Phosphate is crucial in energy transfer and in the metabolism of carbohydrate, protein, and fat. Phosphate serves as the principal urinary buffer (HPO₄, H₂PO₄), constituting most of titratable acidity.

Renal tubular reabsorption of filtered phosphate is reduced (phosphate excretion increased) by parathyroid hormone, expansion of extracellular fluid volume, increased intake of sodium, hypercalcemia, calcitonin, glucocorticoids, and growth hormone. Likewise, proximal tubular dysfunction such as occurs in myeloma kidney may have a similar effect.

Hypophosphatemia may occur in the presence of normal phosphate stores. Serious depletion of body phosphate stores may exist with low, normal, or high concentrations of phosphorus in serum. Leading causes of hypophosphatemia are listed in Table 21–10.

Hypophosphatemia is a reversible cause of respiratory muscle hypocontractility and impaired tissue oxygenation by causing a decrease in the erythrocyte 2,3-diphosphoglycerate concentration in patients with COPD and asthma. Mechanisms of hypophosphatemia include intracellular shifts of phosphorus related to the correction of respiratory acidosis and the use of drugs that increase renal phosphate excretion such as theophylline, corticosteroids, loop diuretics, and b2adrenergic bronchodilators. Transient defects in renal tubular function, such as decreases in the renal threshold of phosphate excretion and increases in the fractional excretion of calcium and magnesium, are common in patients with chronic alcoholism and account in part for the high prevalence of hypophosphatemia, hypomagnesemia, and hypocalcemia in these patients. These renal defects reverse within a month of abstinence.

A. Symptoms and Signs: Acute, severe hypophosphatemia (0.1–0.2 mg/dL) can lead to acute hemolytic anemia with increased erythrocyte fragility, impaired oxygen delivery to tissues, increased susceptibility to infection from impaired chemotaxis of leukocytes, and platelet dysfunction with petechial hemorrhages. Rhabdomyolysis, encephalopathy (irritability, confusion, dysarthria, seizures, and coma), and heart failure are uncommon but serious manifestations.

Chronic severe depletion may be manifested by anorexia, pain in muscles and bones, and fractures.

B. Laboratory Findings: In addition to hypophosphatemia, evidence of anemia due to hemolysis may be present (eg, elevated serum lactate dehydrogenase). Rhabdomyolysis results in elevated serum creatine kinase (which contains mostly the MM fraction but also some MB fraction) and, in many cases, myoglobin in the urine. Other values vary according to the cause. Renal glycosuria and hypouricemia together with hypophosphatemia indicate Fanconi's syndrome. In chronic depletion, radiographs and biopsies of bones show changes resembling those of osteomalacia.

Treatment is best directed toward prophylaxis by including phosphate in repletion and maintenance fluids. A rapid decline in calcium levels can occur with parenteral administration of phosphate; therefore, when possible, oral replacement of phosphate is preferable. For parenteral alimentation, 620 mg (20 mmol) of phosphorus is required for every 1000 nonprotein kcal to maintain phosphate balance and to ensure anabolic function. A daily ration for prolonged parenteral fluid maintenance is 620–1240 mg (20–40 mmol) of phosphorus. For asymptomatic hypophosphatemia (serum phosphorus 0.7–1 mg/dL), an infusion should provide 279–310 mg (9–10 mmol)/12 h until the serum phosphorus exceeds 1 mg/dL. A magnesium deficit often coexists and should be treated simultaneously. In administering phosphate-containing solutions, serum creatinine and calcium must be monitored to guard against hypocalcemia.

For oral use, phosphate salts are available in skim milk (approximately 1 g [33 mmol]/L). Tablets or capsules of mixtures of sodium and potassium phosphate may be given to provide 0.5–1 g (18–32 mmol) per day.

Contraindications to therapy with phosphate salts include hypoparathyroidism, renal insufficiency, tissue damage and necrosis, and hypercalcemia. When hyperglycemia due to any cause is treated, phosphate accompanies glucose into cells, and hypophosphatemia may ensue.

A. Symptoms and Signs: The clinical manifestations are those of the underlying disorders (eg, chronic renal failure, hypoparathyroidism). Hyperphosphatemia in chronic renal failure leads to secondary hyperparathyroidism and renal osteodystrophy.

B. Laboratory Findings: In addition to elevated phosphate, other blood chemistry values are those characteristic of the underlying disease.