Iron Metabolism

Iron Intake (Dietary) :

   • average North American adult diet = 10-20 mg iron daily.

  • steady state absorption is 5-10% (0.5-2 mg/d); enhanced by citric acid and ascorbic acid (vitamin C); reduced by polyphenols (e.g. in tea), phytate (e.g. in bran), dietary calcium, and soy protein.

  • males more likely to have positive iron balance; up to 20% of menstruating females have negative iron balance.

Iron Absorption and Transport :

 • dietary iron is absorbed in the duodenum (absorption impaired in IBD and celiac disease).

 • in circulation, the majority of non-heme iron is bound to transferrin which transfers iron from enterocytes and storage pool sites (macrophages of the reticuloendothelial system and hepatocytes) to RBC precursors in the BM.

Iron Levels :

 • hepcidin is a hormone produced by hepatocytes that regulates systemic iron levels.

 ■ binds to iron exporter ferroportin (on duodenal enterocytes and reticuloendothelial cells) and induces its degradation, thereby inhibiting iron export into circulation (iron trapping in reticuloendothelial system cells and diminished absorption of iron) .

■ hepcidin production is: 

 ◆ increased in states of iron overload (inhibiting additional iron absorption) and infammation (mediating anemia of chronic disease through iron trapping).

  ◆ decreased in states where erythropoiesis is increased (e.g. hemolysis) or oxygen tension is low .

Iron Storage:

• ferritin 
 ■ ferric iron (Fe3+) complexed to a protein called apoferritin (liver, spleen, and BM are main ferritin storage sites).
 ■ small quantities are present in plasma in equilibrium with intracellular ferritin.
  ■ also an acute phase reactant – can be spuriously elevated despite low iron stores in response to a stressor • 
hemosiderin.
  ■ aggregates or crystals of ferritin with the apoferritin partially removed.
  ■ macrophage-monocyte system is the main source of hemosiderin storage.

Iron Indices:

 • BM aspirate:

 gold standard test for assessment of iron stores (rarely done)

 • serum ferritin: most important blood test for iron stores .

■ decreased in iron defciency anemia.

  ■ elevated in infection, infammation, malignancy, liver disease, hyperthyroidism, and iron overload.

 • serum iron:

measure of all non-heme iron present in blood.

 ■ varies signifcantly daily 

• TIBC: 

indirect measure of total amount of transferrin present in blood .

■ normally, one third of TIBC is saturated with iron.

 ■ increased TIBC has high specifcity for decreased iron, low sensitivity.

 •saturation

 ■ serum iron divided by TIBC, expressed as a proportion or a percentage

 • sTfR

 ■ refects the availability of iron at the tissue level.

 ■ transferrin receptor is expressed on the surface of erythroblasts and is responsible for iron uptake – some are cleaved of and are present in circulation as sTfR

 ■ in iron defcient states, more transferrin receptors are expressed on erythroblasts leading to an increase in sTfR 

■ sTfR also increased during extramedullary hematopoiesis (i.e. thalassemia syndromes) 

■ low in reduced erythropoiesis and iron overload 

■ useful in determining iron defciency in the setting of chronic infammatory disorders