What is phosphorus?
Phosphorus (P) is an essential macronutrient and intracellular anion, required for the cellular processes of growth, maintenance and repair.
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Phosphorus deficiency disease (hypophosphatemia) is a condition wherein serum phosphorus (phosphate) levels drops below 2.5 mg/dL (0.8 mmol/L). Severe phosphorus deficiency can manifest as widespread organ dysfunction. Phosphorus deficiency diseases have multifactorial aetiologies and may present multiple causes in the same patient.Phosphorus deficiency is primarily caused by inadequate intake, increased excretion or by shift from extracellular to intracellular space. Certain hereditary diseases, blood cancers, hepatic failure, presence of certain tumors, antacid abuse, alcoholism and certain medications can also promote hypophosphatemia. Severe Phosphorus deficiency disease can result in multiorgan dysfunction and death.
Phosphorus deficiency signs and symptoms
Common signs of phosphorus deficiency include general weakness, anxiety, lack of appetite and body pains. The major symptoms are, low cardiac output, respiratory depression, fragile bones, stiff joints, mental status changes and double vision. Acute hypophosphatemia (less than 1 mg/dL) can lead to damage of skeletal muscle tissue, white cell dysfunction, the abnormal breakdown of red blood cells, delirium and coma, which may culminate in death. In children there is decreased growth rate, poor bone and tooth development and their malformation.Phosphorus food sources
Nutritional deficiency of phosphorus does not normally occurs. All protein-rich foods are good source of phosphorus. These include, milk and dairy products, meat products, poultry products, eggs, soya products, seeds, nuts, legumes, carbonated cola beverages and whole grains.Serum phosphorus as phosphate normally ranges from 2.5 to 4.5 mg/dL in adults. The Food & Nutrition Board of the Institute of Medicine, has set the daily Adequate Intake (AI) of phosphorus for adults as 700 mg per day. Considering the harmful effects of too much phosphorus, a Tolerable Upper Intake Level (UL) per day is set at 4 grams.
Phosphorus functions in the human body
- Next to calcium, phosphorus is the most abundant mineral in the human body. Along with calcium, phosphorus is required for building strong bones and teeth. Nearly 85% of P in the body is found in the bone and teeth. The rest is found in the cells and tissues and extracellular fluids.
- The main component of bone and tooth enamel is hydroxyapatite, with the formula Ca5(PO4)3(OH) formed from calcium and phosphorus.
- Adenosine triphosphate (ATP) is a nucleoside triphosphate. Phosphorus is an essential component of ATP and it transports chemical energy within cells for metabolism.
- P is needed for the metabolism of carbohydrates and fats to produce energy.
- It has a important role in the synthesis of protein, amino acids and nucleic acids.
- It is a component of phospholipids which are structural components of cell membranes.
Phosphorus deficiency disease causes
Hypophosphatemia is primarily caused by inadequate intake, increased excretion or by shift from extracellular to intracellular space.Inadequate intake and malnutrition
Severe acute malnutrition and protein energy malnutrition can lead to very low serum levels of this mineral. Other related causes are:- Malabsorption due to gastrointestinal injury,
- bariatric surgery,
- alcohol induced impaired phosphate absorption,
- alcoholism related malnutrition,
- alcohol withdrawal related respiratory alkalosis,
- excessive intake of antacids,
- lack of vitamin D and
- chronic use of phosphate binders such as sucralfate and aluminum-containing antacids.
Increased excretion
- Anticonvulsants like phenobarbital and carbamazepine may increase levels of alkaline phosphatase and remove phosphate from the body.
- Corticosteroids may increase phosphorus excretion in the urine.
- The treatment of diabetic ketoacidosis with high doses of insulin and IV fluids may lower serum levels of phosphates by increased cell uptake and also renal excretion.
- The use of loop diuretics like acetazolamide and bisphosphonates can increase the loss of phosphorus in renal excretion.
- Oncogenic osteomalacia, characterized by acquired hypophosphatemic rickets and the hereditary forms of hypophosphatemic rickets may increase renal phosphate wasting. Mutation in the FGF23 gene and its overexpression causes the renal loss of phosphorus.
- In hyperparathyroidism proximal renal tubule phosphate transport is inhibited leading to hypophosphatemia.
- Phosphate may be lost from the gut due to chronic diarrhea and severe vomiting.
Shift from extracellular to intracellular space
Refeeding syndrome occurs as a result of restitution of nutrition to patients who are starved or severely malnourished. Refeeding increases the basal metabolic rate and with the increase in the nutrients, there is increased glycogen, fat and protein synthesis. As this process requires phosphorus and other electrolytes, there is drastic shift of these electrolytes from serum to intracellular space. The drop in serum phosphorus can lead to cardiac arrhythmias, confusion, coma, convulsions, cardiac failure and death.Respiratory alkalosis is a higher than normal blood serum pH from low carbon dioxide levels in the plasma. Low carbon dioxide levels in the serum causes intracellular carbon dioxide to freely diffuse out of the cell. The drop in intracellular carbon dioxide levels and subsequent increase in cellular pH triggers glycolysis resulting in massive uptake of phosphate into the cells, especially muscle cells. This shift leads to very low serum phosphorus levels and the consequences.
The incidence of low phosphorus levels in high in hospitalized patients, those undergoing intensive care, those suffering from sepsis, chronic alcoholics, patients passing through major trauma, patients with chronic obstructive pulmonary disease and in patients with advanced kidney disease.
Phosphorus deficiency diseases
Chronic low levels of serum phosphorus can lead to osteoporosis, osteomalacia, increased susceptibility to infection, muscle weakness, muscle loss and muscle damage, respiratory difficulties and neurological impairments.Osteoporosis
A healthy bone has a normal balance of calcium and phosphorus in required proportions. Having low levels of phosphorus can lead to loss of calcium from the bones. The loss results in the disease of porous bones, known as osteoporosis. The bone loses its mass and becomes weak and brittle.Osteomalacia
Low levels of phosphorus, calcium and vitamin D causes osteomalacia. A disease of bones, making bones soft and prone to fractures, malformation and deformation.Phosphorus deficiency disease is reported in patients with acute hepatic failure and those undergone partial hepatectomy for transplantation. Low phosphorus level is also observed in cases of hematopoietic cell transplantation. Kidney transplant recipients are also prone to develop hypophosphatemia.
Several genetic phosphate wasting diseases like X-linked hypophosphatemic rickets, vitamin D resistant rickets and autosomal dominant hypophosphatemic rickets may manifest in childhood. Hereditary hypophosphatemic rickets with hypercalciuria is a rare disease manifesting as hypophosphatemia and hypercalciuria. Vitamin D–resistant rickets is an autosomal recessive disease characterized by hypocalcemia, hypophosphatemia and hyperparathyroidism.
Phosphorus deficiency disease treatment
Phosphate deficiency can be corrected by oral or intravenous fluid replacement therapy. A typical regimen is 15 mg/kg oral phosphate, given in three to four divided doses to minimize gastric irritation. During IV administration care must be taken monitor phosphorus levels every two hours for effecting replacement.Advertisements
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References: 1.Sherman RA, Mehta O. Dietary phosphorus restriction in dialysis patients: potential impact of processed meat, poultry, and fish products as protein sources. Am J Kidney Dis. 2009;54(1):18-23. 2.Steven M. Brunelli, Stanley Goldfarb. Hypophosphatemia: Clinical Consequences and Management. JASN July 2007 vol. 18 no. 7 1999-2003. 3.Shuto E, Taketani Y, Tanaka R, Harada N, Isshiki M, Sato M, Nashiki K, Amo K, Yamamoto H, Higashi Y, Nakaya Y, Takeda E. Dietary phosphorus acutely impairs endothelial function. J Am Soc Nephrol. 2009;20(7):1504-12 |
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