A. Introduction

1. Fourth most abundant cation in the body
2. Second most prevalent intracellular cation after potassium
3. Total body Mg ~23gm or ~1 mole
   1. Some 50-60% is in bone
   2. Extracellular (non-bone) Mg ~1% of total
   3. Remainder is intracellular
4. Normal serum levels are 0.7-0.9 mmol/L, or 1.6-2.2 mg/dL

B. Functions

1. Normal function of many enzymes
2. Complexed with ATP
   1. Critical in all ATP-enzyme interactions
   2. Involved in cellular energy metabolism
3. Essential for DNA and RNA synthesis
4. Membrane stabilization
5. Nerve conduction
6. Ion transport, particularly calcium channel activity
7. Deficiencies are most concerning, leading to abnormalities in any/all of above

C. Normal Physiology

1. Intracellular Mg level is the most critical parameter for normal function
2. Mg moves from intracellular to extracellular fluids
3. Total body Mg depends primarily on:
   1. Gatrointestinal absorption
   2. Renal excretion
4. Average daily intake of Mg is 300-350mg
5. Intestinal absorption occurs by:
   1. Saturable transport system
   2. Passive diffusion
6. Mg is filtered out in the kidney (along with other ions)
   1. About 100mg is filtered daily into the urine
   2. Very little reabsorption at the proximal tubule
   3. About 70% of Mg is reabsorbed in the thick ascending loop of Henle
   4. The remaining Mg is (optionally) reabsorbed in the distal tubule
   5. Major regulator of reabsorption is serum Mg2+ level itself
   6. Hypercalcemia and NaCl reaborption also affect Mg reabsorption

D. Causes of Hypomagnesemia

1. Most causes are iatrogenic
2. Particularly common in hospitalized (sick) patients
   1. Gastrointestinal Losses
   2. Renal Losses
   3. Drug Induced Losses
3. Gastrointestinal Losses
   1. Prolonged nasogastric suction
   2. Diarrhea
   3. Malabsorption syndromes
   4. Steatorrhea
   5. Short bowel syndrome
   6. Acute pancreatitis
   7. Severe malnutrition
   8. Intestinal fistulae
4. Renal Losses
   1. Parenteral fluid therapy
   2. Volume expanded conditions: heart failure, cirrhosis, nephrotic syndrome
   3. Hypercalcemia, hypercalciuria
   4. Osmotic diuresis: diabetes, mannitol
   5. Phosphate depletion
   6. Hungry-bone syndrome
   7. Correction of chronic systemic alkalosis
   8. Postobstructive Nephropathy (with diuresis)
   9. Kidney transplantation
   10. Primary renal tubular magnesium wasting
5. Drugs
   1. Diuretics: thiazide or loop type
   2. Aminoglycosides
   3. Antibiotics
   4. Amphotericin B
   5. Cisplatinum
   6. Cyclosporine
   7. Foscarnet
   8. Pentamidine

E. Manifestations of Hypomagnesemia

1. Systems Affected
   1. Neuromuscular
   2. Cardiovascular
   3. Metabolic
   4. Bone
2. Neuromuscular
   1. Trousseau and Dhvostek signs
   2. Carpopedal spasm
   3. Seizures
   4. Vertigo
   5. Ataxia
   6. Depression
   7. Psychosis
3. Cardiovascular
   1. Widened QRS complex
   2. Prolonged PR interval
   3. T wave inversion
   4. U wave (mainly with hypocalcemia)
   5. Increased sensitivity to digitalis and other cardiac glycosides
   6. Hypokalemia associated problems
4. Metabolic
   1. Carbohydrate intolerance
   2. Hyperinsulinemia
   3. Atherosclerosis
   4. Hypokalemia - both increased renal wasting and reduction in intracellular K+ levels [2]
5. Bone
   1. Osteoporosis
   2. Osteomalacia

F. Treatment

1. Depends on severity
2. When possible, oral intake is preferred over intravenous
3. IV dosing required for arrhythmias, seizures or severe neuromuscular signs
4. May give 4-8 mmol bolus, with 25 mmol in 24 hours total
5. Oral tablets can be used, and provide ~3mmol per tablet
6. In general, 5-8 tablets can be given in a 24 hour period

G. Hypermagnesemia

1. Nearly always iatrogenic
2. Manifestations
   1. Hypotension
   2. Bradycardia
   3. ECG abnormalities
   4. Respiratory depression
   5. Altered mental status

References

1. Weisinger JR and Bellorin-Font E. 1998. Lancet. 352(9125):391
2. Gennari FJ. 1998. NEJM. 339(7):451