eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Hypomagnesemia
Updated: May 5, 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.1 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.2
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.
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.
Less than 40% of dietary magnesium is absorbed throughout the small intestine (predominantly in the ileum) and in the colon. 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.
Elimination is predominantly renal. The threshold for urinary excretion is near the normal serum concentration. Thus, when serum levels rise above 2.5 mEq/L, magnesium excretion increases dramatically. Conversely, the kidney retains a strong capacity to resorb magnesium, and the main site for reabsorption is the thick ascending loop of Henle.
(A) Magnesium reabsorption in the thick ascending limb of the loop of Henle. The driving force for the reabsorption against a concentration gradient is a lumen-positive voltage gradient generated by the reabsorption of NaCl. FHHNC = Familial hypomagnesemia with hypercalciuria and nephrocalcinosis. ADH = autosomal dominant hypocalcemia. FHH/NSHPT = Familial hypomagnesemia/neonatal severe hyperparathyroidism. (B) Magnesium reabsorption in the distal convoluted tubule. Active transcellular transport is mediated by an apical entry through a magnesium channel and a basolateral exit, presumably via a Na+/Mg2+ exchange mechanism. HSH = Hypomagnesemia with secondary hypocalcemia. GS = Gitelman syndrome. IDH = Isolated dominant hypomagnesemia. Source: Konrad M, Schlingmann KP, Gudermann T: Insights into the molecular nature of magnesium homeostasis. Am J Physiol Renal Physiol 2004; 286: F599-F605.
Several factors may impair renal reabsorption, such as volume expansion, ethanol ingestion, hypercalcemia,3 and diuretic administration (eg, osmotic, thiazide, loop). Of these 3 types of diuretics, loop diuretics have the greatest effect on renal magnesium wasting because of their site of action.4
Pathophysiology
Hypomagnesemia is widespread among hospitalized patients. Hypomagnesemia has been reported in as many as 60% of ICU patients. Prolonged administration of magnesium-free parenteral fluids may be a contributing factor. Prolonged nasogastric suction, infectious diarrhea, steatorrhea, inflammatory bowel disease, and GI neoplasms may cause hypomagnesemia. A congenital defect in GI magnesium absorption has also been described.
Incidence of hypomagnesemia among people with alcohol dependence is approximately 25% and mainly is due to magnesium diuresis caused by alcohol.
Several drugs can cause increased urinary loss of magnesium. Magnesium deficiency is especially common in patients receiving furosemide diuretics, but all diuretics play a role. A congenital defect in tubular reabsorption of magnesium has also been described.
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.5
Frequency
United States
Although the incidence of hypomagnesemia in the general population has been estimated at less than 2%, hospitalized patients are more prone to develop hypomagnesemia. Exact inpatient incidence is unknown. Recent studies of ICU patients have estimated frequencies in that setting as high as 60%.
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
Symptomatic hypomagnesemia may manifest clinically as CNS and neuromuscular hyperexcitability. Early manifestations may include painful muscle cramps, nausea, vomiting, and lethargy.
Physical
At serum magnesium levels less than 1 mEq/L, patients with hypomagnesemia may 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 include irritability, disorientation, depression, and psychosis. Reversible respiratory muscle failure may occur in severe hypomagnesemia.
In an analogous fashion to hypermagnesemia, the rate of development of hypomagnesemia may be more important than the absolute value in terms of symptom development.
More on Hypomagnesemia |
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| Differential Diagnoses & Workup: Hypomagnesemia |
| Treatment & Medication: Hypomagnesemia |
| Follow-up: Hypomagnesemia |
| Multimedia: Hypomagnesemia |
| References |
| Further Reading |
| Next Page » |
References
Inui D, Yamaguchi H, Nakataki E, Oto J, Imanaka H, Nishimura M. [A case of severe convulsion induced by hypophosphatemia and hypomagnesemia]. Masui. Feb 2009;58(2):212-4. [Medline].
Forest A, Lemaire A, Boddaert J, Verny M. [Effects of hypomagnesemia.]. Rev Med Interne. Apr 15 2009;[Medline].
Apa H, Kayserili E, Agin H, Hizarcioglu M, Gulez P, Berdeli A. A case of hypomagnesemia with secondary hypocalcemia caused by Trpm6 gene mutation. Indian J Pediatr. Jun 2008;75(6):632-4. [Medline].
Yalavarthy R, Parikh CR. Instructive case. An instructive case of severe hypomagnesemia. Nephrology (Carlton). Oct 2008;13(7):657-8. [Medline].
Curiel-García JA, Rodríguez-Morán M, Guerrero-Romero F. Hypomagnesemia and mortality in patients with type 2 diabetes. Magnes Res. Sep 2008;21(3):163-6. [Medline].
Knochel JP. Disorders of Magnesium Metabolism. Harrison's Principles of Internal. 1994;2:2187-2189. [Medline].
Nadler JL, Rude RK. Disorders of Magnesium Metabolism. Clinical Disorders of Fluid and Electrolyte Metabolism. 1995;24:623-637. [Medline].
Reinhart RA. Magnesium metabolism. Archives of Internal Medicine. 1988;148:2415-2420. [Medline].
Rodriguez-Hernandez H, Gonzalez JL, Rodriguez-Moran M, Guerrero-Romero F. Hypomagnesemia, insulin resistance, and non-alcoholic steatohepatitis in obese subjects. Arch Med Res. Jul-Aug 2005;36(4):362-6. [Medline].
Rude RK, Singer FR. Magnesium deficiency and excess. Ann Rev Med. 1981;32:245-259. [Medline].
Tong GM, Rude RK. Magnesium deficiency in critical illness. J Intensive Care Med. Jan-Feb 2005;20(1):3-17. [Medline].
Topf JM, Murray PT. Hypomagnesemia and hypermagnesemia. Rev Endocr Metab Disord. May 2003;4(2):195-206. [Medline].
Further Reading
- Relevant clinical guidelines include the following:
- Atrial fibrillation
- Advanced life support: 2005 International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations
- Management of alcohol withdrawal delirium: An evidence-based practice guideline
- European Federation of Neurological Societies guidelines on management of neurological problems in liver transplantation
- Relevant clinical trials include the following:
- Related eMedicine topics include the following:
- Hypomagnesemia (Nephrology)
- Hypomagnesemia (Emergency Medicine)
- Hypoparathyroidism
- Hypermagnesemia
- Infant of Diabetic Mother
Keywords
hypomagnesemia, magnesium, Mg, subnormal serum magnesium, infectious diarrhea, steatorrhea, inflammatory bowel disease, GI neoplasms, diabetic ketoacidosis, irritability, disorientation, depression, psychosis, treatment, diagnosis, low magnesium levels
