Phosphorus, Calcium and Magnesium Interactions

by Herbert C. Mansmann, Jr., M.D.

Phosphorus is the second most abundant element of the human body. About 80% is in bones. The RDA is 700 mg/day, and the regular diet contains 1026 mg in women and 1455 in men. Phosphorus is present as phosphate in biologic systems. It is the concentration of elemental (or inorganic) phosphorus that is measured in the clinical laboratory, although the terms phosphorus and phosphate tend to be used interchangeably.

PHOSPHORUS PLASMA CONTENT

The plasma phosphorus concentration in normal adults ranges from 2.5 to 4.5 mg/dL (0.80 to 1.44 mmol/L). It is highest in summer and lowest in winter; much higher (up to 6 to 7 mg/dL or 1.92 to 2.24 mmol/L) in growing children and adolescents than in adults; and it is increased by pregnancy and immobilization.

UNITS OF PHOSPHATE MEASUREMENT – The plasma phosphate concentration is usually measured in units of mg/dL or mmol/L. To convert between these units, the following calculations can be used:

. 1 mmol of phosphate = 31 mg of elemental phosphorus

. 1 mmol/L of phosphate = 3.1 mg/dL (or 31 mg/L) or phosphorus

. 1 mg of phosphorus = 0.032 mmol of phosphate

. 1 mg/dL of phosphorus = 0.32 mmol/L of phosphate

Urinary phosphate excretion in the steady state is roughly equal to net phosphate absorption, which is primarily determined by phosphate intake. Usual values for 24-hour phosphate excretion range from 400 to 1000 mg (13 to 32 mmol).

The hyperphosphatemia during growth is appropriate, since it promotes calcium phosphate precipitation in bone. The rise in the plasma phosphate concentration in this setting is due primarily to increased proximal phosphate reabsorption that is mediated by growth hormone-induced release of insulin-like growth factor I.

Phosphorus is a major anion that has its highest concentration in the intracellular fluid. Phosphorus and calcium have similar and opposite effects. Both electrolytes need Vitamin D for intestinal absorption and are present in the teeth and bones. Parathyroid hormone decreases serum phosphorus levels by stimulating the renal tubules to excrete phosphorus and increases serum calcium levels by pulling calcium from the bone. It is a vital element needed in the formation of bones and teeth and for neuromuscular activity. As an essential component of the cell, it is incorporated into the enzymes needed for metabolism, e.g., adenosine triphosphate (ATP), a transmission of hereditary traits, and acts as an acid-base buffer.

CAUSES OF HYPOPHOSPHATEMIA

Hypophosphatemia when combined with phosphate depletion (that is, when not due solely to phosphate movement into the cells) can cause a variety of signs and symptoms. The manifestations depend in large part upon the severity and chronicity of the phosphate depletion, with the plasma phosphate concentration usually being below 1.0 mg/dL (0.32 mmol/L) in symptomatic patients.

Hypophosphatemia can occur within 3-4 days after an inadequate nutrient intake. Vomiting and diarrhea cause hypophosphatemia. Initially, the kidneys compensate by decreasing urinary phosphate excretion; however, a continuous inadequate intake of phosphorus results in extracellular fluid shift to the cells in order to replace phosphorus loss in the intracellular fluid. The major conditions associated with symptomatic hypophosphatemia are chronic alcoholism, intravenous hyperalimentation without phosphate, and the chronic ingestion of antacids. Severe hypophosphatemia can also be seen during treatment of diabetic ketoacidosis and with prolonged hyperventilation; however, symptoms are unusual in these setting since the phosphate depletion is not chronic.

Parathyroid hormone promotes renal excretion of phosphorus (phosphate and calcium reabsorption). When there is a high serum concentration of phosphorus, aluminum containing antacids decrease hyperphosphatemia and its symptoms. Hyperphosphatemia causes hypocalcemia.

Symptoms

Nervous system dysfunction – is a well recognized problem in hypophosphatemia. In experimentally induced hypophosphatemia in humans, there is muscle weakness, apathy, and intention tremor and patients are made bedridden (Shils p164). Other symptoms develop in sequence with hypophosphatemia are irritability, apprehension, muscle weakness, numbness, paresthesias confusion, obtundation, convulsions, and coma.

OF SKELETAL AND SMOOTH MUSCLE - hypophosphatemia-induced manifestations of muscle dysfunction include a proximal myopathy (affecting skeletal muscle), and dysphagia and ileus (affecting smooth muscle). In addition, acute hypophosphatemia superimposed upon preexisting severe phosphate depletion can lead to rhabdomyolysis. Although CPK elevations are fairly common in hypophosphatemia, clinically significant rhabdomyolysis has been described almost exclusively in alcoholics and in patients receiving hyperalimentation without phosphate supplementation.

OF Magnesium DEFICIENCT- (posted elsewhere) but both phosphorus (P) and potassium (K) deficits induce MgD (1.p244). Moreover, an excess of P, Ca or alcohol tend to inhibit Mg absorption (1.p19). Yet, without simultaneous P intake, glucose load induces in fact a uMg wasting (Durlich p115). P therapy must be used strictly as a remedy for low blood P, because P overload causes reduced serum Mg and serum Ca (Durlach p164). On p233 he states that one should never prescribe Ca and P therapy together. Moreover, “With oral repletion, it is better to administer at different times calcium and/or phosphorus and magnesium so that either of the first two do not inhibit absorption of the last” (Durlach p244).

This becomes very relevant when one observes the amount of “soda”, containing phosphoric acid consumed for breakfast and during the day in the USA. The natural P/Ca ratio of 1.5/1 (with milk), becomes 4/1 with soda. It is known that an excess of P or Ca increases the Mg requirement (Seelig p8).

Osteopenia, (softening of the bones) associated with hypophosphatasia, has been shown to occur in utero, as well as in infants, childhood, and adults (Seelig p315). Convulsions also have been observed.

TREATMENT

DRUG CONCENTRATIONS – Phosphorus supplements are used in the treatment of hypophosphatemia, hypercalciuria, and hypercalcemia. In the last 2 settings, phosphate can form insoluble calcium phosphate complexes in the gut, thereby limiting intestinal calcium absorption, and in the plasma, thereby mildly lowering the plasma calcium concentration.

The following preparations are available for both oral and intravenous use:

Oral

. K-Phos Neutral^(TM) – each tablet contains 250 mg of phosphorus, 13 meq of sodium and 1.1 meq of potassium.

. Neutra-Phos^(TM) – each capsule or 75 mL of solution contains 250 mg of phosphorus and 7.1 meq each of sodium and potassium.

. Neutra-Phos K^(TM) – each capsule or 75 mL of solution contains 250 mg of phosphorus and 14.2 meq of potassium.

Intravenous
. Potassium phosphate – each mL contains 3 mmol of phosphate (93 mg of phosphorus) and 4.4 meq of potassium; 5 and 15 mL vials are available.

. Sodium phosphate – each mL contains 3 mmol of phosphate (93 mg of phosphorus) and 4 meq of sodium; 15 and 30 mL vials are available.

Usual dosages – The dose of phosphorus given varies with the underlying disorder. Oral therapy is given in divided doses to minimize diarrhea.

. Phosphate depletion – 2.5 to 3.5 g (80 to 110 mmol) per day in 3 to 4 divided doses.

. Severe, symptomatic hypophosphatemia (plasma phosphate concentration less than 1 mg/dL or 0.32 mmol/L) in the patient requiring parenteral therapy – 10 mg (320 ┬Ámol)/kg per day until the plasma phosphate concentration reaches 2 mg/dL (0.64 mmol/L).

. Hypercalciuria and recurrent calcium stones – 2.0 to 2.5 g (64 to 80 mmol) per day in 3 to 4 divided doses. In addition to decreasing calcium absorption, phosphate supplementation also enhances the urinary excretion of pyrophosphate, an inhibitor of calcium precipitation.

. Hypercalcemia – 1 to 3 g (32 to 96 mmol) per day in divided doses.

. Hypophosphatemic rickets – 1 to 4 g (32 to 128 mmol) per day in divided doses.

References

  1. Durlach, J, Magnesium in Clinical Practice. 1988, John Libbey & Co.,Ltd, London.
  2. Seelig, M.S. Magnesium Deficiency in the Pathogenesis of Disease. 1980, Pleum Medical Book Co., New York.

Shils ME, et el. Modern Nutrition in Health and Disease, 9th Ed., 1999, 157-198.

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