Overview of Disorders of Phosphorus Metabolism in Animals

Several disorders of phosphorus metabolism occur in domestic animals. These include hyperphosphatemia, hypophosphatemia, and postparturient hemoglobinuria.

Phosphorus (P) is a macromineral with a plethora of important biological 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, which inherently depends on the capacity to phosphorylate intermediate metabolites and 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 encountered as a stable inorganic phosphate (Pi), as an organic phosphate ester, or as a phospholipid. By far the largest fraction of the body phosphorus (approximately 85% of total body phosphorus) is deposited in the skeleton as calcium phosphate and hydroxyapatite. Phosphorus stored in bone is metabolically inert. However, it can be mobilized readily in states of phosphorus deficiency.

The remainder of the phosphorus in the body forms the metabolically active phosphorus pool, which is predominantly located in the intracellular space (ICS) (approximately 14%). Less than 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 or as phospholipids. Extracellular Pi is largely (approximately 85%) encountered as ionized (either H₂PO₄^– or HPO₄^2–), while approximately 10% is bound to protein, and 5% is complexed with other minerals such as calcium or magnesium (1).

Disorders of phosphorus metabolism can be caused by disturbances directly related to phosphorus homeostasis (primary phosphorus balance disturbances) or by ailments that are not immediately related to the phosphorus balance but involve secondary phosphorus balance disturbances. The most common primary phosphorus balance disturbance is caused by diets with insufficient phosphorus content, as in ruminants grazing on arid and phosphorus-deficient soils.

The most common form of secondary disturbance of phosphorus metabolism is prolonged anorexia, often observed in patients with chronic disease. Other ailments leading to secondary phosphorus balance disorders are primary hyperparathyroidism, renal secondary hyperparathyroidism, calcium balance disturbances, and other conditions associated with osteodystrophy.

Phosphorus metabolism disturbances can also be characterized as chronic and acute. Chronicity refers to the duration of presence of the underlying cause, while acuity is related to the occurrence of clinical signs, which might not match the duration of the phosphorus balance disturbance.

Typical clinical signs of chronic disturbances of phosphorus balance are unthriftiness, delayed development and growth of juvenile animals, bone deformities, anorexia, and pica. Ailments classified as acute phosphorus balance disorders include postparturient hemoglobinuria and the hypophosphatemic downer cow syndrome of cattle. These conditions are typically present in dairy cows at the onset of lactation. However, it is generally thought that a period of phosphorus deprivation before calving is required to result in overt disease. The sudden increase of phosphorus loss through the mammary gland in early lactation is presumed to overwhelm the counterregulation ability of a previously phosphorus-deficient but clinically healthy cow.

Diagnosing disorders of phosphorus metabolism is challenging, as there is currently no clinical or blood biochemical parameter allowing unambiguous identification of affected individuals. It is standard practice in veterinary medicine to make a diagnosis of a phosphorus balance disorder by measuring the blood Pi concentration. This parameter, however, only provides a crude indication of phosphorus uptake from feed shortly before sampling. It is of little diagnostic value in assessing the status of various tissues or the total phosphorus balance of the body.

Most conditions generally held to be caused by a disruption of phosphorus metabolism, including postparturient hemoglobinuria, hypophosphatemic recumbency in ruminants, or anorexia and pica, have been linked to a phosphorus balance disturbance, and more specifically to hypophosphatemia, on the basis of empirical observation. Notably, many of these conditions could not be reproduced experimentally, and a plausible underlying mechanism for the observed clinical signs that is associated with a disturbance of phosphorus balance has not yet been elucidated.