Disorders of Mg2+ Homeostasis

DISORDERS OF Mg²⁺  HOMEOSTASIS

Magnesium is required to maintain the structures of ribosomes, nucleic acids and numerous proteins and acts as a cofactor for over 300 enzymes, including those involved in energy metabolism and protein synthesis. It is also required for normal cell permeability and neuromuscular functions. The usual dietary intake of Mg²⁺ is about 15 mmol day^–1 and approximately 30% of this is absorbed in the GIT, the rest is lost in the feces. The adult human body contains over 1200 mmol of Mg²⁺ (Figure 8.18). Approximately 750 mmol is found in bone and about 450 mmol in muscle and soft tissues. The ECF contains only 15 mmol. Approximately 55% of plasma Mg²⁺ occurs as free ionized Mg²⁺, 32% is protein-bound and 13% complexed with P_i or citrate.

The kidneys lose 5 to10 mmol of Mg²⁺ daily but losses are adjusted to control Mg²⁺ homeostasis. An increased dietary intake of Mg²⁺ results in increased renal loss and vice versa. This is achieved principally by adjusting the reabsorption of Mg²⁺ by cells of the proximal tubules and loop of Henle. A number of factors influence the rate of excretion of Mg²⁺ including hypercalcemia and hypophosphatemia that decrease renal reabsorption and PTH, which stimulates renal retention.

The reference range for serum Mg²⁺ is 0.8–1.2 mmol dm^–3. Hypo- and hypermagnesemia refer to concentrations below and above the reference range respectively. Note that measurements of the concentration of Mg²⁺ in plasma or serum are unreliable indicators of its body status since only 1% of body Mg²⁺ occurs in the ECF.

The clinical effects of hypomagnesemia are similar to those seen in hypo-calcemia and include tetany, muscle weakness, convulsions and cardiac arrhythmias. These effects are related to the role of Mg²⁺ in neuromuscular function. The causes of hypomagnesemia include decreased intake as in starvation , poorly managed parenteral nutrition or malabsorption. Increased losses of Mg²⁺ as in osmotic diuresis in diabetics , diuretic therapy, hyperaldosteronism and excessive losses from the GIT in prolonged diarrhea, GIT fistula and laxative abuse can also cause hypomagnesemia. The use of anticancer drugs , such as cisplatinum, can damage the kidneys and prevent the renal reabsorption of Mg²⁺. In alcoholism , hypomagnesemia is believed to occur due to increased renal excretion, inadequate dietary intake, vomiting and diarrhea.

In many cases, the cause of hypomagnesemia is determined by clinical examination. However, measuring the urinary Mg²⁺ may be useful as the amount of Mg²⁺ excreted per day decreases with decreased intake. If hypomagnesemia occurs with increased renal excretion then losses are likely to be due to renal damage. Hypercalcemia may increase renal Mg²⁺ excretion causing hypomagnesemia but hypocalcemia may occur in hypomagnesemia due to hypoparathyroidism.

In hypomagnesemia, the underlying cause should be treated wherever possible. Oral Mg²⁺ supplements may be adequate for mild cases but severe Mg²⁺ deficiency together with malabsorption may require intravenous infusions of Mg²⁺.

The clinical effects of hypermagnesemia are also largely related to the role of Mg²⁺ in neuromuscular activities and include muscular weakness, respiratory paralysis and, in very severe cases, cardiac arrest. Acute or chronic renal failures are the commonest causes of hypermagnesemia; others include its release from damaged cells from, for example, crush injuries. Mild hypermagnesemia may occur in mineralocorticoid deficiency, as in Addison’s disease. In rare cases, hypermagnesemia may occur from an increased oral or parenteral intake of Mg²⁺ or from the use of Mg²⁺ containing antacids or laxatives. When this does occur, it is usually combined with renal failure. The management of hypermagnesemia involves treating the underlying cause wherever possible. Hypermagnesemia due to renal failure may require dialysis.