Phosphorus (P) is a macromineral with a plethora of important biologic functions. In addition to being essential for the structural stability of bones and teeth, cell membranes (phospholipids), and nucleic acid molecules, phosphorus plays an important role in metabolic activity such as carbohydrate and energy metabolism that inherently depends on the capacity to phosphorylate intermediate metabolites and to store energy released during oxidation in high-energy phosphate bonds such as ATP or phosphocreatine. Phosphorus is an integral component of 2,3-DPG, a compound that regulates oxygen release from hemoglobin and therefore is critical for oxygen delivery to tissues. Inorganic phosphorus (phosphate, PO4, or Pi) is also an important buffer in urine for monogastric species and rumen fluid for ruminants.
In the body, phosphorus is present as a stable inorganic phosphate (Pi), an organic phosphate ester, or a phospholipid. By far the largest fraction of the body phosphorus (~85% of total body phosphorus) is incorporated into bone in an insoluble inorganic phosphate form (dihydroxyapatite). The remainder is largely located in the intracellular space (ICS, ~14%), while <1% of the total body phosphorus is found in the extracellular space (ECS), which includes blood serum or plasma. In the ECS, phosphorus is present either as Pi, forming the metabolically relevant fraction, or as phospholipids. The extracellular Pi fraction is largely (~85%) ionized (either H2PO4– or HPO42–), while ~10% is protein bound and 5% is complexed with other minerals such as calcium or magnesium.
The concentration of Pi in the ECS and thus in serum is dictated by the equilibrium between Pi uptake from the digestive tract; Pi excretion in urine (monogastric species), saliva (ruminants), and milk; the uptake or release of Pi from bone; and compartmental Pi shifts between the ECS and ICS. Accordingly, hypophosphatemia that is defined as subnormal serum or plasma Pi concentration can be caused by decreased oral phosphorus uptake, increased phosphorus loss, increased cellular phosphorus uptake, or a combination of these factors. Only increased phosphorus loss and decreased oral phosphorus uptake can result in phosphorus depletion of the body.
Compartmental shifts of phosphorus between the ICS and ECS, in contrast, have a strong effect on the extracellular Pi concentration but not on the overall availability of phosphorus in the body. It follows that the Pi concentration in serum or plasma is an unreliable parameter to assess the phosphorus status of an animal. Despite the difficult interpretation of the serum Pi concentration, it is still the most commonly used measurement of phosphorus status in veterinary medicine.