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Overview of Calcium Phosphate Vitamin D Physiology

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 4 ↑ 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 4 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