationofIronAbsorption

RegulationofIronAbsorptioninDuodenum

RegulationofIronAbsorptioninDuodenumbyHepcidin

RoleofTransferrininIronTransportinhumanbody

DietaryironcontentandIronabsorption

TranslationofFerritinmRNAinIronMetabolism

FerritinandIronMetabolismI

IronMetabolism-TransferrinTransferrin:1.Glycoprotein2.molecularweight-7650003.functions:TransportformofIron4.indicatorofnutritionalstatusà inflammationtransferrindecreased5.synthesisinlivercells6.Normallevel:250mg/dl7.Halflife:7-10days8.OnemoleculeofTransferrinbindstwoferrousiron.9.Transferrinisuseful‘index’ofnutritionalstatus.10.TIBC:(Totalironbindingcapacity)providedbyTransferrin-à400μg/100ml(1/3rd capacityutilized)120μg/100ml(serumIron)11.Irondeficiencyanemia: TIBC↑,Transferrin↑, Iron↓, Ferritin↓

IronMetabolism–TransferrinFerroxidase /Cu

Apotransferrin+2Fe²⁺+1/2O₂Transferrin(combined)+2Fe³⁺+H ₂OInblood,cerruloplasmin is‘Ferroxidase ’

IronMetabolism-FerritinFerritin:1.Glycoprotein2.Function:Storageformiron3.Organforstorage:Liver,spleen,bonemarrow,musclecells4.Ferritinconcentrationdecreasesinirondeficiencyanemia5.Apo- protein+4000Ironatomsà Ferritin6.NormalplasmaconcentrationofFerritin=07.Irontoxicity:FerritinfoundinplasmaIronattachedtoproteinà Heme(asTransferrin,Ferritin)

OverviewofIronMetabolism

IronToxicityqSerumIronconcentration:>50mg/dlqSign&symptoms1. Nausea2. Vomiting3. Diarrhea4. Oxidativestress(unabsorbedIrongeneratefreeradical)5. Hemosiderosis

IronToxicity:HemochromatosisandHemosiderosis

IronToxicity- HemosiderosisqTotalcontentofbody>25-30gm1. Hemosiderinà goldenbrowngranulesseeninspleen&liver

(PrussianBluereactionpositive)à partiallydenaturedFerritin(25%iron)

2. Occursinpersonreceivingrepeatedbloodtransfusioneghemophilicchildren(thereforeonlyplasmafractionshouldbegiventohemophiliapatients.

3. ProlongedparenteralIronsupplementsà Ironoverload4. Primaryhemosiderosis :abnormalgeneonchromosomeà iron

absorptionincreasedà transferrinincreasedà excessIrondepositsà tissuedamage

5. CookinginIronvessels:Bantutribe,cornstaplediet(lowphosphatecontentincreasedIronabsorption)

Hemosiderosis

DiagnosisofHemosiderosis

Effects of Hemosiderosis inhumanbody

TriadassociatedwithIronToxicity

IronToxicity- Hemosiderosis

Pancreas• Bronzediabetes

Skin• Yellowbrowndiscoloration

liver• Cirrhosis

IronToxicity- Hemosiderosis

qTreatmentofHemosiderosis1.Phlebotomyeveryweek(tillFerritin&Ironlevelnormal)2.Desterroxamine :chelatingagent–Ironchelatingagent(Ferroxamine )à excretedinurine

HIFANDIRONMETABOLISM

Ironabsorptioninirondeficiencyanemia

Roleofhepcidin andApo-transferrininIronmetabolism