Chronic phosphorus deficiency is commonly caused by inadequate feed intake or inadequate phosphorus content in the ration over an extended period of time. This can be observed in grazing animals in arid regions with low phosphorus content in soil. Phosphorus depletion can also result from chronic renal tubular disease due to impaired renal reabsorption of phosphorus (eg, Fanconi syndrome) or primary hyperparathyroidism causing increased renal excretion. Hypophosphatemia is a common finding in horses with chronic renal failure.
Acute phosphorus losses associated with hypophosphatemia are a well recognized problem in high-yielding dairy cows at the onset of lactation. The sudden loss of large amounts of phosphorus through the mammary gland at a time when dry matter intake is at its nadir seems to transiently overwhelm the counter-regulating mechanism, resulting in hypophosphatemia and phosphorus depletion.
Hypophosphatemia without phosphorus depletion may occur after oral or parenteral carbohydrate administration and after parenteral insulin administration as a result of increased cellular phosphorus uptake in combination with glucose. Alkalemia and respiratory alkalosis enhance cellular phosphorus uptake and therefore also have a hypophosphatemic effect.
Signs of chronic phosphorus depletion are most commonly observed in cattle fed a phosphorus-deficient diet over several months. Young animals grow slowly, develop rickets, and tend to have rough hair coats, whereas adult animals in early stages may become lethargic, anorectic, and lose weight. Decreased milk production and fertility have erroneously been attributed to phosphorus depletion. These signs appear to be the result of decreased energy and protein intake in animals that are anorectic because of the phosphorus depletion. In later stages, animals may develop pica as well as osteomalacia, abnormal gait, lameness, and eventually recumbency.
Acute hypophosphatemia has been associated with anorexia, muscle weakness, muscle and bone pain, rhabdomyolysis, increased fragility of RBC, and ensuing intravascular hemolysis. Other potential effects of hypophoshatemia are neurologic signs presumably related to the altered energy metabolism, impaired cardiac and respiratory function (decreased contractility of striated and heart muscle), and dysfunction of WBC and platelets that are believed to be caused by ATP depletion.
In cattle, hypophosphatemia occurring at the onset of lactation is widely believed to be associated with periparturient recumbency and the downer cow syndrome. (See bovine secondary recumbency see Bovine Secondary Recumbency.) This association is based on empirical observation and thus far is not supported by unequivocal evidence. Postparturient hemoglobinuria is another rare condition observed in high-yielding dairy cows in the first days of lactation; it is characterized by acute intravascular hemolysis and hemoglobinuria, frequently with fatal outcome.
It is not well understood whether the above-mentioned clinical signs and conditions are caused by hypophosphatemia or if they require concomitant phosphorus depletion of the animal.
Necropsy findings in cases of chronic phosphorus depletion are those specific to rickets or osteomalacia. Carcasses appear emaciated with dull hair coat. Fractures of ribs, vertebrae, or the pelvis, as well as widened growth plates and costochondral junctions, angular deformities, and shortened long bones are common.
Phosphorus depletion is not readily diagnosed in living animals. Because animals with chronic phosphorus depletion can maintain serum concentrations within normal limits by mobilizing phosphorus from bone, and because the serum concentration can be decreased even in the absence of phosphorus depletion, the concentration in serum or plasma is an unreliable method of assessing phosphorus homeostasis. Considerable diurnal variation further complicates the interpretation of serum phosphorus concentrations. Dextrose administered parenterally before blood sampling can decrease the serum phosphorus concentration by >30%; 4–6 hr should elapse between the end of dextrose infusion and blood sampling to allow the serum phosphorus concentration to return to baseline.
The most accurate indication of the phosphorus homeostasis is obtained from determination of bone calcium and phosphorus content in a rib biopsy. The extent of bone resorption activity can be determined by measuring hydroxyproline, an amino acid liberated from collagen as bone is demineralized. Radiographic examination of bone reveals reduced radiopacity in animals with chronic phosphorus depletion.
Feed samples can be submitted to determine the phosphorus content in the ration, allowing an estimate of phosphorus intake if the daily feed intake is known. In grazing animals, the phosphorus concentration in either soil or in a fecal sample can be determined and used as an indirect and crude parameter to assess adequacy of the dietary phosphorus content.
Chronic phosphorus depletion and hypophosphatemia is most effectively treated by providing sufficient amounts of feed with adequate phosphorus content; however, the most appropriate treatment approach for acute phosphorus depletion and hypophosphatemia is controversial. The IV administration of phosphorus-containing solutions is often recommended as the most appropriate approach to correct acute depletion or hypophosphatemia. In small animals, this is achieved by slow IV infusion of sodium phosphate salt solutions, or in the case of concomitant hypokalemia, of potassium phosphate solutions. In cattle, rapid administration of sodium phosphate salt solutions is recommended. Mono- or dibasic phosphate salts (either Na2HPO4 or NaH2PO4), in contrast, when infused rapidly IV increase the serum phosphorus concentration. Tribasic phosphate (Na3PO4) is a caustic detergent that should not be used under any circumstances for oral or IV phosphorus supplementation. A problem with the IV infusion of phosphorus salt solutions is that unbound phosphorus in plasma reaching the kidneys is filtered by the renal glomeruli and must then be reabsorbed in the renal tubules. Because tubular reabsorption is a saturable process, infusing phosphorus at a rate that increases plasma concentration above the renal threshold disproportionally increases renal excretion and only transiently increases the plasma [Pi]. This explains the very short-lived effect of <2 hr of sodium phosphate solutions when administered as an IV bolus as recommended for cattle. Rapid administration of sodium phosphate salts causes transient but severe hyperphosphatemia and, therefore, may cause hypocalcemia due to precipitation of calcium phosphate salts. This risk of calcium phosphate precipitation also precludes the parenteral administration of phosphate salts in combination with parenteral calcium infusions. Infusing phosphate salts slowly over several hours results in a more sustained effect and reduces the risk of hypocalcemia. Currently no solution containing sodium phosphate salts labeled by the FDA for IV administration in cattle is available; therefore, any effective IV phosphate administration is off-label.
In cattle, solutions containing not phosphate but phosphite (PO3), hypophosphite, or organic phosphorus compounds such as butaphosphan or toldimphos are often used to supplement phosphorus IV. These are frequently used in combination with calcium, magnesium, and other minerals. These compounds appear to be unsuitable as a source of phosphorus in mammals that are unable to convert phosphite or the above mentioned organic compounds into phosphate (PO4) and, therefore, do not contribute to the biologically active plasma phosphorus pool.
Mild to moderate phosphorus depletion can effectively be treated by oral phosphorus supplementation, either by adding dairy products to the diet (monogastric species) or by providing solutions of sodium-phosphate salts for oral consumption. Oral administration provides a rapid increase in plasma phosphorus concentration and is safe and effective, but may not be appropriate in vomiting and possibly in diarrheic animals. In cattle, oral sodium phosphate salts increase plasma Pi within <2 hr and exert a sustained effect lasting >12 hr even in early lactating cows with presumably decreased rumen motility.
Phosphorus depletion in healthy grazing animals is prevented by assuring sufficient feed intake with adequate phosphorus content. In animals grazing on phosphorus-deficient soils, depletion may be prevented by fertilizing the soils with phosphorus or by supplementing feeds or the water supply with phosphate salts. In the dairy industry, overfeeding phosphorus is more common because of the widely held but incorrect assumption that feeding phosphorus in excess of the daily requirements improves fertility and milk production. Current research consistently confirms that phosphorus concentration of 0.42% in dry matter is adequate for high-yielding dairy cows.
Currently, no effective approach to prevent hypophosphatemia and phosphorus depletion at the onset of lactation is known. Feeding higher amounts of dietary phosphorus during the last weeks of gestation is contraindicated, because it decreases the intestinal absorption rate of phosphorus and increases the risk of periparturient hypocalcemia. The dietary Ca:P ratio that appears to be essential in horses and other species to prevent secondary hypo- or hyperparathyroidism is not important in ruminants. Cattle tolerate Ca:P ratios between 1:1 and 8:1, provided the ration meets minimal requirements for both minerals. This peculiarity in ruminants can be explained by the high salivary phosphorus concentration (5- to 10-fold the concentration in serum) and the large amounts of saliva produced that alter the Ca:P ratio of the rumen content considerably.
Last full review/revision July 2011 by Walter Gruenberg, DrMedVet, MS, PhD, DECAR, DECBHM