Hypophosphataemia is defined as a serum phosphate concentration < 0.8 mmol/L.

The normal serum concentration of phosphate is 0.8-1.5 mmol/L. Hypophosphataemia is a common electrolyte abnormality that is estimated to affect up to 5% of patients admitted to hospital.

In certain populations, hypophosphataemia is common such as those who are malnourished or suffering from refeeding syndrome. In alcoholics, it may be seen in up to 50%. In patients with paracetamol overdose, it is a good prognostic marker that signifies hepatic recovery.

Phosphate physiology

The human body contains approximately 1000 g of phosphate of which 80-90% is found in bone.

Phosphate is an essential ion for formation of nucleic acids, normal cellular function and bone mineralisation. The addition (by a kinase) or removal (by a phosphatase) of a phosphate molecule is important for the regulation of enzymes

Approximately 1000 g of phosphate is contained within the human body, which is distributed between different structures:

  • Bone: 80-90%
  • Intracellular: 10-14%
  • Extracellular: 1%

Dietary phosphate

Our normal daily intake of phosphate is 800-1500 mg. Most foods contain phosphate and the majority is absorbed from the gastrointestinal tract (70-90%) with the remaining being excreted in faeces.

The absorption of phosphate, which predominantly occurs in the small intestines, may be blocked by aluminium, calcium or magnesium containing antacids.

Phosphate regulation

Phosphate is predominantly an intracellular ion with only 1% composing the extracellular pool. This extracellular concentration is closely regulated by diet, hormones (e.g. parathyroid hormone) and acid-balance.

Excess phosphate can be excreted by the kidneys in the proximal and distal convoluted tubules. The proximal convoluted tubule may also reabsorb phosphate in the context of low levels via a sodium phosphate cotransporter. The principal regulators of this process are vitamin D and parathyroid hormone (PTH).

Vitamin D

  • Activation of vitamin D enhances intestinal phosphate reabsorption
  • Vitamin D deficiency or inhibition of activation decreases intestinal phosphate reabsorption


  • High levels inhibit phosphate reabsorption in the kidneys, which promotes excretion
  • Low levels promote phosphate reabsorption in the kidneys

PTH also leads to bone resorption, which leads to an increase in extracellular phosphate and calcium. If renal function is normal, the increased inhibition of phosphate reabsorption causes a net loss of phosphate. However, in the context of renal impairment the bone resorption causes a net gain of phosphate leading to chronic hyperphosphataemia.

Other molecules more recently discovered to play a role in phosphate regulation include fibroblast growth factor 23 (FGF23), phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and stanniocalcin.


Hypophosphataemia is a common manifestation of refeeding syndrome.

Hypophosphataemia develops by four main mechanisms:

  • Redistribution of phosphate
  • Decreased absorption of phosphate (intestines)
  • Increased excretion of phosphate (kidneys)
  • Removal by renal replacement therapy (RRT): commonly encountered in intensive care in patients on continuous RRT

Redistribution of phosphate

Increased cellular metabolism leads to the rapid utilisation of phosphate, which leads to the transfer of phosphate from the extracellular pool into cells leading to hypophosphataemia.

There are three conditions commonly associated with this phenomenon:

  • Refeeding syndrome: this refers to rapid shifts in serum electrolytes following reintroduction of food after a period of malnourishment or starvation. It can cause life-threatening arrhythmias and sudden death.
  • Respiratory alkalosis: acute hyperventilation leads to a reduction in the plasma concentration of carbon dioxide which raises the pH of blood. A similar effect occurs intracellularly, which stimulates phosphofructokinase. This enzyme stimulates glycolysis leading to increased use of phosphate and withdrawal from the extracellular pool.
  • Hungry bone syndrome: commonly seen post-operatively (e.g. after parathyroidectomy) in patients with pre-existing primary or tertiary hyperparathyroidism. The chronic demineralisation of bone from high PTH means as soon as the PTH stimulus is removed there is rapid remineralisation utilising serum phosphate and calcium.

Decreased absorption of phosphate

Poor oral intake or medications that inhibit phosphate absorption (e.g. antacids, phosphate binders, proton pump inhibitors) can lead to hypophosphataemia.

Poor oral intake leading to hypophosphataemia is usually combined with a concurrent pathology (e.g. diarrhoea), otherwise the extracellular phosphate concentration is relatively preserved. However, marked intracellular depletion of phosphate then occurs on reintroduction of diet with dangerous hypophosphataemia.

Increased excretion of phosphate

Phosphate excretion may be increased in primary or tertiary hyperparathyroidism due to the effect of PTH on the kidneys. Other causes can include vitamin D deficiency, drugs and inherited disorders (e.g. Fanconi syndrome).

NOTE: Fanconi syndrome refers to defective proximal tubule function and may be inherited or acquired.


Hypophosphataemia can cause a wide range of clinical manifestations due to intracellular phosphate loss.

Low phosphate levels lead to a marked reduction in the intracellular phosphate pool that affects normal cellular function. As all cells in the body rely on phosphate for intracellular mechanisms, it can lead to a wide range of problems affecting neurological, cardiopulmonary, musculoskeletal and haematological systems.

There are two principal problems associated with hypophosphataemia:

  • Reduced 2,3-diphosphoglycerate (DPG): this is important for the release of oxygen to peripheral tissue. Reduced levels leads to less release from haemoglobin in peripheral gas exchange.
  • Reduced adenosine triphosphate (ATP): this is the cellular energy currency. Without ATP, energy-rich cellular functions fail.

These two mechanisms lead to organ dysfunction:

  • Neurological: irritability, altered mental status, paraesthesia, seizure, coma
  • Cardiopulmonary: arrhythmias, increased ventilator requirement in intensive care
  • Musculoskeletal: dysphagia, ileus and in severe cases rhabdomyolysis.
  • Haematological: haemolysis, reduce white cell function and coagulation defects may be seen (usually rare features)

Clinical features

Severe hypophosphataemia can lead to profound weakness, altered mental status and rhabdomyolysis.

Clinical features usually depend on the severity and chronicity of hypophosphataemia. Acute severe hypophosphataemia, as seen in refeeding syndrome, can be life-threatening.

Mild hypophosphataemia is typically asymptomatic. In more severe disease a number of features may be seen:

  • Lethargy
  • Weakness
  • Bone pain
  • Altered mental status
  • Neurological sequelae (e.g. paraesthesia, seizures)
  • Ileus
  • Rhabdomyolysis
  • Arrhythmias

Diagnosis & investigations

The diagnosis of hypophosphataemia is based on a serum phosphate < 0.8 mmol/L.

A bone profile will identify the reduced phosphate level and this is commonly requested in patients who are acutely unwell presenting to hospital or at risk of malnutrition.

Other blood tests may be useful to determine the underlying cause, these include:

  • Full blood count
  • U&E
  • Bone profile
  • Magnesium
  • Parathyroid hormone
  • Vitamin D levels
  • Creatine kinase (if rhabdomyolysis suspected)
  • Arterial blood gas (if respiratory alkalosis suspected)

All patients require an ECG as hypophosphataemia is associated with a prolonged QT interval and cardiac arrhythmias. Further investigations depend on the underlying cause and may include urinary phosphate levels in suspected tubular disorders.


The management of hypophosphataemia involves oral or intravenous replacement.

It is important to determine and treat the underlying cause. This includes assessing a patients body mass index, malnutrition score and risk of refeeding syndrome.

Usually short courses of replacement are enough to replace deficit, but more extended courses may be needed, especially if the patient is suffering from active refeeding. If hypophosphataemia is due to vitamin D deficiency, vitamin D replacement is required.


  • Phosphate-Sandoz (1 tablet) = 16.1 mmol phosphate, 20.4 mmol sodium, 3.1 mmol potassium
  • Polyfusor (500 mls) = 50 mmol phosphate, 81 mmol sodium, 9.5 mmol potassium.
  • Glycophos (20-40 mls) = 20-40 mmol phosphate, 40-80 mmol sodium, 0 mmol potassium

Oral replacement

Phosphate-Sandoz is typically used for levels of phosphate around 03-0.8 or 0.5-0.8 mmol/L depending on trust guidelines. Typical dose one tablet BD.

Common side effects of oral phosphate replacement are diarrhoea and abdominal discomfort.

Intravenous replacement

Intravenous doses of phosphate are recommended for severe or symptomatic hypophosphataemia. It is also used where the oral route is unsuitable. Intravenous phosphate replacement is potentially dangerous due to precipitation with calcium leading to hypocalcaemia. Therefore, intravenous replacement is often given slowly over 12-24 hours. Always follow local protocols.

  • Phosphate polyfusor
  • Glycophos

Care should be taken in patients with reduced renal function as it can lead to hyperphosphataemia.


Patients at risk of refeeding syndrome need daily monitoring of phosphate levels in addition to magnesium and potassium. Replacement should continue as long as necessary and usually combined with parenteral B vitamins (e.g. Pabrinex).

Last updated: May 2021
Author The Pulsenotes Team A dedicated team of UK doctors who want to make learning medicine beautifully simple.

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