Question 20

College Answer

The answer structure should have utilized the headings provided in the question. Many candidates described the physiology of calcium, which while related, did not attract marks. The distribution section required not only the sites of distribution but also the percentages found in each. The regulation should have included both primary and secondary mechanisms and an outline on the factors affecting renal excretion, intestinal absorption and release from bone etc. An outline of the physiological role of phosphate required a broad knowledge of physiological processes.

Discussion

• Distribution of phosphate:
  • 85% stored as bone
  • 14% stored as intracellular phosphate
  • 1% in extracellular fluid
  • Circulating phosphate is 53% free, 15% protein-bound, 47% complexed with calcium and magnesium
• Absorption of phosphate:
  • 40mmol/day is normal oral intake; plus another 5mmol/day is generated in the metabolism of phospholipids and proteins
  • Absorbed in the intestine by passive and active mechanisms:
    • Passive mechanism is paracellular
    • Active mechanism is co-transport with sodium, and is regulated
• Elimination of phosphate:
  • Total daily phosphate loss: 30mmol excreted renally, 15mmol via stool. 
  • Most of is reabsorbed in the proximal (70%) and distal (10-20%) tubules
• Regulation of phosphate:
  • ​​​​​​​Intestinal and bone recovery increased by calcitriol and PTH
  • Renal reabsorption increased by calcitriol and thyroxine
  • Renal elimination increased by acidosis, PTH, corticosteroids, hypokalemia
• Physiological role of phosphate:
  • ​​​​​​​Structural role: Bone mineral, phospholipid of cell membrane, DNA and RNA
  • Regulatory role: Secondary messenger (IP3); also protein activity is turned on and off by phosphorylation and dephosphorylation
  • Metabolic role: 
    • Co-factor in oxygen transport (as 2,3-DPG)
    • Trapping glucose in cells (as glucose-6-phosphate)
    • Synthesis of ATP (it's the P in ATP)
    • Acid-base regulation (urinary and intracellular buffering)

Penido, Maria Goretti MG, and Uri S. Alon. "Phosphate homeostasis and its role in bone health." Pediatric nephrology 27.11 (2012): 2039-2048.

Lederer, Eleanor. "Regulation of serum phosphate." The Journal of physiology 592.18 (2014): 3985-3995.

Baker SB, Worthley LI. The essentials of calcium, magnesium and phosphate metabolism: part I. Physiology. Crit Care Resusc. 2002 Dec;4(4):301-6

Sabbagh, Yves, et al. "Intestinal phosphate transport." Advances in chronic kidney disease 18.2 (2011): 85-90.