Phosphorus has many important biological functions, making it an essential cellular component of any living cell. In living organisms, phosphorus is present as a stable inorganic phosphate salt (PO₄), as an organic phosphate ester, or as phospholipids. The largest fraction of phosphorus is found in an insoluble inorganic phosphate (Pi) form in bones and teeth (85% of total body stores). Almost all of the remaining phosphorus (14%) is found in the intracellular fluid, whereas <1% of the total body phosphorus is found in the extracellular fluid as Pi or phospholipids. Most of the extracellular Pi (85%) is ionized (either H₂PO₄^– or HPO₄^2–), approximately 10% is protein bound, and 5% is complexed with other minerals such as calcium or magnesium.

In addition to being essential for the structural stability of bones and teeth (dihydroxyapatite), cell membranes (phospholipids), and nucleic acid molecules, phosphorus plays an important role in carbohydrate and energy metabolism that inherently depend on the capacity to phosphorylate intermediate metabolites and to store energy released during oxidation in high energy P-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 is an important buffer in the extracellular fluid and in urine.

Because phosphorus is a predominantly intracellular electrolyte and as a charged molecule cannot freely permeate through cell membranes, the extracellular Pi concentration is not a good estimate of the intracellular or the total body phosphorus content. Nonetheless, in daily practice the serum or plasma Pi concentration is the most commonly used parameter to determine a deregulation of phosphorus homeostasis. The concentration of Pi in the extracellular fluid and thus in serum or plasma is dictated by the equilibrium between phosphorus uptake from the GI tract; phosphorus excretion in urine (monogastric species), saliva (ruminants), and milk; the uptake or release of phosphorus from bone; and to a large extent from the compartmental phosphorus shifts between intra- and extracellular space. Hypophosphatemia therefore can be the result of decreased uptake, increased loss, increased cellular uptake, or a combination of these factors. Only increased loss and decreased uptake are consistent with phosphorus depletion of the organism, while cellular phosphorus uptake is a highly dynamic process that is strongly influenced by acid-base homeostasis and carbohydrate metabolism.

Last full review/revision July 2011 by Walter Gruenberg, DrMedVet, MS, PhD, DECAR, DECBHM