Phosphorus is one of the most abundant elements in the human body. Most phosphorus in the body is complexed with O2 as phosphate (PO4). About 85% of the about 500 to 700 g of PO4 in the body is contained in bone, where it is an important constituent of crystalline hydroxyapatite. In soft tissues, PO4 is mainly found in the intracellular compartment as an integral component of several organic compounds, including nucleic acids and cell membrane phospholipids. PO4 is also involved in aerobic and anaerobic energy metabolism. RBC 2,3-diphosphoglycerate (2,3-DPG) plays a crucial role in O2 delivery to tissue. Adenosine diphosphate (ADP) and ATP contain PO4 and use chemical bonds between PO4 groups to store energy. Inorganic PO4 is a major intracellular anion but is also present in plasma. The normal serum inorganic PO4 concentration in adults ranges from 2.5 to 4.5 mg/dL (0.81 to 1.45 mmol/L). PO4 concentration is 50% higher in infants and 30% higher in children, possibly because of the important roles these PO4-dependent processes play in growth.
The typical American diet contains about 800 to 1500 mg of PO4. The amount in the stool varies depending on the amount of PO4 binding compounds (mainly Ca) in the diet. Also, like Ca, GI PO4 absorption is enhanced by vitamin D. Renal PO4 excretion roughly equals GI absorption to maintain PO4 balance. PO4 depletion can occur in various disorders and normally results in conservation of PO4 by the kidneys. Bone PO4 serves as a reservoir, which can buffer changes in plasma and intracellular PO4.
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.
Hyperphosphatemia is serum phosphate (PO4) concentration > 4.5 mg/dL (> 1.46 mmol/L). Causes include chronic renal failure, hypoparathyroidism, and metabolic or respiratory acidosis. Clinical features may be due to accompanying hypocalcemia and include tetany. Diagnosis is by serum PO4. Treatment includes restriction of PO4 intake and administration of PO4-binding antacids, such as Ca carbonate.
The usual cause of hyperphosphatemia is a decrease in renal excretion of PO4. Advanced renal insufficiency (GFR < 30 mL/min) reduces excretion sufficiently to increase serum PO4. Defects in renal excretion of PO4 in the absence of renal failure also occur in pseudohypoparathyroidism and hypoparathyroidism. Hyperphosphatemia can also occur with excessive oral PO4 administration and occasionally with overzealous use of enemas containing PO4.
Hyperphosphatemia occasionally results from a transcellular shift of PO4 into the extracellular space that is so large that the renal excretory capacity is overwhelmed. This transcellular shift occurs most frequently in diabetic ketoacidosis (despite total body PO4 depletion), crush injuries, and nontraumatic rhabdomyolysis as well as in overwhelming systemic infections and tumor lysis syndrome.
Major causes of hyperphosphatemia include
Hyperphosphatemia plays a critical role in the development of secondary hyperparathyroidism and renal osteodystrophy in patients with advanced chronic kidney disease as well as in patients on dialysis. Lastly, hyperphosphatemia can be spurious in cases of hyperproteinemia (multiple myeloma or Waldenström's macroglobulinemia), hyperlipidemia, hemolysis, or hyperbilirubinemia.
Hyperphosphatemia can lead to hypocalcemia by causing Ca and PO4 precipitation into soft tissues, especially when the serum Ca × PO4 product is chronically > 55 in patients with chronic kidney disease.
Symptoms and Signs
Most patients with hyperphosphatemia are asymptomatic, although symptoms of hypocalcemia, including tetany, can occur when concomitant hypocalcemia is present. Soft-tissue calcifications are common among patients with chronic kidney disease.
Hyperphosphatemia is diagnosed by PO4 concentration. When the etiology is not obvious (eg, rhabdomyolysis, tumor lysis syndrome, renal failure, overingestion of PO4,-containing laxatives), additional evaluation is warranted to exclude hypoparathyroidism or pseudohypoparathyroidism, which is end-organ resistance to parathyroid hormone (PTH—see Electrolyte Disorders: Pseudohypoparathyroidism). False elevation of serum PO4 also should be excluded by measuring serum protein, lipid, and bilirubin concentrations.
The mainstay of treatment in patients with renal failure is reduction of PO4 intake, which is usually accomplished with avoidance of foods containing high amounts of PO4 and with use of PO4-binding drugs taken with meals. Because of the possibility of aluminum-related osteomalacia, Ca carbonate and Ca acetate replace aluminum-containing antacids in patients with end-stage renal disease. Because of the possibility of excessive Ca × PO4 product causing vascular calcification in dialysis patients taking Ca-containing binders, a PO4-binding resin without Ca, sevelamer, is widely used in dialysis patients in doses of 800 to 2400 mg tid with meals. Lanthanum carbonate, another PO4 binder that lacks Ca, can also be used in dialysis patients. It is given in doses of 500 to 1000 mg tid with meals.
Last full review/revision May 2009 by James L. Lewis, III, MD
Content last modified February 2012