A patient with chronic kidney disease stage 4 develops secondary hyperparathyroidism. Which sequence of events correctly explains its pathophysiology?

• A Phosphate retention → hyperphosphataemia → FGF-23 rise → parathyroid gland hypertrophy
• B Reduced 24-hydroxylase activity → excess calcitriol → feedback inhibition of parathyroid glands
• C Metabolic acidosis → calcium efflux from bone → hypercalcaemia → PTH suppression
• D Reduced renal 1α-hydroxylase → low calcitriol → reduced intestinal Ca2+ absorption → hypocalcaemia → PTH secretion ✓

Explanation

In CKD, reduced functional renal mass decreases 1α-hydroxylase enzyme activity, impairing conversion of 25-hydroxycholecalciferol to active calcitriol [1,25(OH)2D3]. Low calcitriol reduces intestinal calcium absorption and also reduces calcitriol-mediated suppression of parathyroid glands. The resulting hypocalcaemia (and FGF-23 rise independently) stimulates PTH secretion — secondary hyperparathyroidism. Phosphate retention and FGF-23 contribute as additional factors in the CKD-MBD syndrome, but the primary initiating mechanism taught in physiology is the 1α-hydroxylase → calcitriol → hypocalcaemia → PTH sequence.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.