Magnesium Disorders

Question 1

Magnesium Background

Answer 1

Second most abundant intracellular and fourth most abundant cation in body 70% to 80% exists as free ionized Mg2+ and 20% to 30% as protein-bound or complexed

Question 2

Magnesium Background Physiological Functions of Magnesium

Answer 2

Serves as cofactor for all enzymatic reactions requiring ATP (ATP-ase) “kinases” Enzyme activator for neuromuscular excitability and cell permeability

Question 3

Magnesium Background Physiological Functions of Magnesium

Answer 3

Regulator of ion channels and mitochondrial function Critical element in cellular proliferation and apoptosis Important factor in both cellular and humoral immune reactions

Question 4

Magnesium Background Magnesium Metabolism

Answer 4

Input: GI absorption: a. Passive paracellular absorption when there is a high concentration gradient between intestinal lumen and epithelial cells b. Active transport via transient receptor potential melastatin channel TRPM6 in large intestines where there is a low intraluminal magnesium content. TRPM6 is also present in the distal convoluted tubules in the kidneys where it determines the final urinary magnesium loss. 1. Autosomal recessive mutation of TRPM6 is associated with hypomagnesemia with secondary hypocalcemia. Hypomagnesemia results from both poor GI absorption and urinary loss. 2. Affected individuals may present with seizures/tetany perinatally. 3. Treatment is high-dose oral administration of magnesium sulfate for absorption via passive paracellular pathway.

Question 5

Magnesium Background Magnesium Metabolism

Answer 5

Cellular shift, redistribution: a. Bones are the principal reservoirs of Mg2+ and do not readily exchange with extracellular Mg2+. In negative Mg2+ balance, bone Mg2+ shift into plasma does not occur for weeks. Acute maintenance of plasma Mg2+ relies on renal reabsorption. b. Cellular influx increases with catecholamines, refeeding syndrome, treatment of metabolic acidosis, hungry bone syndrome seen after parathyroidectomy or in patients with diffuse osteoblastic metastases. c. Redistribution: Mg2+ deposition in necrotic tissues, for example, acute pancreatitis

Question 6

Magnesium Background Magnesium Metabolism

Answer 6

Output: a. There is a physiologic GI magnesium loss of ~40 mg/d from pancreatic and salivary secretions. b. GI loss: chronic diarrhea, steatorrhea c. Renal loss

Question 7

Renal Metabolism of Magnesium

Answer 7

Glomerular filtration: 70% to 80% of plasma Mg2+ is ultrafilterable in the ionic form. Ultrafilterability of Mg2+ is dependent on glomerular filtration, volume and acid–base status, serum content of anions, and glomerular basement membrane integrity

Question 8

Renal Metabolism of Magnesium

Answer 8

Question 9

Renal Metabolism of Magnesium

Answer 9

Proximal tubules: 15% to 25% is reabsorbed, mainly passive, and proportional to Na+ and H2O reabsorption

Thick ascending limb loop of Henle (TALH):

a. 65% to 75% is reabsorbed paracellularly. Recall this is facilitated by the positively charged lumen created via K+ recycling through ROMK and the tight junction protein claudin 16 (CLD) + CLD19 (See Bartter and Gitelman Syndromes)
b. Mutation of CLD16 or CLD19 is associated with severe hypomagnesemia, hypercalciuria, and nephrolithiasis.

Question 10

Renal Metabolism of Magnesium

Answer 10

Distal convoluted tubules: 5% to 10% of total filtered Mg2+ (or 70% to 80% of Mg2+ delivered from TALH) is reabsorbed via TRPM6. Mg2+ reabsorption may be facilitated by the positive intraluminal voltage created by K+ secretion via Kv1.1 and the negative intracellular voltage created by Na+/K+exchange via 3Na+-2K+-ATPase. Binding of epidermal growth factor (EGF) to its receptor in DCT induces shuttling of cytoplasmic TRPM6 to the apical cell surface for efficient Mg2+ reabsorption

Question 11

Renal Metabolism of Magnesium

Answer 11