Magnesium is the fourth most common body cation (after sodium, potassium, and calcium) and the second most common intracellular cation (after potassium). About half is located in soft tissue and muscle cells and about half is in bone. Only 1%-5% is extracellular. Most body magnesium is derived from food intake. About one third of dietary magnesium is absorbed, with the absorption site being the small intestine. Body magnesium is excreted by the kidney, primarily through glomerular filtration. Some tubular reabsorption also takes place. About 33% of serum magnesium (literature range, 15%-45%) is bound to serum proteins, 15% is complexed, and about 50% is free in the ionized form. Of the protein-bound fraction, about 75% is attached to albumin and most of the remainder to alpha-1 and alpha-2 globulin. Albumin thus carries about 30% (range, 25%-33%) of total serum magnesium. PTH is a very important regulator of magnesium blood levels through regulation of renal tubule reabsorption.

Magnesium is important in protein synthesis, enzyme activation, and oxidative phosphorylation. It influences renal exchange of potassium and hydrogen ions and affects calcium levels. It also has an important role in nervous system control of muscle at the neuromuscular junction, where it slows neuromuscular impulse transmission by inhibiting acetylcholine. The major clinical symptoms of magnesium disorders are neuromuscular. Magnesium deficiency enhances muscle fiber excitability due to increased activity of acetyl-choline; this is manifested by muscle tremor, which can progress to seizures and tetany. Mental abnormalities include confusion, anxiety, and hallucination. Magnesium excess conversely displays antagonism of nerve impulse transmission and results in muscle weakness. Magnesium also exerts some effect on heart muscle. Decreased magnesium levels may produce or aggravate cardiac arrhythmias, whereas toxic levels of magnesium may be associated with heart block. Hypomagnesemia also potentiates the toxic effects of digitalis.

Magnesium deficiency. Magnesium deficiency has been reported in about 10% (range, 7%-11%) of hospitalized patients. Some of the etiologies of hypomagnesemia are listed in the box. In addition, it has been reported that hypomagnesemia frequently accompanies hyponatremia (22%-27% of hyponatremic patients); hypocalcemia (22%-32% of patients); and hypophosphatemia (25%-29% of patients). Several studies also found that hypomagnesemia is frequent in patients with hypokalemia (38%-42%), but one study reported only 7%. Postoperative patients on IV feeding are reported to have a short-term, temporary 20% decrease in serum magnesium levels. Similar findings have been reported 12-24 hours after acute myocardial infarction, returning to previous levels by 48 hours, but not all studies agree.

Excess magnesium. Increased serum magnesium levels are most often due to oliguric renal failure, which prevents excretion of magnesium. Overuse of magnesium compounds is an occasional etiology.

Laboratory tests. RBCs contain 2-3 times the concentration of magnesium found in serum. Artifactual hemolysis thus may produce a significant increase in assay values. Skeletal muscle contains about 10 times the serum concentration. Since about 30% of serum magnesium is bound to albumin, and assays measure total magnesium levels, hypoalbuminemia will artifactually decrease serum magnesium levels.

Magnesium Disorders
Magnesium deficiency
IV fluids without magnesium
Severe diarrhea
Diabetic ketoacidosis
Congestive heart failure
Artifact (hypoalbuminemia)
Certain medications
Loop and thiazide diuretics
Magnesium excess
Oliguric renal failure
Overuse of magnesium-containing compounds
Artifactual (specimen hemolysis)

Various reports emphasize that serum magnesium values may not always truly reflect total body magnesium levels, since serum values may be falsely elevated in dehydration and falsely decreased in hemodilution with or without clinical edema or hypoalbuminemia. However, this problem is not unique to magnesium.