Download - Calcium Metabolism
Ca METABOLISM
byDr. Suman Kumar
DNB-orthopaedicsDDU hospital
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
HUMAN BODY COMPOSITONIN 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
Ca IN BONEBONES THE IMPORTANT STORAGE POINT FOR
CALCIUMSKELETAL CALCIUM ACCRETION 1ST SIGNIFICANT
DURING 3RD TRIMESTER OF FETUSACCELERATES THROUGH CHILDHOOD &
ADOLESCENCEPEAK IN EARLY ADULTHOOD ~30YR WHN PEAK BONE
MASS REACHEDPEAK BONE MASS- MAX AMOUNT OF BONE ACHIEVEDDECLINES THEREAFTER @ ≤1-2%PER YR
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
Ca IN BONETWO TYPES OF Ca POOL IN BONE :- 1)READILY EXCHANGEABLE POOL-SMALLER
RESORVOIR (0.5-1% OF BONE Ca) 2)SLOWLY EXCHANGEABLE POOL-STABLETWO INDEPENDENT HOMEOSTSTIC SYSTEM:- 1ST SYSTEM REGULTES PLASMA CALCIUM 2NDCONCERNED WITH BONE REMODELINGTWO SYSTEM INTERACTING WITH EACH OTHER
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
2ND HOMEOSTATIC SYSTEMCONCERNED WITH BONE REMODELLINGCONSTANT INTERPLAY OF BONE RESORPTION
& DEPOSITIONMEDIATED BY COUPLED OSTEOBLASTIC &
OSTEOCLASTIC ACTIVITY95% OF BONE FORMATION IN ADULTCa EXCHANGE BETWEEN PLASMA & STABLE
POOL @7.5mmol/d(250-500mg/d)
Ca IN ECFTOTAL 1-2 gm Ca IN ECFNORMAL [s.Ca ]=8.5-10.4mg/dL(2.1-
2.6mmol/L) IN ADULT3 DISTINCT FORM OF Ca IN ECF- a.IONIZED b.COMPLEXED c.PROTEIN BOUND
Ca IN ECFPLASMA 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
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⁺]
Ca IN ECFPRTEIN 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⁺]
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
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)]
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
Male and Female Age Calcium (mg/day) Pregnancy & Lactation
0 to 6 months 210 N/A7 to 12 months 270 N/A1 to 3 years 500 N/A
5 to 8 years 800 N/A9 to 13 years 1300 N/A14 to 18 years 1300 1300
19 to 50 years 1000 1000
51+ years 1200 N/A
Ca-ABSORPTION IN INTESTINETWO 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
Ca-ABSORPTION IN INTESTINEACTIVE- 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)
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
Ca-ABSORPTION IN INTESTINELOW 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
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
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
Ca HOMEOSTASIS
Ca HOMEOSTASISECF Ca IS CONTROLLED BY CLASSICAL –VE
FEEDBACK SYSTEMPTH ACTS ON BONE,KIDNEY & ON VIT-D VIT-D ACTS ON BONE & INTESTINECALCITONIN ACTS OPPOSITE OF PTHs. Ca LEVEL CONTROLS LEVEL OF
PTH,CALCITONIN
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
Ca HOMEOSTASIS
Ca HOMEOSTASISPTH & VIT-D ACTS ON OSTEOCLASTS -
MOBILIZES Ca TO PLASMAVIT-D ACTS ON INTESTINAL CELLS – INCREASES
ABSORPTION OF CaPTH ACTS ON KIDNEY- MORE Ca REABSORBED,
ALSO MORE 1,25(OH)₂-D FORMED→ MORE Ca ABSORBED IN INTESTINE
DISORDER OF Ca METABOLISM• RICKETS• OTEOMALACIA• OSTEOPOROSIS• HYPOCALCEMIA• HYPERCALCEMIA
THANK YOU