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Hypophosphatemia

By

James L. Lewis III

, MD, Brookwood Baptist Health and Saint Vincent’s Ascension Health, Birmingham

Reviewed/Revised Sep 2023
View PATIENT EDUCATION

Hypophosphatemia is a serum phosphate concentration < 2.5 mg/dL (0.81 mmol/L). Causes include alcohol use disorder, burns, starvation, and diuretic use. Clinical features include muscle weakness, respiratory failure, and heart failure; seizures and coma can occur. Diagnosis is by serum phosphate concentration. Treatment consists of phosphate supplementation.

Etiology of Hypophosphatemia

Hypophosphatemia has numerous causes.

Clinically significant acute hypophosphatemia occurs in relatively few clinical settings, including the following:

Acute severe hypophosphatemia with serum phosphate < 1 mg/dL (< 0.32 mmol/L) is most often caused by

  • Transcellular shifts of phosphate often superimposed on chronic phosphate depletion

Chronic hypophosphatemia usually is the result of decreased renal phosphate reabsorption. Causes include the following:

Severe chronic hypophosphatemia usually results from a prolonged negative phosphate balance. Causes include

  • Chronic starvation or malabsorption, often in patients with alcohol use disorder, especially when combined with vomiting or copious diarrhea

  • Long-term ingestion of large amounts of phosphate-binding aluminum, usually in the form of antacids

Patients with advanced chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is long-standing, progressive deterioration of renal function. Symptoms develop slowly and in advanced stages include anorexia, nausea, vomiting, stomatitis, dysgeusia... read more Chronic Kidney Disease (especially those on dialysis) often take phosphate binders with meals to reduce absorption of dietary phosphate. The prolonged use of these binders can cause hypophosphatemia, particularly when combined with greatly decreased dietary intake of phosphate.

Symptoms and Signs of Hypophosphatemia

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 alcohol use disorder.

Hematologic disturbances of profound hypophosphatemia include hemolytic anemia, decreased release of oxygen from hemoglobin, and impaired leukocyte and platelet function.

Diagnosis of Hypophosphatemia

  • Serum phosphate levels

Hypophosphatemia is diagnosed by a serum phosphate 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 test results or signs of cirrhosis in patients with suspected alcohol use disorder).

Treatment of Hypophosphatemia

  • Treat underlying disorder

  • Oral phosphate replacement

  • IV phosphate when serum phosphate is < 1 mg/dL (< 0.32 mmol/L) or symptoms are severe

Removal of the cause of hypophosphatemia may include stopping phosphate-binding antacids or diuretics or correcting hypomagnesemia.

Oral treatment

Treatment of the underlying disorder and oral phosphate replacement are usually adequate in asymptomatic patients, even when the serum concentration is very low. Phosphate can be given in doses up to about 1 g orally 3 times a day in tablets containing sodium phosphate or potassium phosphate.

Oral sodium phosphate or potassium phosphate may be poorly tolerated because of diarrhea. Ingestion of 1 L of low-fat or skim milk provides 1 g of phosphate and may be more acceptable.

Parenteral treatment

Parenteral phosphate is usually given IV. It should be administered in any of the following circumstances:

IV administration of potassium phosphate (as buffered mix of K2HPO4 and KH2PO4) is relatively safe when renal function is well preserved. Parenteral potassium phosphate contains 93 mg (3 mmol) phosphorus and 170 mg (4.4 mEq or 4.4 mmol) potassium per mL. The usual dose is 0.5 mmol phosphorus/kg (0.17 mL/kg) IV over 6 hours. Patients with alcohol use disorder may require 1 g/day during total parenteral nutrition; supplemental phosphate is stopped when oral intake is resumed.

If patients have impaired renal function or serum potassium > 4 mEq/L (> 4 mmol/L), sodium phosphate preparations generally should be used; these preparations also contain 3 mmol/mL of phosphorus and are thus given at the same dose.

Serum calcium and phosphate concentrations should be monitored during therapy, particularly when phosphate 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 phosphate should be given over 6 hours. Close monitoring is done, and more rapid rates of phosphate administration should be avoided to prevent hypocalcemia Hypocalcemia Hypocalcemia is a total serum calcium concentration < 8.8 mg/dL (< 2.20 mmol/L) in the presence of normal plasma protein concentrations or a serum ionized calcium concentration < 4... read more , hyperphosphatemia Hyperphosphatemia Hyperphosphatemia is a serum phosphate concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic kidney disease, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical... read more , and metastatic calcification due to excessive calcium phosphate product.

Key Points

  • Acute hypophosphatemia most often occurs in patients with of alcohol use disorder, burns, or starvation.

  • Acute severe hypophosphatemia can cause serious neuromuscular disturbances, rhabdomyolysis, seizures, coma, and death.

  • Chronic hypophosphatemia may be due to hormonal disorders (eg, hyperparathyroidism, Cushing syndrome, hypothyroidism), chronic diuretic use, or use of aluminum-containing antacids by patients with chronic kidney disease.

  • Hypophosphatemia is usually asymptomatic, but severe chronic depletion can cause anorexia, muscle weakness, and osteomalacia.

  • Treat the underlying disorder, but some patients require oral, or rarely, IV phosphate replacement.

Drugs Mentioned In This Article

Drug Name Select Trade
Calcidol, Calciferol, D3 Vitamin, DECARA, Deltalin, Dialyvite Vitamin D, Dialyvite Vitamin D3, Drisdol, D-Vita, Enfamil D-Vi-Sol, Ergo D, Fiber with Vitamin D3 Gummies Gluten-Free, Happy Sunshine Vitamin D3, MAXIMUM D3, PureMark Naturals Vitamin D, Replesta, Replesta Children's, Super Happy SUNSHINE Vitamin D3, Thera-D 2000, Thera-D 4000, Thera-D Rapid Repletion, THERA-D SPORT, UpSpring Baby Vitamin D, UpSpring Baby Vitamin D3, YumVs, YumVs Kids ZERO, YumVs ZERO
Elixophyllin, Quibron T, Quibron T/SR, Respbid, Slo-Bid, Slo-Phyllin, Theo X, Theo-24, Theo-Bid Duracap, TheoCap, Theochron, Theo-Dur, Theo-Dur Sprinkle , Theolair, Theolair SR, Theovent LA, T-Phyl, Uni-Dur, Uniphyl
K-Phos, Phospho-Trin
View PATIENT EDUCATION
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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