Page 225 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Disorders of Magnesium: Magnesium Deficit and Excess 215

in the thick ascending limb with no change in sodium and Tubular
chloride reabsorption. 20 A similar genetic anomaly has fluid Cell Interstitial fluid
been documented in Japanese Black cattle that develop
early renal failure. 72,111,142 When compared with each
other, renal handling of magnesium and calcium appear
to be similar in both the bovine and human conditions. 112
0.2 mM 0.5 mM 0.6 mM
Changes in the transepithelial voltage and paracellular 2+ + Insulin?
Mg
permeability to magnesium strongly influence magne- 2+ ? +
sium absorption from the thick ascending limb. 35,66 Mg TRPM6 ? Na
± TRPM7
Increases in salt movement from the lumen will concur-
? Peptide hormone
rently elevate the transepithelial electrical potential and + R receptor (PTH, calcitonin,
facilitate magnesium absorption. Numerous factors can glucagon, ADH)
influence both of these properties resulting in an increase – G
or decrease in magnesium absorption. Hormones such as CaSR
parathyroid hormone, calcitonin, glucagon, antidiuretic + Aldosterone
hormone, aldosterone, and insulin all act to increase mag- + Vitamin D 3
nesium absorption from the lumen. 35 Conversely, prosta- –10 mV –70 mV 0 mV
glandin E 2 , hypokalemia, hypophosphatemia, and
acidosis can all act to decrease magnesium absorption. 35
In addition to the above influences on paracellular
absorption of magnesium, a basolateral extracellular Figure 8-3 Magnesium transport in the distal convoluted tubule.
receptor, termed the calcium/magnesium sensing recep- Magnesium transport occurs exclusively via transcellular
mechanisms down a favorable electrical gradient and is postulated to
tor or cation-sensing receptor (CASR) also appears to occur through TPRM6 ion channels. Basolateral movement of
play a crucial role. 35,62,153 The CASR senses extracellular magnesium is postulated to occur via a sodium-magnesium
calcium and magnesium concentrations at the basolateral transporter. Several peptide hormones exert a positive influence on
membrane and is coupled to intracellular inhibitory G magnesium reabsorption by binding to a peptide hormone receptor
proteins, which will inhibit and neutralize the effect of (PTH, parathyroid hormone; ADH, antidiuretic hormone) or via
other hormonal influences mentioned above. 35,37,62,153 non–receptor-mediated mechanisms. The cation sensing receptor
Activation of the CASR in the loop appears to decrease (CaSR) has a net negative influence on magnesium reabsorption
salt absorption (sodium, magnesium, and calcium). 37,62 by inhibiting the positive effects of other hormones. TRPM7 ion
To what effect, if any, the CASR may play a role in altering channels may be involved in basolateral magnesium sensing by the cell.
the permeability of PCLN-1 to magnesium transport is
not known. Some researchers have suspected that there
is a selective effect on paracellular permeability to magne-
sium that cannot adequately be explained by changes in Reabsorption of magnesium in the DCT appears to
voltage and hormonal influences, leading to speculation occur only through active transcellular routes. Passive
that the CASR may influence PCLN-1 permeability. 38 paracellular transport does not appear to occur to any sig-
The CASR is also found throughout the gut, and nificant degree. As a result, the absorption of magnesium
although its function there, related to magnesium bal- via this route is an energy-requiring saturable process.
ance, is not completely understood, it likely plays a very The transcellular transport of magnesium is dependent
similar role in both organs. 81 on favorable transepithelial concentration and voltage
gradients, similar to the gut. 37 Evidence suggests that
Distal Convoluted Tubule the principle entry for magnesium into the cell is through
The distal convoluted tubule (DCT) does not appear to the unique transient receptor protein TRPM6. 190
act as a mass transporter of magnesium as the ascending While there is evidence that the influx of magnesium
loop does, but instead is the site for many complex into the cell occurs via TRPM6, there is not yet a
influences to determine the final magnesium excretion documented mechanism of magnesium efflux from the
(Fig. 8-3). The DCT normally reabsorbs approximately basolateral cell membrane. Several authors speculate,
10% to 15% of the filtered magnesium. 37,153 When neces- based on available evidence, that a sodium/magnesium
sary it can be very efficient at reabsorbing magnesium, countertransporter is likely to exist. 37,153,190 The pres-
reabsorbing as much as 70% to 80% of the magnesium ence of a sodium/magnesium countertransporter
that is delivered from the thick ascending limb. 37,153 appears to exist in human red blood cells and insulin
There does not appear to be any ability to further reab- appears to be at least one of the regulating influences
sorb or secrete magnesium in nephron segments distal on its function. 55
to the DCT, thus the final concentration of magnesium Although the precise mechanisms for magnesium entry
in the urine is principally determined by the DCT. and exit from the DCT cells remain to be completely