Hypomagnesaemia

Notes

Overview

Hypomagnesaemia is defined as a serum magnesium concentration < 0.7 mmol/L.

Hypomagnesaemia is a very common electrolyte disturbance that can be seen in up to 65% of intensive care unit patients.

Magnesium is commonly lost in the gastrointestinal tract and kidneys. Even small deficits in the net magnesium balance will lead to hypomagnesaemia. This is due to minimal rapid exchange between serum magnesium and the boney reserve.

The normal range of serum magnesium is 0.7-1.1 mmol/L. Hypomagnesaemia is defined as a serum concentration < 0.7 mmol/L, which is commonly found with other electrolyte derangement including hypokalaemia and hypocalcaemia.

Magnesium physiology

Magnesium is principally absorbed from the intestines and excreted by the kidneys.

Magnesium is absorbed in the intestines and excreted in the kidney via urine. Bone is the main reservoir of magnesium in the body, but exchange with serum concentrations is not freely accessible.

Intestinal absorption

The average daily intake of magnesium is 15 mmol, of which 5 mmol (one third) is absorbed and the rest is lost in the bowel. The principle site of absorption is the small bowel, but the colon can absorb a small amount.

Renal handling

The kidneys are the principle site of magnesium excretion via the urine. An estimated 80% of serum magnesium is filtered at the glomerulus. From here the principle site of reabsorption is the Loop of Henle in the thick ascending limb. 

  • Proximal tubule: 15% reabsorbed 
  • Distal tubule: 5-10% reabsorbed
  • Loop of Henle: 60-70% reabsorbed

Reabsorption of magnesium is by passive diffusion due to a favourable electrical gradient generated by the Na-K-2Cl cotransporter. Therefore, loop diuretics, which affect sodium and chloride reabsorption in the loop of Henle can affect magnesium reabsorption. Other diuretics such as thiazides also increase magnesium urinary excretion. 

Other factors that influence magnesium reabsorption in the nephron include:

  • Plasma magnesium concentration: this is the main influence on reabsorption and thus urinary excretion
  • Plasma calcium concentration: hypercalcaemia inhibits magnesium reabsorption
  • Others: hormones (e.g. parathyroid hormone, glucagon), electrolytes (e.g. hypokalaemia, hypophosphataemia)

Magnesium regulation

There are no major hormones that regulates magnesium and interaction with the magnesium stores in bone is slow. Therefore, a negative magnesium balance (e.g. from inadequate intake) quickly leads to hypomagnesaemia. 

As magnesium is reliant on urinary excretion for clearance, positive magnesium balance (e.g. intravenous infusion) in the context of renal impairment can leads to hypermagnesaemia.

Aetiology

Magnesium is predominantly lost from the gastrointestinal tract and kidneys.

Gastrointestinal loss

The predominant cause of hypomagnesaemia is reduced dietary intake leading to a negative magnesium balance. This is commonly seen in alcoholic or severely malnourished patients

Magnesium may be seen in both vomiting and diarrhoea. Diarrhoeal losses account for more cases as the lower gastrointestinal content contains a higher concentration of magnesium.

Rarely, an inherited disorder of magnesium absorption may be the cause. This is autosomal recessive or X-linked recessive.

Proton pump inhibitors

Hypomagnesaemia has been described in chronic use of proton pump inhibitors (PPI) such as omeprazole. Hypomagnesaemia in the context of PPI use is much more common with concurrent diuretic use. PPIs are suspected to inhibit the magnesium transport receptor TRPM6

Renal loss

There are multiple mechanisms by which magnesium can be lost in the urine:

  • Medications: Diuretics (loop and thiazide). Aminoglycosides (antibiotic). Amphotericin B (anti-fungal agent). Digoxin. 
  • Alcohol: alcohol has a direct tubular effect on magnesium reabsorption. Affect is minor, but alcoholics have multiple mechanisms for hypomagnesaemia that contribute collectively.
  • Post-transplantation: commonly seen in patients treated with calcineurin inhibitors (e.g. tacrolimus)
  • Hypercalcaemia: typically seen in hypercalcaemia secondary to hyperparathyroidism
  • Renal recovery following injury: may be seen during recovery of acute tubular necrosis or following post-obstructive diuresis
  • Inherited: numerous inherited conditions due to mutations in ionic channels can lead to hypomagnesaemia (e.g. Gitelman syndrome)

Clinical features

Hypomagnesaemia can lead to neuromuscular excitability.

Neuromuscular

  • Tremor
  • Tetany (muscle spasms)
  • Seizures
  • Weakness
  • Delirium
  • Coma

Cardiovascular

Hypomagnesaemia can affect the myocardium leading to dangerous atrial and ventricular arrhythmias. 

  • Palpitations
  • Chest pain

Calcium disorders

Features of hypocalcaemia may occur because it impairs the action of PTH leading to resistance and at higher levels reduced secretion. 

  • Paraesthesia (numbness and tingling sensation)
  • Tetany
  • CNS disturbance: Seizures, irritability, confusion
  • Cardiovascular disturbance: chest pain, palpitations
  • Trousseau's sign and Chvostek's sign

Other electorate disturbances

Hypokalaemia is seen in 40-60% of patients with hypomagnesaemia. This can be due to the shared aetiologies, but also normal levels of magnesium have an inhibitory effect on luminal potassium (ROMK) channels that prevent potassium efflux. 

In the absence of magnesium replacement, potassium replacement has limited effect.

Diagnosis & investigations

The diagnosis of hypomagnesaemia is based on a serum magnesium concentration <0.7 mmol/L.

Hypomagnesaemia is a common finding on routine testing. Patients presenting with a suggestive aetiology (e.g. alcohol excess, malnutrition, diarrhoea) need magnesium testing.

Hypomagnesaemia commonly occurs with other electrolyte abnormalities so it is important to collect a full set of blood tests. Urinary magnesium collections can be used to determine between renal and gastrointestinal losses, but this is seldom completed in clinical practice.

Bloods

  • FBC
  • U&Es
  • LFTs
  • Bone profile
  • Magnesium
  • +/- PTH (if hypocalcaemia present) 

ECG

Hypomagnesaemia typically causes an QT prolongation and increases the risk of atrial/ventricular ectopics, atrial tachycardias and polymorphic ventricular tachycardia.

Management

The management of hypomagnesaemia involves oral or intravenous replacement.

It is important to determine and treat the underlying cause. This includes reviewing the medical history for any culprit medications. Usually short courses of replacement are enough to replace deficit, but more extended courses may be needed.

Dosing

1 gram magnesium  = 4 mmol magnesium = 96 mg magnesium

Oral replacement

  • Magnesium glycerophosphate: 2 tablets (1 tablet = 4 mmol) three times a day
  • Magnesium aspartate: 6.5g sachet (1 sachet = 10 mmol) twice a day.

Common side-effects of oral magnesium replacement are abdominal discomfort and diarrhoea. Oral replacement may be poorly tolerated.

Intravenous replacement

Intravenous doses of magnesium are needed for severe or symptomatic hypomagnesaemia (e.g. seizures, tetany, arrhythmias). Intravenous magnesium replacement requires cardiac monitoring and the duration of administration depends on hospital policy and indication.

  • Magnesium sulphate: 2-5 g (1g = 4 mmol) in 100-250 mls of normal saline over 1-4 hours (always follow local policy and requires cardiac monitoring). Repeat doses can be given as necessary

Patients unable to tolerate oral preparations usually require intravenous administration. Care should be taken in patients with reduced renal function as it can lead to hypermagnesaemia.

Inefficiency of intravenous replacement

Intravenous magnesium greatly inhibits magnesium reabsorption from the Loop of Henle. This can lead to 50% of the intravenous magnesium load being excreted in the urine. Therefore, unless symptomatic, the oral route is preferred.

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