Calcium metabolism

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Calcium metabolism

  1. 1. CaMETABOLISM by Dr. Suman Kumar DNB-orthopaedics DDU hospital
  2. 2. GENERAL CONSIDERATION Ca, THE MOST ABUNDANT BODY-MINERAL PRESENT MAINLY IN BONES & TEETH GIVING STRUCTURAL SUPPORT ALSO PRESENT IN ECF & INSIDE DIFFERENT CELLS, NEEDED FOR MUSCLE CONTRACTION, HORMONES & ENZYMES SECRETION, HELPING NEURONS IN SENDING MESSAGES, BLOOD-COAGULATION etc. CONSTANT NORMAL LEVEL FOR PROPER FUNCTION
  3. 3. HUMAN BODY COMPOSITONIN ADULT HUMAN BODY 1-2 kg CaAVERAGE ADULT MAN-1300gm & WOMEN-1000gm≥ 99% IN SEKELETON AS HYDROXYAPATITE [Ca10(PO4)6(OH)2] PROVIDING MECHANICAL STABILITY1% IN ECF & OTHER CELLS FOR DIFFERENT FUNCTIONS
  4. 4. Ca IN BONEBONES THE IMPORTANT STORAGE POINT FOR CALCIUMSKELETAL CALCIUM ACCRETION 1ST SIGNIFICANT DURING 3RD TRIMESTER OF FETUSACCELERATES THROUGH CHILDHOOD & ADOLESCENCEPEAK IN EARLY ADULTHOOD ~30YR WHN PEAK BONE MASS REACHEDPEAK BONE MASS- MAX AMOUNT OF BONE ACHIEVEDDECLINES THEREAFTER @ ≤1-2%PER YR
  5. 5. Ca IN BONE Ca IN BONE AS HYDROXYAPATITE [Ca10(PO4)6(OH)2] IN THE FORM OF CRYSTAL LATTICE Na+, K+, Mg2+, & F-, ALSO ARE PRESENT IN THE CRYSTAL LATTICE
  6. 6. Ca IN BONETWO TYPES OF Ca POOL IN BONE :- 1)READILY EXCHANGEABLE POOL-SMALLER RESORVOIR (0.5-1% OF BONE Ca) 2)SLOWLY EXCHANGEABLE POOL-STABLETWO INDEPENDENT HOMEOSTSTIC SYSTEM:- 1ST SYSTEM REGULTES PLASMA CALCIUM 2NDCONCERNED WITH BONE REMODELINGTWO SYSTEM INTERACTING WITH EACH OTHER
  7. 7. 1ST HOMEOSTATIC SYSTEM• IT REGULATES PLASMA CALCIUM• 500mmol/d Ca MOVES IN & OUT OF READILY EXCHANGEABLE POOL INTO PLASMA• READILY EXCHANGEABLE POOL IN CHEMICAL EQUILIBRIUM WITH ECF
  8. 8. 2ND HOMEOSTATIC SYSTEMCONCERNED WITH BONE REMODELLINGCONSTANT INTERPLAY OF BONE RESORPTION & DEPOSITIONMEDIATED BY COUPLED OSTEOBLASTIC & OSTEOCLASTIC ACTIVITY95% OF BONE FORMATION IN ADULTCa EXCHANGE BETWEEN PLASMA & STABLE POOL @7.5mmol/d(250-500mg/d)
  9. 9. Ca IN ECFTOTAL 1-2 gm Ca IN ECFNORMAL [s.Ca ]=8.5-10.4mg/dL(2.1- 2.6mmol/L) IN ADULT3 DISTINCT FORM OF Ca IN ECF- a.IONIZED b.COMPLEXED c.PROTEIN BOUND
  10. 10. Ca IN ECFPLASMA Ca:2 FORMS- 1.DIFFUSIBLE(60%)-CAN CROSS CELL- MEMB; 2 TYPES- a)IONIZED: Ca²⁺(50% OF TOTAL ECF Ca) b)COMPLEXED TO HCO3¯,CITRATE,PHOSPHATE etc.(10%) 2.NON-DIFFUSIBLE(40%)-PROTEIN BOUND
  11. 11. Ca IN ECF• ONLY IONIZED Ca²⁺ EXERTS BIOLOGICAL EFFECTS• DEGREE OF COMPLEX FORMATION DEPENDS ON AMBIENT pH, *Ca²⁺+ & *COMPLEXING IONS]• AT HIGH pH, MORE ANIONS BIND TO Ca²⁺ →LOW *Ca²⁺+
  12. 12. Ca IN ECFPRTEIN BOUND Ca- 90% BOUND TO ALBUMIN-READILY REVERSIBLE -10% WITH GREATER AFFINITY TO β- GLOBULIN, α₂-GLOBULIN, α₁-GLOBULIN & γ- GLOBULIN-CHANGES IN pH→CHANGES IN [PROTEIN BOUND Ca]- ↑pH →↑PROTEIN-ANION & BINDS TO Ca²⁺→↓*Ca²⁺+
  13. 13. Ca & PLASMA PROTEIN TOTAL [PLASMA Ca] CHANGES WITH CHANGE IN [PLASMA PROTEIN] A CHANGE IN 1 gm/dL OF *ALBUMIN+→ CHANGE IN 0.8 mg/dL OF TOTAL Ca EACH 1 gm/dL ↓IN ALBUMIN →↑0.8mg/dL OF TOTAL Ca 1g/L ↓ IN ALBUMIN →↑0.02mmol/L OF s.Ca
  14. 14. CORRECTED Ca-LEVEL• CORRECTED Ca-LEVEL(mg/dL)= measured total Ca(mg/dL) + 0.8[4.0-s.Albumin level(gm/dL)] where 4.0 is the average s.Albumin level• CORRECTED Ca-LEVEL(mmol/L)= )= measured total Ca(mmol/L)+0.02[40-s.Albumin level(in gm/L)]
  15. 15. DIETARY INTAKE OF Ca• SOURCES-MILK & DAIRY PRODUCTS, FISHES, LEAFY GREEN VEGETABLES etc.• Ca OF LEAFY GREEN VEGETABLES POORLY ABSORBED-PRESENCE OF PHYTATES WHICH COMPLEX WITH Ca
  16. 16. Male and Female Age Calcium (mg/day) Pregnancy & Lactation0 to 6 months 210 N/A7 to 12 months 270 N/A1 to 3 years 500 N/A5 to 8 years 800 N/A9 to 13 years 1300 N/A14 to 18 years 1300 130019 to 50 years 1000 100051+ years 1200 N/A
  17. 17. Ca-ABSORPTION IN INTESTINETWO TYPES : ACTIVE-TRANSCELLULAR PASSIVE-PARACELLULAR PASSIVE DIFFUSION-FACILITATED -5% OF DAILY INTAKE -COUNTERBALANCED BY DAILY INTESTINAL Ca LOSS(MUCOSAL & BILLIARY SECRETION,SLOUGHED CELLS) ~150mg/d
  18. 18. Ca-ABSORPTION IN INTESTINEACTIVE- IN DUODENUM & PROXIMALJEJUNUM -1,25-(OH)₂D DEPENDENT -20-70% OF DAILY INTAKE3 STEPS- Ca ENTRY ACROSS MUCOSAL CELL -DIFFUSION THROUGH CELL -ACTIVE EXTRUSION ACROSS SEROSALMEMBRANE(ENERGY DEPENDENT)
  19. 19. Ca-ABSORPTION IN INTESTINE• CALCITRIOL i.e. 1,25-(OH)₂D ENHANCES ALL 3 STEPS• TRPV6 (transient recptor potential channel)IN PROXIMAL BOWEL MEDIATES MUCOSAL ENTRY OF Ca• TRPV6 IS VIT-D DEPENDENT• CALBINDIN-D9K ENHANCES EXTRUSION OF Ca BY Ca-ATPase• 1,25-(OH)₂D UPREGULATES BOTH CALBINDIN- D9K & Ca-ATPase
  20. 20. Ca-ABSORPTION IN INTESTINELOW Ca-INTAKE→↑ed FRACTIONAL ABSORPTION OF Ca DUE TO ACTIVATION OF VIT-DHIGH Ca INTAKE→ACTIVE TRANSPORT MECHANISM SATURATED &1,25(OH)₂-D ↓ → DECREASED Ca ABSORPTION
  21. 21. ROLE OF KIDNEY IN Ca METABOLISM 8-10 gm/d Ca FILTERED ≥98% REABSORBED-65%IN PCT & REST IN cTAL & DT cTAL CELLS HAVE PARACELLIN-1 RESPONSIBLE FOR Ca ABSORPTION ↑ed s.Ca LEVEL INHIBITS PARACELLIN-1 & Ca-ABSORPTION IN cTAL 10% Ca ABSORBED IN DT BY TRANSCELLULAR PROCESS
  22. 22. ROLE OF KIDNEY IN Ca METABOLISM IN DCT Ca MOVES ACROSS CELL WITH HELP OF CALBINDIN-D28K, Ca²⁺-ATPase &Na⁺/Ca⁺EXCHANGERS ALL OF THESE PROCESS ↓CONTROL OF PTH KIDNEY IS ALSO THE SITE OF ACTIVATION OF VIT-D ↓ INFLUENCE OF PTH
  23. 23. Ca HOMEOSTASIS
  24. 24. Ca HOMEOSTASISECF Ca IS CONTROLLED BY CLASSICAL –VE FEEDBACK SYSTEMPTH ACTS ON BONE,KIDNEY & ON VIT-DVIT-D ACTS ON BONE & INTESTINECALCITONIN ACTS OPPOSITE OF PTHs. Ca LEVEL CONTROLS LEVEL OF PTH,CALCITONIN
  25. 25. Ca HOMEOSTASIS↓BONE RESORPTION SUPPRESS PTH↑URINARY LOSS↓1,25(OH)₂ D PRODUCTION RISING BLOOD Ca²⁺ NORMAL BLOOD Ca²⁺ FALLING BLOOD Ca²⁺↑ BONE RESORPTION↓ URINARY LOSS STIMULATE PTH↑ 1,25(OH)₂ D PRODUCTION
  26. 26. Ca HOMEOSTASIS
  27. 27. Ca HOMEOSTASISPTH & VIT-D ACTS ON OSTEOCLASTS - MOBILIZES Ca TO PLASMAVIT-D ACTS ON INTESTINAL CELLS – INCREASES ABSORPTION OF CaPTH ACTS ON KIDNEY- MORE Ca REABSORBED, ALSO MORE 1,25(OH)₂-D FORMED→ MORE Ca ABSORBED IN INTESTINE
  28. 28. DISORDER OF Ca METABOLISM• RICKETS• OTEOMALACIA• OSTEOPOROSIS• HYPOCALCEMIA• HYPERCALCEMIA
  29. 29. THANK YOU

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