Calcium metabolism

1. Ca METABOLISM by Dr. Suman Kumar DNB-orthopaedics DDU hospital

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. HUMAN BODY COMPOSITON IN ADULT HUMAN BODY 1-2 kg Ca AVERAGE ADULT MAN-1300gm & WOMEN- 1000gm ≥ 99% IN SEKELETON AS HYDROXYAPATITE [Ca 10 (PO 4 ) 6 (OH) 2 ] PROVIDING MECHANICAL STABILITY 1% IN ECF & OTHER CELLS FOR DIFFERENT FUNCTIONS

4. Ca IN BONE BONES THE IMPORTANT STORAGE POINT FOR CALCIUM SKELETAL CALCIUM ACCRETION 1 ST SIGNIFICANT DURING 3 RD 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. Ca IN BONE Ca IN BONE AS HYDROXYAPATITE [Ca 10 (PO 4 ) 6 (OH) 2 ] IN THE FORM OF CRYSTAL LATTICE Na + , K + , Mg 2+ , & F - , ALSO ARE PRESENT IN THE CRYSTAL LATTICE

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:- 1 ST SYSTEM REGULTES PLASMA CALCIUM 2 ND CONCERNED WITH BONE REMODELING TWO SYSTEM INTERACTING WITH EACH OTHER

7. 1 ST 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. 2 ND 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. 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. 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. 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. Ca IN ECF PRTEIN BOUND Ca- 90% BOUND TO ALBUMIN-READILY REVERSIBLE -10% WITH GREATER AFFINITY TO β -GLOBULIN, α ₂-GLOBULIN, α₁ -GLOBULIN & γ -GLOBULIN -CHANGES IN pH→CHANGES IN [PROTEIN BOUND Ca] - ↑pH →↑PROTEIN-ANION & BINDS TO Ca²⁺ →↓[Ca²⁺]

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. 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. 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. Male and Female Age Calcium (mg/day) Pregnancy & Lactation 0 to 6 months 210 N/A 7 to 12 months 270 N/A 1 to 3 years 500 N/A 5 to 8 years 800 N/A 9 to 13 years 1300 N/A 14 to 18 years 1300 1300 19 to 50 years 1000 1000 51+ years 1200 N/A

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. Ca-ABSORPTION IN INTESTINE ACTIVE - IN DUODENUM & PROXIMAL JEJUNUM -1,25-(OH)₂D DEPENDENT -20-70% OF DAILY INTAKE 3 STEPS- Ca ENTRY ACROSS MUCOSAL CELL -DIFFUSION THROUGH CELL -ACTIVE EXTRUSION ACROSS SEROSAL MEMBRANE(ENERGY DEPENDENT)

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. 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. 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. 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. Ca HOMEOSTASIS

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. Ca HOMEOSTASIS ↓BONE RESORPTION ↑URINARY LOSS ↓1,25(OH)₂ D PRODUCTION NORMAL BLOOD Ca²⁺ ↑ BONE RESORPTION ↓ URINARY LOSS ↑ 1,25(OH)₂ D PRODUCTION SUPPRESS PTH RISING BLOOD Ca²⁺ FALLING BLOOD Ca²⁺ STIMULATE PTH

26. Ca HOMEOSTASIS

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. DISORDER OF Ca METABOLISM RICKETS OTEOMALACIA OSTEOPOROSIS HYPOCALCEMIA HYPERCALCEMIA

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