Phosphate Metabolism

Serum phosphate concentrations vary much more than serum calcium concentrations. The normal range is 2.5 to 4.5 mg/dL (0.8 to 1.5 mmol/L) of phosphorus as inorganic phosphate. Eighty percent of the body's phosphate is stored in bone as hydroxyapatite; the remaining 20% is largely organic. Phosphate-containing nucleic acids, nucleotides, phospholipids, and phosphoproteins are vital to energy metabolism, membrane function, and cell replication.

Hypophosphatemia

A serum concentration of inorganic phosphorus < 2.5 mg/dL (< 0.8 mmol/L).

Etiology

Mild hypophosphatemia is common in the elderly and probably results from decreased intake and impaired intestinal absorption of phosphate. The age-related increase in parathyroid function might also lower the renal threshold for tubular reabsorption of phosphate. Severe hypophosphatemia (serum concentrations < 1.5 mg/dL [< 0.5 mmol/L]) usually results from prolonged, severe decreased dietary intake and impaired absorption or from renal tubular dysfunction. Vomiting, acidosis, and alcoholic ketoacidosis may also contribute to hypophosphatemia. Aluminum hydroxide antacids, renal dialysis, and a rapid recovery of renal function after acute renal failure or transplantation are other causes of phosphate loss. Serum phosphate concentrations may also be extremely low with relatively mild degrees of intracellular phosphate depletion when extracellular phosphate rapidly shifts into the cells. This shift usually occurs when insulin and glucose are administered together in the treatment of diabetes.

Symptoms and Signs

Hypophosphatemia is usually asymptomatic. However, chronic severe hypophosphatemia can cause anorexia, muscle weakness, and osteomalacia. Rhabdomyolysis, hemolytic anemia, and impaired leukocyte and platelet function may occur, as may progressive encephalopathy, coma, and death.

Treatment

Because IV phosphate therapy can cause hypocalcemia and soft tissue calcification and because many elderly patients have impaired renal function and do not handle phosphate loads well, IV phosphate must be administered cautiously, even when serum concentrations are extremely low. Patients with severe phosphate depletion often have depleted concentrations of other ions, particularly potassium and magnesium; determining which abnormality is causing the symptoms can be difficult. However, patients with extremely low phosphate concentrations and evidence of impaired central nervous system (CNS) function and muscular weakness should receive IV sodium phosphate; those who also have a potassium depletion should also receive IV potassium phosphate. Serum calcium, inorganic phosphate, potassium, and magnesium concentrations should be monitored.

Oral phosphate supplements are usually unnecessary in patients with adequate diets. However, in hypophosphatemic patients who also have hypercalcemia, these supplements may lower the serum calcium concentration. Elderly patients have difficulty taking > 1 to 2 g/day of oral phosphate, even when administered in divided doses, because of diarrhea.

Hyperphosphatemia

A serum concentration of inorganic phosphorus > 4.5 mg/dL (> 1.5 mmol/L).

Hyperphosphatemia occurs most commonly in patients with chronic renal failure. In rare cases, severe hyperphosphatemia occurs in patients who undergo rapid cell lysis with release of phosphate. This condition can occur in patients with leukemia or other tumors who receive chemotherapy. Excessive intake of phosphate rarely causes hyperphosphatemia, partly because a high phosphate concentration leads to diarrhea and partly because renal excretion is efficient. Hyperphosphatemia caused by large volumes of phosphate-containing enemas has been reported. If the serum phosphate concentration is extremely high, calcium phosphate salts are deposited in bone and soft tissue, and the serum calcium concentration may fall, producing tetany. Most patients are asymptomatic.

Treatment

When renal function is normal and hydration is maintained, hyperphosphatemia is usually transient. If tetany occurs, IV calcium may be needed. (Caution: Excessive administration of IV calcium in the presence of a high phosphate concentration can cause deposition of calcium phosphate salts and lead to acute kidney, blood vessel, and lung damage.)

In chronic renal failure, hyperphosphatemia can be controlled by a low phosphate intake and administration of calcium or aluminum salts, which bind phosphate.