Phosphorus

Phosphorus

PKGhatak,MD

An adult has about 1gm of Phosphorus (phosphate levels are expressed in terms of phosphorus) in the body, of which 80% is in the tissues and the rest is in the fluid of the extracellular space. The intracellular phosphate is chemically bound to the bones, cell wall, mitochondria, various intermediate products of glucose, fat and proteins metabolism, enzymes, and are integral parts of DNA and RNA, high energy compounds like ATP, ADP; 80 % of which is bound to calcium in the bones in the form hydroxyapatite. The tissue-bound phosphate is called Organic Phosphate, in short Organophosphate. In medical practice, organophosphates are not measured.

Extracellular phosphate is Inorganic Phosphate. It is present as Dihydrogen phosphate (H2PO4) and Monohydrogen Phosphate (HPO4) in a ratio of 4:1 at pH of 7.4. Normal blood levels of phosphate vary with age, time of the day, food intake, and pH of the blood. It is higher in children and pregnancy. The normal range of blood phosphates, expressed as phosphorus, is 3.5 to 4.5 mg/dl. To convert it to mmol/L – multiply the phosphate value by 0.323.

Phosphorus and Calcium are like twin brothers – always together; and also have sibling rivalry. When the product of blood phosphate and calcium goes over 70 (phosphate in mg/dl multiplied by calcium in mg/dl) soft tissue calcification, mostly in the eyes, heart, lungs, and skin may occur. To prevent this from happening, the one having a lower concentration in the blood is prevented from getting into the blood from the gut or eliminated by the kidneys by the other one, like a stronger eagle chick pushing the weaker ones out of the nest. When blood calcium levels are low, more phosphate is lost in the urine and phosphate concentration is brought to par with calcium like a true twin.

Red meat, milk and beans are good sources of phosphorus. A normal diet contains about 1.5 gm of phosphate, 80 % of it is absorbed from the gut and the rest is eliminated in the stool. Most of the phosphate is absorbed in the jejunum, then the duodenum and ileum. Absorption in the gut is a passive process, more phosphate is in the food and has a slow transient time more phosphate is absorbed. Increase Sodium load in the diet produces more phosphate absorption. Vitamin D and its analogs increase phosphate absorption. Antacids containing aluminum bind with phosphate in the gut and make it unavailable for absorption. 90% of phosphate in the blood is free, and the rest is bound to protein. Phosphate concentrations in the blood and cells are about the same and phosphate moves in and out of cells easily, direction depends upon the pH of the blood.

Kidneys:

In 24 hours about 1.5 gm of phosphate is filtered by the kidneys; 90% of filtered phosphate is reabsorbed in the proximal tubules by a passive process and is dependent on the Sodium transport system. Some reabsorption of filtered phosphate takes place in the distal tubules. Parathyroid hormone and growth hormone depress phosphate resorption.

Phosphate controlling Hormones: 
Parathyroid hormone, Fibroblast Growth Factor-13 (FGF-23) and Calcitriol (active vitamin D3).

The parathyroid hormone produced by parathyroid glands prevents the reabsorption of filtered Phosphate in proximal renal tubules.
Fibroblast growth factor-23 is a peptide hormone produced in bones by Osteocytes and Osteoblasts when the serum phosphate level is high. It depresses phosphate reabsorption in proximal renal tubules like parathormone. FGF-23 lowers serum calcitriol levels by decreasing the conversion of D2 to D3 and increases the degradation D3 by stimulating the 24-hydroxylase enzyme.
Calcitriol (active D3). It mobilizes calcium and phosphate from bone by increasing Osteoclasts activities. It also increases the abortion of dietary calcium and phosphates in the small intestine. Calcitriol activities in the small intestine are over and above its action on osteoclasts and in the end bone loss of calcium does not take place.

Role of Inorganic phosphate:
It has a vital role in maintaining normal functions of cells of the entire body including red cells, white blood cells, platelets, oxygen transport system and blood pH. It maintains the bone structure and its stability, muscle functions and transmembrane resting potential.

High blood Phosphate is called Hyperphosphatemia.

Failure to eliminate phosphate via urine is the most important cause. Any disruption of the balance between the phosphate absorption in the gut and elimination by the kidneys will have a profound effect on the blood levels of phosphate. 
Renal causes of hyperphosphatemia are - a low GFR as seen in renal failure.
Increased phosphate reabsorption due to hypoparathyroidism, hyperthyroidism, acromegaly, juvenile hypogonadism, insulin, growth hormone.
Vitamin D, high serum calcium, and magnesium increase phosphate absorption.

Phosphate levels are high in situations of increased phosphate load as seen in excessive use of laxatives containing phosphate, a diet containing high phosphate, transfusion of old red cells due to hemolysis. Rapid tissue breakdown releases plenty of phosphates - examples are lymphomas, tissue necrosis due to ischemia, gangrene and crush injury. High levels are also present in extracellular and intracellular volume contraction, magnesium deficiency and familial intermittent hyperphosphatemia.

Conditions where Phosphate levels are low – (Hypophosphatemia).

1. Hyperventilation, respiratory alkalosis and metabolic alkalosis - due to the movement of phosphate from the blood into the cells.

2. GI loss. Due to diarrhea, and vomiting.

3. Renal loss. Due to excess parathormone and renal failure. In congenital conditions like Fanconi syndrome, Wilson's disease, and glycogen storage disease.

4. Vitamin D deficiency.

5. Multiple myeloma, heavy metal poisoning, amyloidosis, renal transplant, vitamin D resistant rickets, a rapid expansion of blood volume by saline and bicarbonate, early stages of acute tubular necrosis and use of potent diuretics.

6. Alcoholism. Due to multiple factors.

7. Starvation.

8. IV hyperalimentation

In a clinical situation of significant hypophosphatemia, the urine should be phosphate free. If phosphate is present in the urine, then the cause is renal.

Treatment of hypophosphatemia.
Generally, patients are very sick and require iv phosphate replacement along with treatment of the underlying cause. Since low blood levels do not reflect the true value of the total body phosphate content frequent blood level determination is required to correct hypophosphatemia.

Treatment of hyperphosphatemia.
Restricting phosphate intake, use of phosphate-binding antacids, alkalization of urine and correcting the underlying cause often is not enough and hemodialysis may be required at times. However, dialysis is also not very satisfactory in removing excess phosphate from the body.

 

Phosphate in organic form is an essential part of the cell membrane, DNA and RNA of nuclei and RNA of mitochondria of all nucleated cells of the body. Red Blood Cells must have adequate levels of 2, 3 diphosphoglycerates to deliver oxygen to tissues. All cellular enzymatic reactions require phosphate organic compounds. Energy generation, ATP formation is phosphate dependent. Additionally, phosphate is the second most important buffer and calcium pyrophosphate provides bone and teeth stability and strength. 

Updated 2020

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