Phosphorus and phosphate are often spoken of interchangeably, although phosphorus is only one component of phosphate. The semantic problem is even more confusing because an order for “phosphate” assay usually results in laboratory measurement of inorganic phosphorus. However, much of the body phosphorus is a part of phosphate compounds. About 80%-85% of body phosphorus is found in bone and about 10% in skeletal muscle. Most body phosphorus is intracellular, where it represents the most abundant intracellular anion. Phosphorus is a part of phospholipid compounds in all cell membranes, adenosine triphosphate energy-transfer compounds, nucleic acids, the compound 2,3-diphosphoglyceric acid (which regulates oxygen affinity for hemoglobin), various enzymes, and the principal urinary acid-base buffer system. Phosphorus is acquired through food and absorbed through the small intestine. About 90% is extracted from serum by the kidney with about 85%-90% being normally reabsorbed by the renal proximal tubules. Serum phosphorus values change considerably during the day (variation of 2 mg/100 ml [0.65 mmol/L] within a reference range of 2.5-4.5 mg/100 ml [0.81-1.45 mmol/L]), with lowest values at 10-11 A.M. and highest at 10 P.M. -3 A.M. Therefore, values are usually higher in the late afternoon and evening than in the morning. Some of these changes are due to dietary factors and some to shifts between intracellular and extracellular localization. Phosphate excretion is low about 9 A.M.-1 P.M., high about 3 P.M. -8 P.M., low again about midnight-1 A.M., and high again about 3-5 A.M. Administration of glucose leads to a temporary shift of phosphorus from an extracellular to an intracellular location. If a glucose load is given orally, trough serum phosphorus values are found about 2 hours postprandially, and preingestion values are regained about 5 hours postprandially.

Hypophosphatemia

Most clinical abnormalities involving phosphorus are associated with hypophosphatemia. Symptoms include confusion, disorientation, delirium, and sometimes seizures, thus resembling the symptoms of hyponatremia and other metabolic encephalopathies. In addition, there is skeletal muscle weakness that may progress to actual myopathy. In chronic severe hypophosphatemia there may be bone abnormalities such as osteomalacia and pseudofractures, as well as hematologic abnormalities such as decrease in oxygen delivery by RBCs and a tendency toward hemolysis. WBC function may be disturbed, with an increased incidence of fungal and bacterial infection. Mild hypophosphatemia, on the other hand, is usually asymptomatic clinically and biochemically.

The overall incidence of hypophosphatemia ranges from 2%-22% in hospitalized patients. The great majority of patients demonstrate only a mild degree of abnormality and no clinical effects. The box lists conditions more likely to be associated with severe hypophosphatemia. For example, severe hypophosphatemia may appear in chronically malnourished persons who undergo rapid refeeding with low-phosphate nutrients (nutritional recovery syndrome). In many of the conditions listed under severe phosphate deficiency, onset of hypophosphatemia may not appear until 1 or more days after onset of illness. The other conditions on the list frequently produce hypophosphatemia but usually only of moderate degree. Even more conditions may produce mild disorder. There is an association of hypophosphatemia with hypomagnesemia, especially in alcoholics.

Selected Disorders Associated With Serum Phosphate Abnormality

Phosphate decrease*
Parenteral hyperalimentation
Diabetic acidosis
Alcohol withdrawal
Severe metabolic or respiratory alkalosis
Antacids that bind phosphorus
Malnutrition with refeeding using low-phosphorus nutrients
Renal tubule failure to reabsorb phosphate (Fanconi’s syndrome; congenital; vitamin D deficiency)
Glucose administration
Nasogastric suction
Malabsorption
Gram-negative sepsis
Primary hyperthyroidism
Chlorothiazide diuretics
Therapy of acute severe asthma
Acute respiratory failure with mechanical ventilation
Phosphate excess
Renal failure
Severe muscle injury
Phosphate-containing antacids
Hypoparathyroidism
Tumor lysis syndrome

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*Low phosphate diet can magnify effect of phosphorus-lowering disorders.

In one study, the most common etiology was medication known to induce hypophosphatemia without phosphate supplements. This most often occurred in association with surgery. The second most common etiology was gram-negative sepsis.

Hyperphosphatemia

The most common cause of hyperphosphatemia is renal failure. Other causes are listed in the box on this page. Hyperlipidemia or RBC hemolysis may produce artifactual phosphate elevation. Hyperphosphatemia may lead to hypocalcemia.