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Aims Hormone Control of Calcium Metabolism Calcium Homeostasis Hormone Control Calcium Metabolism Vitamin D PTH Calcitonin Other hormones Suwattanee Kooptiwut, MD., MSc., Ph.D. Calcium and Phosphate function 1 Calcium homeostasis 2 Vitamin D synthesis THE ONLY “IN” BONE SKIN DIETARY HABITS, SUPPLEMENTS BLOOD CALCIUM LIVER 7-DEHYDROCHOLESTEROL INTESTINAL ABSORPTION VITAMIN D3 KIDNEY 25(OH)VITAMIN D 25-HYDROXYLASE 1α-HYDROXYLASE hν KIDNEYS VITAMIN D3 25(OH)VITAMIN D (25-HCC) URINE THE PRINCIPLE “OUT” 3 1,25(OH)2 VITAMIN D (1,25-DHCC) (ACTIVE METABOLITE) TISSUE-SPECIFIC VITAMIN D RESPONSES 4 Vitamin D action (enterocyte) Vitamin D action GUT Ca2+ and PO4 3-absorption from the gut epithelium Eletrochemical gradient Ca2+ binding protein (CaBP) or by affecting Ca2+ transport directly Ca2+ ATPase pump Ca2+from enterocyte to blood BONE mineralization from blood Ca2+ to bone 5 IMCal: Intestinal membrane calcium binding protein 6 Vitamin D action Abnormal Vitamin D secretion KIDNEY tubular calcium resorption, possibly by the action of CaBP PARATHYROID Inhibit transcription of the PTH gene (feedback regulation) Vitamin D deficit Uncalcified osteoid tissue Clinical syndromes broadly categorized as Rickets and Osteomalacia. Decreased blood calcium. Vitamin D excess Hypercalcemia (rare). 7 Rickets / Osteomalacia 8 Parathyroid hormone (PTH) 84-amino acids polypeptide hormone PTH is released from the chief cells of the parathyroid gland. A decreased in plasma Ca2+mediates the release of PTH through calcium receptor. Increased cAMP in the chief cells is involved in this process. 9 10 PTH actions (Kidney) Direct 11 PTH increases resorption of Ca2+in the distal tubules. PTH increases PO43 - and HCO3- excretion in the urine. 12 PTH actions (Kidney) Indirect PTH actions (Bone) PTH 1-α hydroxylase 1,25 DHCC 25 HCC Intestinal absorption of Ca2+ PTH acts on osteoblasts to inhibit the synthesis of collagen (inhibition of bone formation). PTH acts on osteoblasts to stimulate secretion of cytokines, which acts on the osteoclasts to promote demineralization and Ca2+release (osteoclastic bone resorption) 13 PTH actions (Bone) 14 PTH actions (Bone) PTH also activates Ca2+pumps within the surface osteoblasts to move Ca2+out of bone fluid and into the extracellular fluid (ECF). PTH (basal level) Osteoblasts Bone formation Osteoclasts Bone resorption Bone remodeling 15 PTH actions 16 Calcium, PTH, and Vitamin D feedback loop PTH BONE RESORPTION Bone Bone resorption Parathyroid glands URINARY LOSS SUPPRESS PTH 1,25(OH)2 D PRODUCTION RISING BLOOD Ca2+ Calcium retention Blood calcium NORMAL BLOOD Ca2+ FALLING BLOOD Ca2+ Vitamin D3 Kidney BONE RESORPTION Dietary calcium absorption Intestine URINARY LOSS STIMULATE PTH 1,25(OH)2 D PRODUCTION 17 18 Abnormal PTH secretion PTH deficit Calcitonin 32 amino acids peptide. parathyroidectomy Hypocalcemia signs and symptoms Calcitonin is released from parafollicular (C or clear cells) of the thyroid gland. PTH excess Increased plasma Ca2+can stimulate calcitonin release. Primary hyperparathyroidism is the most common cause of hypercalcemia. The defect lies with the parathyroid tissue ex. adenoma cAMP is the second messenger in the secretory process. Secondary hyperparathyroidism The defect is from other tissue such as chronic renal disease. Hypercalcemia signs and symptoms 19 Parafollicular cells 20 Calcitonin action The exact physiologic role of calcitonin is uncertain. BONE the osteclastic acitivity. KIDNEY Ca2+excretion in urine. 21 Calcium homeostasis THE ONLY “IN” Other Hormones Calcitonin Vit D DIETARY HABITS, SUPPLEMENTS 22 BONE PTH BLOOD CALCIUM INTESTINAL ABSORPTION Calcitonin Active vitamin D PTH KIDNEYS Vit D PTH GH, IGFs Activate chondrocytes intestinal Ca2+absorption. renal PO43 – reabsorption. Thyroid hormone Physiological level: Increase bone formation. URINE THE PRINCIPLE “OUT” 23 Excess: Increase bone resorption by decrease1,25 DHCC and increase renal Ca2+excretion. 24 Sex hormones Estrogen PTH action on bone Androgen PTH action on kidney Bone resorption Ca2+ excretion Sex hormones Osteoporosis Bone formation 25 Other Hormones Glucocorticoids GI Ca2+absorption. Renal Ca2+excretion. PTH. Osteoporosis 27 26