PARATHYROID AND CALCIUM HOMEOSTASIS Dr. Nirmal Arya JR-1 Department of pharmacology and Therapeutics KGMU Lucknow

INTRODUCTION Calcium constitute 2% of body weight or 1-1.5kg in an adult Over 99% of this is stored in bone rest being distributed in plasma and all tissues and cells Normal plasma calcium is 9-11 mg /dl. Calcium 50% ionized and physiologically important. 50% unionized – 40% bound to plasma protein mainly albumin. -10% form complex with citrate, phosphate and carbonate.

Plasma Calcium Level Regulation Precisely by three hormones Parathormone (PTH) Calcitonin Calcitriol (active form of Vit-D) They controls intestinal absorption, bone and plasma level of calcium.

Parathyroid Hormone (Parathormone) It is synthesized in parathyroid gland. Parathyroid gland- contains two types of cells Chief cell which prominently contain Golgi apparatus & Endoplasmic reticulum, secretory granule – it synthesized & secrete PTH. Oxyphil cell containing oxyphil granules. Parathormone (PTH) is polypeptide hormone. It is synthesized in parathyroid gland as pre/pro-PTH by secretory granule containing 115 amino acid.

After synthesis pre/pro-PTH enters into Endoplasmic reticulum. 25 amino acids are removed in Endoplasmic reticulum. From Endoplasmic reticulum pre/pro-PTH enters into Golgi apparatus where 6 amino acids are removed. Now 84 amino acid polypeptide PTH is packaged in secretory granule and released as main secretory product of chief cell.

Regulation of PTH secretion Secretion of PTH is regulated by plasma Ca++ through calcium sensing receptor (CaSR) , that is a G-protien receptor on the surface of parathyroid cells. Fall in plasma Ca++ induces PTH release and rise inhibits secretion by decreasing cAMP in parathyroid cells.

PTH and Calcium regulation PTH receptor is a G-Protien coupled receptor which on activation increases cAMP formation and intracellular calcium in target cells In bone , the target cell is the osteoblast because PTH receptors are not expressed on the surface of the osteoclasts Acting on the osteoblast , PTH induces a factor response for activation of nuclear Factor-KB-Ligand (RANKL) which diffuse and combine with RANK on osteoclast precursors and transform them into osteoclast as well as activate osteoclast

CALCITONIN Calcitonin is hypocalcaemic hormone. It is 32 amino acid single chain polypeptide Produced by parafollicular ‘C’ cells of thyroid gland. Synthesis and secretion of calcitonin is regulated by plasma Calcium concentration itself : Rise in plasma calcium increases its synthesis. Fall in plasma calcium decreases calcitonin release. The plasma t1/2 of calcitonin is 10 min, but its action lasts for several hours.

VITAMIN - D Vitamin D is the collective name given to substances synthesized in the body and found in foods. D3 :- cholecalciferol – synthesized in skin under the influence of UV rays. D2 :- calciferol – present in food – yeasts, fungi, bread , milk. D1 :- found in food

FORMATION :- 7 – Dehydrocholesterol ( synthesized in skin ) UV light cholecalciferol ( vitamin D3 ) liver 25 α hydroxylation calcifediol kidney 1α hydroxylation calcitriol ( active form )

Effect of vit-D on calcium level Increase absorption of calcium and phosphate from intestine. Increase resorption of calcium and phosphate from bone. Increases reabsorption of calcium and phosphate from renal tubule.

Clinical aspect On increase PTH level – cause may be- Primary due to hyperplasia of parathyroid gland & parathyroid adenoma. Secondary due to – chronic kidney disease vit. D deficiency malabsorption of calcium Clinical features- Osteoporosis, pathological fracture, sub periosteal resorption in phalynges

Systemic feature – Nausea & vomiting, Bony pain due to increased osteoclast activity. Abdominal pain, constipation. Renal calculi & osmotic diuresis. Treatment- Hydration & loop diuretics (calciuric effect) Bisphosphonate (osteoclast inhibitor) Calcitonin

BISPHOSPHONATES Inhibit bone resorption and prevent osteoporosis BPN is grouped into 3 generation a) first generation BPN :- i) Etidronate ii) Tiludronate b) Second generation BPN :- i) Pamidronate ii) Alendronate c) Third generation BPN :- i) Risedronate ii) Zoledronate

USES OF BPN :- Osteoporosis Paget’s disease Hypercalcemia of malignancy Osteolytic bone metastasis

Effect due to decrease level of PTH – Mainly due to parathyroidectomy. It causes decrease plasma calcium level & hypocalcemic tetany. Treatment – for temporary relief, injection of calcium salt is given. - for long term injection of PTH can be given

Vitamin D and its clinical aspect due to deficiency due to excess causes hypercalcemia In children In adult causes osteomalacia Cause rickets

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