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Hypomagnesemia

Hypomagnesemia is a common entity occurring in up to 12% of hospitalized patients. The incidence rises to as high as 60 to 65% in patients in intensive care settings in which nutrition, diuretics, hypoalbuminemia, and aminoglycosides may play important roles.

Symptomatic magnesium depletion is often associated with multiple biochemical abnormalities such as hypokalemia, hypocalcemia, and metabolic alkalosis. As a result, it is often difficult to ascribe specific clinical manifestations solely to hypomagnesemia.

Hypokalemia is a common event in hypomagnesemic patients, occurring in 40 to 60% of cases. This relationship is in part due to underlying disorders that cause both magnesium and potassium loss, such as diuretic therapy.

The most classical sign of severe hypomagnesemia (<1.0 mEq/L, 0.5 mmol/L, or 1.2 mg/dl) is hypocalcemia. Early in vitro studies showed that a reduction in extracellular magnesium concentration stimulated the secretion of parathyroid hormone (PTH) in the absence of changes in calcium concentration. However, immunoreactive PTH levels in most hypomagnesemic-hypocalcemic patients have been either normal or low (and in some cases undetectable), indicating inappropriately low PTH secretion. Further evidence for a suppressive effect of hypomagnesemia on PTH secretion is the observation that, in the majority of these patients, parenteral magnesium supplementation leads to a rapid rise in plasma PTH levels. Several other factors play a role in the mechanism of the hypocalcemia.

Failure of hormone secretion cannot explain all of the hypocalcemia, as bone resistance to PTH also plays a role. Studies in isolated perfused bone have shown that magnesium depletion interferes with the generation of cAMP in response to perfusion with PTH. Why this occurs is not clear. It is possible that severe hypomagnesemia.

Several findings suggest that PTH resistance may be of greater importance than diminished secretion in most patients. In general, PTH-induced release of calcium from bone is substantially impaired when the plasma magnesium concentration falls below 0.8 mEq/L (1 mg/dl or 0.4 mmol/L); in comparison, diminished PTH secretion.

Vitamin D Deficiency.

Low plasma levels of calcitriol (1,25-dihydroxyvitamin D, the most active metabolite of vitamin D) have been noted in hypocalcemic, hypomagnesemic subjects and can contribute to the fall in the plasma calcium concentration.

A small number of patients have been reported with hypocalcemia responsive to magnesium administration in the absence of detectable hypomagnesemia . In most of these patients, other tests suggested the presence of magnesium depletion (presumed isolated cellular depletion), such as alcoholism or diarrhea.

These findings, however, do not conclusively demonstrate that intracellular magnesium depletion is the cause of unexplained hypocalcemia in patients with a normal plasma magnesium concentration. Most patients with chronic alcoholism and diarrhea have tissue magnesium depletion that is independent of the presence or absence of hypocalcemia. Sepsis, hypoalbuminemia, stress, and vitamin D deficiency are among the many factors.

Causes of Hypomagnesemia

Approximately one-third of dietary magnesium is absorbed (120 mg) principally in the small bowel. In addition, there is secretion of approximately 40 mg in intestinal secretions and absorption of another 20 mg in the large bowel. Balance is achieved by the urinary excretion of the approximately 100 mg that is absorbed.

Gastrointestinal Losses

Gastrointestinal secretory losses, which contain some magnesium, are continuous and not regulated. Although the obligatory losses are not large, marked dietary deprivation can lead to progressive magnesium depletion. Magnesium loss will also occur when the intestinal secretions are incompletely reabsorbed as with most disorders.

Renal Losses

Urinary magnesium losses can be inappropriately increased by inhibition of sodium reabsorption in those segments in which magnesium transport passively follows that of sodium or, by a primary defect in renal tubular magnesium.

Both loop and thiazide diuretics can inhibit net magnesium reabsorption, while the potassium-sparing diuretics may enhance magnesium transport and lower magnesium excretion. The degree of hypomagnesemia induced by these proximal sodium, water, and magnesium reabsorption.

Expansion of the extracellular fluid volume can decrease passive magnesium transport. If sustained, mild hypomagnesemia may ensue as in primary hyperaldosteronism.

Hypomagnesemia is common in alcoholic patients admitted to the hospital; in one study, for example, the prevalence was 30%. Excessive urinary excretion of magnesium occurred in 18 of the 38 patients with hypomagnesemia. The defect in urinary excretion appears to reflect alcohol-induced tubular dysfunction that is reversible within 4 weeks.

Calcium and magnesium seem to compete for transport in the thick ascending limb of the loop of Henle.

Many nephrotoxic drugs can produce urinary magnesium wasting. Included in this group are the aminoglycoside antibiotics, amphotericin B, cisplatin, pentamidine, and cyclosporine.

Magnesium wasting can occur as part of the tubular dysfunction seen with recovery from acute tubular necrosis, following renal transplantation, during a postobstructive diuresis, or in patients with Bartter's syndrome.

Primary renal magnesium wasting is an unusual disorder that may present sporadically or as a familial disease. In some patients, magnesium wasting is also associated with abnormalities in calcium and potassium transport.

Treatment

The route of magnesium repletion varies with the severity of the clinical manifestations. As an example, the hypocalcemic-hypomagnesemic patient with tetany or the patient suspected of having hypomagnesemic-hypokalemic ventricular arrhythmias.

It must be appreciated that the plasma magnesium concentration is the major regulator of magnesium reabsorption in the loop of Henle, the major site of active magnesium transport. Thus, an abrupt elevation in the plasma magnesium concentration.

For these reasons, oral replacement should be given in the asymptomatic patient, preferably with a sustained-release preparation. There are several such preparations currently available, including Slow Mag^® containing magnesium chloride and Mag-Tab SR^® containing magnesium lactate. These preparations provide 5 to 7 mEq (2.5 to 3.5 mmol or 60 to 84 mg).