Phosphate is the forgotten anion in the CICM SAQs. Fortunately for us all, the college have never asked any questions about it. It appears in the Required Reading section purely for completeness (though the author is acute aware that the pursuit of completeness may lead one to contemplate disorders of molybdenum homeostasis, etc). Oh's Manual dwells briefly on phosphate and offers two Blue Boxes to describe its behaviour (Boxes 93.8 and 93.9, p. 957-958). In the published literature, the best information is concentrated behind paywalls (as in the UpToDate articles). For the freegan, the best available article (forming the core of this summary) is from Subramanian et al (2000). The latter offers an excellent table of mechanisms for hypophosphataemia (Table 1), which has been reorganised into the list of causes below:

Causes of Hypophosphataemia

Decreased intake

  • Parenteral nutrition
  • Malnutrition
  • Alcoholism
  • Calcium supplements
  • Phosphate binders (eg. sevelamer)
  • Vitamin D resistance/deficiency
     

Increased excretion

Renal losses

  • Hyperparathyroidism
  • Vitamin D deficiency
  • Vitamin-D-resistant rickets
  • Renal tubular acidosis
  • Primary renal phosphate wasting (congenitial)
  • Fanconi syndrome
  • Osmotic diuresis

Gastrointestinal losses

  • Diarrhoea (especially steatorrhoea)

Other losses

  • Haemodialysis
  • Burns
  • Pancreatitis third-spacing

Compartment shift

Carbohydrate infusion

  • Sugars (glucose, etc)
  • Lactate (eg. Hartmanns)
  • Glycerol

Hormonal effects

  • Insulin
  • Calcitonin
  • Catecholamines
  • Glucagon
  • Refeeding syndrome

Alkalosis

Rapid cellular proliferation

  • Erythopoietin therapy
  • Hungry bone syndrome
  • Leukaemic blast crisis
Clinical Features of Hypophosphataemia

Neurological manifestations

  • Irritability
  • Hallucinations
  • Delirium
  • Seizures
  • Coma
  • Increased risk of osmotic demyelination

Cardiovascular manifestations

  • Impaired cardiac contractility, cardiomyopathy
  • Propensity towards arrhythmias

Biochemical abnormalities

  • Hypercalciuria
  • Increased bone resorption
  • Increased calcitriol (1,25-dihydroxyvitamin D)

Musculoskeletal manifestations

  • Weakness
  • Proximal myopathy
  • Dysphagia
  • Ileus
  • Slowed ventilator weaning
  • Rhabdomyolysis
  • Osteopenia and rickets (long term)

Haematological abnormalities

  • Decreased red cell 2,3-DPG levels (a left shift)
  • Increased RBC rigidity, and propensity to haemolysis
  • Impaired clot retraction
  • Leukocyte dysfunction
  • Thrombocytopenia

 

Generally speaking, these manifestations are late. The serum phosphate level needs to fall to below 0.3mmol/L before there are problems.

References

Ruppe, Mary D., and Suzanne M. Jan de Beur. ". Disorders of Phosphate Homeostasis." Primer on the metabolic bone diseases and disorders of mineral metabolism (2008): 317-325.

Knochel, James P. "The pathophysiology and clinical characteristics of severe hypophosphatemia." Archives of Internal Medicine 137.2 (1977): 203-220.

Subramanian, Rajesh, and Romesh Khardori. "Severe hypophosphatemia: Pathophysiologic implications, clinical presentations, and treatment." Medicine 79.1 (2000): 1-8.