Expressed in µg/dL, this is a measure of the concentration of iron in serum at the moment the sample was drawn. This iron circulates bound to transferrin (Tf), but is freed by acidification of the serum prior to its measurement in the assay. Hemolysis may interfere in some assays due to the contribution of iron from hemoglobin. Serum iron concentration can change very rapidly in normal subjects with no change in total body iron. The magnitude of this variation is such that transient levels suggestive of iron deficiency or overload may occur.

Causes of hypoferremia

Serum iron levels in Shetland Ponies with experimentally-induced acute inflammation (commencing day zero) compared to normal control animals. Reproduced with permission from Smith and Cipriano, Vet Pathol. 24:354-356 (1987)

The most common causes of low serum iron are transient variation, inflammatory cytokines (which inhibit iron absorption and prevent iron release into circulation) and iron deficiency (from decreased intake or absorption or blood loss).

• Random transient variation in a healthy subject: In dogs, this is related to fluctuations in endogenous cortisol levels.
• Decreased absorption or intake: Absorption,which occurs in the duodenum, is influenced by pH, vitamin C, hepcadin (decreases), copper (an essential component of haephestin, which permits release of iron from intestinal cells), dietary content (e.g. milk is low in iron) and intestinal disease.
• Increased loss: Since much of the body's iron stores are found in red blood cells (hemoglobin), chronic persistent external hemorrhage will result in iron deficiency. This type of blood loss usually occurs from the gastrointestinal, urinary, reproductive and respiratory tracts (e.g. epistaxis).
• Sequestration: Iron is sequestered within cells (typically iron storage cells such as macrophages or hepatocytes) in inflammatory or chronic disease states or (sometimes) portosystemic shunts.
  • Inflammation: Low iron is due to inflammatory cytokine-induced synthesis of ferritin and hepcidin. Interleukins (IL-1, IL-6, TNFα) stimulate apoferritin synthesis resulting in sequestration of iron within macrophages. This decreases iron values in plasma and increases iron stores. Hepcidin is a key mediator of low iron and subsequently the anemia of inflammatory disease in inflammatory or chronic disease states. Hepcidin is an antimicrobrial protein produced in the liver. It negatively regulates iron absorption in the intestine and iron release from macrophages. Hepcidin mRNA synthesis is stimulated by TNFα and IL-6. High values inhibit iron absorption and decrease iron release from macrophages. Studies done at Cornell University have shown that low iron in serum or plasma is a sensitive marker of acute inflammation in horses (see Borges et al 2007).
  • Portosystemic shunts: Iron appears to be sequestered in hepatocytes in some animals, resulting in low iron stores and microcytosis.
• Unknown mechanisms or miscellaneous:
  • Corticosteroids: Causes decreased iron (as much as half) in cattle.
  • Mild trauma: Iron levels can decrease quickly even in relatively mild/acute injuries and trivial infections (eg, colds in humans). This may be cytokine-mediated.
  • Malnutrition: This can also decrease serum iron in cattle, by unknown mechanisms.

• Random transient variation in normal subject
• Iron overload: Oral or parenteral overdosage, repeated transfusions, primary hemochromatosis which occurs in Mynah birds and some breeds of cattle.
• Release from intracellular stores: The liver is one of the major storage sites of iron, where iron is seen in Kupffer cells and in hepatocytes. In some cases of necrotizing hepatitis, high iron levels (with 100% transferrin saturation) will be seen. This can be a marker of hepatic necrosis in dogs and horses.
• Increased red cell turnover: Iron is turned over rapidly each day, as part of normal red blood cell turnover (destruction of effete red blood cells). If there is excessive red blood cell turnover in the peripheral blood or in the bone marrow, high iron levels (with high % transferrin saturation) may be seen. This occurs in hemolytic anemias or disordered/abnormal erythropoiesis, such as primary myelodysplasia or ineffective erythropoiesis.
• Decreased erythropoiesis: Since red blood cells are the main utilizers of iron (to make hemoglobin), decreased or absent erythroid progenitors in marrow may result in incresaed serum iron, e.g. bone marrow aplasia/hypoplasia)a
• Miscellaneous:
  • Corticosteroid excess (exogenous or endogenous): Causes increased serum iron (up to 2x) in horses and dogs.