Metabolism of iron and its clinical significance
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Transcript of Metabolism of iron and its clinical significance
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