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Hypophosphatemia is defined as serum phosphate levels below 2.5 mg/dl or 0.8 mmol/l.


Patients with severe acute hypophosphatemia may have the following clinical features on presentation:

Chronic hypophosphatemia may present with the following clinical features:

Other clinical findings that may be present in cases with hypophosphatemia include:

The symptoms of hypophosphatemia can also be broken down with respect to the organ systems involved as follows:

  • Central nervous system: ATP depletion that develops secondary to severe hypophosphatemia may cause metabolic encephalopathy. Initial symptoms of metabolic encephalopathy include paresthesias and irritability, which may progress to seizures, confusiondelirium, and coma in later stages [3] [4] [5].
  • Cardio-pulmonary system: ATP depletion secondary to sever hypophosphatemia (<1 mg/dl or <0.32 mmol/l) leads to weakness of the diaphragm [6] [7] and impairs myocardial contractility [7]. This may result in a fall in cardiac output thus causing heart failure.
  • Musculoskeletal system: The most common effects of hypophosphatemia on the musculoskeletal systme include dysphagia, proximal myopathy [8] and ileus. Additionally, a superimposed severe acute hypophosphatemia may also cause rhabdomyolysis [9] [10], but is usually observed in cases with hyperalimentation wihout phosphate replacement and alcoholics [10].
  • Hematopoietic system: The synthesis of all cell lines of the hematopoietic system may be affected by hypophosphatemia.
  • Hypophosphatemia is a seldom but potentially fatal complication of the nutritional recovery or refeeding syndrome in patients with protein-calorie malnutrition or starvation.[ncbi.nlm.nih.gov]
  • Malnutrition may result in a phosphate-deficient state owing to a chronically insufficient phosphate intake. Concomitant iron deficiency is common and often supplemented by the intravenous route.[ncbi.nlm.nih.gov]
  • […] and adenosine triphosphate has been associated with central and peripheral nervous system complications and can be observed in various diseases and conditions related to respiratory alkalosis, alcoholism (alcohol withdrawal), diabetic ketoacidosis, malnutrition[ncbi.nlm.nih.gov]
  • Acute hypophosphatemia may be mild (phosphorus level, 2-2.5 mg/dL), moderate (1-1.9 mg/dL), or severe ( 1 mg/dL) and commonly occurs in clinical settings such as refeeding, alcoholism, diabetic ketoacidosis, malnutrition/starvation, and after surgery[ncbi.nlm.nih.gov]
  • In the context of additional indices of malnutrition (low albumin, low BMI or severe overhydration), hypophosphatemic patients presented higher mortality risk.[ncbi.nlm.nih.gov]
  • Saccharated ferric oxide is widely used in Japan for iron-deficiency anemia. While it has been shown that saccharated ferric oxide induces hypophosphatemic osteomalacia, the mechanism of this hypophosphatemia remains to be clarified.[ncbi.nlm.nih.gov]
  • FDA-regulated Device Product: No Additional relevant MeSH terms: Anemia Anemia, Iron-Deficiency Deficiency Diseases Hypophosphatemia Hematologic Diseases Anemia, Hypochromic Iron Metabolism Disorders Metabolic Diseases Malnutrition Nutrition Disorders[clinicaltrials.gov]
  • The following tests may be done: Kidney function tests Vitamin D blood test Exam and testing may show: Anemia due to too many red blood cells being destroyed ( hemolytic anemia ) Heart muscle damage ( cardiomyopathy ) Treatment depends on the cause.[nlm.nih.gov]
  • Signs and symptoms include - Muscle dysfunction and weakness, mental status changes, rhabdomyolysis, hemolytic anemia, etc. Of course, it has a immunological consequence too - White cell dysfunction causing worsening of infections.[immense-immunology-insight.blogspot.com]
Congestive Heart Failure
  • An 85-year-old African American woman was admitted to the hospital for congestive heart failure exacerbation. The patient was incidentally found to be profoundly hypophosphatemic and was also diagnosed with multiple myeloma at this hospitalization.[ncbi.nlm.nih.gov]
  • During the period with hypophosphatemia, the patient suffered from very intense fatigue and weakness (she was unable to walk), anorexia, diarrhea and tenesmus.[ncbi.nlm.nih.gov]
Cutaneous Manifestation
  • A spectrum of extra-osseous/extra-cutaneous manifestations that included both benign and malignant neoplasms was present in many subjects, though osteosarcoma remains unreported.[ncbi.nlm.nih.gov]
Carpopedal Spasm
  • This case reports an adolescent girl presenting with episodes of carpopedal spasms and difficulty in walking with laboratory tests suggestive of Gitelman's syndrome along with hypophosphatemia.[ncbi.nlm.nih.gov]
  • Hypophosphatemia may be severe in conditions such as refeeding syndrome, diuretic phase after sustaining burns, hyperalimentation, consumption of antacids when on dialysis therapy for uremia, alcohol withdrawal, diabetes mellitus and respiratory alkalosis[symptoma.com]
Unable to Walk
  • During the period with hypophosphatemia, the patient suffered from very intense fatigue and weakness (she was unable to walk), anorexia, diarrhea and tenesmus.[ncbi.nlm.nih.gov]
Focal Neurologic Deficit
  • Patients with severe acute hypophosphatemia may have the following clinical features on presentation: Myalgia Focal neurological deficits Seizures Evidence of heart failure Disorientation Chronic hypophosphatemia may present with the following clinical[symptoma.com]
Tonic-Clonic Seizure
  • After 20 hours of pediatric intensive care unit stay, he presented 2 tonic-clonic seizures followed by apnea. One hour later, he had cardiorespiratory arrest, requiring cardiovascular support and mechanical ventilation.[ncbi.nlm.nih.gov]


In most cases, history findings alone are sufficient to diagnose hypophosphatemia. However, if the diagnosis is not clear, a urine phosphate excretion test should be ordered, using either fractional excretion of filtered phosphate from a random urine sample or a 24 hour urine collection. 

By definition, a serum phosphate level of less than 2.5 mg/dl or 0.81 mmol/l is called as hypophosphatemia. The majority of the causes leading hypophosphatemia are apparent from the history itself but if the clinical presentation is insufficient to accurately determine the cause, appropriate laboratory work-up should be ordered.

  • Gitelman's syndrome is a hereditary disorder occurring due to loss of functional mutations of the gene encoding the distal convoluted tubule sodium chloride cotransporter (NCCT) and is characterized by hypokalemic metabolic alkalosis, hypomagnesemia and hypocalciuria[ncbi.nlm.nih.gov]
Phosphate Decreased
  • To elucidate these phosphate decreases, we have followed serum phosphate and urinary phosphate excretion in four patients with severe acute pancreatitis.[link.springer.com]
  • On admission the arterial gas analysis showed non lactic metabolic acidosis (pH 7.17; base excess [BE] -20.3; lactic acid 0.8 mMol/L), with hypoxemia and critical hypocapnia. Despite therapy with bicarbonate the acidosis persisted.[ncbi.nlm.nih.gov]


Hypophosphatemia can be treated by phosphate replacement by oral route. Patients presenting with symptoms of severe hypophosphatemia or a serum phosphate level less than 0.5 mEq/L must receive intravenous (IV) phosphate supplementation.

Oral phosphate supplementation

Asymptomatic cases can be treated with oral replacement of phosphate, together with treatment of the underlying condition. Oral phosphate formulations are available as sodium phosphate and potassium phosphate, which can be administered at a maximum dose of 1 gram, three times a day, but they may cause diarrhea. Patients that develop severe diarrhea may be advised consumption of one liter of skim or low fat milk (provides 1 gram phosphate per liter). The treatment plan should also include simultaneous treatment of the underlying condition, which may include correction of hypomagnesemia or even discontinuation of certain medications such as diuretics or antacids.

Parenteral phosphate supplementation

Parenteral phosphate is mostly administered by IV route. It is the preferred route for phosphate replacement in the following conditions:

In patients with normal renal function, IV potassium phosphate formulation is preferred and if the renal function is impaired, IV sodium phosphate formulation is preferred. Potassium phosphate is administered at a dose of 2.5 mg/kg or 0.08 mmol/kg IV over a period of 6 hours. Alcoholics may need a higher dose (>1 gram/day) when receiving concurrent TPN. IV phosphate replacement is discontinued when patient is resumed on oral intake. Serum calcium and phosphate concentrations must be monitored throughout the duration of therapy, especially in known cases of renal impairment. The usual reference value for a maximum dose of phosphate supplementation is 7 mg/kg body weight over 6 hours.

Rapid intravenous administration of phosphate may lead to hyperphosphatemia, metastatic calcification and hypocalcemia. Intravenous phosphate therapy has also been associated with fatal arrythmias and renal failure (due to metastatic calcification).

It is suggested that the dosing of intravenous phosphate to be supplemented should take into account the weight of the patient and the severity of hypophosphatemia [11] [12]. The regimens suggested are:

  • 0.08 to 0.24 mmol/kg over 6 hours, with a maximum total dose of 30 mmol for serum phosphate levels greater than or equal to 1.3 mg/dl or 0.40 mmol/l
  • 0.25 to 0.50 mmol/kg over 8 to 12 hours, with a maximum total dose of 80 mmol in cases having a serum phosphate level less than 1.3 mg/dl or 0.40 mmol/l

Hypophosphatemia that develops secondary to persistent urinary phosphate wasting is rather challenging to manage as phosphate supplementation simply prompts a greater excretion of phosphate, with little to no change in the ongoing depletion of serum phosphate levels. In such cases, dipyridamole have demonstrated significant increase in serum phosphate levels, with the effect peaking after 9 months of therapy.


Hypophosphatemia usually has excellent prognosis if it occurs secondary to a treatable cause. Patients with eating disorders (treated by initiating normal diet), antacid abuse (treated by discontinuing the antacid), hyperparathyroidism (advised parathyroidectomy) and vitamin D deficiency (advised vitamin D replacement) are among several causes of hypophosphatemia for which an effective treatment is available. However, certain conditions such as X-linked hypophosphatemic rickets and vitamin D resistant rickets presently have partially effective treatment regimens and often lead to lifelong skeletal anomalies


Hypophosphatemia is diagnosed in approximately 2% of patients admitted for inpatient care, with a greater prevalence in cases with preexisting risk factors (10% of hospitalized alcoholics develop hypophosphatemia).

Acute hypophosphatemia (serum level <1 mg/dl or <0.32 mmol/l) that may have significant clinical implications may occur in the following conditions:

Acute severe hypophosphatemia usually results from a trancellular shift of phosphate and frequently occurs in the setting of chronic phosphate deficiency. A poor renal resorption of phosphate leads to chronic hypophosphatemia. It can be caused by:

Longstanding negative phosphate balance can lead to severe chronic hypophosphatemia, the causes being:

  • Malabsorption or chronic starvation, especially with associated diarrhea and/or vomiting
  • Chronic ingestion of aluminium based medications, such as antacids, in large quantities. Aluminium binds to phosphate leading to hypophosphatemia. This becomes a greater concern in cases with end stage renal disease on dialysis, since they have low dietary intake of phosphate and dialysis adds to the loss by depleting serum phosphate levels.


Approximately 1-5% of all hospitalized patients are diagnosed with hypophosphatemia that is mild in severity and a symptomatic. Almost 40-80% patients presenting with diabetic ketoacidosissepsis, or alcoholism are diagnosed with hypophosphatemia during their inpatient treatment course. Studies have showed that up to 55% patients that underwent partial hepatectomy for a transplantation and patients with acute hepatic failure, developed hypophosphatemia secondary to increased cellular phosphate consumption during liver regeneration. 50-80% of kidney transplant recipients develop hypophosphatemia in the period immediately following the transplant, which may persist throughout the life of the new tissue. Hypophosphatemia may also occur secondary to metabolic syndrome.

Hypophosphatemia has no sex specific or race specific variation in occurrence. However, the only exception is X-linked hypophosphatemic rickets which is predominantly found in Caucasians and male children. Patients of any age group may present with hypophosphatemia, although the acquired form is frequently diagnosed in late adolescence to adulthood. Hyposphosphatemia in late adolescence is commonly due to eating disorders but at later age, the condition is more commonly found in association with tumors, malabsoprtion, alcoholism, and vitamin D deficiency.

Sex distribution
Age distribution


The majority of clinical features attributed to hypophosphatemia occur secondary to intracellular depletion of phosphate that subsequently affects all organ systems. This occurs due to:

  • An increase in the affinity of hemoglobin for oxygen due to a decrease in 2,3 diphosphoglycerate (2,3 DPG) level in red blood cells (RBCs) leading to a decrease in oxygen offloading at the tissue level [2].
  • Severe hypophosphatemia leads to depletion of intracellular ATP that in-turn inhibits all ATP-dependent cellular functions.

Hypophosphatemia may be caused by insufficient intake or increased excretion of phosphate. It may also be caused by a shift of serum phosphate from extracellular to intracellular space.

The conditions that cause hypophosphatemia secondary to increased loss of phosphate from the body include: 

  • Refeeding syndrome
  • Intestinal malabsorption, especially if associated with a poor diet
  • Deficiency of vitamin D: Impairs absorption of phosphate in the kidneys

The conditions that cause hypophosphatemia secondary to increased loss of phosphate from the body include: 

  • Hyperparathyroidism: Parathormone inhibits transportation of phosphate in the proximal tubules in the kidneys leading to hypothyroidism, but is generally mild in severity. 
  • Forced saline diuresis: All transport functions of proximal convoluted tubules is inhibited by forced saline diuresis, however, the hypophosphatemia that consequently develops is mild in severity.
  • Vitamin D deficiency: Impairs phosphate absorption in the kidneys

The shift of phosphate from extracellular to intracellular space can lead to exacerbation of hypophosphatemia due to pre-existing pathologies such as refeeding syndrome, hungry bone syndrome, ongoing treatment for diabetic ketoacidosis and acute respiratory alkalosis.


Patients that develop hypophosphatemia secondary to a pathology leading to poor oral intake like dental issues, poor socioeconomic status or dysphagia due to any reason, must be advised dietary counseling and monitoring. Cases diagnosed with eating disorders like bulimia or anorexia need to be counseled and should be initiated on dietary therapy. Individuals that present with recurring hypophosphatemia must be advised to refrain from overt use of antacids.


The state where serum phosphate levels fall below 2.5 mg/dl or 0.8 mmol/l is called hypophosphatemia. The condition can be caused by sustaining burns, use of diuretics, starvation and alcohol consumption. It usually presents as weakness of muscles, heart failure, and respiratory failure and can lead to seizures and/or coma. It can be easily diagnosed by evaluating the serum phosphate levels and is treated by supplementing phosphate. 

Hypophosphatemia may be severe in conditions such as refeeding syndrome, diuretic phase after sustaining burns, hyperalimentation, consumption of antacids when on dialysis therapy for uremiaalcohol withdrawal, diabetes mellitus and respiratory alkalosis. Supplementation of phosphate may also help avoid or reverse anemia and therefore may be considered for cases at risk of hypophosphatemia, in addition to those already diagnosed with hypophosphatemia. Severe hypophosphatemia may also be noted in cases receiving treatment for diabetic ketoacidosis and with prolonged hyperventilation. Theses patients usually will not exhibit typical symptoms of hypophosphatemia since the depletion of phosphate is acute and not chronic [1].

Patient Information

Hypophosphatemia is a condition wherein the level of phosphate in the blood is lower than normal. This may develop over a long time, which results in chronic hypophosphatemia. The most common reason for chronic hypophosphatemia is excess loss of phosphate. Generally, symptoms associated with this condition will appear only when phosphate levels have become very low. Initially, patients experience weakness of muscles, but later as the condition progresses, they may develop coma or stupor, that may eventually lead to death. In mild form of the disease, patients may experience weakness, loss of appetite and pain with possible fracturing of bones. 



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  3. Weisinger JR, Bellorín-Font E. Magnesium and phosphorus. Lancet 1998; 352:391.
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  9. Knochel JP. Hypophosphatemia and rhabdomyolysis. Am J Med 1992; 92:455.
  10. Singhal PC, Kumar A, Desroches L, et al. Prevalence and predictors of rhabdomyolysis in patients with hypophosphatemia. Am J Med 1992; 92:458.
  11. Taylor BE, Huey WY, Buchman TG, et al. Treatment of hypophosphatemia using a protocol based on patient weight and serum phosphorus level in a surgical intensive care unit. J Am Coll Surg 2004; 198:198.
  12. Subramanian R, Khardori R. Severe hypophosphatemia. Pathophysiologic implications, clinical presentations, and treatment. Medicine (Baltimore) 2000; 79:1.

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Last updated: 2019-07-11 21:44