Magnesium is an essential mineral in man (1). It is required for the activities of enzymes, for neuromuscular function and cell signalling, and as a structural component e.g. within mineralised bone and for the conformation of macromolecules such as DNA and proteins. There is current interest in the pharmacological use of magnesium in conditions such as acute myocardial infarction and eclampsia.
Clinical conditions in which the serum magnesium concentration should be measured include: unexplained neuromuscular irritability particularly in the absence of hypocalcaemia; refractory hypokalaemia, hypocalcaemia and hyponatraemia; unexplained electrolyte disturbances; myocardial infarction; refractory cardiac arrhythmias; alcoholism; diuretic therapy; parenteral nutrition; severe or chronic diarrhoea; pharmacological use of magnesium.
Laboratory Indices of Magnesium Status
Magnesium in plasma represents less than 1% of the total body load. Nevertheless, because it is readily accessible, the plasma concentration is widely used in studies of magnesium status. Within the plasma approximately one third is bound to proteins and of the ultra filterable fraction more than 90% is ionised with just a small proportion complexed with anions such as citrate and phosphate.
The main disadvantage of the plasma magnesium concentration is that it provides little information relevant to concentrations of intracellular magnesium. It is established that hypomagnesaemia is indicative of magnesium deficiency but normal levels can be found even though where there is depletion of the metal within tissues. However, because of the convenience and simplicity, measurement of magnesium in serum or plasma is usually the first, and often the only test of magnesium status undertaken in clinical investigations.
Muscle contains much of the intracellular magnesium and the function of cardiac muscle in particular is dependent on the magnesium concentration. Practically, specimens of muscle cannot readily be obtained, even by biopsy, hence the interest in analyses of other cell types.
Erythrocyte magnesium concentrations are relatively simple to determine, but the reference range is wide. Although recommended by a few workers (2) most others, including ourselves, have concluded that the data are uninformative (3). Leucocytes, however, are representative of typical cellular material. Harvests of all leucocyte cell types from a blood specimen yield mixtures of cells, with a wide range of normal results. More reliable data are derived from an homogeneous group of monocytes or polymophonuclear cells and results from different workers are in good agreement (4,5). The measurement requires a large volume of blood to be collected (20-30 ml) and the separation of leucocytes has to be commenced as soon as possible, which limits the availability of the test to specially organised studies or clinics. Consequently, there are only a small number of research or other groups in a position to undertake these measurements.
As might be expected from the discussions above, leucocyte magnesium was reported not to correlate with concentrations in either plasma or erythrocyte. In contrast, concentrations of magnesium in monocytes and muscle biopsy specimens were correlated in specimens collected from human subjects and from animals.
As the functions of magnesium ions and bound magnesium are quite different, analytical speciation studies can be considered. Ion selective electrodes are available to determine Mg2+ in plasma with the normal concentrations at around 0.6 mmol/L but measurement of intracellular Mg2+ is more complicated. Fluorescent complexes have been used to measure Mg2+ in intact cells but recent interest has focused on the use in in vivo 31P-nuclear magnetic resonance (6,7).
The importance of suitable precautions for the collection of specimens must be mentioned. Because of the high concentrations in blood cells, haemolysis must be avoided and the plasma or serum should be separated within a few hours of the blood being collected. In many circumstances only very small changes in magnesium concentrations may be evident and these can be obscured or mimicked by traces of contamination.
References:
Ryan MF. The role of magnesium in clinical biochemistry: an overview. Annals of Clinical Biochemistry 1991; 28: 19-26
Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991; 337: 757-760.
Hinds G, Bell NP, McMaster D, McCluskey DR. Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome. Annals of Clinical Biochemistry 1994; 31: 459-461
Martin BJ, Lyon TDB, Walker W, Fell GS. Mononuclear blood cell magnesium in older subjects; evaluation of its use in clinical practice. Annals of Clinical Biochemistry 1993; 30: 23-27.
Loun B, Astles R, Copeland KR, Sedor FA. Intracellular magnesium content of mononuclear blood cells and granulocytes isolated from leukaemic, infected and granulocyte colony-stimulating factor-treated patients. Clinical Chemistry 1995; 41: 1768-1772
London RE. Methods for measurement of intracellular magnesium: NMR and fluorescence. Annual Review of Physiology 1991; 53: 241-258
Ryschon TW, Rosenstein DL, Rubinow DR, Niemela JE, Elin RJ, Balaban RS. Relationship between skeletal muscle intracellular ionised magnesium and measurements of blood magnesium. Journal of Laboratory and Clinical Medicine, 1996; 127: 207-213.