Phosphate

Phosphate is abundant in the body and is an important intracellular and extracellular anion. Much of the phosphate inside cells is covalently attached to lipids and proteins. Phosphorylation and dephosphorylation of enzymes are important mechanisms in the regulation of metabolic activity. Most of the body’s phosphate is in bone (Fig 37.1). Phosphate changes accompany calcium deposition or resorption of bone. Control of ECF phosphate concentration is achieved by the kidney, where tubular reabsorption is reduced by PTH. The phosphate that is not reabsorbed in the renal tubule acts as an important urinary buffer.

Plasma inorganic phosphate

At physiological hydrogen ion concentrations, phosphate exists in the ECF both as monohydrogen phosphate and as dihydrogen phosphate. Both forms are together termed ‘phosphate’, and the total is normally maintained within the limits 0.80–1.40 mmol/L. Sometimes the term ‘inorganic phosphate’ is used to distinguish these forms from organically bound phosphate such as in ATP. Approximately 20% of plasma phosphate is attached to protein, although in contrast to the binding of calcium, this is of little significance.

In plasma, calcium and phosphate often have a reciprocal relationship. In particular, if phosphate rises, calcium falls.

Hyperphosphataemia

Persistent hyperphosphataemia may result in calcium phosphate deposition in soft tissues. Causes of a high serum phosphate concentration include:

Hypophosphataemia

Severe hypophosphataemia (<0.3 mmol/L) is rare and causes muscle weakness, which may lead to respiratory impairment. The symptomatic disorder requires immediate intravenous infusion of phosphate. Modest hypophosphataemia is much more common. Alcoholic patients are especially prone to hypophosphataemia.

Causes of a low serum phosphate include:

Magnesium

Although the biological and biochemical importance of magnesium ions (Mg²⁺) is well understood, the role of this cation in clinical medicine is sometimes overlooked. Magnesium ions are the second most abundant intracellular cations, after potassium. Some 300 enzyme systems are magnesium activated, and most aspects of intracellular biochemistry are magnesium dependent, including glycolysis, oxidative metabolism and transmembrane transport of potassium and calcium.

As well as these intracellular functions, the electrical properties of cell membranes are affected by any reduction in the extracellular magnesium concentration. Any detailed consideration of magnesium biochemistry has to take into account the interactions between Mg²⁺, K⁺ and Ca²⁺ ions.

Magnesium influences the secretion as well as the action of PTH. Severe hypomagnesaemia may lead to hypoparathyroidism and refractory hypocalcaemia, which is usually easily correctable by magnesium supplementation.

Magnesium homeostasis

Since magnesium is an integral part of chlorophyll, green vegetables are an important dietary source, as are cereals and animal meats. An average dietary intake is around 15 mmol per day which generally meets the recommended dietary intake. Children and pregnant or lactating women have higher requirements. About 30% of the dietary magnesium is absorbed from the small intestine and widely distributed to all metabolically active tissue (Fig 37.2).

Serum magnesium

Hypermagnesaemia is uncommon but is occasionally seen in renal failure. Hypomagnesaemia is usually associated with magnesium deficiency. The symptoms of hypomagnesaemia are very similar to those of hypocalcaemia: impaired neuromuscular function such as tetany, hyperirritability, tremor, convulsions and muscle weakness.

Magnesium deficiency

Since magnesium is present in most common foodstuffs, low dietary intakes of magnesium are associated with general nutritional insufficiency. Symptomatic magnesium deficiency can be expected as a result of: