Hormonal regulation of calcium and phosphorus homeostasis.

1. Hormonal regulation of calcium and phosphorus homeostasis.

2. Calcium • Regulate neuromuscular excitability • Blood coagulation • Secretory processes • Membrane integrity • Plasma membrane transport • Enzyme reactions • Release of hormones and neurotransmitters • Bone mineralization

4. Phosphorus Important role in cellular metabolism source of of energy in cellular reactions Component of phospholipids in membranes

5. Calcium Homeostasis James T. McCarthy & Rajiv Kumar

6. Hormonal Regulators • Calcitonin (CT) • Lowers Ca++ in the blood • Inhibits osteoclasts • Parathormone (PTH) • Increases Ca++ in the blood • Stimulates osteoclasts • 1,25 Vitamin D3 • Increases Ca++ in the blood • Increase Ca++ uptake from the gut • Stimulates osteoclasts

10. Renal tubular reabsorption of Calcium 80-85 of calcium is reabsorbed at proximal tubule and medullary loop of henle (passive transport According to physiologic needsat the DISAL tubule and adjacent cortical thick ascending limb ( where PTH, Vit D exert its effect) CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.

11. Renal tubular reabsorption of phosphorus Most of the inorganic phosphorus in serum is ultrafilterable at the level of the glomerulus. CCT—cortical collecting tubule; IMCD—inner medullary collecting duct or tubule; PST—proximal straight tubule.

12. MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS • It is dependent on • Intestinal • Bone • Renal function

13. MAINTENANCE OF CALCIUM AND PHOSPHATE HOMEOSTASIS • It is dependent on • Intestinal • Bone • Renal function • Na Cl and KCL complete absorbtion at intestine but CALCIUM AND PHOSPHATE is incomplete • * because of the requirement for vitamin D and formation of insoluble salts like; Calcium phosphate,calcium oxalate and magnesium phosphate at the intestinal lumen

14. Calcitonin • Is synthesized by parafollicular cells of thyroid gland • Affects the metabolism of Са and Р • Promotes the transferring of Са2+ from blood into bones • Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine)

15. Increase of calcitonin • hypocalciemia • hypophosphatemia • hyperphosphaturia • Decrease of calcitonin • - hypercalciemia • hyperphosphatemia • hypophosphaturia

16. PARATHYROID GLANDS Parathyroid hormone - protein • Affects the metabolism of Са and Р • Promotes moving of Са2+ from bones into blood • Inhibits reabsorption of Р in kidneys (decreases the content of Р in blood due to its excretion with urine) • Stimulates the absorption of Ca in the intestine • Дія зв’язана з вітаміном D (утворює активну форму вітаміну D в нирках)

18. Vitamin D 2 Main regulators of Calcium and phosphorus: PARATHYROID HORMONE • PTH ( Parathyroid hormone) • 84 amino peptide • Molecular mass if 9.5 kilodalton • no carbohydrate or other covalently bound molecules • Full biologic activity resides in the amino terminal third of the molecule • PTH 1-34 has full biologic activity while region 25-34 is for receptor binding • Is a fat soluble steroid • That is present in the diet and can be synthesized from the skin

19. PARATHYROID HORMONE A polypeptide secreted from the parathyroid glands in response to a decrease in the plasma concentration of ionized calcium

20. Parathyroid Hormone Precursor of PTH are: • PreproPTH differs from proPTH by having additional 25 amino acid amino terminal * it is the hydrophobic end • *at Rough endoplasmic reticulum

21. Parathyroid Hormone • Precursor of PTH are: B. ProPTH differs from native hormone by having an amino terminal highly basic hexapeptide extension * it is hydrophobic end * at PTH golgi apparatus

22. PTH increases Ca concentration by: 1. In the presenc e of permissive amounts of vitamin D it stimulates bone resorptionrelease of calcium phosphates 2. Enhances intestinal Calcium and phosphate absorption promotes formation of vit D 3. It augments renal calcium reabsorption

23. PTH • Regulation of Synthesis • Biosynthesis is regulated by levels of calcium • An acute decrease of Ca results in marked increase of PTH mRNA increase of PTH synthesis • Effects is at the level of gene transciption, MRNA stability, mRNA translation • Rate of degradation of PTH is low if low calcium and high if calcium is high • 1, 25 (OH)2D3 receptor complex binds with vitamin D in the promoter region of PTH gene and inhibits transcription decreases the production of PTH • PTH synthesis can be enhanced by the size and number of PTH producing chief cells in cases of prolonged hypocalcemia

24. Hypofunction • hypocalciemia • hyperphosphatemia • hypophosphaturia • tetanus • Hyperfunction(Recklinghausen’s disease) • hypercalciemia • hypophosphatemia • hyperphosphaturia • osteoporosis • Accumulation of Са in tissues

25. Hyperparathyroidism: adenoma or hyperplasia or ectopic

26. Hypocalcemia

27. Vitamin D Metabolism

28. Regulation of Metabolism and synthesis of 1,25()H)2-D3

29. UV Cholesterol precursor 7-dehydrocholesterol Vitamin D3 25 Vitamin D3 1,25 Vitamin D3 Low plasma Ca++ increase kidney enzymes 1,25 Vitamin D3 • Increases Ca++ uptake from the gut • Increase transcription and translation of Ca++ transport proteins in gut epithelium • Minor roll: also stimulates osteoclasts • Increase Ca++ resorption from the bone

30. Images of Rickets Wrist expansion: cupping and fraying of hypertrophied metaphyseal plate Rachitic Rosary Bone demineralization and deformity Rotten-stump epiphysis