Page 227 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Magnesium: Magnesium Deficit and Excess 217

oceans contained large quantities of magnesium, and the intracellular cycling of calcium in muscle cells. It is a
earth’s crust at the time was predominantly composed of cofactor for the Ca 2þ ATPase that rapidly shunts intracel-
iron-magnesium silicate. As early plants perfected photo- lular calcium back into the sarcoplasmic reticulum after
synthesis, magnesium played a core role in energy pro- the contraction cycle is complete. In addition, there is
duction as a component of chlorophyll. As animal life some evidence to suggest that extracellular magnesium
developed, magnesium played another core role in the may act as a calcium channel blocker for some cell mem-
production of ATP. In fact, as life has developed on earth, brane bound calcium channels, limiting the influx of
magnesium and calcium appear to have played comple- extracellular calcium into the cytosol. 77,100 Intracellular
mentary roles to each other, with magnesium being and extracellular magnesium levels thus play an important
involved in energy production and cell metabolism, and role in cardiac excitability, contraction, and conduction
calcium’s role defined more by the essential role it plays through their regulatory effects on calcium movement.
in structural stability (bone) and movement (neuromus- Cardiac conduction electrophysiology is complex and
cular activity). Magnesium’s evolution as a “behind the involves finely orchestrated movement of sodium and cal-
scenes” ion that keeps the inner machinery of the cell run- cium ions into and potassium out of the myocytes to
ning smoothly and supplied with ample amounts of propagate an action potential and depolarize the cell.
energy has perhaps contributed to the long period of time Rapid restoration of these electrolytes against their nor-
in which it received little clinical attention. Recently, mal electrochemical gradients occurs to allow the cell
however, this electrolyte has been placed under greater to repolarize itself and prepare for the next action poten-
scrutiny and it has been the focus of research activity. tial to occur. Magnesium has several roles in this process.
Magnesium plays a pivotal role in many cellular meta- First, magnesium is a cofactor for the ionic pumps that
bolic processes. Although magnesium is the second most rapidly pump sodium out of the cell, potassium back into
abundant intracellular cation, most of the intracellular the cell, and calcium out of the cell or back into the sar-
magnesium is bound to numerous molecules that regu- coplasmic reticulum. In addition, magnesium serves as an
6
late energy production, storage, and use. Magnesium important gating mechanism to control the movement of
plays a vital role in the mitochondria during oxidative intracellular calcium as described above, and it also acts to
phosphorylation and during anaerobic metabolism of prevent the leak of potassium from inside the cell. Intra-
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glucose. In addition, magnesium participates in a num- cellular calcium overload triggered during myocardial
ber of other important intracellular events, such as the ischemia by mediators such as lysophosphatidylcholine
synthesis and degradation of DNA, the binding of (LPC) has been implicated as an important cause of ven-
ribosomes to RNA, adenine nucleotide synthesis, and tricular arrhythmias that result from ischemic
the production of important intracellular second conditions. 122 Magnesium may act as an antiarrhythmic
messengers such as cyclic AMP. 6,118 Perhaps most well agent by limiting intracellular calcium overload in such
known is magnesium’s function as a cofactor with ATP conditions. 122
as the driving force behind intracellular ion pumping Cardiac arrhythmias are clinical manifestations that can
activity. Significant ion pumps, such as the membrane arise from derangements of intracellular or extracellular
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þ
bound Na -K þ ATPase, HCO 3 ATPase, and Ca 2þ electrolyte concentrations of magnesium, potassium,
ATPase, all require Mg 2þ -ATP to maintain effective ionic and calcium. 76,129 Common arrhythmias documented
gradients within and outside the cell. 6,100 As a result, in humans in which magnesium deficiency has been
magnesium has an important function in maintaining implicated as a cause of, or contributing to the severity
appropriate intracellular potassium concentrations and of, include: atrial fibrillation, supraventricular tachycar-
serves to regulate cytoplasmic calcium concentrations dia, torsades de pointes, ventricular ectopy, ventricular
by stimulating the sequestration of calcium into the tachycardias, and toxic digitalis arrhythmias. 126,137,182
endoplasmic and sarcoplasmic reticula. The importance Some but not all of these arrhythmias may have an asso-
of magnesium’s intracellular role becomes apparent ciation with hypomagnesemia in veterinary patients, but
clinically in several conditions. no definitive studies have documented the prevalence of
various pathophysiologic causes of arrhythmias.
CARDIOVASCULAR SYSTEM Magnesium’s effect on the peripheral vasculature is
Contraction of both cardiac and smooth muscle is a com- also significant. Magnesium appears to control or exert
plex sequence of events that is orchestrated by many a powerful role in calcium cycling in the smooth muscle
factors and requires rapid shifting of intracellular ions of the peripheral vasculature, with higher intracellular
to maintain appropriate concentration gradients. Intra- concentrations of magnesium producing a relaxing or
cellular calcium, released from the sarcoplasmic reticulum vasodilating effect. 90,100,152 Low concentrations of intra-
or entering the cell from the extracellular space, is the cellular magnesium appear to have the opposite or
initiating factor in muscle contraction. Magnesium (both vasoconstricting effect. As a result, magnesium deficiency
intracellular ionized magnesium level and extracellular has been implicated as a potential contributing cause in
level) plays an important regulatory role in the the constellation of causes of systemic hypertension. 90,152