• Total body calcium level is apprx. 1000gm –
• Apprx. 99% calcium remains in bones as
• Apprx 1% in the intracellular and 0.1% in
extra cellular fluids.
• Plasma calcium level is 9mg – 11mg/dl (2-
4. FUNCTIONS OF CALCIUM:
1. Skeletal muscle contraction.
2. Smooth muscle contraction.
3. Transmission of nerve impulse.
4. Skeletal bone and teeth
5. Acts as a second messenger or
some hormonal regulation.
6. Blood coagulation system.
• Nerve and muscle cells become
• Paresthesia or tingling
• Tetany- latent or manifest.
• Muscle cramps carpopedal
spasms, intestinal spasm,
• Seizures- local or generalized.
• Cardiac rhythm disturbance
(prolong QT interval).
7. CALCIUM HOMEOSTASIS
• must be tightly regulated to maintain
• Two system involve:
A)Major organ system i.e. intestine,
kidney and bone.
B)Major hormones involved are,
parathyroid hormone, active vitamin
D3 and calcitonin.
10. Calcium flux INTO and OUT of blood
• “IN” FACTORS: Intestinal absorption, Bone
• OUT” FACTORS: Renal excretion, Bone
formation (Ca incorporation into bone).
• Balance between “IN” AND “OUT” factors
done by :
• ORGAN PHYSIOLOGY OF GUT, BONE, AND
• HORMONE FUNCTION OF PTH AND
VITMAMIN D, CALCITONIN.
11. CALCIUM HOMEOSTASIS
THE ONLY “IN”
THE PRINCIPLE “OUT”
12. INTESTINAL HANDLING OF CALCIUM
• Approx 1000 mg calcium ingested per
• Approx.250 -350 mg(20%-30%) is
absorbed and others secreted through
• Absorption mainly occurs in duodenum
• Absorption is both passive and active.
13. PASSIVE ABSORPTION OF Ca
• Paracellular route, non saturable.
• 5 % ingested Ca absorbed by this
• Indirectly influenced by calcitriol.
Activates protein kinase C
Loosen tight junction
14. ACTIVE ABSORPTION OF Ca
• Transcellular, receptor mediated, 25%
ingested Ca absorbed.
• 1,25(OH)2D mainly controls.
• Calcium is rapidly and reversibly bound
to the calmodulinactin- myosin I
15. ACTIVE ABSORPTION OF Ca
• Calcium binds to calbindin.
• calbindin-calcium complex
dissociates, the free intracellular
calcium is actively extruded
from the cell by Na-Ca
18. RENAL HANDLING OF CALCIUM
• The ultra filterable calcium
equals the total of the ionized
and complexed fractions.
• 10 g of calcium is filtered per
• urine excretion 100 to 200 mg
per 24 hours.
20. CALCIUM REABSORPTION IN PCT.
• parallels that of Na⁺
• 80% by passive
• PTF : GF is 1:1.2.
• Active absorption10-
21. CALCIUM REABSORPTION IN ALH.
• 20%-25% is
• both active and
• Active pathway
proportional to the
• apical NKCC2 and the
generate the “driving
• cinacalcet increases
the abundance of
claudin-14 in tight
• ALH is also influenced
by the CaSR.
23. Effect of diuretics on renal calcium
24. CALCIUM REABSORPTION IN DCT
• 8% - 10% is reabsorbed.
• exclusively via transcellular
1st step: through apical
membrane via TRPV5.
2nd step: binding with
3rd step: extruded via sodium-
calcium exchanger NCX1 and
the plasma membrane
26. Influence of thiazide diuretics
• calcium reabsorption.
• 1st hypothesis:
• 2nd hypothesis: increased
NaCa exchanger in BL
membrane of DCT & CNT.
H₂O& Na absorption in PCT
driving Ca absorption in PCT
28. PARATHYROID HORMON (PTH)
• FOUR parathyroid glands
located behind the thyroid
• Two types of cells
1. Chief cells
2. Oxyphil cells
• Normal plasma PTH
10 -55 pg / mL
• Half life – 10 mins
29. ACTIONS OF PTH
I. Increases calcium and
from the bones.
II. Decreases excretion
of calcium by the
III. Increases the
phosphate by the
IV. Increases intestinal
absorption of calcium
30. BONE RESORPTION INFLUENCED BY
• Bone resorption occurs in two phases:
• Rapid phase: osteocytic osteolysis.
Transfer calcium from canaliculi to the ECF from
bone fluid via osteocytic membrane by
Does not affect bone mass.
Transfer calcium from most recently formed
• Slow phase: done by osteoclast resorption.
31. RAPID PHASE - OSTEOLYSIS
B.FL BECF O.M
33. Slow phase of osteolysis
• Done by OSTEOCLAST.
• Activated by unknown mechanism
Suspected signal by osteocytes and
• Involves two stages
Activation of present osteoclasts
Formation of new osteoclasts
• Observed after several days of PTH
• Long lasting effect can weaken bone.
34. Vitamin D.
• Vitamin D3 (cholecalciferol) is a fat-soluble steroid that
is present in the diet and also can be synthesized in the
skin from 7-dehydrocholestrol(3.2mcg/g skin) in the
presence of uv light.
35. MECHANISM OF ACTION
• 1,25 – dihydroxy cholecalciferol is a
steroid compound (secosteroid)
• Acts via the steroid receptor super family.
• Exposes the DNA – binding domain and
results in increased transcription of some
• Produced by the parafollicular cells
/ C cells of thyroid gland.
• STIMULUS : Increased plasma
Others: β adrenergic agonists,
dopamine and estrogen, GASTRIN,
Decreases absorptive action of
Deposits exchangeable Ca in bone salts
Decreases the formation of osteoclasts
• CLINICAL USE: Used in the treatment of
Hypercalcaemia together with