Phosphate Deficiency and the Phosphate-Depletion Syndrome: Pathophysiology, Diagnosis, and Treatment

Phosphorus depletion describes a state of substantial phosphorus deficiency within all body compartments. Most, but not all times, it is accompanied by hypophosphatemia, a serum phosphorus level of <2.5 mg/dl (<0.81 mmol/L). While hypophosphatemia is rare in the general population, among hospitalized patients, there are several high-risk subgroups, including alcoholics and the severely malnourished (e.g., those with anorexia nervosa and malignancy) [1, 2]. As phosphorus-containing ATP forms the basis of energy that is essential to most physiologic processes, significant deficiency in this element is a threat to health. Severe hypophosphatemia (≤1.0 mg/dl) has been linked to the syndrome of phosphorus depletion, characterized symptomatically by weakness, muscle and bone pain, and anorexia [3]. Animal data, human case reports, and observational human studies have demonstrated multisystem effects, including respiratory and cardiac muscle dysfunction, rhabdomyolysis, osteomalacia, and hemolysis [4]. Given the diverse and central role of phosphorus, intuition would suggest that the phosphorus-depletion syndrome enhances risk for mortality, especially in the critically ill patient. However, while observational data shows an association between severe hypophosphatemia and mortality, confounding by a variety of comorbid conditions in the critically ill makes causality difficulty to prove [2].