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General Considerations
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Magnesium is the second most abundant intracellular cation and the fourth most common cation in the human body. It plays an essential role in a variety of cellular processes including enzyme activities involving adenosine triphosphate (ATP), energy metabolism, nucleic acid and protein synthesis, regulation of ion channels, and stabilization of membrane structures. The importance of magnesium in the body is reflected in the diverse clinical effects that accompany disorders of magnesium homeostasis. The average size adult contains approximately 24 g (1 mol, 2000 mEq) of magnesium. It is predominantly stored in bone (55–60%) and the intracellular compartments of muscle (20%) and soft tissues (20%) and it exchanges very slowly with extracellular magnesium. Therefore, skeletal and intracellular magnesium is an ineffective buffer in the setting of acute extracellular magnesium loss.
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Approximately 1% of total body magnesium is in the extracellular fluid (ECF) and is composed of three fractions: 60–65% is free, ionized, and physiologically active; 30% is protein bound; and the balance is complexed to citrate, phosphate, and other anions. In clinical practice, magnesium status is assessed by measurement of total serum magnesium. Serum magnesium concentrations normally average 1.7–2.3 mg/dL (1.4–2.1 mEq/L). Given the intracellular nature of this cation, serum magnesium concentrations poorly reflect total body status.
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Daily magnesium intake in the typical American diet averages 300–360 mg/day. Food sources of magnesium include green vegetables, nuts, and whole grains, as well as some meats and seafood. Of dietary magnesium 30–40% is absorbed in the gut, primarily by the small intestine, with smaller amounts being absorbed in the colon. There is some magnesium in intestinal secretions (approximately 20–40 mg), but under normal circumstances their contribution to overall magnesium elimination is minimal. However, these losses can become quite substantial in diarrheal states or with biliary fistulas.
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The kidney is the main organ responsible for magnesium homeostasis. Approximately 70–80% (2.4 g) of the total serum magnesium is filtered by the kidneys. Under normal circumstances 95–97% is reabsorbed by the tubules. The plasma magnesium concentration is the most important determinant of renal magnesium excretion. Less than 5% (120 mg) is normally excreted in urine. However, hypomagnesemia results in conservation of magnesium by normal kidneys leading to a fractional excretion of less than 0.5% (12 mg) per day. Conversely, the kidneys increase excretion of magnesium to approximate the filtered load during periods of increased intake or excess magnesium administration.
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In contrast to many of the other electrolytes (ie, Na+, K+, and Ca2+), control of magnesium reabsorption does not appear to be tightly regulated by a specific hormone. Parathyroid hormone, calcitonin, vitamin D, glucagon, antidiuretic hormone, aldosterone, sex steroids, and β-adrenergic agonists can affect magnesium handling in experimental studies, but it is not known if these effects have an important role in humans.
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While the proximal tubule is the major site of reabsorption of other ions, ...