Hormonal control of calcium and phosphate metabolism 19/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Parathyroid Hormone 19/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) PTH producing cells 19/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Calcium – Phosphate Homeostasis PTH Calcitonin 1g/d Ca2+ Food 10% Ca2+ Calcium Bone Turnover Absorption 100% PO4- Phosphate Filtration reabsorption Feces 90% Ca2+ Urine 19/09/2018 Dr. Omary Chillo (MD, PhD)

Different Forms of Calcium Most of the Calcium in the body is stored in the bones as hydroxyapatite (99%) Calcium in the plasma (1%) 1. Free ionized form – 50% Physiologically active 2. Bound to proteins (albumin) - 41% 3. Complexed with anions (phosphate, citrate)– 9% 19/09/2018 Dr. Omary Chillo (MD, PhD)

Different Forms of Phosphate Most of the Phosphate in the body is stored in the bones (85%) Most of the remainder is intracellular (14%) as a component of phospholipids in cell membranes, DNA, RNA, ATP and ADP The small fraction of phosphate that is in the serum exists as circulating phospholipids, and inorganic phosphate HPO4-- Inorganic Phosphate Physiologically active H2PO4 19/09/2018 Dr. Omary Chillo (MD, PhD)

Hormones involved in Ca2+ and PO4 Balance Parathyroid Hormone Calcitriol (active Vit D) Derived from diet or a cholesterol-derived precursor with help from UV light Composed of 84 aa polypeptide Produced by parathyroid gland Enzymes from the liver and kidney are essential for active vit. D formation Net effect Serum Calcium Serum Phosphate Net effect Serum Calcium Serum Phosphate 19/09/2018 Dr. Omary Chillo (MD, PhD)

Synthesis and Regulation of PTH Parathyroid Hormone Secreted by the chief cells PTH is primarily regulated by serum calcium PHT Serum Calcium Serum Calcium PHT Magnesium also regulates PTH release just like serum calcium 19/09/2018 Dr. Omary Chillo (MD, PhD)

Synthesis and Regulation of Calcitriol Serum Phosphate Serum Phosphate PTH Vit.D 25-hydroxylase Vit.D 1ɑ-hydroxylase 1, 25(OH)cholecalciferol (Calcitriol) 7-dehydrocholesterol Cholecalciferol (vit.D3) 25(OH)cholecalciferol (Calcidiol) Ergocalciferol (vit.D2) Dietary Sources e.g. Fish 19/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Hormonal Action in Calcium – Phosphate Homeostasis PTH Ca2+/PO4 Calcitriol Blood Ca2+/PO4 Ca2+/PO4 Calcium Phosphate PTH + - PTH Calcitonin + + Filtration Calcitriol Net Effect PTH: Calcium, Phosphate Calcitriol: Calcium, Phosphate Urine 19/09/2018 Dr. Omary Chillo (MD, PhD)

The pH effect on Calcium – Phosphate Metabolism Serum pH PTH Urinary excretion of Phosphate Buffering of H+ excretion in distal tubule Serum pH 19/09/2018 Dr. Omary Chillo (MD, PhD)

Disorders of Calcium and Phosphate Metabolism Hypercalcemia PTH excess production (tumors of the parathyroid gland) Depresses nervous system Decreases muscle activity Constipation Lack of appetite Vitamin D excess Excessive dietary intake of Ca2+ Thiazide diuretics 19/09/2018 Dr. Omary Chillo (MD, PhD)

Hypocalcemia Disorders of Calcium and Phosphate Metabolism Increases Nervous system excitement Tetanic contrations Seizures Increases muscle activity Aging Malnutrition Menopause Hypothyroidism 19/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) The Bone Physiology 19/09/2018 Dr. Omary Chillo (MD, PhD)

Dr. Omary Chillo (MD, PhD) Thanks 19/09/2018 Dr. Omary Chillo (MD, PhD)