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Overview of Disorders of Phosphorus Metabolism

By Walter Gruenberg, DrMedVet, MS, PhD, DECAR, DECBHM, Department of Farm Animal Health, Utrecht University

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 the body.

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. Because only increased phosphorus loss and decreased phosphorus uptake are associated with phosphorus depletion of the body but compartmental shifts of phosphorus between the ICS and ECS can strongly affect the extracellular Pi concentration, the serum Pi concentration 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.