Hypophosphataemia

Hypophosphataemia is characterised by abnormally low levels of phosphate in the blood, which can lead to significant clinical consequences due to phosphate’s essential role in cellular energy production, muscle function, and bone mineralisation. Severe cases of hypophosphataemia can be life-threatening, especially in critically ill patients.

Clinical Features of Hypophosphataemia

Phosphate depletion affects multiple organ systems, leading to a broad range of symptoms. These can be grouped as follows:

  1. Neurological Manifestations:
    • Irritability, tremor, cramps, paraesthesia.
    • Hallucinations, delirium.
    • Seizures, coma.
    • Increased risk of osmotic demyelination syndrome.
  2. Cardiovascular Manifestations:
    • Recuced cardiac contractility.
    • Arrhythmias.
  3. Musculoskeletal Manifestations:
    • Generalised weakness and proximal myopathy.
    • Reduced GI motility, dysphagia, ileus.
    • Increased bone resorption, osteopenia and rickets.
    • Severe cases may result in rhabdomyolysis.
  4. Haematological Abnormalities:
    • Decreased red cell 2,3-diphosphoglycerate (2,3-DPG) levels (left shift in the oxyHb dissociation curve).
    • Increased red blood cell rigidity and propensity to haemolysis.
    • Impaired clot retention, thrombocytopaenia.
  5. Biochemical Abnormalities:
    • Hypercalciuria, increased bone resorption.
    • Elevated calcitriol (1,25-dihydroxyvitamin D).

Causes of Hypophosphataemia

Hypophosphataemia can result from decreased intake, increased excretion, or a shift of phosphate from the extracellular to the intracellular compartment.

Category Examples
Decreased Intake Parenteral nutrition without phosphate supplementation, malnutrition, alcoholism.
Vitamin D deficiency or resistance, phosphate binders (e.g. sevelamer).
Increased Excretion Renal losses: Hyperparathyroidism, Vitamin D deficiency, Fanconi syndrome, diuretics, alkalosis.
Gastrointestinal losses: Diarrhoea, especially steatorrhoea, vomiting.
Other losses: Haemodialysis, burns, pancreatitis third-spacing.
Intracellular Compartment Shift Carbohydrate infusion: Refeeding syndrome, insulin administration.
Hormonal effects: Calcitonin, catecholamines/sympathetomimetics (e.g. salbutamol, theophylline), glucagon.
Rapid cellular proliferation: Leukaemic crisis, erythropoietin therapy.

Diagnostic Approach

To confirm hypophosphataemia and evaluate the underlying cause, the following steps should be taken:

  1. Serum Phosphate Levels:
    • Normal phosphate levels: 0.8–1.5 mmol/L.
    • Mild hypophosphataemia: 0.6–0.8 mmol/L.
    • Severe hypophosphataemia: <0.6 mmol/L.
  2. Associated Electrolyte and Hormone Levels:
    • U&Es (Urea and Electrolytes): To assess renal function and electrolyte status.
    • Calcium and magnesium: To identify associated disturbances, especially given the close interaction between calcium, phosphate, and magnesium.
    • Parathyroid hormone (PTH): Helps distinguish causes like primary hyperparathyroidism.
  3. Fluid Status and Clinical Examination:
    • Assess for signs of dehydration or fluid overload.
    • ECG to check for signs of arrhythmias, especially if associated with electrolyte imbalances.

Management of Hypophosphataemia

The management of hypophosphataemia depends on its severity and whether there are symptoms or ECG changes:

  1. Oral Phosphate Replacement:
    • For mild hypophosphataemia (0.6–0.8 mmol/L) without symptoms.
    • Phosphate Sandoz (PO): 1–2 tablets (up to three times daily) until phosphate levels normalise.
  2. Intravenous Phosphate Replacement:
    • For severe hypophosphataemia (<0.6 mmol/L) or when there are symptoms or ECG changes.
    • IV phosphate polyfusor: 50 mmol in 500 mL (0.9% saline or 5% dextrose) over 12–24 hours, depending on the deficit.
  3. Correction of Underlying Causes:
    • Review drug chart for medications like diuretics or phosphate binders that may contribute to phosphate loss.
    • Monitor and manage fluid balance.
    • Address coexisting conditions like refeeding syndrome or alkalosis.

Key Takeaways

  • Symptoms: Neuromuscular and cardiovascular symptoms such as weakness, arrhythmias, and confusion are common. Long-term complications include osteopenia and rhabdomyolysis.
  • Causes: Hypophosphataemia results from decreased intake, renal losses, or intracellular shifts, often seen in refeeding syndrome and insulin administration.
  • Management: Mild cases are treated with oral phosphate supplements, while severe cases with symptoms or ECG changes require intravenous phosphate replacement.