Total Iron Binding Capacity (TIBC)


Apotransferrin is a β-1 globulin that is produced in the liver. When iron (ferric form or Fe3+) binds to apotransferrin, it is called transferrin. Transferrin is the iron transport protein in plasma. It is responsible for shuttling iron between sites of absorption, storage and utilization for the biosynthesis of iron-containing macromolecules. Donation of iron by Tf requires the interaction with specific receptors on the recipient cells. Such transferrin receptors have been identified on the surface of reticulocytes, hepatocytes, lymphocytes, fibroblasts and rapidly proliferating cells (that require iron for metabolism).

For clinical purposes, TIBC is considered as a measure of transferrin (Tf) concentration in serum or plasma (albeit indirect). Expressed as µg/dL of iron-binding capacity, TIBC is determined by adding excess iron to a sample in order to saturate Tf. The TIBC thus represents the amount of this added excess iron that is needed to saturate Tf plus the iron that was already bound to the Tf.

Synthesis occurs mainly in the hepatocyte, where rate of synthesis is influenced by multiple factors including:

  • Iron content of hepatocyte - increased iron content inhibits synthesis, decreased content increases synthesis. This inverse relationship is reflected in serum Tf levels in humans, making TIBC of value in assessing iron metabolism.

  • Inflammatory disease in the host - inflammation or other tissue injury can result in increased levels of interleukin-1 and other inflammatory cytokines. Among many other effects, these mediators causes alterations in hepatocyte protein synthesis such that Tf and albumin production (both of which are called negative acute phase proteins) are decreased in favor of the positive acute phase reactants (e.g., haptoglobin, C-reactive protein and serum amyloid A, etc), which increase in plasma.
Causes of increased TIBC
  • Iron deficiency stimulates apotransferrin synthesis in humans and woodchucks, causing an increased TIBC. Such an increase in TIBC does not occur as reliably in dogs and cats with iron deficiency, but may occur in large animals.
  • Acute viral hepatitis in man and necrotizing hepatitis in dogs (mechanism unclear - could be an artifact from release of high concentrations of storage iron from hepatocytes).
  • Artifact of very high serum iron.
Causes of decreased TIBC
  • Decreased production by the liver: Apotransferrin production is downregulated in acute phase reactions (e.g. secondary to inflammation, chronic disease, neoplasia). Aporansferrin may also be decreased in acute or chronic synthetic liver failure and with portosystemic shunts. In humans, low TIBC is a good marker (with low albumin) of severe malnutrition.
  • Loss of transferrin: Tf is a low molecular weight protein that can be lost concurrently with albumin in protein-losing conditions (e.g. renal and gastrointestinal disease).

up
 up
 up