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