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For further information, see CMDT Part 21-10: Hypophosphatemia

Key Features

Essentials of Diagnosis

  • Severe hypophosphatemia may cause tissue hypoxia and rhabdomyolysis

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

  • Parathyroid hormone (PTH) and fibroblast growth factor (FGF23) are the major factors that increase urine phosphate

General Considerations

  • Leading causes of hypophosphatemia are listed in Table 21–8

  • 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

  • Moderate hypophosphatemia (1.0–2.4 mg/dL [or 0.32–0.79 mmol/L])

    • Occurs commonly in hospitalized patients

    • May not reflect decreased phosphate stores

  • Severe hypophosphatemia (< 1 mg/dL [or 0.32 mmol/L])

    • The affinity of hemoglobin for oxygen increases, impairing tissue oxygenation and cell metabolism, resulting in muscle weakness or even rhabdomyolysis

    • Common and multifactorial in alcoholic patients

  • In chronic obstructive pulmonary disease and asthma, hypophosphatemia can occur from

    • Xanthine derivatives causing shifts of phosphate intracellularly

    • Phosphaturic effects of beta-adrenergic agonists, loop diuretics, xanthine derivatives, and corticosteroids

Table 21–8.Causes of hypophosphatemia.

Clinical Findings

Symptoms and Signs

  • Acute, severe hypophosphatemia (< 1.0 mg/dL [or < 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 failure are uncommon but serious manifestations

    • Hematologic manifestations include acute hemolytic anemia from erythrocyte fragility, platelet dysfunction with petechial hemorrhages, and impaired chemotaxis of leukocytes (leading to increased susceptibility to gram-negative sepsis)

  • Chronic severe depletion may cause

    • Anorexia

    • Pain in muscles and bones

    • Fractures

  • In patients with alcoholism

    • Vomiting, diarrhea, and poor dietary intake contribute to hypophosphatemia

    • Long-term use results in a decrease in the renal threshold of phosphate excretion



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