Overview of Calcium, Phosphate, and Vitamin D Physiology
Note: In circulation, 40% of Ca2+ is bound to plasma proteins, mainly albumin, 10% is complexed with citrate, and 50% is unbound and biologically active.
Bone
PTH binds to osteoblasts
↑ Osteoblast production of receptor activator of nuclear factor kappa-B ligand (RANKL) and ↓ expression of osteoprotegerin (OPG), a decoy receptor for RANKL
RANKL binds to receptor activator of nuclear factor kappa-B (RANK) on osteoclasts
↑ Osteoclast differentiation and activity
↑ Ca2+ resorption from bone into blood
Sensed by Calcium-Sensing Receptor on Chief Cells of the Parathyroid Gland
− −
↑ Serum phosphate (PO4) ↓ Serum calcium (Ca2+)
Parathyroid Gland releases Parathyroid Hormone (PTH) into the blood, which acts on the kidneys and the bones
Kidney
↑ Activation of Transient Receptor Potential Vanilloid subfamily member 5 (Ca2+ channel)
in the distal convoluted tubule
↓ Expression of 24-hydroxylase enzyme (which functions to catabolize calcitriol)
↑ Expression of 1α- hydroxylase enzyme
↑ Conversion of 25-hydroxy vitamin D (Calcidiol) to the
active form, 1,25-dihydroxy vitamin D (Calcitriol)
↑ Calcitriol Small Intestine
↑ Endocytosis of sodium phosphate co-transporters NaPi-2a and NaPi-2c, which reabsorb PO4 from ultrafiltrate in the renal tubules
↓ Reabsorption of PO 4
↓ Serum PO
Calcitriol negatively feeds back on parathyroid gland to inhibit PTH production
↑ Expression of sodium phosphate co- transporters NaPi-2a and NaPi-2b that absorb PO4 from intestinal lumen
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↑ Expression of apical epithelial Ca2+ channels (Transient Receptor Potential Vanilloid subfamily member 6)
↑ Entry of Ca2+ on apical side of enterocytes
↑ Reabsorption of Ca2+ in the distal convoluted tubule through Ca2+ channels
↑ Reabsorption of PO
↑ Expression of cytoplasmic Calbindin-D
↑ Transport of Ca2+ across enterocytes
↑ Absorption of Ca2+ in small intestine
↑ Serum Ca+2
↑ Expression of basolateral plasma membrane calcium ATPase
↑ Extrusion of Ca2+ from enterocytes into bloodstream
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Authors: Samin Dolatabadi, Hannah Yaphe Reviewers: Amanda Henderson, Meena Assad, Brooke Fallis, Yan Yu*, Hanan Bassyouni* * MD at time of publication
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Complications
First published Oct 15, 2017, updated Nov 11, 2021 on www.thecalgaryguide.com