Magnesium Metabolism

Maintaining normal serum magnesium concentration depends mainly on dietary intake, although renal and intestinal mechanisms usually conserve magnesium. Magnesium, a cation abundant in the body, is distributed almost equally between bone and soft tissue. Intracellular magnesium is needed for many enzyme activities, particularly those involving nucleotide phosphate metabolism, and plays a vital role in DNA, RNA, and protein synthesis. Unlike serum calcium concentration, serum magnesium concentration is not tightly regulated and can vary considerably depending on diet and changes in cellular uptake. The normal serum magnesium concentration is 1.7 to 2.2 mg/dL (1.4 to 1.8 mEq, 0.7 to 0.9 mmol/L). About 20 to 30% of serum magnesium is bound to plasma proteins; magnesium may compete with calcium for protein binding.

Evidence of primary regulation of serum magnesium is scant, but high concentrations can inhibit parathyroid hormone (PTH) secretion, presumably acting at the same sites as extracellular calcium. Although low magnesium concentrations may stimulate PTH secretion transiently, marked depletion (< 0.9 mg/dL [< 0.4 mmol/L]) can impair PTH secretion, possibly leading to hypocalcemia.

Hypomagnesemia

Serum magnesium concentration < 1.7 mg/dL (< 1.4 mEq, < 0.7 mmol/L).

Common in elderly patients, mild to moderate hypomagnesemia is probably not an accurate reflection of intracellular or bone stores, which can be maintained long after serum concentrations begin to decrease. Nevertheless, hypomagnesemia is a warning sign that depletion may develop. Conversely, tissue depletion of magnesium may occur with normal serum concentrations.

Etiology

Causes of magnesium depletion include dietary deprivation, renal loss, and GI disorders, including vomiting, diarrhea, and malabsorption syndrome. Renal loss can occur in many conditions, including aldosterone excess, diuretic therapy, and diabetes mellitus. A few patients develop severe magnesium depletion because of a primary defect in renal tubular reabsorption of magnesium. Alcoholism often causes magnesium depletion. Serum magnesium concentrations fall rapidly in some patients after parathyroid adenomas are removed, presumably because of a rapid uptake in bone.

Symptoms and Signs

Symptoms and signs are nonspecific. Neuromuscular irritability and muscle weakness are common. Because hypomagnesemia is often associated with low serum concentrations of calcium, potassium, and phosphate, attributing particular symptoms or signs to magnesium depletion is difficult. Magnesium depletion may cause arrhythmias and increased sensitivity to cardiac glycosides and may contribute to hypertension and atherosclerosis.

Treatment

When possible, magnesium depletion should be avoided by maintaining adequate dietary intake. Mild hypomagnesemia can usually be reversed with a magnesium-rich diet. If hypomagnesemia has been prolonged or if parathyroid and cell functions are likely to be impaired, 50% magnesium sulfate (4 mEq/mL) 2.5 mL IM can be given. Patients at high risk of hypotension should receive a smaller dose. Magnesium sulfate can be given IV (1 mEq/kg) but only as a more dilute solution (<= 10%) over 24 hours with half the dose given in the first 3 hours and the remaining half over the rest of the day.

Replacement of magnesium by the oral route is difficult because magnesium salts are powerful laxatives and because magnesium depletion often occurs in persons with GI disorders. Small amounts of oral magnesium hydroxide or magnesium chloride can be used, but some patients require magnesium sulfate IM at regular intervals to prevent deficiency.

When hypomagnesemia occurs with calcium, potassium, or phosphate deficiencies, correcting the hypomagnesemia makes treating the other deficiencies easier.

Hypermagnesemia

Serum magnesium concentration > 2.5 mg/dL (> 2.0 mEq/L, > 1 mmol/L).

Hypermagnesemia is rare except in renal failure or after parenteral magnesium administration. It can depress central nervous system and cardiac functions. ECG changes include PR prolongation, QRS widening, and T-wave amplitude increase. Furosemide or ethacrynic acid, administered IV, increases magnesium excretion if hydration is maintained and renal function is adequate. Severe magnesium intoxication requires 10 to 20 mL of 10% calcium gluconate given IV, together with circulatory and respiratory support. Dialysis is required occasionally.