IRON METABOLISM DISORDERS - Columbia University

IRON METABOLISM DISORDERSANEMIADefinition Decrease in the number of circulatingred blood cells Most common hematologic disorder byfar1

ANEMIACauses Blood loss Decreased production of red blood cells(Marrow failure) Increased destruction of red blood cells– Hemolysis Distinguishedgbyy reticulocytey count– Decreased in states of decreased production– Increased in destruction of red blood cellsANEMIACauses - Decreased Production Cytoplasmic production of protein– Usually normocytic (MCV 80-100 fl) ormicrocytic (MCV 80 fl) Nuclear division/maturation– UsuallyUll macrocyticti (MCV 100 fl)2

ANEMIACauses - Cytoplasmic Protein Production Decreased hemoglobin synthesis– Disorders of globin synthesis– Disorders of heme synthesis Heme synthesis– Decreased Iron– Iron not in utilizable form– Decreased heme synthesisIRON DEFICIENCY ANEMIAPrevalenceCountryMen (%) Women(%)S. India635N. India64Latin America 417Israel1429PolandSweden7USA113PregnantWomen (%)56803847223

IRON Functions as electron transporter; vital for life Must be in ferrous (Fe 2) state for activity In anaerobic conditions, easy to maintainferrous state Iron readily donates electrons to oxygen, Îsuperoxide radicals, H2O2, OH radicals Ferric (Fe 3) ions cannot transport electrons orO2 Organisms able to limit exposure to iron hadmajor survival advantageIRONBody Compartments - 75 kg manStores1000 mgTissue170 mgAbsorption 1 mg/day4 mgExcretion 1 mg/dayRed Cells2400 mg4

IRON CYCLECIRCULATING RBCsFe RBC PRECURSORFerritinFeFeFeFeFeTransferrin LULAR IRON TRANSPORTFe 2TransferrinTransferrin receptorH LysosomeH H H Fe 25

IRONCauses of Iron Deficiency Blood Loss––––Gastrointestinal TractMenstrual Blood LossUrinary Blood Loss (Rare)Blood in Sputum cythemia Vera Increased Iron Utilization Malabsorption– Tropical Sprue– Gastrectomy– Chronic atrophic gastritis Dietary inadequacy (almost never sole cause) Combinations of aboveDAILY IRON 429Age3227201014200Absorbed IronRequirement (mg/day)R2.5Females6

IRON ABSORPTION16Iron (mg/day)14121086420Iron in DietIronSolubilizedIron UptakeIron AbsorbedGI ABSORPTION OF IRON7

FERRITIN/TRANSFERRIN REGULATIONIRON ABSORPTION1001010.10.118102080100 200IronAbsorbed(mg/day)0 010.01Iron Ingested (mg/day)8

IRON DEFICIENCY ANEMIAProgression of Findings Stainable Iron, Bone Marrow AspirateSerum Ferritin - Low in Iron DeficiencyDesaturation of transferrinSerum Iron dropsTransferrin (Iron Binding Capacity) IncreasesBlood Smear - Microcytic, Hypochromic;Aniso- & Poikilocytosis Anemia9

IRON DEFICIENCY versus ACDSerum IronTransferrinFerritinIron DeficiencyACDSoluble Transferrin Receptor Measure of ferrokinetic activity Elevated in iron deficiency Not usually elevated in anemia ofchronic inflammation (not an acutephase reactant) Still not widely available Expensive May replace iron binding capacity &/orferritin18

SUMMARYIron Metabolism Disorders Most common form of anemiaSymptom of pathologic processPrimary manifestation is hematologicTreatment requires:– Replacement therapy– Correction of underlying cause (if possible) Iron excess more dangerous than irondeficiency19

Definition Decrease in the number of circulating red blood cells Most common hematologic disorder byMost common hematologic disorder by far. 2 ANEMIA Causes Blood loss Decreased production of red blood cells (Marrow failure) Increased destruction of red blood cells