Hypomagnesemia

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

Hypomagnesemia is an electrolyte disturbance in which there is an abnormally low level of magnesium in the blood. Usually a serum level less than 0.7 mmol/l is used as reference. It must be noted that hypomagnesemia is not equal to magnesium deficiency. Hypomagnesemia can be present without magnesium deficiency and vice versa.

It may result from a number of conditions including inadequate intake of magnesium, chronic diarrhea, malabsorption, alcoholism, chronic stress, diuretic use and other disorders.

The prefix hypo- means low (contrast with hyper-, meaning high). The middle magnes refers to magnesium. The end portion of the word, -emia, means ‘in the blood’ (note, however, that hypomagnesemia is usually indicative of a systemic magnesium deficit).

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. 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.

Magnesium deficiency is not uncommon in hospitalized patients. Elevated levels of magnesium (hypermagnesemia), however, are nearly always iatrogenic. 10-20% of all hospital patients, and 60-65% of patient in the intensive care unit (ICU) have hypomagnesemia. Hypomagnesiemia is underdiagnosed, as testing for serum magnesium levels is not routine. Hypomagnesemia results in increased mortality. Causes of hypomagnesemia can be Alcoholism, Diuretic use, Antibiotics, stress, Gastrointestinal causes, Diabetes mellitus, Malabsorption, and Acute pancreatitis

Hypomagnesemia should be differentiated from other causes of abnormal parathyroid hormone levels for example, hypoparathyroidism (genetic and idiopathic), acrodysostosis and pseudohypoparathyroidism.

The following patients have high risk of hypoglycemia development, critically ill patients, hospitalized patients, burned patients, head and neck cancer patients treated with cetuximab

Hypomagnesemia can lead to neuromuscular, neurological, cardiovascular, endocrine, renal, and biochemical manifestations.

Deficiency of magnesium causes weakness, muscle cramps, cardiac arrhythmia, increased irritability of the nervous system with tremors, athetosis, jerking, nystagmus and an extensor plantar reflex. In addition, there may be confusion, disorientation, hallucinations, depression, epileptic fits, hypertension, tachycardia and tetany.

Signs and symptoms of hypomagnesemia include anything from mild tremors and generalized weakness to cardiac ischemia and death.

The diagnosis can be made by finding a plasma magnesium concentration of less than 0.7mmol/l. Since most magnesium is intracellular, a body deficit can be present with a normal plasma concentration. In addition to hypomagnesemia, up to 40% cases will also have hypocalcemia while in up to 60% of cases, hypokalemia will also be present.

ECG changes are non-specific and include a slight prolongation of conduction (a prolonged QT interva) and the depression of the ST segment. Magnesium depletion increases susceptibility to arrhythmogenic effects of drugs such as isoproterenol and cardiac glycosides and this includes supraventricular and ventricular arrhythmias. Torsade de pointes (repetitive polymorphous ventricular tachycardia with prolongation of QT interval) has been reported in cases of hypomagnesaemia. Torsade de pointes and other arrhythmias have been successfully treated with magnesium. However, this may be a pharmacological effect, independent of underlying magnesium deficiency.

Other diagnostic studies can include evaluation for the underlying cause of hypomagnesemia. This requires a thorough investigation for the presence of diabetes mellitus, alcoholism, gastrointestinal conditions involving poor absorption and/or poor nutritional intake, or a family history of hypomagnesemia without or without other electrolyte abnormalities, and a complete list of medications used. The suspected underlying etiology may be confirmed with urinary studies based on its mechanism via renal wasting or extrarenal cause. Patients with hypomagnesemia due to renal Mg2+ wasting have been suggested to present with a fractional excretion of Mg2+ greater than 4%, whereas those with extrarenal causes present with a much lower percentage, typically 2% or less.

Treatment of hypomagnesemia depends on the degree of deficiency and the clinical effects. Oral replacement is appropriate for patients with mild symptoms, while intravenous replacement is indicated for patients with severe clinical effects.

There are no established measures for the primary prevention of hypomagnesemia

There are no established measures for the secondary prevention of hypomagnesemia.

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

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.

• The body contains 22-26 grams of magnesium (1,000 mmols)^[1]. 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)^[1]
  • Of the protein bound fraction, 60–70% is associated with albumin and the rest is bound to globulins^[2].
  • 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^[1]
• 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)^[3].
• 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^[4]

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:^[5]

• 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

Hypomagnesemia should be differentiated from other causes of abnormal parathyroid hormone(PTH) and parathyroid hormone resistance like Blomstrand chondrodysplasia, acrodysostosis, hypoparathyroidism and pseudohypoparathyroidism.^[1][2][3][4]