eMedicine Specialties > Pediatrics: General Medicine > Endocrinology

Hypomagnesemia

Author: James E Springate, MD, Associate Professor of Pediatrics, State University of New York at Buffalo; Attending Physician, Department of Pediatrics, Division of Pediatric Nephrology, Women & Children's Hospital of Buffalo
Coauthor(s): Gunjeet K Kala, MD, Clinical Instructor, Division of Pediatric Nephrology, University of Buffalo State University of New York School of Medicine and Biomedical Sciences, Women and Children's Hospital of Buffalo
Contributor Information and Disclosures

Updated: Sep 18, 2009

Introduction

Background

Magnesium (Mg) is the second-most abundant intracellular cation and, overall, the fourth-most abundant cation. Almost all enzymatic processes using phosphorus as an energy source require magnesium for activation. Magnesium is involved in nearly every aspect of biochemical metabolism (eg, DNA and protein synthesis, glycolysis, oxidative phosphorylation). Almost all enzymes involved in phosphorus reactions (eg, adenosine triphosphatase [ATPase]) require magnesium for activation. Magnesium serves as a molecular stabilizer of RNA, DNA, and ribosomes. Because magnesium is bound to ATP inside the cell, shifts in intracellular magnesium concentration may help regulate cellular bioenergetics such as mitochondrial respiration.

Extracellularly, magnesium ions block neurosynaptic transmission by interfering with the release of acetylcholine. Magnesium ions also may interfere with the release of catecholamines from the adrenal medulla. Magnesium has been proposed as an endogenous endocrine modulator of the catecholamine component of the physiologic stress response.

The total body content of magnesium in adults is about 2,000 mEq or 24 g. No data are available for children. Approximately 60% of total body magnesium is located in bone and the remainder is in the soft tissues. This soft tissue intracellular compartment comprises about 38% of total body magnesium; relatively higher concentrations are found in skeletal muscle and liver. Because less than 2% is present in the extracellular fluid (ECF) compartment, serum levels do not necessarily reflect the status of total body stores.

Serum concentration typically ranges from 1.8-2.5 mEq/L. Approximately a third of this is protein-bound. Analogous to plasma calcium, the free (ie, unbound) fraction of magnesium is the active component. No accurate method exists to assess ionized serum magnesium.

Magnesium is primarily absorbed in the small intestine at a rate ranging from 34 -3% of dietary intake. Absorption occurs primarily in the jejunum and ileum via ionic diffusion (passive) and at low concentrations through active transport processes. The sigmoid colon also has some capacity for magnesium absorption. A minimal daily intake of 0.3 mEq/kg of body weight has been suggested to prevent deficiency. Infants and children tend to have higher daily requirements.

The kidney is an important regulator of magnesium homeostasis. Magnesium elimination is predominantly renal; in adults, approximately 2.5 g of magnesium is filtered daily, 96% of which is reclaimed along the nephron. The threshold for urinary excretion is near the normal serum concentration. Thus, when serum levels rise above 2.5 mEq/L, magnesium excretion dramatically increases. Conversely, the kidney retains a strong capacity to reabsorb magnesium when serum levels fall. The main site for reabsorption is the thick ascending loop of Henle (70% of filtered load). Movement of magnesium in this nephron segment is passive and affected by both the lumen-positive transepithelial voltage as well as the highly negatively charged tight junction protein claudin-16, formerly known as paracellin-1. Active reabsorption of magnesium occurs in the distal convoluted tubule (5-10% of filtered load).

Pathophysiology

Hypomagnesemia is widespread among hospitalized patients and has been reported in as many as 60% of ICU patients.¹ Prolonged administration of magnesium-free parenteral fluids may be a contributing factor. In general, the etiology of hypomagnesemia is usually a result of either renal or GI losses.

Renal causes are related to either primary tubular defects in reabsorption or disorders of tubular sodium reabsorption. These disorders include Gitelman syndrome and familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Effects of certain disease states or medications include diabetes, postobstructive diuresis, diuretic phase of acute tubular necrosis, loop or thiazide diuretics, cisplatin, aminoglycosides, pentamidine, foscarnet, tacrolimus, and cyclosporine A. The incidence of hypomagnesemia among people with alcohol dependence is approximately 25% and is mainly due to magnesium dieresis caused by alcohol. Severe hypomagnesemia may occur during the recovery phase of diabetic ketoacidosis. Patients with diabetes who have chronically poor glycemic control may have a total body magnesium deficit, possibly caused by ineffective insulin-mediated cellular uptake of magnesium as well as osmotic diuresis from glucosuria.²

GI causes are often related to prolonged nasogastric suction, infectious diarrhea, steatorrhea, inflammatory bowel disease, intestinal fistulas, malnutrition, primary infantile hypomagnesemia (autosomal recessive disease), and intestinal neoplasms.

Frequency

United States

Although the incidence of hypomagnesemia in the general population has been estimated at less than 2%, some studies have estimated that 75% of Americans do not meet the recommended dietary allowance of magnesium.³

Age

Although no comprehensive studies have addressed the actual incidence of hypomagnesemia stratified by age group, neonates may be more predisposed to develop hypomagnesemia. The mechanism for this is unknown, although several studies suggest that neonates have an increased requirement for intracellular magnesium in growing tissues.

Clinical

History

Magnesium deficiency and hypomagnesemia are often asymptomatic. Severe symptomatic hypomagnesemia may manifest clinically as tetany and generalized seizures. Early manifestations may include muscle cramps, nausea, vomiting, and lethargy.

At least 10 inherited disorders of magnesium handling cause hypomagnesemia.⁴ A careful family history is important, particularly when acquired causes of hypomagnesemia have been excluded.

Physical

At serum magnesium levels less than 1 mEq/L, patients have tremor, hyperactive deep-tendon reflexes, hyperreactivity to sensory stimuli, muscular fibrillations, positive Chvostek and Trousseau signs, and carpopedal spasms progressing to tetany. Mental status changes may become evident and may include irritability, disorientation, depression, and psychosis. Cardiac arrhythmias and reversible respiratory muscle failure can also occur in severe hypomagnesemia.

In a fashion analogous to hypermagnesemia, the rate of development of hypomagnesemia may be more important than the absolute value in terms of symptom development.

Causes

Major causes of magnesium deficiency include the following:

• GI disorders
  • Long-term parenteral fluid therapy without supplementation
  • Prolonged nasogastric suction/vomiting
  • Diarrhea
  • Malabsorption syndromes
  • Extensive bowel resection
  • Intestinal or biliary fistulas
  • Acute pancreatitis
• Renal disorders
  • Osmotic diuresis (eg, diabetes mellitus)
  • Hypercalcemia
  • Medications (eg, diuretics, aminoglycosides, calcineurin inhibitors)
  • Alcohol
  • Postobstructive diuresis
  • Diuretic phase of acute tubular necrosis
  • Inherited tubular diseases (eg, Gitelman syndrome, familial hypomagnesemia with hypercalciuria/nephrocalcinosis)

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