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Endocrine Regulation of Calcium and Phosphate Metabolism

Endocrine Regulation of Calcium and Phosphate Metabolism. Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C516, Block C, Research Building, School of Medicine Tel: 88208252 Email: wanghuiping@zju.edu.cn. Outline. Hormonal Regulation of [Ca 2+ ] Action of PTH

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Endocrine Regulation of Calcium and Phosphate Metabolism

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  1. Endocrine Regulation of Calcium and Phosphate Metabolism Huiping Wang (王会平), PhD Department of Physiology Rm C516, Block C, Research Building, School of Medicine Tel: 88208252 Email: wanghuiping@zju.edu.cn

  2. Outline • Hormonal Regulation of [Ca2+] • Action of PTH • Action of vitamin D(1,25- (OH)2-D3) • Action of calcitonin

  3. Endocrine Regulation of Calcium and Phosphate Metabolism • Hormonal control: • PTH, vitamin D(1,25- (OH)2-D3), calcitonin • Major regulatory organs: • intestine, bone, kidneys

  4. Vitamin D • Vitamin D, after its activation to the hormone 1,25(OH)2D, is one of the major regulators of Ca & Pi metabolism • Sources of vitamin D: • produced in the skin by UV radiation (D3) • ingested in the diet (D3 rich in fish, liver, milk) Vitamin D is not a “classic hormone” because it is not produced by an endocrine gland. However, its metabolite acts as a hormone by the mechanism similar to that of thyroid and steroid hormones

  5. Formation of Active Vitamin D • Sunlight (290-315 nm) stimulates skin cell to produce previtamin D3 which is then converted to vitamin D3 • Over exposure to sunlight converts previtamin D3 to inactive products • Vitamin D has very little intrinsic biological activity and must undergo successive hydroxylations in order to act as a hormone • In liver, it is hydroxylated to 25-OH-D which is transported to kidney to form 1,25-(OH)2-D or 24,25-(OH)2-D • 1,25-(OH)2-D is the most potent vitamin D metabolite

  6. Actions of 1,25-(OH)2-D3 • Acts through nuclear receptors • Intestine • increases Ca absorption • stimulates phosphate absorption • Bone • stimulates Ca and Pi resorption • provides Ca and Pi from old bone to mineralize new bone • kidney • Enhances Ca and Pi reabsorption of renal tubule

  7. Rickets • Deficiency of vitamin D causes inadequate mineralization of new bone matrix (lowered ratio of mineral/organic matrix) • Caused by deficiency of vitamin D activity (dietary deficiency, insufficient sun exposure, liver/kidney diseases) • Symptoms: decreased mechanical strength and distortion especially in the long bones of legs.

  8. Parathyroid Glands • 4 glands located behind the thyroid • each gland weighs 30-50 mg • main cell type: • chief cells • Parathyroid Hormone

  9. Parathyroid Hormone (PTH) • Polypeptide

  10. PTH Actions • Major target organs • bone •  Bone resorption by stimulating osteoclasts and osteocytes and inhibiting osteoblasts • kidney • Reabsorption of Ca++ and excretion of phosphate • intestinal tract (indirect effect) • Absorption of calcium from the small intestine • Overall effect • increase plasma [Ca2+] • decrease plasma [Pi]

  11. Factors Affecting PTH Secretion • Caand PTH form a negative feedback pair • 1,25-(OH)2-Dand PTH form negative feedback loop

  12. Hypocalcemia damage to blood supply during thyroidectomy

  13. Calcitonin • Parafollicular or C cells • Peptide • Action • Plasma [Ca2+] • Bone • by inhibiting osteoclasts (for bone resorption) & stimulating calcium uptake by bones • By inhibiting synthesis and activity of osteoclasts • Kidney • Regulation: [Ca2+] • It plays no role in normal day-to-day regulation of plasma calcium regulation in humans • Calcitonin is used in • acute treatment of hypercalcemia • alternative of estrogen for treating osteoporosis in women

  14. Hormonal Regulation of [Ca2+]

  15. A patient with parathyroid deficiency 10 days after inadvertent damage to the parathyroid glands during thyroid surgery would probably have QUIZ A. low plasma phosphate and Ca2+ levels and tetany B. low plasma phosphate and Ca2+ levels and tetanus C. a low plasma Ca2+ level, increased muscular excitability, and a characteristic spasm of the muscles of the upper extremity (Trousseau’s sign) D. high plasma phosphate and Ca2+ levels and bone demineralization E. increased muscular excitability, a high plasma Ca2+ level, and bone demineralization

  16. A patient with parathyroid deficiency 10 days after inadvertent damage to the parathyroid glands during thyroid surgery would probably have QUIZ A. low plasma phosphate and Ca2+ levels and tetany B. low plasma phosphate and Ca2+ levels and tetanus C. a low plasma Ca2+ level, increased muscular excitability, and a characteristic spasm of the muscles of the upper extremity (Trousseau’s sign) D. high plasma phosphate and Ca2+ levels and bone demineralization E. increased muscular excitability, a high plasma Ca2+ level, and bone demineralization

  17. Which of the following is not involved in regulating plasma Ca2+ levels? QUIZ A. Kidneys B. Skin C. Liver D. Lungs E. Intestine

  18. Which of the following is not involved in regulating plasma Ca2+ levels? QUIZ A. Kidneys B. Skin C. Liver D. Lungs E. Intestine

  19. Summary • Hormonal Regulation of [Ca2+] • PTH: [Ca2+] • Vitamin D(1,25- (OH)2-D3): [Ca2+] • Calcitonin: [Ca2+]

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