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Calcium metabolism,ppt

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Calcium metabolism,ppt

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  1. 1. CALCIUM METABOLISM MODERATOR: DR.S.P.SAIKIA ASSIST. PROF. PRESENTER: DR.S.H.RANNA PGT,ORTHO. 30-03-2016
  2. 2. INTRODUCTION • Total body calcium level is apprx. 1000gm – 1200mg. • Apprx. 99% calcium remains in bones as reservoir. • Apprx 1% in the intracellular and 0.1% in extra cellular fluids. • Plasma calcium level is 9mg – 11mg/dl (2- 2.5 mmol/dl).
  3. 3. DISTRIBUTION OF CALCIUM
  4. 4. FUNCTIONS OF CALCIUM: 1. Skeletal muscle contraction. 2. Smooth muscle contraction. 3. Transmission of nerve impulse. 4. Skeletal bone and teeth formation. 5. Acts as a second messenger or some hormonal regulation. 6. Blood coagulation system.
  5. 5. HYPOCALCEMIA • Nerve and muscle cells become hyper excitable. • Paresthesia or tingling sensation. • Tetany- latent or manifest. • Muscle cramps carpopedal spasms, intestinal spasm, bronchospasm, laryngospasm, stridor etc. • Seizures- local or generalized. • Cardiac rhythm disturbance (prolong QT interval).
  6. 6. HYPERCALCEMIA: • CVS: Signs of heart block, hypertension. • CNS : Drowsiness, lethargy,headaches,depression,irritability,c onfusion,coma,etc • GIT: Anorexia, Nausea, Vomiting, Constipation. • Musculoskeletal: weakness, muscle flaccidity, bone pain. • Others: polyurea, flank pain, renal calculi.
  7. 7. CALCIUM HOMEOSTASIS • must be tightly regulated to maintain physiological stability. • Two system involve: A)Major organ system i.e. intestine, kidney and bone. B)Major hormones involved are, parathyroid hormone, active vitamin D3 and calcitonin.
  8. 8. PROTEIN BINDING OF CALCIUM: 41%(1mmol/dl)
  9. 9. Calcium flux INTO and OUT of blood • “IN” FACTORS: Intestinal absorption, Bone resorption. • OUT” FACTORS: Renal excretion, Bone formation (Ca incorporation into bone). • Balance between “IN” AND “OUT” factors done by : • ORGAN PHYSIOLOGY OF GUT, BONE, AND KIDNEY • HORMONE FUNCTION OF PTH AND VITMAMIN D, CALCITONIN.
  10. 10. CALCIUM HOMEOSTASIS DIETARY CALCIUM INTESTINAL ABSORPTION ORGAN PHYSIOLOGY ENDOCRINE PHYSIOLOGY DIETARY HABITS, SUPPLEMENTS BLOOD CALCIUM BONE KIDNEYS URINE THE ONLY “IN” THE PRINCIPLE “OUT” ORGAN PHYS. ENDOCRINE PHYS. ORGAN, ENDOCRINE
  11. 11. INTESTINAL HANDLING OF CALCIUM • Approx 1000 mg calcium ingested per day. • Approx.250 -350 mg(20%-30%) is absorbed and others secreted through faces. • Absorption mainly occurs in duodenum & jejunum. • Absorption is both passive and active.
  12. 12. PASSIVE ABSORPTION OF Ca • Paracellular route, non saturable. • 5 % ingested Ca absorbed by this route. • Indirectly influenced by calcitriol. 1,25(OH)2 D Activates protein kinase C Loosen tight junction Ca movements
  13. 13. ACTIVE ABSORPTION OF Ca • Transcellular, receptor mediated, 25% ingested Ca absorbed. • 1,25(OH)2D mainly controls. • Calcium is rapidly and reversibly bound to the calmodulinactin- myosin I complex.
  14. 14. ACTIVE ABSORPTION OF Ca • Calcium binds to calbindin. • calbindin-calcium complex dissociates, the free intracellular calcium is actively extruded from the cell by Na-Ca exchanger.
  15. 15. Factors affecting calcium absorption in gut INCREASED DECREASED Active vitamin D3 Parathyroid hormone. Acidic Pᴴ. Growth hormone. High po4 content in diet. High vegetable fibre. High fat content. Corticosteroid treatment. Estrogens deficiency. Advanced age. Gastrectomy. Intestinal malabsorption syndrome. DM Renal failure
  16. 16. RENAL HANDLING OF CALCIUM • The ultra filterable calcium equals the total of the ionized and complexed fractions. • 10 g of calcium is filtered per day. • urine excretion 100 to 200 mg per 24 hours.
  17. 17. calcium phosphorus magnesium
  18. 18. CALCIUM REABSORPTION IN PCT. • parallels that of Na⁺ and H₂O. • 80% by passive diffusion. • PTF : GF is 1:1.2. • Active absorption10- 15% ⁺ PTH, CT
  19. 19. CALCIUM REABSORPTION IN ALH. • 20%-25% is reabsorbed. • both active and passive routes. • Active pathway proportional to the transtubular electrochemical driving force.
  20. 20. Cont… • apical NKCC2 and the ROMK channel generate the “driving force”. • cinacalcet increases the abundance of claudin-14 in tight junction. • ALH is also influenced by the CaSR.
  21. 21. Effect of diuretics on renal calcium handling: • Furosemide NKCC2 ROMK NK ATPase Na 2Cl K CALCIUM CALCIUM TALH lumen blood
  22. 22. CALCIUM REABSORPTION IN DCT • 8% - 10% is reabsorbed. • exclusively via transcellular route. 1st step: through apical membrane via TRPV5. 2nd step: binding with calbindin28k. 3rd step: extruded via sodium- calcium exchanger NCX1 and the plasma membrane calcium-ATPase PMCA1b.
  23. 23. Cont.. • PTH and CT stimulate calcium absorption. • Calcitriol [1, 25(OH)2D] stimulates calcium absorption.
  24. 24. Influence of thiazide diuretics • calcium reabsorption. • 1st hypothesis: • 2nd hypothesis: increased NaCa exchanger in BL membrane of DCT & CNT. Not proved. ECF depletion calcium filtrate H₂O& Na absorption in PCT driving Ca absorption in PCT
  25. 25. Factors that alter renal regulation of calcium Increase Calcium Absorption Decrease Calcium Absorption Hyperparathyroidism Hypoparathyroidism calcitriol Low calcitriol level Hypocalcaemia Hypercalcaemia Volume contraction Extracellular fluid expansion Metabolic alkalosis Metabolic acidosis Thiazide diuretics Loop diuretics
  26. 26. PARATHYROID HORMON (PTH) • FOUR parathyroid glands located behind the thyroid gland. • Two types of cells 1. Chief cells 2. Oxyphil cells • Normal plasma PTH 10 -55 pg / mL • Half life – 10 mins
  27. 27. ACTIONS OF PTH I. Increases calcium and phosphate absorption from the bones. II. Decreases excretion of calcium by the kidneys. III. Increases the excretion of phosphate by the kidneys. IV. Increases intestinal absorption of calcium and phosphate.
  28. 28. BONE RESORPTION INFLUENCED BY PTH: • Bone resorption occurs in two phases: • Rapid phase: osteocytic osteolysis. Transfer calcium from canaliculi to the ECF from bone fluid via osteocytic membrane by osteocytes. Does not affect bone mass. Transfer calcium from most recently formed calcium crystals. • Slow phase: done by osteoclast resorption.
  29. 29. RAPID PHASE - OSTEOLYSIS BONE ECF OSTEOCYTIC MEMBRANE OCTEOCYTES BONE FLUID B.FL BECF O.M
  30. 30. Ca Ca Ca Ca Ca Ca Ca Ca Ca BONEBONE FLUID OSTEOCYTIC MEMBRANE ECF PTH
  31. 31. Slow phase of osteolysis • Done by OSTEOCLAST. • Activated by unknown mechanism Suspected signal by osteocytes and osteoblasts. • Involves two stages Activation of present osteoclasts Formation of new osteoclasts • Observed after several days of PTH stimulation. • Long lasting effect can weaken bone.
  32. 32. Vitamin D. • Vitamin D3 (cholecalciferol) is a fat-soluble steroid that is present in the diet and also can be synthesized in the skin from 7-dehydrocholestrol(3.2mcg/g skin) in the presence of uv light.
  33. 33. MECHANISM OF ACTION • 1,25 – dihydroxy cholecalciferol is a steroid compound (secosteroid) • Acts via the steroid receptor super family. • Exposes the DNA – binding domain and results in increased transcription of some mRNAs.
  34. 34. Actions of vitamin D
  35. 35. Calcitonin • Produced by the parafollicular cells / C cells of thyroid gland. • STIMULUS : Increased plasma calcium Others: β adrenergic agonists, dopamine and estrogen, GASTRIN, glucagon..
  36. 36. Cont.. • ACTIONS:  Decreases absorptive action of osteoclasts  Deposits exchangeable Ca in bone salts  Decreases the formation of osteoclasts • CLINICAL USE: Used in the treatment of  PAGET’S DISEASE. Hypercalcaemia together with bisphophonate.
  37. 37. THANK YOU…ALL

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Transcript

  1. 1. CALCIUM METABOLISM MODERATOR: DR.S.P.SAIKIA ASSIST. PROF. PRESENTER: DR.S.H.RANNA PGT,ORTHO. 30-03-2016
  2. 2. INTRODUCTION • Total body calcium level is apprx. 1000gm – 1200mg. • Apprx. 99% calcium remains in bones as reservoir. • Apprx 1% in the intracellular and 0.1% in extra cellular fluids. • Plasma calcium level is 9mg – 11mg/dl (2- 2.5 mmol/dl).
  3. 3. DISTRIBUTION OF CALCIUM
  4. 4. FUNCTIONS OF CALCIUM: 1. Skeletal muscle contraction. 2. Smooth muscle contraction. 3. Transmission of nerve impulse. 4. Skeletal bone and teeth formation. 5. Acts as a second messenger or some hormonal regulation. 6. Blood coagulation system.
  5. 5. HYPOCALCEMIA • Nerve and muscle cells become hyper excitable. • Paresthesia or tingling sensation. • Tetany- latent or manifest. • Muscle cramps carpopedal spasms, intestinal spasm, bronchospasm, laryngospasm, stridor etc. • Seizures- local or generalized. • Cardiac rhythm disturbance (prolong QT interval).
  6. 6. HYPERCALCEMIA: • CVS: Signs of heart block, hypertension. • CNS : Drowsiness, lethargy,headaches,depression,irritability,c onfusion,coma,etc • GIT: Anorexia, Nausea, Vomiting, Constipation. • Musculoskeletal: weakness, muscle flaccidity, bone pain. • Others: polyurea, flank pain, renal calculi.
  7. 7. CALCIUM HOMEOSTASIS • must be tightly regulated to maintain physiological stability. • Two system involve: A)Major organ system i.e. intestine, kidney and bone. B)Major hormones involved are, parathyroid hormone, active vitamin D3 and calcitonin.
  8. 8. PROTEIN BINDING OF CALCIUM: 41%(1mmol/dl)
  9. 9. Calcium flux INTO and OUT of blood • “IN” FACTORS: Intestinal absorption, Bone resorption. • OUT” FACTORS: Renal excretion, Bone formation (Ca incorporation into bone). • Balance between “IN” AND “OUT” factors done by : • ORGAN PHYSIOLOGY OF GUT, BONE, AND KIDNEY • HORMONE FUNCTION OF PTH AND VITMAMIN D, CALCITONIN.
  10. 10. CALCIUM HOMEOSTASIS DIETARY CALCIUM INTESTINAL ABSORPTION ORGAN PHYSIOLOGY ENDOCRINE PHYSIOLOGY DIETARY HABITS, SUPPLEMENTS BLOOD CALCIUM BONE KIDNEYS URINE THE ONLY “IN” THE PRINCIPLE “OUT” ORGAN PHYS. ENDOCRINE PHYS. ORGAN, ENDOCRINE
  11. 11. INTESTINAL HANDLING OF CALCIUM • Approx 1000 mg calcium ingested per day. • Approx.250 -350 mg(20%-30%) is absorbed and others secreted through faces. • Absorption mainly occurs in duodenum & jejunum. • Absorption is both passive and active.
  12. 12. PASSIVE ABSORPTION OF Ca • Paracellular route, non saturable. • 5 % ingested Ca absorbed by this route. • Indirectly influenced by calcitriol. 1,25(OH)2 D Activates protein kinase C Loosen tight junction Ca movements
  13. 13. ACTIVE ABSORPTION OF Ca • Transcellular, receptor mediated, 25% ingested Ca absorbed. • 1,25(OH)2D mainly controls. • Calcium is rapidly and reversibly bound to the calmodulinactin- myosin I complex.
  14. 14. ACTIVE ABSORPTION OF Ca • Calcium binds to calbindin. • calbindin-calcium complex dissociates, the free intracellular calcium is actively extruded from the cell by Na-Ca exchanger.
  15. 15. Factors affecting calcium absorption in gut INCREASED DECREASED Active vitamin D3 Parathyroid hormone. Acidic Pᴴ. Growth hormone. High po4 content in diet. High vegetable fibre. High fat content. Corticosteroid treatment. Estrogens deficiency. Advanced age. Gastrectomy. Intestinal malabsorption syndrome. DM Renal failure
  16. 16. RENAL HANDLING OF CALCIUM • The ultra filterable calcium equals the total of the ionized and complexed fractions. • 10 g of calcium is filtered per day. • urine excretion 100 to 200 mg per 24 hours.
  17. 17. calcium phosphorus magnesium
  18. 18. CALCIUM REABSORPTION IN PCT. • parallels that of Na⁺ and H₂O. • 80% by passive diffusion. • PTF : GF is 1:1.2. • Active absorption10- 15% ⁺ PTH, CT
  19. 19. CALCIUM REABSORPTION IN ALH. • 20%-25% is reabsorbed. • both active and passive routes. • Active pathway proportional to the transtubular electrochemical driving force.
  20. 20. Cont… • apical NKCC2 and the ROMK channel generate the “driving force”. • cinacalcet increases the abundance of claudin-14 in tight junction. • ALH is also influenced by the CaSR.
  21. 21. Effect of diuretics on renal calcium handling: • Furosemide NKCC2 ROMK NK ATPase Na 2Cl K CALCIUM CALCIUM TALH lumen blood
  22. 22. CALCIUM REABSORPTION IN DCT • 8% - 10% is reabsorbed. • exclusively via transcellular route. 1st step: through apical membrane via TRPV5. 2nd step: binding with calbindin28k. 3rd step: extruded via sodium- calcium exchanger NCX1 and the plasma membrane calcium-ATPase PMCA1b.
  23. 23. Cont.. • PTH and CT stimulate calcium absorption. • Calcitriol [1, 25(OH)2D] stimulates calcium absorption.
  24. 24. Influence of thiazide diuretics • calcium reabsorption. • 1st hypothesis: • 2nd hypothesis: increased NaCa exchanger in BL membrane of DCT & CNT. Not proved. ECF depletion calcium filtrate H₂O& Na absorption in PCT driving Ca absorption in PCT
  25. 25. Factors that alter renal regulation of calcium Increase Calcium Absorption Decrease Calcium Absorption Hyperparathyroidism Hypoparathyroidism calcitriol Low calcitriol level Hypocalcaemia Hypercalcaemia Volume contraction Extracellular fluid expansion Metabolic alkalosis Metabolic acidosis Thiazide diuretics Loop diuretics
  26. 26. PARATHYROID HORMON (PTH) • FOUR parathyroid glands located behind the thyroid gland. • Two types of cells 1. Chief cells 2. Oxyphil cells • Normal plasma PTH 10 -55 pg / mL • Half life – 10 mins
  27. 27. ACTIONS OF PTH I. Increases calcium and phosphate absorption from the bones. II. Decreases excretion of calcium by the kidneys. III. Increases the excretion of phosphate by the kidneys. IV. Increases intestinal absorption of calcium and phosphate.
  28. 28. BONE RESORPTION INFLUENCED BY PTH: • Bone resorption occurs in two phases: • Rapid phase: osteocytic osteolysis. Transfer calcium from canaliculi to the ECF from bone fluid via osteocytic membrane by osteocytes. Does not affect bone mass. Transfer calcium from most recently formed calcium crystals. • Slow phase: done by osteoclast resorption.
  29. 29. RAPID PHASE - OSTEOLYSIS BONE ECF OSTEOCYTIC MEMBRANE OCTEOCYTES BONE FLUID B.FL BECF O.M
  30. 30. Ca Ca Ca Ca Ca Ca Ca Ca Ca BONEBONE FLUID OSTEOCYTIC MEMBRANE ECF PTH
  31. 31. Slow phase of osteolysis • Done by OSTEOCLAST. • Activated by unknown mechanism Suspected signal by osteocytes and osteoblasts. • Involves two stages Activation of present osteoclasts Formation of new osteoclasts • Observed after several days of PTH stimulation. • Long lasting effect can weaken bone.
  32. 32. Vitamin D. • Vitamin D3 (cholecalciferol) is a fat-soluble steroid that is present in the diet and also can be synthesized in the skin from 7-dehydrocholestrol(3.2mcg/g skin) in the presence of uv light.
  33. 33. MECHANISM OF ACTION • 1,25 – dihydroxy cholecalciferol is a steroid compound (secosteroid) • Acts via the steroid receptor super family. • Exposes the DNA – binding domain and results in increased transcription of some mRNAs.
  34. 34. Actions of vitamin D
  35. 35. Calcitonin • Produced by the parafollicular cells / C cells of thyroid gland. • STIMULUS : Increased plasma calcium Others: β adrenergic agonists, dopamine and estrogen, GASTRIN, glucagon..
  36. 36. Cont.. • ACTIONS:  Decreases absorptive action of osteoclasts  Deposits exchangeable Ca in bone salts  Decreases the formation of osteoclasts • CLINICAL USE: Used in the treatment of  PAGET’S DISEASE. Hypercalcaemia together with bisphophonate.
  37. 37. THANK YOU…ALL

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