Calcium Physiology

• Regulation of serum calcium level depends on the actions of vitamin D and parathyroid hormone (PTH).
  • Vitamin D modulates intestinal absorption of calcium
  • PTH modulates calcium via renal calcium retention/excretion and bone resorption
• Measured calcium levels depend on the amount bound to albumin, which can be affected by nutrition and acid-base status. When albumin concentration is low, ionized calcium measurement or corrected total calcium calculation is required to accurately assess calcium levels.

Vitamin D:

• Vitamin D is produced in the skin in response to sunlight and is also provided by dietary sources and supplements.
• Vitamin D activation requires hydroxylation:
  • First by the liver to 25-hydroxyvitamin D (Calcifediol)
    • 25-Hydroxyvitamin D is the storage form of vitamin D in the body
    • Measurement of 25-Hydroxyvitamin D is the most appropriate test to assess vitamin D deficiency
  • Then by the kidney to the active form of 1,25-dihydroxyvitamin D (calcitriol).

Response to Hypocalcemia

• The initial response to a decline in serum calcium is an increase in PTH secretion
  • Decreases renal calcium excretion
  • Increases calcium resorption from bone
    • PTH-mediated mobilization of calcium from bone over months to years in response to chronic negative calcium balance can lead to metabolic bone disease
  • Induces renal conversion of 25-Vit D to 1,25-Vit D, which subsequently increases intestinal calcium absorption

Response to Hypercalcemia

• Suppression of PTH secretion, leads to robust excretion of calcium by the kidneys provided that circulating volume is adequate.
  • In contrast to the response to hypocalcemia, bone and intestinal changes do not significantly contribute to the correction of hypercalcemia.

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