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Hypomagnesemia

Hypomagnesemia is defined as a serum magnesium level below 1.7 mg/dL.

Most patients with borderline hypomagnesemia are asymptomatic.

Hypomagneemia is present 3 to 10% of the general population and its prevalence is increased among individuals with type two diabetes and hospitalized patients, especially those in the ICU.

Hypomagnesia is associated with an elevated risk of death from any cause and death from cardiovascular causes.

May cause hypocalcemia, paresthesias, and seizures.

Hypomagnesemia can lead to hypocalcemia as it interferes with the action of parathormone. 

More than 60% of the body’s  magnesium stores reside in bone, and nearly 70% of serum magnesium circulates freely, not bound to plasma proteins.

Unbound in magnesium is freely filtered at the glomerulus and it enters the tubules where more than 95% of filtered magnesium is reabsorbed by the kidneys.
Magnesium is reabsorbed primarily at the ascending loop of Henle, and the last site of regulation is the distal convoluted tubule, were a positive lumen potential is required for reabsorption paracellularly.

Can be responsible for neurological, respiratory and cardiovascular symptoms.

Hypomagnesemia is seen in 2% of the general population, 10-20% in hospitalized patients, 50-60% in intensive care unit patients, 60-80% of alcoholics, and 25% of diabetics.

Associated with impaired intake in alcoholics, undernourished, with intestinal malabsorption syndrome, prolonged vomiting and with the use of nasogastric tubes and in ICU setting.

Hypomagnesemia may result from inadequate dietary intake, increased gastrointestinal, loss, reduced renal reabsorption, or redistribution of magnesium from the extracellular to the cellular space.

Excessive renal losses seen with loop diuretics, thiazide and saline infusions, and interstitial nephritis.

In patients with heart failure, the critically ill, and patients recently undergoing dialysis is associated with the high mortality rate.

Hypomagnesemia is the most common electrolyte abnormality associated with chronic alcohol use disorder.

The mechanism of hypomagnesemia with alcoholism includes decreased magnesium intake in malnourished individuals, increased G.I. losses and alcohol induced renal tubular damage.

Hypomagnesemia in alcohol use disorder is often associated with liver dysfunction and worse prognosis.

For every 0.49 mg of deciliter serum reduction there is a 30% increase in cardiovascular disease.

Hypomagnesemia confers a predisposition to electrical irritability/arrhythmias, including atrial fibrillation, torsades de pointes and long QT syndrome.

Low magnesium levels are associated with endothelial dysfunction, vascular contraction, increased vascular tone and vascular  fibrosis all characteristic features of hypertension.

Low serum magnesium levels are associated with an increased incidence of hospitalization and increased mortality, especially when associated with concurrent hypokalemia.

Seen with hyperaldosterone states such as primary hyperaldosteronism, cirrhosis, congestive heart failure and fluid depletion.

Can be seen with osomotic diuresis associated with diabetes mellitus.

Hypomagnesemia is common in type two diabetes with renal magnesium wasting and increased albumin binding in the blood.

Insulin resistance results in increased renal magnesium reabsorption, and increased magnesuria..

Seen with nephrotoxic drugs cisplatin, amphotericin, aminoglycoside antibiotics.

Associated with hypokalemia, hypercalcemia and hypercalciuria.

Associated with lesions of the proximal tubules, such as Fanconi’s disease and interstitial nephritis.

Magnesium absorbed in the small intestine, mainly in the ileum, via active and passive transport mechanisms.

Magnesium excreted in the stool and urine.

Regulation of serum levels of magnesium under renal control.

Most renal absorption of magnesium occurs in the proximal tubule and the ascending limb of the loop of Henle.

Magnesium in the presence of hypomagnesememia the kidney may excrete as little as 1 mEq/L.

Magnesium in times of deficiency may be removed from bone.

Low blood magnesium makes spontaneous cardiac muscle depolarization more likely.

Hypomagnesemia is sometimes caused by the proton-pump inhibitor (PPI) inhibitors.

Hypomagnesemia is usually associated with other electrolyte derangements, including hypocalcemia, hypokalemia, and metabolic alkalosis.

Only in severe cases of hypomagnesemia with serum levels of less than 1.2 mg/dL do symptoms, such as neuromuscular irritability, cardiovascular abnormalities and metabolic disorders become evident.

Treatment depends on the degree of deficiency and the clinical status.

Non-Renal hypomagnesaemia:
Redistributive such as refeeding or insulin therapy
Reduced magnesium intake
Reduced gastrointestinal absorption as with proton pump inhibitors
Alcohol use
Diabetes
 Renal wasting hypomagnesaemia:
Diuretics
Antimicrobials as with amphotericin B, aminoglycosides
Calcineurin Inhibitors as with cyclosporine, tacrolimus
Epidermal growth factor receptor inhibitors cetuximab
 
 Cytotoxic drugs as with cis-platinum, carboplatinum
Hypercalcemia
Hyperthyroidism
Hyperparathyroidism
Alcohol use
Diabetes
In evaluating hypomagnesaemia, the initial step is to differentiate renal versus non-renal losses using urine magnesium testing.
24 hour urine magnesium levels are recommended as spot urines for magnesium very with diet, diurnal circadian rhythm, and because the 24 hour measure allows an assessment of daily urine volume.
Renal magnesium wasting is defined as a fraction excretion of magnesium greater than 4%, or a daily urinary magnesium excretion of more than 1 mmol per day.
24 hour urine creatinine is estimated to be 15 mg per kilogram per deciliter in females and 20 mg per kilogram per day in males.
Polyuria is a common cause of renal magnesium wasting with increased urinary transit time, reducing the contact time of electrolytes and tubular epithelial cells, attenuating the ability to establish a transepithelial voltage gradient and reducing the tubular reabsorption of magnesium.

Oral replacement is appropriate for a mild process, while IV replacement is indicated for severe clinical disease.

Mild hypomagnesemia is managed with oral supplements which are most effectively absorbed as organic salts rather than inorganic salts.

A common side effect of oral magnesium supplementation is diarrhea.

Impaired renal function may increase toxicity of magnesium administration.

Diarrhea is most common adverse effect of oral magnesium.

In resistant cases pharmacological inhibition of the epithelium sodium channel with amiloride or triamterene in patients with normal renal function,increases serum magnesium.

Sodium glucose cotransporter type 2 increases serum magnesium levels, especially in diabetics.

Intravenous therapy is with 2-4 g of 50% magnesium sulfate diluted in saline or dextrose IV over 30-60 minutes, is indicated impatience with hyper magnesia that is refractory oral treatment.

In cases of life-threatening arrhythmias intravenous push of the magnesium sulfate is appropriate.

Intravenously administered magnesium may alter cardiac conduction, leading to heart block in digitalized patients decrease respiratory rate, impair deep tendon reflexes.

Renal function should be monitored when magnesium is administered parenterally.

Administering magnesium intravenously may produce significant hypertension or asystole.

If an overdose occurs, calcium gluconate, 10-20 mL of 10% solution IV, can be given as antidote for hypermagnesemia.

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