Parathyroid and other glands in calcium homeostasis.pptx

parathyroid gland

1. CALCIUM AND PHOSPHATE METABOLISM DR SARAH OKIYA ANESTHESIOLOGIST ADJUCNT LECTURER

2. outline Calcium and phosphate: role and distribution The parathyroid gland in calcium and phosphate homeostasis Vitamin D in calcium and phosphate homeostasis Other hormones involved in calcium and phosphate homeostasis

3. objectives Understand the importance of maintaining homeostasis of body calcium and phosphate concentrations, and how this is accomplished. Identify the major hormones and other factors that regulate calcium and phosphate homeostasis and their sites of synthesis as well as targets of their action.

4. introduction: CALCIUM Calcium is physiologically important ( 2 nd messenger in cells, blood clotting, muscle contraction, nerve function) 99% stored in bone: readily exchangeable and slowly exchangeable 40% of Calcium in plasma bound to proteins I.E. albumin and globulin 60% is either free ionized Ca2+or bound to phosphate, citrate and bicarbonate Free ionized calcium is physiologically active Serum levels:2.2-2.6mmol/l

5. Activity 1 State 5 roles of calcium

6. Calcium balance depend on: intestinal absorption renal excretion bone resorption and remodeling

7. FACTORS THAT INFLUENCE CALCIUM BALANCE Age Pregnancy Alkalosis Disease ACTIVITY 2: explain how each of the factors above affect calcium balance

8. phosphate Occurs in form of ATP, cAMP, 2,3 DPG, bound to proteins Phosphorylation and dephosphorylation is involved in regulation of proteins/enzymes 85-90% exists bound to the skeleton. Outside of bone it occurs as organic phosphate and inorganic(Pi) as PO3-,HPO2-, H2PO-.

9. Absorbed in the duodenum by a sodium phosphate transporter (Na-Pi Iib ) Absorption increased by 1,25 dihydrocholecalciferol Pi is filtered in the glomerulus and 85-90% reabsorbed via Na-Pi IIa

10. PARATHYROID GLAND Present at the upper and lower poles of posterior aspect of the thyroid gland Consist chief cells and oxyphil cells Parathyroid cells have Ca2+ sensing receptors Serum Ca2+ binds these sensing receptors Low serum calcium activates production of PTH

11. Parathyroid Hormone Produced by chief cells of the parathyroid gland rER Golgi apparatus secretory granules Prepro PTH proPTH PTH 115amino acids 90amino acids 84amino acids Cleaved by kupfer cells of the liver and excreted in urine. T1/2 10mins

12. ACTIONS OF PTH Acting via 3 receptor types ( hPTH / PTHrP , hPTH2-R, CPTH) causes a)kidneys Reabsorption of Ca by DCT and collecting ducts Inhibit phosphate reabsorption ( Phosphaturic action) Activation of vit D in the kidneys b)Bone Increased bone resorption Increased osteoblastic and osteoclastic activity

13. Indirect effect on intestinal absorption through the effect of vit D

14. Regulation of PTH Negative feedback by calcium on Ca Receptor ( CaR ) a g-protein coupled receptor whose activation inhibits PTH secretion 1,25 dihydrocholecalciferol reduces pre-pro-PTH mRNA ↑ phosphate ↑ binding of calcium →↓ Ca activating a negative feedback loop thus inhibits 1,25 dihydrocholecalciferol Mg2+ is required for normal PTH secretion and tissue response.

15. VITAMIN D: Group of sterols Cholesterol 7 dehydrocholesterol cholecalciferol (vit D3 liver ɑ- hydroxylase 1,25 dihydrocholecalciferol 25 hydroxycholecalciferol kidney 24 hydroxylase kidney 24,25 dihydrocholecalciferol

16. Role of 1,25dihydocholecalciferol ↑ intestinal absorption of Ca2+ thru increased expression of Ca2+ channels TRPV6 and calbindin 9k ↑ renal reabsorption of Ca2+ via TRPV5 ↑ osteoblastic activity ↑ osteoclastic activity

17. Regulation of 1,25 dihydrocholecalciferol Negative feedback by ↑ Ca2+ on ɑ-hydroxylase Negative feedback by low PO4+ on ɑ-hydroxylase Activation of ɑ-hydroxylase by PTH Negative feedback of 1,25 dihydrocholecalciferol on ɑ-hydroxylase

18. What is rickets? What causes rickets

19. calcitonin Produced by C-cells/parafollicular cells of the thyroid. T1/2 10mins Secretion increased by β -adrenergic agonists Dopamine, Estrogens Gastrin, Cholecystokinin (CCK), Glucagon Secretin

20. Calcium and Phosphate lowering effect Inhibit osteoclastic activity-bone resorption ↑ renal excretion

21. Other hormones Glucocorticoids ↓serum Ca2+ thru inhibition of osteoclasts, ↓intestinal absorption and ↑renal excretion In the long term they cause bone resorption and ↓osteoblastic bone synthesis leading to osteoporosis GH causes net positive balance: ↑intestinal absorption, ↑ renal exretion

22. Insulin like growth factor promotes protein synthesis in bone Thyroid hormones cause hypercalcemia, calciuria and occasionally osteoporosis Estrogen prevents osteoporosis by inhibition of cytokines on osteoclasts Insulin stimulates bone growth

23. Thank you DANKE Yalama Merci Otio mno

24. references Ganongs review of medical physiology 24 th edition BRS physiology by Linda Constanzo 5 th edition