Disorders of Magnesium

Dr Ibrahim Shiham, MD DM Nephrology Resident NAMS, July 2011

Introduction - Magnesium

Magnesium is an important constituent of intracellular fluid where it affects a number of cellular and whole body functions. It participates in more than 300 enzymatic reactions, especially those processes involving the production and utilization of adenosine triphosphate (ATP).
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About two-thirds of the body's magnesium is located in the skeleton and one-third is in the intracellular fluid; only about 1% is in the extracellular fluid (0.3% in the serum). About one-third of the magnesium in serum is bound to proteins; the rest is ionized. Normal Serum Magnesium is expressed as : 1.3-2.1 mEq/L, 0.65-

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Hypomagnesemia and Magnesium Deficiency The terms hypomagnesemia and Mg2+ deficiency tend to be used interchangeably. However, there is a complex relationship between total body Mg2+ stores, serum Mg2+ concentrations, and the Mg2+ level in different intracellular compartments. With extracellular fluid Mg2+ accounting for only 1% of total body

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Etiology and Diagnosis

Mg2+ deficiency may be caused by:
1.

2.

3.

decreased intake or intestinal absorption; increased losses via the GI tract, kidneys, or skin; or rarely, sequestration in the bone compartment The first step in determining the etiology is to distinguish between renal Mg2+ wasting and extrarenal causes of Mg2+ loss by performing

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Nutritional Deficiency Mg2+ deficiency by dietary means in normal individuals is surprisingly difficult because nearly all foods contain significant amounts of Mg2+ and renal adaptation to conserve Mg2+ is very efficient. Nevertheless, Mg2+ deficiency of nutritional origin can be observed, particularly in two clinical settings: alcoholism and parenteral feeding.
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EXTRARENAL CAUSES hypomagnesemia

Redistribution To Bone Compartment Hypomagnesemia may occasionally accompany the profound hypocalcemia of hungry bone syndrome observed in some patients with HPT and severe bone disease immediately after parathyroidectomy. In such cases, a high bone turnover state exists, and sudden removal of excess PTH is believed to result in virtual cessation of bone resorption, with a continued high rate of bone formation and consequent sequestration of both Ca2+ and Mg2+ into bone mineral. Renal Magnesium Wasting The diagnosis of renal Mg2+ wasting is made by demonstrating an inappropriately high rate of renal Mg2+ excretion in the face of hypomagnesemia. Polyuria Renal Mg2+ wasting occurs with osmotic diuresis, as in the severe hyperglycemic state of diabetic ketoacidosis. Extracellular Fluid Volume Expansion Chronic therapy with Mg2+-free parenteral fluids, either
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Renal Magnesium Wasting continued Defective Na Reabsorption in Distal Nephron Loop diuretics inhibit the apical membrane Na+/K+/2Cl- cotransporter of the TAL and abolish the transepithelial potential difference, thereby inhibiting paracellular Mg2+ reabsorption. Hypomagnesemia is therefore a frequent finding in patients receiving chronic loop diuretic therapy.
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Clinical Manifestations of Hypomagnesemia

Cardiac Neuromuscular Metabolic Hypokalemia Non-specific T wave changes Muscle weakness U waves Prolonged QT and QU interval Repolarization alternans Ventricular ectopy Monomorphic ventricular tachycardia Torsades de pointes Ventricular fibrillation Enhanced digitalis toxicity Positive Trousseau and Chvostek signs Tetany Vertical and horizontal nystagmus Paresthesias Generalized seizures Multifocal motor seizures
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Muscle tremor and twitching Hypocalcemia

Prevention of Hypomagnesemia

Mg2+ deficiency may sometimes be prevented. Individuals whose dietary intake has been reduced or who are being maintained by parenteral nutrition should receive Mg2+ supplementation. The recommended daily allowance of Mg2+ in adults is 420 mg (35 mEq) for men and 320 1010 mg (27 mEq) for women.

Treatment of Hypomagnesemia

It seems prudent to replete all Mg2+-deficient patients with a significant underlying cardiac or seizure disorder, patients with concurrent severe hypocalcemia or hypokalemia, and patients with isolated asymptomatic hypomagnesemia if it is severe (1.4 mg/dL).
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Intravenous Replacement

Treatment of Hypomagnesemia
Oral Replacement Oral Mg2+ administration is used either initially for repletion of mild cases of hypomagnesemia or for continued replacement of ongoing losses in the outpatient setting after an initial course of intravenous repletion. Potassium-Sparing Diuretics In patients with inappropriate renal 1212

Hypermagnesemia
Etiology In states of body Mg2+ excess, the kidney has a very large capacity for Mg2+ excretion. Once the apparent renal threshold is exceeded, most of the excess filtered Mg2+ is excreted unchanged into the final urine; the serum Mg2+ concentration is then determined by the GFR.

Thus, hypermagnesemia generally 1313

Etiology - hypermagnesemia
Renal Insufficiency In chronic renal failure, the remaining nephrons adapt to the decreased filtered load of Mg2+ by markedly increasing their fractional excretion of Mg2+. Thus serum Mg2+ levels are usually well maintained until the creatinine clearance falls below about 20 mL/min. Even in advanced renal insufficiency, significant hypermagnesemia is rare unless the patient has received exogenous Mg2+ in the form of antacids, cathartics, or enemas

Excessive Mg2+ Intake Hypermagnesemia can occur in individuals with a normal GFR when the rate of Mg2+ intake exceeds the renal excretory capacity. It has been reported with excessive oral ingestion of Mg2+-containing antacids and cathartics and with the use of rectal Mg sulfate enemas and is common with large parenteral doses of Mg2+, such as those given for preeclampsia. Toxicity from enterally administered Mg2+ salts is particularly common in patients with inflammatory disease, obstruction, or perforation of the gastrointestinal tract

Miscellaneous Modest elevations in serum Mg2+ (less than 4 mEq/L) have occasionally been described in patients receiving lithium therapy, as well as in postoperative and in those with bone metastases, milk-alkali syndrome, FHH, hypothyroidism, pituitary dwarfism, and Addison disease.

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Mg2+ toxicity is a serious and potentially fatal condition. Progressive hypermagnesemia is usually associated with a predictable sequence of symptoms and signs. Initial manifestations, observed once the serum Mg2+ level exceeds 4 mg/dL to 6 mg/dL, are hypotension, nausea, vomiting, facial flushing, urinary retention, and ileus.
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Clinical Manifestations of Hypermagnesemia

Treatment of Hypermagnesemia

Mild cases of Mg2+ toxicity in individuals with good renal function may require no treatment other than cessation of Mg2+ supplements because renal Mg2+ clearance is usually quite rapid. In the event of serious toxicity, particularly cardiac toxicity, temporary antagonism of the effect of Mg2+ may be achieved by the 1616 administration of intravenous Ca2+

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