Hypophosphatemia is serum phosphate (PO4) concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcoholism, burns, starvation, and diuretic use. Clinical features include muscle weakness, respiratory failure, and heart failure; seizures and coma can occur. Diagnosis is by serum PO4 concentration. Treatment consists of PO4 supplementation.
Hypophosphatemia occurs in 2% of hospitalized patients but is more prevalent in certain populations (eg, it occurs in up to 10% of hospitalized patients with alcoholism).
Hypophosphatemia has numerous causes, but clinically significant acute hypophosphatemia occurs in relatively few clinical settings, including the following:
Acute severe hypophosphatemia with serum PO4 < 1 mg/dL (< 0.32 mmol/L) is most often caused by transcellular shifts of PO4, often superimposed on chronic PO4 depletion.
Chronic hypophosphatemia usually is the result of decreased renal PO4 reabsorption. Causes include the following:
Severe chronic hypophosphatemia usually results from a prolonged negative PO4 balance. Causes include
Ingestion of aluminum is particularly prone to cause PO4 depletion when combined with decreased dietary intake and dialysis losses of PO4 in patients with end-stage renal disease.
Symptoms and Signs
Although hypophosphatemia usually is asymptomatic, anorexia, muscle weakness, and osteomalacia can occur in severe chronic depletion. Serious neuromuscular disturbances may occur, including progressive encephalopathy, seizures, coma, and death. The muscle weakness of profound hypophosphatemia may be accompanied by rhabdomyolysis, especially in acute alcoholism. Hematologic disturbances of profound hypophosphatemia include hemolytic anemia, decreased release of O2 from Hb, and impaired leukocyte and platelet function.
Hypophosphatemia is diagnosed by a serum PO4 concentration < 2.5 mg/dL (< 0.81 mmol/L). Most causes of hypophosphatemia (eg, diabetic ketoacidosis, burns, refeeding) are readily apparent. Testing to diagnose the cause is done when clinically indicated (eg, suggestive liver function test results or signs of cirrhosis in patients with suspected alcoholism).
Treatment of the underlying disorder and oral PO4 replacement are usually adequate in asymptomatic patients, even when the serum concentration is very low. PO4 can be given in doses up to about 1 g po tid in tablets containing Na or K PO4. Oral Na or K PO4 may be poorly tolerated because of diarrhea. Ingestion of 1 L of low-fat or skim milk provides 1 g of PO4 and may be more acceptable. Removal of the cause of hypophosphatemia may include stopping PO4 binding antacids or diuretics or correcting hypomagnesemia.
Parenteral PO4 is usually given IV. It should be administered in any of the following circumstances:
IV administration of KPO4 (as buffered mix of K2HPO4 and KH2PO4) is relatively safe when renal function is well preserved. NaPO4 (rather than KPO4) preparations generally should be used in patients with impaired renal function. The usual parenteral dose of KPO4 is 2.5 mg (0.08 mmol)/kg IV over 6 h. Patients with alcoholism may require ≥ 1 g/day during TPN; supplemental PO4 is stopped when oral intake is resumed. Serum Ca and PO4 concentrations should be monitored during therapy, particularly when PO4 is given IV or to patients with impaired renal function. In most cases, no more than 7 mg/kg (about 500 mg for a 70-kg adult) of PO4 should be given over 6 h. Close monitoring is done and more rapid rates of PO4 administration should be avoided to prevent hypocalcemia, hyperphosphatemia, and metastatic calcification due to excessive Ca × PO4 product.
Last full review/revision March 2013 by James L. Lewis, III, MD
Content last modified October 2013