Hypomagnesemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Huda A. Karman, M.D.

Overview

The body contains 22-26 grams of magnesium (1,000 mmols). Of this, 60% is located in bone (30% of which is exchangeable and functions as a reservoir to stabilize the serum concentration), 20% in skeletal muscle, 19% in other soft tissues, and < 1% in extracellular fluid. For this reason, blood levels of magnesium are not an adequate means of establishing the total amount of available magnesium. The normal total serum magnesium ranges between 1.7-2.3 mg/dl (0.70 and 1.10 mmol/L). Around 20% of this is protein bound, 65% is ionized and the rest is bound with various anions/chelators (i.e. ATP, ADP, proteins, bicarbonate and citrate). Of the protein bound fraction, 60–70% is associated with albumin and the rest is bound to globulins. Around 5-10% of magnesium is free and is essential in regulating intracellular magnesium. Magnesium is a cofactor in more than 300 enzyme regulated reactions. Most importantly forming and using ATP, i.e. kinase. There is a direct effect on sodium- (Na), potassium- (K) and calcium (Ca)channels. Serum ionized magnesium concentration (0.54–0.67 mmol/L) and is narrower than calcium. Acid base disturbances (metabolic acidosis or alkalosis) have little effect on the distribution of serum magnesium. The concentration of magnesium in CSF is around 1.1 mmol/L (55% is free and 45% is bound with other compounds). The higher ultrafiltrable magnesium in CSF compared to serum is due to active transport of magnesium across the blood-brain barrier.

Pathophysiology

Homeostasis

• The body contains 22-26 grams of magnesium (1,000 mmols). Of this, 60% is located in bone (30% of which is exchangeable and functions as a reservoir to stabilize the serum concentration), 20% in skeletal muscle, 19% in other soft tissues, and < 1% in extracellular fluid.
• Blood levels of magnesium are not an adequate means of establishing the total amount of available magnesium.
• The normal total serum magnesium ranges between 1.7-2.3 mg/dl (0.70 and 1.10 mmol/L).
  • Around 20% of this is protein bound
  • 65% is ionized
  • The rest is bound with various anions/chelators (i.e. ATP, ADP, proteins, bicarbonate and citrate)
  • Of the protein bound fraction, 60–70% is associated with albumin and the rest is bound to globulins.
  • Around 5-10% of magnesium is free and is essential in regulating intracellular magnesium.
• Magnesium is a cofactor in more than 300 enzyme regulated reactions. Most importantly forming and using ATP, i.e. kinase.
• There is a direct effect on sodium- (Na), potassium- (K) and calcium (Ca)channels.
• Serum ionized magnesium concentration (0.54–0.67 mmol/L) and is narrower than calcium
• Acid base disturbances (metabolic acidosis or alkalosis) have little effect on the distribution of serum magnesium. The concentration of magnesium in CSF is around 1.1 mmol/L (55% is free and 45% is bound with other compounds).
• The higher ultrafiltrable magnesium in CSF compared to serum is due to active transport of magnesium across the blood-brain barrier.

• Magnesium is abundant in nature. It can be found in green vegetables, chlorophyll, coca-derivatives, nuts, wheat, seafood, and meat.
• It is resorbed through the small intestine, and to a lesser degree in the colon. The rectum and sigmoid colon can absorb magnesium. Hypermagnesemia has been reported after enemas containing magnesium.
• Forty percent of dietary magnesium is absorbed. Hypomagnesemia stimulates and hypermagnesemia inhibits this absorption.

• The kidneys regulate the serum magnesium. About 2400 mg of magnesium passes through the kidneys, of which 5% (120 mg) is excreted through urine.
• The loop of Henle is the major site for Mg-homeostasis and 60% is resorbed.

• Magnesium homeostasis comprises three systems: kidney, small intestine, and bone
• In the acute phase of magnesium deficiency there is an increase in absorption in the distal small intestine and tubular resorption in the kidneys. When this condition persists serum magnesium drops and is corrected with magnesium from bone tissue.
• The level of intracellular magnesium is controlled through the reservoir in bone tissue

Metabolism

Magnesium is a cofactor in more than 300 enzyme regulated reactions. Most importantly forming and using ATP, i.e. kinase. Magnesium also has direct several effects on sodium- (Na), potassium- (K) and calcium (Ca)channels:

• Potassium
  • Potassium channels inhibited by magnesium
  • Hypomagnesemia results in increased efflux of intracellular Mg.
  • The cell loses potassium which then is excreted by the kidneys, resulting in hypokalemia.
• Calcium
  • Release of calcium from the sarcoplasmic reticulum is inhibited by magnesium
  • Hypomagnesemia stimulate the release of calcium and thereby an intracellular level of calcium.
  • This effect similar to calcium inhibitors makes it "nature's calcium inhibitor."
• Parathyroid hormone
  • Hypomagnesemia inhibits the release of parathyroid hormone, which can also result in hypocalcemia
  • It decreases the sensitivity of skeletal muscle receptors to parathyroid hormone
• Bronchi
  • Relaxation of bronchial smooth muscle it causes bronchodilation.
• Neurological
  • Reducing electrical excitation
  • Blocking release of acetylcholine
  • Blocking N-methyl-D-aspartate, an excitatory neurotransmitter of the central nervous system

References