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Calcium 1

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Calcium metabolism

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Calcium 1

  1. 1. Calcium Homeostasis Dr. Hettiarachchi Lead - Anaesthesia and SICU SBSCH shaankh@icloud.com
  2. 2. Ca2+ - Essential intracellular signalling molecule
  3. 3. Variety of extracellular functions1. Blood coagulation 2. Muscle contraction 3. Nerve function
  4. 4. 1,25- Dihydroxycholecalcif erol Three hormones
  5. 5. Three hormones Parathyroid hormone (PTH)
  6. 6. Calcitonin Three hormones
  7. 7. Plasma calcium ion concentration 1.2 mmol/L Or 2.4 mEq/L (Because calcium is a divalent ion)
  8. 8. Calcium metabolism in an adult human
  9. 9. Vitamin D
  10. 10. Intestinal absorption of calcium
  11. 11. Terminology Transient Receptor Potential Vanilloid - type 6 (TRPV6) Calbindin-D – Calbindin D9K, Calbindin D28K Na+ /Ca 2+ exchanger (NCX1) Ca2+ - dependent ATPase
  12. 12. Mechanism of action of 1,25 DHCC Transcriptional regulator in its ligand- bound form (TRPV6) Calbinding ∞ absorbed
  13. 13. No 1,25 DHCC is produced when plasma Ca2+ level is high
  14. 14. 1 α-hydroxylase is stimulated by PTH And Low levels of plasma Ca 2+
  15. 15. Phosphate Inhibits 1α hydroxylase (direct)
  16. 16. Facilitates Ca2+ reabsorption in the proximal tubules in kidneys Actions of Vitamin D
  17. 17. TRPV5 receptors (Kidney)
  18. 18. Increases the synthetic activity of osteoblasts Vitamin D Necessary for normal calcification of matrix
  19. 19. osteoprotege rin ligand OPGL
  20. 20. Vitamin D Stimulation of osteoblasts brings about a secondary increase in the activity of osteocla sts
  21. 21. Four principal actions of vitamin D 4. Acts directly on the parathyroid glands to decrease preproPTH mRNA 1. Increase Bone resorption 2. Increase GI Ca2+ absorption through Ca2+ channel and pump upregulation 3. Ca 2+ reabsorption via increased TRPV5 expression in the proximal tubules
  22. 22. Hypocalcemic tetany Extensive spasms of skeletal muscles A decreasein extracellular Ca2+ exerts a net excitatory effect on nerve
  23. 23. Severe Laryngospasm Airway obstruction and fatal asphyxia
  24. 24. pH and Ca2+ binding When pH is increasing, Ca2+ binding with protein also is increasing
  25. 25. PHOSPHAT E Required for synthesis of ATP and 2,3- diphosphoglycerate (2,3-DPG)
  26. 26. Proximal,Phosphate,PTH Phosphate Reabsorbed in Proximal tubule A small percentage is rebsorbed by the DCT
  27. 27. PTHinhibits phosphate reabsorption by degradation of Na+-Pi Co-transporters in the renal epithelium’s apical membrane When ECF phosphate levels are low Na+-Pi Co- transporters retain phosphate
  28. 28. Increasedplasma phosphate 1. Lowers plasma levels of free Ca 2+ to stimulates PTH secretion 2. Inhibit the formation of 1,25- dihydroxycholecalciferol
  29. 29. Parathyroid gland
  30. 30. Chief cells Oxyphil cells
  31. 31. Chief cells Contain prominent Golgi apparatus, endoplasmic reticulum, secretary granules. Synthesize and secrete PTH
  32. 32. Oxyphil cells Contain oxyphil granules and large numbers of mitochondria in their cytoplasm
  33. 33. PTH
  34. 34. When plasma Ca2+ raised 1. Ca2+ is sensed by a GPCRlinked to PLC. PLC liberates DAG and IP3 2. DAGactivates PKC 3. PKC inhibits PTH release 4. IP3 starts Ca2+ release from the ER 5. A rise in intracellular free Ca2+ also inhibits PTH secretion
  35. 35. PKC and Ca2+ effects together cause plasma Ca2+ to fall through PTH Reduced reabsorption from the renal tubule and decreased bone resorption
  36. 36. Mechanism of action
  37. 37. Actions of PTH
  38. 38. Increase bone resorption and mobilize Ca2+ Osteoprotegerin ligand (OPGL)
  39. 39. Phosphaturic action Due to a decrease in reabsorption of phosphate via effects on NaPi -IIa in the proximal tubules
  40. 40. Increase Ca2+ reabsorption by increasing TRPV5 open probability Increased reabsorption of Ca2+ in the distal tubules
  41. 41. Increased reabsorption of Ca2+ in the distal tubules
  42. 42. Increased formation of 1,25-dihydroxycholecalciferol This increases Ca2+ absorption from the intestine (indirectly)
  43. 43. Lithium Desensitizes parathyroid cells to Ca2+ So Higher levels are required to suppress PTH release PTH secretion increases 1. Renal Ca2+ reabsorption 2. Bone resorption
  44. 44. CALCITONIN Ca 2+ - lowering hormone Produced by the parafollicular cells (clear or C cells) of the thyroid gland
  45. 45. Calcitonin SECRETION When Ca2+ level is 9.5 mg/dL Calcitonin ∞ Ca2+
  46. 46. Stimuli for calcitonin secretion β-Adrenergic agonists Dopamine Oestrogens Gastrin cholecystokinin (CCK) glucagon secretin
  47. 47. Zollinger–Ellison syndrome (Supraphysiological value of gastrin concentration is found) Calcitonin
  48. 48. Receptors for calcitonin are found in and Calcitonin
  49. 49. ACTIONS of Calcitonin 1. lowers Ca2+ and PO4 -3 levels 2. Inhibit bone resorption 3. inhibits the activity of osteoclasts 4. Increases Ca2+ excretion in the urine
  50. 50. EFFECTS OF OTHER HORMONES & HUMORAL AGENTS ON CALCIUM METABOLISM
  51. 51. Glucocorticoids Lower plasma Ca2+ levels by inhibiting osteoclast formation and activity but long term they cause osteoporosis by decreasing bone formation and increasing bone resorption
  52. 52. Decrease bone formation by inhibiting protein synthesis in osteoblasts Glucocorticoids Decrease the absorption of Ca2+ and PO4 3– from the intestine Increase the renal excretion of Ca2+ and PO4 3–
  53. 53. Growth hormone Increases Ca2+ excretion in the urine, but it Increases intestinal absorption of Ca2+ (Greater) Net positive calcium balance Insulin-like growth factor I (IGF-I) generated by the action of growth hormone stimulates protein synthesis in bone
  54. 54. Thyroid hormones Hypercalcemia Hypercalciuria (in some instances, osteoporosis)
  55. 55. Insulin Increases bone formation (significant bone loss in untreated diabetes)
  56. 56. Estrogens Prevent osteoporosis by inhibitingthe stimulatory effects of certain cytokineson osteoclasts
  57. 57. 1. With regards to calcium metabolism a. It is the ionised calcium concentration which influences the physiological effects b. The normal value of ionised calcium is 2.12 2.65mmol/l c. Calcitonin plays a major role in calcium homeostasis in humans d. Absorption of Ca2+ from the GI tract is regulated by parathyroid hormone e. 98-99% of filtered calcium is reabsorbed in the kidney
  58. 58. 2. TFFFT
  59. 59. 2. Total plasma calcium: a) increases with phosphate b) increases with a rise in albumin, c) changes its degree of ionisation with pH changes d) is decreased in osteoporosis e) is affected by vitamin D
  60. 60. 3. A patient with parathyroid deficiency 10 days after inadvertent damage to the parathyroid glands during thyroid surgery would probably have 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 spasm of the muscles of the upper extremity (Trousseau sign). D. high plasma phosphate and Ca2+ levels and bone demineralization. E. increased muscular excitability, a high plasma Ca2+ level, and bone demineralization.
  61. 61. 6. Which of the following is not involved in regulating plasma Ca 2+ levels? A. Kidneys B. Skin C. Liver D. Lungs E. Intestine
  62. 62. 5. In an experiment, a rat is infused with a small volume of a calcium chloride solution, or sodium chloride as a control. Compared to the control condition, which of the following would result from the calcium load? A. Bone demineralization B. Increased formation of 1,25-dihydroxycholecalciferol C. Decreased secretion of calcitonin D. Decreased blood coagulability E. Increased formation of 24,25-dihydroxycholecalciferol
  63. 63. 7. 1,25-Dihydroxycholecalciferol affects intestinal Ca2+ absorption through a mechanism that A. includes alterations in the activity of genes B. activates adenylyl cyclase C. decreases cell turnover D. changes gastric acid secretion E. involves degradation of apical calcium channels
  64. 64. 8. Which of the following would you expect to find in a patient whose diet has been low in calcium for 2 months? A. Increased formation of 24,25 dihydroxycholecalciferol B. Decreased amounts of calcium-binding protein in intestinal epithelial cells C. Increased parathyroid hormone secretion D. A high plasma calcitonin concentration E. Increased plasma phosphate

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