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
[Ca10(PO4)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 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. 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. 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 REMODELING
TWO SYSTEM INTERACTING WITH EACH OTHER

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. 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. 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, α₂-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

17. 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

18. 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

19. 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)

21. 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

23. 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

24. 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

26. 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

27. Ca HOMEOSTASIS

28. 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

29. 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

30. Ca HOMEOSTASIS

31. 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

34. DISORDER OF Ca METABOLISM
• RICKETS
• OTEOMALACIA
• OSTEOPOROSIS
• HYPOCALCEMIA
• HYPERCALCEMIA

35. THANK YOU