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Ionised calcium restored and the loop closed

Effect · Negative feedback

The three effector organs return calcium to its set point on three different timescales, and the restored ionised calcium closes the loop at the parathyroid calcium-sensing receptor, switching PTH off. There is no pituitary and no releasing hormone anywhere in this axis.

Traced from the start

  1. Fall in ionised calciumRise in ionised calcium
  2. Calcium-sensing receptor on parathyroid chief cells
  3. Parathyroid hormone
  4. Thyroid parafollicular (C) cells
  5. Calcitonin
  6. Phosphate load and hyperphosphataemia
  7. Osteocyte phosphate sensing
  8. Cholecalciferol from skin and diet
  9. Hepatic 25-hydroxylation
  10. Fibroblast growth factor 2325-hydroxyvitamin D (calcifediol)
  11. Distal convoluted and connecting tubule: calcium reabsorptionBone: osteoblast-osteoclast couplingRenal proximal tubule: 1-alpha-hydroxylase
  12. Ionised calcium restored and the loop closed

Detail

Minutes
PTH-driven distal tubular calcium reabsorption, and calcium efflux from bone fluid
Hours to days
Osteoclastic bone resorption
Days
Calcitriol-driven intestinal absorption, the only arm that adds calcium to the body rather than moving it about
Loop closure
Risen ionised calcium activates the parathyroid calcium-sensing receptor and inhibits PTH: a short-loop negative feedback with no pituitary involvement
Phosphate
Phosphate released from bone with the calcium is cleared by PTH-driven phosphaturia, so serum phosphate falls while calcium rises

When it goes wrong

Loop failure from hypoparathyroidism, severe vitamin D deficiency or hypomagnesaemia

Hypocalcaemia: perioral paraesthesia, carpopedal spasm, positive Chvostek and Trousseau signs, prolonged QT, laryngospasm and seizures

Hungry bone syndrome after parathyroidectomy for severe hyperparathyroidism

Abrupt withdrawal of PTH from an avid skeleton: profound, prolonged hypocalcaemia with hypophosphataemia and hypomagnesaemia, needing large doses of calcium and calcitriol

Practise this structure

2 questions in the bank tagged Feedback Axis.

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