Question 5

Describe the regulation of plasma calcium concentration.

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College Answer

High scoring answers discussed the three major hormones involved in calcium regulation - parathyroid hormone, vitamin D and calcitonin. For each of these it was expected that candidates include: site of production, stimulus for release, inhibitory factors and actions. In the case of renin it was expected that candidates also include the actions of angiotensin and aldosterone. Very few answers discussed inhibitory factors or negative feedback loops.

Discussion

  • Distribution
    • > 99% of total body calcium is in bone and not easily accessible
    • Less than 1% is in the extracellular fluid (~20-30mmol total)
    • Minimal intracellular concentration (second messenger)
    • In the plasma:
      • 40-45% of calcium circulates bound to albumin
      • 10-15% is bound to other anions such as lactate and phosphate
      • 40-45 % is free and ionised
  • Regulation of calcium intake
    • Absorbed by combination of paracellular and transcellular transport in the ileum
    • Transcellular route carefully regulated by hormones
      • intestinal absorption increased by calcitriol and PTH, 
      • decreased by calcitonin
  • Regulation of bone resorption of calcium
    • Normal daily flux in and out of bone is 12-13 mmol
    • Bone is reabsorbed by osteoclasts; this liberates calcium
    • Osteoclast activity is increased by PTH and decreased by calcitonin
    • Calcitriol has mixed effects; in vitro increased osteoclast activity, and in vivo protective effects in the treatment of osteoporosis
  • Regulation of renal elimination of calcium
    • ​​​​​​​70% is reabsorbed in the proximal tubule
    • 20% is reabsorbed in the thick ascending limb
    • 10% is reabsorbed in the distal convoluted tubule by a mechanism that is regulated by PTH calcitriol and calcitonin:
      • Calcitonin decreases the reabsorption of calcium and phosphate
      • PTH and calcitriol increase the reabsorption of calcium and phosphate 
  • Main hormones involved​​​​​​​
    • PTH is a polypeptide hormone secreted by the parathyroid glands
      • Stimulus for release: hypocalcemia, hypophosphatemia
      • Inhibitory factors: calcitriol, hypermagnesemia
      • Actions: increases plasma calcium by increasing its renal reabsorption and osteoclast activity
      • Also increases Vit D conversion into calcitriol
    • Calcitriol is the metabolic product of Vit D, a fat-soluble vitamin
      • Stimulus for release: hypocalcemia, hypophosphatemia, PTH 
      • Inhibitory factors: decreased sun exposure, decreased functional renal mass, elevated calcium and phosphate levels
      • Actions: increases plasma calcium by increasing its gut absorption and renal reabsorption
      • Inhibits the production of PTH; conflicting effects on osteoclast activity
    • Calcitonin is a polypeptide hormone secreted from parafollicular cells of the thyroid
      • Stimulus for release: hypercalcemia, gastrin 
      • Inhibitory factors: hypocalcemia, somatostatin
      • Actions: decreases plasma calcium by decreasing its renal reabsorption, as well as inhibiting osteoclast activity

References

Mundy, Gregory R., and Theresa A. Guise. "Hormonal control of calcium homeostasis." Clinical chemistry 45.8 (1999): 1347-1352.

Bronner, Felix. "Mechanisms of intestinal calcium absorption." Journal of cellular biochemistry 88.2 (2003): 387-393.

Davies, K. Michael, Karen Rafferty, and Robert P. Heaney. "Determinants of endogenous calcium entry into the gut." The American journal of clinical nutrition 80.4 (2004): 919-923.

Seldin, Donald W. "Renal handling of calcium." Nephron 81.Suppl. 1 (1999): 2-7.

Jeon, Un Sil. "Kidney and calcium homeostasis." Electrolyte & Blood Pressure 6.2 (2008): 68-76.