Erythropoietin (Epo) is the principal hormone responsible for regulating erythrocyte production in the bone marrow.
Epo is produced primarily in the kidneys, and to a lesser extent in the liver, in response to oxygen tension in the blood. When oxygen tension is low, such as at high altitudes, Epo is produced which then signals erythroid precursors in the bone marrow to undergo growth and maturation. Since RBCs carry oxygen to tissues throughout the body, an increase in RBC mass will increase the oxygen carrying capacity in the body. Epo production is regulated by the classic negative feedback system. When oxygen tension in the blood returns to an appropriate level, Epo production in the kidney slows and Epo levels decrease.
Although controversy still exists on the exact location of Epo production in the kidney, most evidence points to type I interstitial cells. These fibroblastic kidney cells are located at the level of the proximal convoluted tubule near the deep cortex and outer medulla. Type I cells act as physiologic oxygen sensors at a level where renal oxygen consumption is high and the oxygen level falls. When oxygen tension in the blood is low, heme proteins are in the deoxy conformation. This triggers the production of Epo. The subsequent number of RBCs recruited by Epo is directly related to the degree of hypoxia. In this way, the body is able to efficiently regulate the oxygen carrying capacity of the blood as needed.
Epo assays must be conducted by a laboratory, and canine-specific tests are not available. Although there are two human assays for Epo that have been approved for use in dogs, the accuracy of the tests is limited by the incomplete homology of Epo between species. Canine Epo is only 85% homologous to the human molecule. Furthermore, current veterinary research has not determined a reference range for Epo concentration in dogs.