Magnesium

Physiology
Magnesium is the fourth most abundant cation in the body after calcium,
sodium, and potassium; it is the second most prevalent intracellular
cation.
The normal body magnesium content in an adult is approximately 1000
• mmol or 22.66 g, of which 50-60% is in bone and the remaining 40-50% is
in the soft tissues. One-third of skeletal magnesium is exchangeable and
probably Serves as a reservoir for maintaining a normal extracellular
magnesium concentration.
Only 1% of the total body magnesium (TBMg) is in extracellular fluid. In
serum, about 55% of magnesium is ionized or free magnesium (Mg2+), 30%
is associated With proteins (primarily albumin), and 15% is complexed with
phosphate, citrate, and other anions. The interstitial fluid concentration is
approximately 0.5 mmoI/L. In CSF, 55% of the magnesium is free or
ionized and the remaining 45% is complexed with other compounds .
Approximately 99% of the TBMg is in bone matrix or is intracellular. About
60% of this total is within bone matrix and the other 40% is within skeletal
muscle, within blood cells, or in the cells of other tissues. Intracellular
magnesium concentration is approximately 1—3 mmoI/L (2.4-7.3 mg/dL).
Within the cell, magnesium is compartmentalized, and most of it is bound
to proteins and negatively charged molecules; approximately 80% of
cytosolic magnesium is bound to ATP. Significant amounts of magnesium
are found in the nucleus, mitochondria, and endoplasmic reticulum. Free
magnesium accounts for 0.5-5.0% of the total cellular magnesium, and is
the fraction that is probably important as a cofactor supporting enzyme
activity.
Function:
Magnesium is essential for the function of more than 300 cellular
enzymes, including those related to the transfer of phosphate groups, all
reactions that require ATP, and every step related to the replication and

transcription of DNA and the translation of mRNA.

Mg is also required for cellular energy metabolism and has an important
role in membrane stabilization, nerve conduction, ion transport, and
calcium channel activity.
In addition, magnesium plays a critical role in the maintenance of
intracellular potassium concentration by regulating potassium movement
through the membranes of the myocardial cells. Thus, magnesium
deficiency can result in a variety of metabolic abnormalities and clinical
consequences including refractory plasma electrolyte abnormalities
(especially depressed potassium) and cardiac arrhythmias most often
observed after stress such as cardiac surgery.
Magnesium Homeostasis:
Total body magnesium depends mainly on gastrointestinal absorption and
renal excretion.
The average dietary intake of magnesium fluctuates between 300-350
mg/day, and the intestinal absorption is inversely proportional to the
ingested amount.
is the principal organ involved in magnesium regulation. The
renal excretion is about 120-140 mg/24 h for a person on a normal diet.
Approximately 70-80% of the plasma magnesium is filtered through the
glomerular membrane. Tubular reabsorption of Mg2+ is different from that
for other ions because the proximal tubule has a limited role and 60-70%
of the reabsorption of Mg2+ takes place within the thick ascending loop of
Henle . Even though the distal tubules reabsorb only 10% of the filtered
Mg2+, they are the major sites of magnesium regulation. Many factors,
both hormonal (e.g., parathyroid hormone, calcitonin, glucagon, and
vasopressin) and nonhormonal (magnesium restriction, acid—base
changes, and potassium depletion), influence both the Henle's loop and
distal tubule reabsorption. However, the major regulator of reabsorption
is the plasma concentration of Mg2+ itself. Increased Mg2+ concentration
inhibits loop transport, whereas decreased concentration stimulates
transport regardless of whether or not there is magnesium depletion. The
mechanisms appear to be regulated by the Ca2+/Mg2+-sensing receptor,
located on the capillary side of the thick-ascending-limb cells, which

senses the changes in Mg2+. Other factors that may also play a role in
magnesium regulation include calcium concentration and rate of sodium
chloride reabsorption.
In magnesium deficiency, serum levels decrease and this leads to reduced
urinary excretion. Later, bone stores of magnesium are affected as the
process of equilibration with bone stores takes place over several weeks.
Since serum only contains about 1% of total body magnesium, it may not
accurately reflect total stores. In general, a low serum level indicates
deficiency and a high level indicates adequate stores. However, the most
common result—a normal level — should be interpreted with caution since
it does not exclude an underlying deficiency. The most accurate
assessment of magnesium status is generally considered to be the loading
test wherein magnesium is given intravenously. Magnesium-deficient
'individuals retain a greater proportion of the load and excrete less in the
urine than normal individuals .However, the test is uncommonly used
because it is difficult to administer.
Hypermagnesemia:
Hypermagnesemia (i.e., plasma Mg2+ concentration > 0.9 mmol/L) is rare
and observed less frequently than hypomagnesemia. Causes are the
following:
Decreased excretion: Renal failure is the most common cause. Also
hypothyrodism & dwarfism may cause a moderate elevation in serum Mg
( T4 and GH cause a decrease in tubular reabsorption of Mg, so deficiency
of either may lead to hypermagnesemia )
Increased intake: Iatrogenic (as antacids or enema containing Mg). Those
most at risk are the elderly and patients with renal insufficiency. Also
MgS04 may be used as a therapy in cases of preeclampsia and can lead to
hypermagnesemia in both the mother and baby
Increased bone loss: as in cases of multiple myeloma, bone carcinoma or
metastasis.
Analytical Techniques
Total Magnesium.
Serum is preferred over plasma for magnesium determination because
anticoagulant interferes with most procedures. Serum magnesium is
usually measured by photometry.
Photometric method : These methods use metallochromic indicators or

dyes that change color upon selectively binding magnesium from the
sample. Some of the chromophores used include calmagite, methylthymol
bluet formazan dye, and magon. In the G?lmpgite photometric method,
which is the one most commonly used, calmagite forms a colored complex
with magnesium in alkaline solution. This complex is stable for over 30
minutes, and its absorbance at 520 nm is directly proportional to the
magnesium concentration in the specimen aliquot.
Atomic absorption spectrophotometry (AAS): the reference method for
total magnesium.
Ionized (Free) Magnesium.
Ionized magnesium can be measured with magnesium ion-selective
electrodes (ISEs). These ISEs employ neutral carrier ionophores that are
selective for Mg2+. However, in addition to Mg2+, these ISEs also measure
Ca2+, thus requiring a chemometric correction to calculate the true free
magnesium levels in the sample.
The changes of ionized magnesium in relation to alterations of pH are
similar to those of ionized calcium, although less well characterized. With
an increase in pH, ionized magnesium is decreased, and with a decrease in
pH, it is increased .
Reference Interval
The reference interval for serum total magnesium in normal adults ranges
between 0.75-0.95 mmol/L (1.7-2.2 mg/dL or 1.5-1.9 mEq/L).
No significant sex or age differences.
Erythrocyte magnesium is about three times that of serum. The
magnesium concentration in CSF is 2.0-2.7 mg/dL (1.0-1.4 mmol/l.).