1. Parathyroid Gland and Related Hormones Vitamin D and Calcitonin Prof. K. Sivapalan

2. 08-01-14Parathyroid Gland and related hormones 2 Structure of Bone

3. 08-01-14Parathyroid Gland and related hormones 3 Cells in Bone Osteocytes- resting cells. Osteoblasts are active in bone formation Calcification occurs only in bone and not usually in tissues. Osteoclasts are responsible for removal of bone Remodeling- continuous removal and formation.

4. 08-01-14Parathyroid Gland and related hormones 4 Bone structure. Collagen fiber laid down by fibroblasts is the basic inter cellular substance. Hydroxyappetite [Ca10(PO4)6(OH)2] crystals + other surface crystals, CaHPO4 are deposited on collagen by osteoblasts. Osteocytes are arranged in Havesian system. Stimuli of bone formation- –stress and strain. –growth factors and hormones. –(calcium and protein)

5. 08-01-14Parathyroid Gland and related hormones 5 Plasma Calcium. Calcium phosphate readily ionizes and equilibrates with plasma. Plasma calcium- –50% bound to protein, –5% complex with anions of plasma, –45% ionized (active).

6. 08-01-14Parathyroid Gland and related hormones 6 Calcium Balance Gain during growth. Plateau- middle age. Loss in old age - osteoporosis.

7. 08-01-14Parathyroid Gland and related hormones 7

8. Phosphorous Total body phosphorus is 500 to 800 g (16.1– 25.8 mol), 85–90% of which is in the skeleton. Total plasma phosphorus is about 12 mg/dL, with two-thirds of this total in organic compounds and the remaining inorganic phosphorus (Pi) mostly in PO43–, HPO42–, and H2PO4–. The amount of phosphorus normally entering bone is about 3 mg (97 µmol)/kg/d, with an equal amount leaving via reabsorption 08-01-14Parathyroid Gland and related hormones 8

9. Vitamin D. Control of synthesis: Feed back in kidney- higher plasma calcium inhibiting [production of inactive 24,25 dihydroxycholycalciferol] Parathormaone stimulation production in kidney 08-01-14Parathyroid Gland and related hormones 9

10. 08-01-14Parathyroid Gland and related hormones 10 Actions of Vitamin D. Increases absorption of Calcium in intestine and kidney [Calbindins in intestine, kidney etc]. Increases osteoclasts in bone. Increase plasma calcium. Bone formation ? Indirect through plasma calcium levels. Differentiation of immune cells and keratinocytes of skin. Rickets is the result of deficiency in children. Low plasma calcium leads to non calcification of epyphysis with excess growth of cartilage and week bone. Adults- osteomalasia.

11. “Anti-aging" protein An "anti-aging" protein called -Klotho (named after Klotho, a daughter of Zeus in Greek mythology who spins the thread of life) has also recently been discovered to play important roles in calcium and phosphate homeostasis, in part by reciprocal effects on 1,25- dihydroxycholecalciferol levels. Mice deficient in -Klotho displayed accelerated aging, decreased bone mineral density, calcifications, and hypercalcemia and hyperphosphatemia. -Klotho plays an important role in stabilizing the membrane localization of proteins important in calcium and phosphate (re)absorption, such as TRPV5 and Na, K ATPase. Likewise, it enhances the activity of another factor, fibroblast growth factor 23 (FGF23), at its receptor. FGF23 thereby decreases renal NaPi-IIa and NaPi-IIc expression and inhibits the production of 1 - hydroxylase, reducing levels of 1,25-dihydroxycholecalciferol (Clinical Box 23–1). 08-01-14Parathyroid Gland and related hormones 11

12. 08-01-14Parathyroid Gland and related hormones 12 CALCITONIN. From para follicular cells of thyroid. 32 amino acids, 3000 mw. Effects- Reduce osteiclastic activity Increase osteoblastic activity. Reduce formation of osteoblasts. Control- calcium feedback.

13. 08-01-14Parathyroid Gland and related hormones 13 PARATHYROID HORMONE gland- 4 lobs, behind thyroid. 84AA, mw- 9500. Half life- 20 min.

14. 08-01-14Parathyroid Gland and related hormones 14 Actions of Parathyroid Hormone Maintenance of plasma calcium. Bone- –increase osteoclastic activity. –reduces osteoblastic activity. Kidney- –increase conversion of Vitamin D. –increase reabsorption of calcium –decrease re-absorption of phosphates. Intestine- –increase calcium absorption- direct action is mild. Main action is through increased Vitamin D.

15. 08-01-14Parathyroid Gland and related hormones 15 Control of Secretion of Parathyroid Hormone. Calcium negative feedback. β adrenergic stimulation increases secretion.

16. 08-01-14Parathyroid Gland and related hormones 16 Hyper Parathyroidism Causes- tumors. (in pregnancy and lactation hypertrophy is normal). Effect- increased plasma calcium. Bone- –increased osteoclastic activity. –easily broken bones, multiple fractures with mild trauma. –X ray- eaten up bone appearence. –increased alkaline phosphatase

17. 08-01-14Parathyroid Gland and related hormones 17 Other effects of Hypercalcaemia. depression of nerves. muscular weakness. constipation abdominal pain peptic ulcer loss of appetite reduced diastole of the heart. unconsciousness. confusion mental retardation delusions hallucinations. metastatic calcification in lungs, kidneys, thyroid, arteries, etc. Renal calculi.

18. 08-01-14Parathyroid Gland and related hormones 18 Hypoparathyroidism Reduced plasma Calcium Tetany. Carpo-pedal spasm (Trousseau's sign) Facial muscle twitch on tapping.- (Chvostek's sign)

19. 08-01-14Parathyroid Gland and related hormones 19 Other effects of Hypoparathyroidism. muscular weakness irritability cataracts calcified basal ganglia. In children, defective tooth development metal retardation emotional labiality. irritability anxiety depression delirium Delusions and psychosis