IRON KINETICS AND LABORATORY ASSESSMENT

 Iron chemistry – Bivalent and Trivalent – For the life of all organisms.
 70% - Total human body Fe transported in blood in Ferrous state to heme portion of Hb (binds,
transports and releases O2).
 In mitochondria – Ferrous ion is transferred to protoporphyrin IX to for heme, 4 heme bound to
4 globin chains - - tetrameric Hb.
 Ferrous ion binds to myoglobin – O2 transport molecule in muscles; myoglobin is monomeric
and O2; bind is irreversible;

Storage form of Fe:

1.Ferritin
2.Hemosiderin
 Contain 25% human body Fe distributed to liver and bone marrow in hepatocytes and
macrophages.
 Less than 1% Fe transported through plasma in Ferric state bound to transferring.

To Dx Fe deficiency:
1.Plasma transferrin
2.Transferrin saturation assay

 Heme-bound Fe – Essential to mitochondrial cytochrome P-450 (CYP 450) in all animals.

 Also known as cytochrome oxidase – An enzyme supports oxidation-reduction Rx like
hydroxylation of organic molecules from free O2.

Storage and Transport Fe – controlled by:

1.Dietary intake
2.Fe loss through bleeding
Fe overload – increased absorption due to:
1.Genetic predisposition
2.Repeated blood transfusion
- Caused fatal heart and liver disease
  Bioavailability of Fe:
 Depends on chemical form.
 Presence of non-Fe foods that promote or inhibit absorption.
 10-20 mg/ day but only 1-2 mg/day is absorbed.

 2 forms of absorbed Fe:

1. Heme – From meat, absorbed more.
2. Non-heme – Inorganic Fe; legumes and leafy vegetables as 90% dietary Fe but only 2% - 20%
absorbed; depends on the status of the individual with dietary enhancers or inhibitors.

 Ascorbate, citrate and other organic acids and amino acids enhance absorption of non-heme Fe
by formation of soluble chelates.
 Cooking in Fe pots increases the amount of Fe consumed.
 Subs that interfere nonheme absorption; - - phytates, polyphenols, PO4, Oxalates and Ca.
 Hemin – 5% - 35% heme Fe absorbed; Fe-containing porphyrin.
 Dietary Fe supplemented with tables or multivitamins with Ferrous sulfate; cereals fortified with
Fe.

Fe Absorption and Excretion

 Duodenum and upper jejunum – sites of maximal Fe absorption.
 For O2 Hb transport – ferrous.
 Converted from ferric nonheme to soluble ferrous by duodenum specific cytochrome b-like
protein, DCYTB.
 Uptake of Heme Fe – on heme carrier protein 1 located on the apical membrane of the
duodenal enterocyte.
 Heme Fe binds to the enterocyte in the mucosal epithelium.
 Divalent metal transporter 1 (DMT) – transporter of ferrous to duodenal epithelium then to
basolateral membrane of enterocyte and exported to portal circulation, mediated by ferroportin
(a basolateral transport protein).
 Ferroportin works in conjunction with a copper - containing Fe oxidase called Hephaestin.
 Hephaestin may facilitate Fe egress by re-oxidation of ferrous to ferric Fe.
  Trivalent Fe(ic) must be bound to transferrin to be transported through the circulation.
 Some Fe remain in the enterocytes as ferritin and release into the circulation over few hours.
 Enterocyte stored ferritin Fe is excreted when the cells are exfoliated in the stool.
 Hepcidin – An anti-microbial peptide produced in the liver acting as negative regulator of
intestinal Fe absorption; suppresses release from macrophage.
 Transferrin – Transporter of ferric iron to hematopoietic and other tissues.
 Transferrin receptors are in larger amount on normoblast and rapidly dividing cells.
 Human have NO means to excrete Fe, instead we regulate Fe by controlling absorption.
 The amount of Fe absorbed is inversely proportional to Fe stores and the rate of erythropoiesis.
 Normal Fe losses occur mainly by defecation (1 mg/day).
 Perspiration and Exfoliation of the skin and dermal appendages – Caused minimal losses.
 Lactation and Menstruation – loss 1 mg/day.

Fe cycle and transport:

 Fe absorbed from GIT and transported via the circulation to the bone marrow.
 Inserted into protoporphyrin IX in the mitochondria of the erythroid precursors to make heme.
 Hb synthesis is completed in the retics stage.
 Fe circulated in RBC as ferrous.
 Fe from senescent RBC turned over macrophage and reused.
 Ferrokinetics – Involve transferrin, transferrin receptor and ferritin. These are regulated by Fe-
responsive protein.
 Bicarbonate ion locks the Fe in place within transferrin by serving as bridging ligand between the
protein and Fe.
 Apotransferrin – Transferrin molecule existing as single-chain glycoprotein.
 Most plasma transferrin are produced by hepatocyte.
 Fe exhibits diurnal variation:
 Highest in AM, lowest in PM
 Serum Fe concentration decreased:
 Inflammatory disorders
 Acute infection
 After immunization
  After myocardial infarction

Lab Assay:
 TIBC (Total Fe Binding Capacity) – Transferrin assay.
 Prussian blue Stain – PB, BM aspirate smear – to see Fe in nucleated RBC.
 Normally NO Fe is detected visually in mature RBC.
 Nucleated RBC containing Fe cells – Sideroblasts and granules called Siderosomes.
 Retics in the BM containing Fe – Siderocytes
 Siderocytes is abnormal findings because Fe granules in retics should NOT be detected at the
light microscope.