Hypophosphatemia
Encyclopedia
Hypophosphatemia is an electrolyte disturbance
in which there is an abnormally low level of phosphate
in the blood
. The condition has many causes, but is most commonly seen when malnourished patients (especially chronic alcoholics) are given large amounts of carbohydrates, which creates a high phosphorus demand by cells, removing phosphate from the blood (refeeding syndrome
).
Because a decrease in phosphate in the blood is sometimes associated with an increase in phosphate in the urine
, the terms hypophosphatemia and "phosphaturia" are occasionally used interchangeably; however, this is improper since there exist many causes of hypophosphatemia besides overexcretion and phosphaturia, and in fact the most common causes of hypophosphatemia are not associated with phosphaturia.
Primary hypophosphatemia is the most common cause of nonnutritional 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
.
Other rarer causes include
Electrolyte disturbance
Electrolytes play a vital role in maintaining homeostasis within the body. They help to regulate myocardial and neurological function, fluid balance, oxygen delivery, acid-base balance and much more. Electrolyte imbalances can develop by the following mechanisms: excessive ingestion; diminished...
in which there is an abnormally low level of phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. The condition has many causes, but is most commonly seen when malnourished patients (especially chronic alcoholics) are given large amounts of carbohydrates, which creates a high phosphorus demand by cells, removing phosphate from the blood (refeeding syndrome
Refeeding syndrome
Refeeding syndrome is a syndrome consisting of metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely malnourished. Renourishment is the process of avoiding refeeding syndrome...
).
Because a decrease in phosphate in the blood is sometimes associated with an increase in phosphate in the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, the terms hypophosphatemia and "phosphaturia" are occasionally used interchangeably; however, this is improper since there exist many causes of hypophosphatemia besides overexcretion and phosphaturia, and in fact the most common causes of hypophosphatemia are not associated with phosphaturia.
Common causes of hypophosphatemia
- Refeeding syndromeRefeeding syndromeRefeeding syndrome is a syndrome consisting of metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely malnourished. Renourishment is the process of avoiding refeeding syndrome...
This causes a demand for phosphate in cells due to the action of phosphofructokinasePhosphofructokinasePhosphofructokinase-1 is the most important regulatory enzyme of glycolysis. It is an allosteric enzyme made of 4 subunits and controlled by many activators and inhibitors...
, an enzyme that attaches phosphate to glucose to begin metabolism of this. Also, production of ATPAdenosine triphosphateAdenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
when cells are fed and recharge their energy supplies, requires phosphate. - Respiratory alkalosisRespiratory alkalosisRespiratory alkalosis is a medical condition in which increased respiration elevates the blood pH...
Any alkalemic condition moves phosphate out of the blood into cells. This includes most common respiratory alkalemia (a higher than normal blood pH from low carbon dioxide levels in the blood), which in turn is caused by any hyperventilation (such as may result from sepsis, fever, pain, anxiety, drug withdrawal, and many other causes). This phenomenon is seen because in respiratory alkalosis carbon dioxide (CO2) 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 glycolysisGlycolysisGlycolysis is the metabolic pathway that converts glucose C6H12O6, into pyruvate, CH3COCOO− + H+...
. Since the process of glycolysis requires phosphate (the end product is adenosine triphosphateAdenosine triphosphateAdenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
), the result is a massive uptake of phosphate into metabolically active tissue (such as muscle) from the serum. It is interesting to note, however, that this effect is not seen in metabolic alkalosisMetabolic alkalosisMetabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range . This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations.-Terminology:*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. - Alcohol abuseAlcohol abuseAlcohol abuse, as described in the DSM-IV, is a psychiatric diagnosis describing the recurring use of alcoholic beverages despite negative consequences. Alcohol abuse eventually progresses to alcoholism, a condition in which an individual becomes dependent on alcoholic beverages in order to avoid...
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 (see above). - MalabsorptionMalabsorptionMalabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...
This includes GI damage, and also failure to absorb phosphate due to lack of vitamin D, or chronic use of phosphate binders such as sucralfateSucralfateSucralfate is a cytoprotective agent, an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Brand names include Sucramal in Italy; Carafate in U.S.A.; Pepsigard, Sucral, Sucrafil, Hapifate in India; Sutra or Musin in parts of South-East Asia; Sulcrate...
, aluminum-containing antacids, and (more rarely) calcium-containing antacids.
Primary hypophosphatemia is the most common cause of nonnutritional rickets
Rickets
Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
. Laboratory findings include low-normal serum calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
, moderately low serum phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
, elevated serum alkaline phosphatase
Alkaline phosphatase
Alkaline phosphatase is a hydrolase enzyme responsible for removing phosphate groups from many types of molecules, including nucleotides, proteins, and alkaloids. The process of removing the phosphate group is called dephosphorylation...
, and low serum 1,25 dihydroxy-vitamin D levels, hyperphosphaturia, and no evidence of hyperparathyroidism
Hyperparathyroidism
Hyperparathyroidism is overactivity of the parathyroid glands resulting in excess production of parathyroid hormone . The parathyroid hormone regulates calcium and phosphate levels and helps to maintain these levels...
.
Other rarer causes include
- Certain blood cancers such as lymphoma or leukemia
- hereditary causes
- hepatic failure
- Tumor-induced osteomalacia
Pathophysiology
Hypophosphatemia is caused by the following three mechanisms:- Inadequate intake (often unmasked in refeeding after long-term low phosphate intake)
- Increased excretion (e.g. in hyperparathyroidism, hypophosphatemic rickets)
- Shift from extracellular to intracellular space (seen in treatment of diabetic ketoacidosisDiabetic ketoacidosisDiabetic ketoacidosis is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in those with type 1 diabetes, but it can occur in those with type 2 diabetes under certain circumstances...
, refeeding, short-term increases in cellular demand (e.g., hungry bones syndrome) and acute respiratory alkalosisRespiratory alkalosisRespiratory alkalosis is a medical condition in which increased respiration elevates the blood pH...
)
Major signs and symptoms
- Muscle dysfunction and weakness. This occurs in major muscles, but also may manifest as: diplopiaDiplopiaDiplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
, low cardiac output, dysphagiaDysphagiaDysphagia is the medical term for the symptom of difficulty in swallowing. Although classified under "symptoms and signs" in ICD-10, the term is sometimes used as a condition in its own right. Sufferers are sometimes unaware of their dysphagia....
, and respiratory depression due to respiratory muscle weakness. - Mental status changes. This may range from irritability to gross confusion, delirium, and coma.
- White cell dysfunction, causing worsening of infections.
- Instability of cell membranes due to low ATP levels: this may cause rhabdomyolysisRhabdomyolysisRhabdomyolysis is a condition in which damaged skeletal muscle tissue breaks down rapidly. Breakdown products of damaged muscle cells are released into the bloodstream; some of these, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure...
with increased CPK, and also hemolytic anemiaHemolytic anemiaHemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
.