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  • Severe hypophosphatemia may cause tissue hypoxia and rhabdomyolysis.

  • Renal loss of phosphate can be diagnosed by calculating the fractional excretion of phosphate (FEPO4).

  • PTH and FGF23 are the major factors that increase urine phosphate.


The leading causes of hypophosphatemia are listed in Table 21–8. Hypophosphatemia may occur in the presence of normal phosphate stores. Serious depletion of body phosphate stores may exist with low, normal, or high serum phosphate concentrations.

Table 21–8.Causes of hypophosphatemia.

Serum phosphate levels decrease transiently after food intake, thus fasting samples are recommended for accuracy. Moderate hypophosphatemia (1.0–2.4 mg/dL [0.32–0.79 mmol/L]) occurs commonly in hospitalized patients and may not reflect decreased phosphate stores.

In severe hypophosphatemia (less than 1 mg/dL [0.32 mmol/L]), the affinity of hemoglobin for oxygen increases through a decrease in the erythrocyte 2,3-biphosphoglycerate concentration, impairing tissue oxygenation and cell metabolism and resulting in muscle weakness or even rhabdomyolysis. Severe hypophosphatemia is common and multifactorial in alcoholic patients. In acute alcohol withdrawal, increased plasma insulin and epinephrine along with respiratory alkalosis promote intracellular shift of phosphate. Vomiting, diarrhea, and poor dietary intake contribute to hypophosphatemia. Chronic alcohol use results in a decrease in the renal threshold of phosphate excretion. This renal tubular dysfunction reverses after a month of abstinence. Patients with chronic obstructive pulmonary disease and asthma commonly have hypophosphatemia, attributed to xanthine derivatives causing shifts of phosphate intracellularly and the phosphaturic effects of beta-adrenergic agonists, loop diuretics, xanthine derivatives, and corticosteroids. Refeeding or glucose administration to phosphate-depleted patients may cause fatal hypophosphatemia.


A. Symptoms and Signs

Acute, severe hypophosphatemia (less than 1.0 mg/dL [0.32 mmol/L]) can lead to rhabdomyolysis, paresthesias, and encephalopathy (irritability, confusion, dysarthria, seizures, and coma). Respiratory failure or failure to wean from mechanical ventilation may occur as a result of diaphragmatic weakness. Arrhythmias and heart ...

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