Page 228 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

218 ELECTROLYTE DISORDERS

The recent discovery of TRPM6 and TRPM7 channels in example of acute central nervous system magnesium defi-
vascular smooth muscle cells further implicates the ciency is grass tetany or grass staggers of cattle. In this
important role magnesium has to play in the complex condition, increased neuronal hyperexcitability and neu-
control of vascular smooth muscle. 166 romuscular transmission occurs, causing severe muscle
Research has also shown that magnesium plays an tetany and seizure activity that frequently results in death.
interesting role in the production of inflammatory Chronic forms of magnesium deficit in humans have also
cytokines and reactive oxygen species that have been been implicated in any number of neurologic and neuro-
postulated to play an important role in many common muscular conditions, including migraine headache, sud-
diseases of the cardiovascular system of den infant death syndrome, age-related dementias,
humans. 90,152,174-177 The origin of this research interest chronic fatigue syndrome, and many other psychiatric
was the cardiac necrosis and lesions in the myocytes of and sleep-related disorders. 46–48,50,52,53 An acute neuro-
animal models fed magnesium deficient diets. 174 The logic condition similar to grass tetany and suspected to
cause of these lesions and cardiac dysfunction appears have been caused by magnesium deficiency has also been
to be the reactive oxygen species that originate from described in a high school football team. 89 The patho-
neuropeptide Substance P induced activation of physiology of the acute and chronic clinical forms of
macrophages, neutrophils, and mast cells and an increase magnesium deficit are likely to be multifactorial, but
in important up-regulating inflammatory cytokines, such several contributing causes have been postulated. A
as tumor necrosis factor-a and interleukin-1. 174-177 decrease in neuronal magnesium concentration is
A study investigating a potential link between feline car- believed to increase the likelihood of calcium binding
diomyopathy and magnesium status has been reported. 59 to prejunctional acetylcholine vesicles increasing release
It was not successful in showing any link between magne- of acetylcholine into the neuromuscular cleft and increas-
sium and feline hypertrophic cardiomyopathy, but ing the likelihood of muscle contractions. 63 In addition,
included only a small number of cats and did not robustly magnesium has been shown to block N-methyl-D-aspar-
evaluate magnesium status. Animal models evaluating tate (NMDA) receptors within the central nervous sys-
cardiac effects of magnesium deficiency have also shown tem. NMDA receptors are involved in numerous
an increased susceptibility to ischemic and reperfusion central nervous system functions, including pain sensa-
injury, indicating that magnesium also has a protective tion and excitatory neurotransmitter activities. 44 Some
antioxidant effect. 100,176 researchers have also speculated that NMDA receptor
The effect of magnesium on the electrocardiograms of blockade by magnesium may play a role in bronchial
dogs fed a magnesium deficient diet has been reported smooth muscle relaxation. 143 Other causes that have
several times with very conflicting results. 115,160,178 been identified as potential contributing factors to neuro-
One study reported a concurrently developing hypokale- muscular effects of magnesium deficit include increased
mia with an increase in peaked T waves and slight depres- excitatory neurotransmitter release, decreased inhibitory
sion of the ST segment in addition to various neurotransmitter release, production of inflammatory
arrhythmias. 115 A second study reported a decrease in neuropeptides (Substance P), antioxidant reserves, and
the PQ and QRS distances and an increased incidence the important influence of magnesium on numerous
of negative T waves but did not evaluate concurrent elec- intracellular second messenger systems. 46,48
trolyte disturbances. 160 A third study reported yet
another set of findings that included an increased inci- ELECTROLYTE DISTURBANCES
dence of mild hypocalcemia, but normokalemia and tran- Numerous concurrent electrolyte disturbances have been
sient RST segment and T wave changes, which were not reported in association with magnesium deficit. Most
consistent or frequent enough to allow the authors to commonly reported, in several species, and best studied
make any definitive conclusions about electrocar- is the depletion of potassium. During a magnesium defi-
178
diographic changes associated with hypomagnesemia. cient state, the simultaneous occurrence of intracellular
potassium loss and decreased ability for potassium to
NEUROMUSCULAR SYSTEM reenter the cell lead to a significant intracellular depletion
The role of magnesium in neuromuscular transmission is of potassium. In some cases, a refractory state of hypoka-
important as evidenced by the severe clinical signs that lemia occurs despite aggressive supplementation with
may manifest in deficient states. Currently our under- potassium and resolves only when the magnesium deficit
standing of the precise role of magnesium in neuromus- has also been corrected. 68,181 Several mechanisms may
cular transmission is limited. In general, magnesium contribute to hypokalemia. Magnesium’s function as a
depletion leads to an increased neuronal excitability and cofactor for most ATPase pumps likely plays a dominant
enhanced neuromuscular transmission, with the opposite role. Reduced Na-K-ATPase function will lead to a net
effects predominating in states of magnesium excess. loss of potassium outside the cell and a net gain of sodium
In small animal patients, neuromuscular signs of hypo- in the cell. 181 In addition, a magnesium deficit also
magnesemia are rare. Perhaps the most instructive decreases the function of the Na-K-Cl cotransport