Question 19

College Answer

Insufficient breadth and depth of knowledge limited candidates’ performance to this question. Candidates were expected to mention normal plasma (0.7 – 1.1 mmol/l) and intracellular (20mmol/l) levels, distribution (approximately 50% of total body magnesium is in bone & 20% in skeletal muscles), clearance (almost solely renal, approaches GFR, renal threshold set at just above normal serum Mg concentration, below which get almost  complete reabsorption), activity (e.g. co-factor in metabolism), effects on muscles (reduces muscle excitability, inhibits excitation-contraction coupling, reduced contractility / weakness / depressed reflexes), effects on nerves (e.g. reduces nerve excitability, blocks NMDA receptors), systemic and coronary vasodilation and inhibits platelet function.

Discussion

• Distribution
  • Total: 5 mmol/kg.  60%  in bone, 39% is intracellular, 1% is extracellular.
  • Normal intracellular concentration 15-20 mmol/L, extracellular 0.7-1.1 mmol/L
  • In the plasma:
    • 40% is protein-bound (just like calcium)
    • 5-10% is complexed with phosphate lactate citrate, just like calcium
    • about 50-55% is available as free biologically active ion. 
• Intake
  • 90% paracellular absorption; 10% saturable active transport
  • 30% of dietary magnesium is absorbed in the intestine
  • More is absorbed in states of magnesium depletion
• Intracellular/extracellular balance
  • Intracellular pool is tightly regulated
  • Extracellular magnesium is exchanged mainly with bone
• Elimination
  • ​​​​​​​Free magnesium ions are ultrafiltered at the glomerulus
  • 10–15% of the filtered magnesium is reabsorbed in the proximal tubule
  • 60–70% is reabsorbed in the thick ascending limb of the loop of Henle
  • 10-15% is reabsorbed in the distal convoluted tubule
  • DCT process is actively regulated by plasma Mg²⁺ concentration; reabsorption is near-total at normal magnesium levels, and decreases in hypermagnesemia
• Physiological function
  • ​​​​​​​Enzyme function: membrane-bound ATPases, kinases, alk phos., enolase
  • Membrane function: cell adhesion, Transmembrane electrolyte flux
  • Structural function: protein folding, polyribosomes, nucleic acids
  • Calcium antagonist: muscle contraction/relaxation, neurotransmitter release (NMDA), action potential conduction, vasodilation/relaxation of smooth muscle
  • Bone metabolism (affects the function of parathyroid hormone)

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