Serum Ferritin Structure: Ferritin is a large protein shell (MW 450,000) comprised of 24 subunits, covering an iron core containing up to 4000 atoms of iron. Function: Ferritin acts as the soluble storage form of iron in tissue (hemosiderin is relatively insoluble). It may serve other functions as well although these are controversial. It is found in most cells of the body, especially macrophages, hepatocytes and erythrocytes. Synthesis occurs in the liver and the rate correlates directly with the cellular iron content. Control of ferritin synthesis occurs post-transcriptionally (at the mRNA level). There are iron- and cytokine-responsive elements in ferritin mRNA. Increased iron or cytokines (such as IL-1, IL-6) promotes ferritin translation, resulting in increased iron storage. This is one of the causes of iron "sequestration" that occurs in animals with chronic or inflammatory disease and will reduce serum iron values. The function of serum ferritin is not known, but the concentration correlates well with the amount of stored iron in normal (and most diseased) subjects. Serum ferritin concentrations are quite stable from day-to-day, in contrast to serum iron. Measurement: Sensitive methods are needed, since serum levels are very low. Immunologic assays requiring species-specific reagents, such as RIA and ELISA, have been employed. Canine and feline-specific ferritin assays are available through Kansas University. Serum ferritin levels in Shetland Ponies with experimentally-induced acute inflammation (commencing day zero) compared to normal control animals. from Smith and Cipriano, Vet Pathol. 24:354-356 (1987) Variation in disease: Low serum ferritin: A decrease in the amount of stored iron is the only known cause for a low serum ferritin result. This is the strong point of this test. However, in dogs, serum ferritin values do not appear to correlate with bone marrow iron stores, and normal ferritin values may be seen in dogs with documented iron deficiency. There is no apparent explanation for this. In cats, ferritin appears to be a better indicator of iron stores than in dogs. High serum ferritin: Increased stored iron (overload) is associated with raised serum ferritin levels (e.g. massive blood transfusions, hemachromatosis). Unfortunately, ferritin is an acute phase reactant protein, so liver disease, infection, inflammation, or malignancy will result in high serum ferritin levels. The concurrent presence of these conditions in an iron-deficient subject may raise serum ferritin concentration to a level not clearly indicative of iron deficiency; or raise the level in a subject with normal iron stores to an extent suggestive of iron overload.

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