Hypophosphataemia (less than 0.7 mmol/L) occurs in as many as 25% of hospital inpatients. However, functional deficiency does not occur until plasma phosphate falls below 0.3 mmol/L. At this concentration, replacement should be considered urgently since hypophosphataemia results in widespread organ dysfunction. If there is insufficient intracellular phosphate, no ATP can be manufactured, which results in widespread organ failure.
The symptoms of phosphate deficiency include haemolysis, thrombocytopenia and poor granulocyte function. Severe muscle weakness, respiratory muscle failure and rhabdomyolysis occur. Confusion, irritability and coma may be due to a metabolic encephalopathy due to phosphate deficiency.
The first diagnostic step is to determine whether hypophosphataemia is due to real deficiency or due to redistribution within the body since the latter is benign. However, in all but short term cases of hypophosphataemia, redistribution is also associated with the conditions that cause renal phosphate loss. Therefore, a pragmatic approach is to consider that individuals with moderately low plasma phosphate (0.48-0.72 mmol/L) do not need replacement unless they have a risk factor for phosphate depletion; whereas if the plasma phosphate is below 0.32 mmol/L, phosphate depletion is likely and replacement should be administered.
Drug induced hypophosphataemia
Shifts of extracellular phosphate into cells
Acute respiratory alkalosis (salicylate poisoning, mechanical ventilation)
Administration of glucose, fructose, insulin therapy, parenteral nutrition
Catecholamine action: epinephrine, dopamine, salbutamol, xanthine derivatives, hypothermiaRapid cellular proliferation (erythropoetin, GM-CSF therapy)
Decreased intestinal phosphate absorption
Increased urinary phosphate excretion
Carbonic anhydrase inhibitors
Diuretics (hydrochlorthiazide, indapamide, furosemide)
Theophylline, bronchodilators, corticosteroids
Drug-induced Fanconi Syndrome
Volume expansion (drug-induced SIADH, administration of saline)
BisphosphonatesEstrogens, mestranolAcyclovirImatimib mesylate
Hypophosphatemia resulting from more than one mechanism
Drug-induced metabolic acidosis (alcohol, toluene)
Drugs that cause vitamin D deficiency or resistance: phenytoin, phenobarbital
Intravenous iron administration
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Liamis G, Milionis HJ, Elisaf M. Medication-induced hypophosphatemia: a review. Q J Med 2010;103:449-459.
Payne RB. Renal tubular reabsorption of phosphate (TmP/GFR): indications and interpretation. Ann Clin Biochem 1998;35:201-206.
Weisinger JR, Bellorin-Font E. Magnesium and phosphorus. Lancet 1998;352:391-396.
JHB 27 Feb 2013