Overview of Disorders of Magnesium Metabolism

Magnesium (Mg) homeostasis is not under direct hormonal control but is mainly determined by absorption from the GI tract; excretion by the kidneys; and the varying requirements of the body for pregnancy, lactation, and growth. Magnesium is the second most common intracellular cation after potassium, with 50%–60% of total body Mg distributed in bone, 40%–50% in soft tissues, and <1% in the extracellular fluid. Therefore, plasma Mg does not provide an indication of intracellular or bone Mg stores. Intracellular Mg is required for activation of enzymes involving phosphate compounds such as ATPases, kinases, and phosphatases; and for synthesis of RNA, DNA, and protein. Magnesium is a cofactor for >300 enzymatic reactions involving ATP, including glycolysis and oxidative phosphorylation. It is also important in the function of the Na⁺/K⁺-ATPase pump, membrane stabilization, nerve conduction, ion transportation, and calcium channel activity. Magnesium also regulates the movement of calcium into smooth muscle cells, giving it a pivotal role in cardiac contractile strength and peripheral vascular tone. Low ionized Mg concentrations accelerate the transmission of nerve impulses. Clinical manifestations of severe hypomagnesemia include muscle weakness, muscle fasciculations, ventricular arrhythmias, seizures, ataxia, and coma.

Similar to calcium, serum total magnesium (tMg) can be divided into three forms. The physiologically active (free) fraction is ionized magnesium (iMg²⁺), whereas the protein-bound and chelated fractions are unavailable for biochemical processes. Serum iMg²⁺ cannot be accurately calculated from serum tMg and albumin concentrations; therefore, serum iMg²⁺ concentration must be determined by direct measurement. Because iMg²⁺ concentrations represent the functional pool of serum Mg, determination of iMg²⁺ may provide a better physiologic assessment of Mg status than does tMg. A commercially available ion-selective electrode for Mg allows routine measurement of iMg²⁺ concentrations.

Magnesium is cleared by glomerular filtration and, in the absence of renal disease, renal homeostatic mechanisms will attempt to maintain Mg balance. When the diet contains excessive Mg, renal tubular resorption decreases, maintaining serum concentrations of Mg within narrow physiologic limits. Renal excretion of Mg may be used to evaluate Mg balance.

IV administration of large doses of Mg is safely used to concurrently diagnose and treat hypomagnesemia. The IV Mg retention test, which involves the determination of urinary Mg retention, has become the gold standard to determine Mg status in human medicine and has been validated in horses, dogs, and cattle. Animals deficient in Mg will retain a large proportion of the administered Mg, whereas animals with sufficient Mg will excrete most of it.

Fractional clearance relates the amount of substance excreted to the amount filtered by the glomerulus without the need for volumetric urine collection. Fractional clearance can be calculated by using concurrently collected spot samples of urine and serum and by measuring the concentrations of creatinine and the electrolyte of interest. This allows assessment of urinary electrolyte excretion without the need for timed urine collections and takes into account variability in urine concentration due to hydration status.

Ruminants are more prone to hypomagnesemia than monogastric animals. The variation in Mg metabolism among species is mainly because of anatomic and physiologic differences in digestive tracts. Ruminants absorb Mg less efficiently than nonruminants (35% vs 70% of intake). The rumen is the main site of absorption, and there are active transport mechanisms. Absorption from the large intestine occurs with high Mg intakes. In nonruminants, the small intestine is the main site of absorption. Species differences in Mg metabolism are attributable to variation in both absorption efficiency of Mg from the gut and reabsorption of Mg by the kidney tubules.