1 / 30

Parathyroid hormone(Parathormone) Lecture NO: 2 nd MBBS

Parathyroid hormone(Parathormone) Lecture NO: 2 nd MBBS. Dr Muhammad Ramzan. Parathyroid hormone (PTH) – the definition. A protein hormone (84 AA.) from the Parathyroid gland that regulates the metabolism of : Calcium and phosphorous in the body It is also called as Parathormone (PTH)

ethelf
Télécharger la présentation

Parathyroid hormone(Parathormone) Lecture NO: 2 nd MBBS

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Parathyroid hormone(Parathormone) Lecture NO: 2nd MBBS Dr Muhammad Ramzan

  2. Parathyroid hormone (PTH) – the definition • A protein hormone (84 AA.) from the Parathyroid gland that regulates the metabolism of : • Calcium and phosphorous in the body • It is also called as Parathormone (PTH) • www.merrium – webster.com

  3. Parathormone (PTH) – the background↑ Ca and↓PO4 ions • PTH is important in bone remodeling via ongoing process of bone resorption and bone formation (Osteogenesis) • PTH elevates calcium level when it is low. • PTH excess causes bone/muscle pain and kidney stones • PTH deficiency produces muscle spasm; numbness in extremities, coagulation disorders and abnormal heart beats • www.webmd.com – www.wikipedia.com

  4. PTH – the target organs - 3 Bone, kidney and Intestine • Target organs are the ones with PTH receptors and include bones, Kidneys (CNS) and Intestine • No receptors for Intestinal mucosa and Osteoclasts • PTH acts via Osteoblasts and Osteocytes • Activates Vit. D in Kidneys through 1- α – hydroxylase to • Increase GIT Ca++ absorption • www. Labtestsonline.org

  5. Target organs of PTH

  6. Biosynthesis of PTH – As Pre Prohormone • PTH is synthesized as a Pre Prohormone in the RER of the Chief cells with115 AAs • Pre-Pro PTH is cleaved by signal peptidase in RER to remove 25 AAs and is converted to Pro- PTH • Pro – PTH - 115 - 25 = 90 amino acids

  7. Pro - PTH is transferred to Golgi 6 AAs are removed • Pro - PTH is transferred to the Golgi Complex and 6 AAs are removed by Clipase for PTH = 84 AAs • PTH is packed/stored as secretary vesicles in Chief cells • Hormone Is released to the circulation in response to a proper physiological stimulus like: • Low Ca++ level in serum/ ECF

  8. Biosynthesis of PTH

  9. Regulation of PTH – 2 pathways • PTH is regulated through negative feed back mechanism • Regulation is through 2 pathways • Direct and • Indirect

  10. Regulation of PTH – Direct pathwayNo role of Calcitonin • It is the interaction B/W Ca++level and PTH secretion • Lowfreecalcium (Ions) in ECF is sensed by the Calcium sensory receptors - Integral membrane proteins • It ↑ the secretion of PTH that elevates Ca++ level by its action on the target organs (bones and Kidneys) • There is no role of Calcitonin • www.vivo. colostate.com

  11. Regulation of PTH – Direct pathway

  12. PTH Regulation – Indirect pathway ↑ Ca, PTH and Calcitonin • It is interaction B/w high serum Ca++, PTH and Calcitonin • High serum Ca++ Induces the following changes • 1. ↓Transcription of mRNA for PTH (synthesis) • 2. Auto degradation of the preformed PTH secretary granules • Secretion of Calcitonin reduces the Ca++ by promoting its renal excretion and bone formation

  13. Homeostasis of blood calciumRole of Calcitonin and PTH

  14. PTH - Mechanism of ActionActivation of GPCR – PTHR1 • PTH is a protein hormone and its action is like the similar ones • PTH binds to the Extracellular domain of the PTHR1 on the membranes of bones to produce some changes • It activates the intracellular α - subunit of the G protein to produce α – GTP in exchange for α- GDP

  15. PTH - Mechanism of action ( PTHR1) activation of adnylate cyclase • α- GTP activates the membranous Adenylate Cyclase of the target cells that convert ATP to cAMP • cAMP is the 2nd messenger • cAMP activates the Protein kinas A, that Phosphorylates the specific intracellular enzymes/ proteins • to execute the hormonal effects - ↑ serum Calcium

  16. Mechanism of Action of PTH – PTHR1

  17. PTH – Alternate mechanismactivation of Phospholipase C • An alternate mechanism of action of PTH • Activated α GTP also stimulates Phospholipase C • It converts membranous Phospholipid, PIP2 into: • IP3 and DAG as 2nd messengers • Both act on the bone, kidneys and intestine to increase extracellular Calcium

  18. PTH mechanism of action – Dual pathways

  19. Metabolic actions of PTH • PTH acts to maintain serum/ECF Calcium between • 9.5 - 11mg/dl and Po4B/W 3 - 4.5 mg/dl • PTH has significant metabolic actions on : • Bones, Kidneys and Intestine

  20. Metabolic role of PTH – the target organs

  21. PTH - Metabolic actions on bone • Bone is a large reservoir of Calcium • PTH enhances the release of Ca and Po4 from the bone by Osteolysis via Osteoclasts - a normal process • Osteolysis is also supported by the : • 1. Membranous Calcium pumpactivated by PTH • 2. Elevated Phosphatases around Osteoclasts

  22. Activated Osteoclasts

  23. Membranous Calcium pump – How it works • Calcium pump causes rapid removal of calcium phosphate from the sites near these cells (Osteoclasts) • Calcium phosphate salts are transported to ECF as: • It alters the permeability of Osteocytes to calcium

  24. Metabolic action on Kidneys↑ Cal. Resorption and Po4 excretion • PTH promotes renalexcretion of Phosphates to decrease its plasma level and 1 • Enhances active resorption of Ca and Mg from the distal tubules and ascending loop of Henley 2 • This increases Calcium phosphate ratio (3:11) and more free Ca++ ions in circulation

  25. Metabolic actions on Kidneys cont.Activation of Vit.D for GIT • PTH promote activation of Vitamin D to 1-25 Dihydroxy Cholecalceferol in kidneys via 1- α- hydroxylase • Vita. D promotes calcium absorption from GIT • It is facilitated by Calbindin (Ca binding protein) • No PTH receptors are present on Intestinal mucosa • PTH has no significant effect on Po4 absorption by GIT

  26. PTH - secretion abnormalities • Parathormone may be secreted in excess or there may be deficiency of PTH secretion • Both abnormalities lead to significant clinical conditions

  27. PTH excess - hyperparathyroidism • Excessive PTH secretion is classified as : • Primary and secondary • Primary one is the result of diseases of parathyroid and is due to tumour of the gland • Results in hypercalcemia, kidney stones and osteoporosis

  28. Hyperparathyroidism - Secondary • Secondary one is due to causes out side the parathyroid • Common cause is the: • 1. Renal disease/ failure as it is unable to reabsorb Calcium and there is fall in blood Ca. • 2. Malnutrition for Calcium and Vit. D produces : • Decalcification of bone leading to rubber bones, • pathological fractures and cyst formation

  29. PTH deficiency – Hyoparathyroidism • It refers to the condition when PTH is produced less than the body requirements. Caused by: • Inborn error of metabolism and autoimmune disorders. • Hyoparathyroidism results in : • 1. Reduction of Serum calcium • 2. Defects in muscle contraction and • 3. Tetany

More Related