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Source: Pai, AB. Disorders of Calcium and Phosphorus Homeostasis. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach, 8th ed. http://accesspharmacy.com/content.aspx?aid=7983818. Accessed August 20, 2012.

  • Serum phosphorus concentrations <2 mg/dL (<0.65 mmol/L)
    • Mild to moderate: 1–2 mg/dL (0.32–0.65 mmol/L)
    • Severe: <1 mg/dL (0.32 mmol/L)

  • Result of decreased gastrointestinal (GI) absorption, reduced tubular reabsorption, extracellular to intracellular redistribution, or other conditions.

  • Decreased GI absorption seen with use of oral phosphate-binding agents and with hyperparathyroidism (decreased absorption of dietary phosphorus).
  • Reduced tubular absorption occurs with:
    • Hyperparathyroidism: elevated parathyroid hormone (PTH) leads to increase in serum calcium and decrease in serum phosphate concentrations.
    • Burn patients experience marked diuretic phase associated with impressive renal loss of phosphate.
  • Extracellular to intracellular phosphate shifts occur with:
    • Severe and prolonged respiratory alkalosis
    • Treatment of diabetic ketoacidosis
    • Drug therapy (e.g., insulin, dextrose solutions, glucagons)
    • Alcohol withdrawal

  • Screening on admission to hospital: 1–3%
  • Hospitalized critically ill patients: 18–28%

  • Routine addition of phosphate in concentrations of 12–15 mmol/L to parenteral nutrition important to prevent severe hypophosphatemia.

  • Chronic use of phosphate-binding agents (e.g., chronic kidney disease [CKD])
  • Peptic ulcer disease
  • Hyperparathyroidism
  • Alcoholism
  • Diabetic ketoacidosis
  • Parenteral nutrition

  • Clinical manifestations depend on chronicity and severity of phosphate depletion.

Signs and Symptoms

  • Symptomatic hypophosphatemia not evident until serum phosphate <1 mg/dL (<0.32 mmol/L)
  • Severe hypophosphatemia has diverse clinical manifestations that affect many organ systems.
  • Neurologic symptoms include:
    • Irritability
    • Apprehension
    • Weakness
    • Numbness
    • Paresthesias
    • Dysarthria
    • Confusion
    • Obtundation
    • Seizures
    • Coma
  • Skeletal muscle dysfunction:
    • Myalgia
    • Bone pain
    • Weakness
    • Potentially fatal rhabdomyolysis
  • Bone:
    • Osteopenia and osteomalacia with chronic hypophosphatemia due to enhanced osteoclastic resorption
  • Cardiopulmonary:
    • Respiratory muscle weakness and diaphragmatic contractile dysfunction can cause acute respiratory failure.
    • Congestive cardiomyopathy
    • Arrhythmias
  • Hematologic:
    • Hemolysis
    • Dysfunctional white blood cells leading to increased risk of infection

Means of Confirmation and Diagnosis

  • Serum phosphorus concentrations <2 mg/dL (<0.65 mmol/L)
  • Symptoms not evident until serum phosphate <1 mg/dL (<0.32 mmol/L)

Laboratory Tests

  • Metabolic panel
    • Serum phosphate
    • Serum calcium
    • Serum magnesium
    • Serum potassium
  • Parathyroid hormone
  • Urinalysis
    • 24-hour urine collection

Differential Diagnosis

  • Dilated cardiomyopathy
  • Encephalopathy
  • Myopathies

  • Reverse signs and symptoms.
  • Normalize serum phosphate concentrations.
  • Manage underlying conditions.

  • Estimation of total body phosphate deficit difficult because phosphate is intracellular electrolyte.
  • Rate of infusion and initial dose of IV phosphate based on:
    • Severity of hypophosphatemia
    • Presence of symptoms
    • Comorbid conditions

  • Asymptomatic patients (or mild to moderate hypophosphatemia)
    • Treat with oral phosphorus supplementation
      • Dose: 1.5–2 g (50–60 mmol) daily in divided doses
      • Goal: correct serum phosphorus concentration in 7–10 days (Table 1).
      • Dose-limiting toxicity: osmotic diarrhea
  • Severe (<1 mg/dL; <0.32 mmol/L) or symptomatic patients
    • Treat with IV phosphorus replacement
    • Infuse 15 mmol of phosphorus in 250 mL of IV fluid over 3 hours.
      • Recommended dosage of IV phosphorus (5–45 mmol or 0.08–0.64 mmol/kg) and infusion recommendations (over 4–12 hours) are highly variable.

Table 1. Phosphorus Replacement Therapy

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