Refeeding syndrome – This causes a demand for phosphate in cells due to the action of hexokinase, an enzyme that attaches phosphate to glucose to begin metabolism of glucose. Also, production of ATP when cells are fed and recharge their energy supplies requires phosphate.
Respiratory alkalosis – Any alkalemic condition moves phosphate out of the blood into cells. This includes most common respiratory alkalemia, which in turn is caused by any hyperventilation. This phenomenon is seen because in respiratory alkalosis carbon dioxide decreases in the extracellular space, causing intracellular CO2 to freely diffuse out of the cell. This drop in intracellular CO2 causes a rise in cellular pH which has a stimulating effect on glycolysis. Since the process of glycolysis requires phosphate, the result is a massive uptake of phosphate into metabolically active tissue from the serum. However, that this effect is not seen in metabolic alkalosis, for in such cases the cause of the alkalosis is increased bicarbonate rather than decreased CO2. Bicarbonate, unlike CO2, has poor diffusion across the cellular membrane and therefore there is little change in intracellular pH.
Metabolic acidosis
Alcohol abuse – Alcohol impairs phosphate absorption. Alcoholics are usually also malnourished with regard to minerals. In addition, alcohol treatment is associated with refeeding, and the stress of alcohol withdrawal may create respiratory alkalosis, which exacerbates hypophosphatemia.
Malabsorption – This includes gastrointestinal damage, and also failure to absorb phosphate due to lack of vitamin D, or chronic use of phosphate binders such as sucralfate, aluminum-containing antacids, and calcium-containing antacids.
Intravenous iron may cause hypophosphatemia. The loss of phosphate is predominantly the result of renal wasting.
Primary hypophosphatemia is the most common cause of non-nutritional rickets. Laboratory findings include low-normal serum calcium, moderately low serum phosphate, elevated serum alkaline phosphatase, and low serum 1,25 dihydroxy-vitamin D levels, hyperphosphaturia, and no evidence of hyperparathyroidism. Hypophosphatemia decreases 2,3-bisphosphoglycerate causing a left shift in the oxyhemoglobin curve. Other rarer causes include:
Hypophosphatemia is caused by the following three mechanisms:
Inadequate intake
Increased excretion
Shift of phosphorus from the extracellular to the intracellular space. This can be seen in treatment of diabetic ketoacidosis, refeeding, short-term increases in cellular demand and acute respiratory alkalosis.
Diagnosis
Hypophosphatemia is diagnosed by measuring the concentration of phosphate in the blood. Concentrations of phosphate less than 0.81 mmol/L are considered diagnostic of hypophosphatemia, though additional tests may be needed to identify the underlying cause of the disorder.
Treatment
Standard intravenous preparations of potassium phosphate are available and are routinely used in malnourished people and alcoholics. Supplementation by mouth is also useful where no intravenous treatment are available. Historically one of the first demonstrations of this was in people in concentration camp who died soon after being re-fed: it was observed that those given milk had a higher survival rate than those who did not get milk. Monitoring parameters during correction with IV phosphate
Phosphorus levels should be monitored after 2 to 4 hours after each dose, also monitor serum potassium, calcium and magnesium. Cardiac monitoring is also advised.
