Ca Homeostasis

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Lecture 52 Ca Homeostasis
Effect on serum calcium
PTH Calcitonin
10mg Vitamin D
Normal serum calcium
2
Ca
Bone
Intestine
Ca
Kidney
3
PTH Chief cells of Parathyroid gland 84 a.a-
9,500 MW 1st 34 Biological Activity
Transcription Translation Pre Pro PTH
Pro PTH PTH
PTH
6 10
Serum Ca
4
Mode of Action of PTH
Bone
Osteoclast number
Receptor for PTH on osteoblasts
Secrete Factors
Osteoclast differentiating Factor
PTH
(RANKL)
Stimulate Osteoclasts
(In the presence of preosteoclasts)
osteoblasts
Kidney

• Inhibits phosphate reabsorption (Proximal and
  distal tubule).
• Stimulates Calcium reabsorption (distal).

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Parathyroid hormone gene related peptide PTHrP
Isolated from Lung tumors Kidney tumors
Responsible for the hypercalcemia of malignancy
6
Calcitonin
32 aa 3,000 mw C cells of thyroid.
Main effect on Bone
Inhibits osteoclastic bone resorption
Osteoclasts shrink in size
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Vitamin D Metabolism

24(OH)ase
24,25(OH)2D3 (inactive metabolite)
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Mechanisms of Action of Steroids
9
1,25(OH)2D3
Intestine calcium binding protein calbindin ep
ithelial calcium channel TRPV6 intestinal
calcium absorption (also phosphate
absorption) Bone stimulates osteoclastic
activity intracellular receptor for 1,25(OH)2D3
in osteoblasts 1,25(OH)2D3 stimulates
synthesis of RANKL Stimulates
osteoclasts (in the presence of
preosteoclasts Kidney enhances the action of
PTH at the distal tubule
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Summary
BONE
KIDNEY
INTESTINE
PTH
osteoclasts
Inhibits phosphate reabsorption (proximal and
distal tubule) Increases calcium reabsorption
(distal tubule)
No direct effect
PTH 1,25(OH)2D3
which calcium
absorption (intestine)
Calcitonin
No effect
(inhibits gastric secretion from stomach)
Urinary calcium excretion (only at
supra-physiological concentration)
SHRINKS osteoclasts
Vitamin D
Calcium absorption
osteoclasts
Enhances action of PTH on calcium at the distal
tubule
(also phosphate absorption)