Download Lectures 52- Dr. Christakos

Lecture 52
Ca++ Homeostasis
Effect on serum calcium
PTH
Normal
serum calcium
Calcitonin
Vitamin D
10mg%
Dietary Ca++
Ca++
ECF
Ca++
Ca++
Intestine
Ca++
Kidney
Ca++
Bone
PTH
Chief cells of Parathyroid gland
84 a.a- 9,500 MW
1st 34
Biological Activity
Transcription
Translation
Pre Pro PTH
Pro PTH
PTH
6
10
Serum Ca++
PTH
Mode of Action of PTH
Bone
Osteoclast number
Receptor for PTH on osteoblasts
Secrete Factors
Osteoclast differentiating Factor
Stimulate Osteoclasts
osteoblasts
(RANKL)
(In the
presence of
preosteoclasts)
Kidney
•Inhibits phosphate reabsorption (Proximal and distal tubule).
•Stimulates Calcium reabsorption (distal).
Parathyroid hormone gene
related peptide
PTHrP
Isolated from
Lung tumors
Kidney tumors
Responsible for the
hypercalcemia of malignancy
Calcitonin
32 aa
3,000 mw
C cells of thyroid.
Main effect on
Bone
Inhibits osteoclastic bone resorption
Osteoclasts shrink in size
Vitamin D Metabolism
*
24,25(OH)2D3
(inactive
metabolite)
nomic Mechanism of Vitamin D Actio
Mechanisms of Action of Steroids
1,25(OH)2D3
Intestine
calcium binding protein
calbindin
epithelial 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
Summary
BONE
PTH
Calcitonin
Vitamin D
KIDNEY
INTESTINE
Inhibits phosphate
reabsorption
(proximal and distal
tubule)
Increases calcium
reabsorption (distal
tubule)
No direct
effect
SHRINKS
osteoclasts
Urinary calcium
excretion (only at
supra-physiological
concentration)
No effect
#osteoclasts
Enhances action
of PTH on
calcium at the
distal tubule
#osteoclasts
PTH
1,25(OH)2D3
which
calcium
absorption
(intestine)
Calcium
absorption
(also
phosphate
absorption)
(inhibits gastric
secretion from
stomach)