Lecture 52Ca++ Homeostasis

PTH

Calcitonin 10mg%

Vitamin D

Normal serum calcium

Effect on serum calcium

Dietary Ca++

Ca++

ECF

Ca++

Ca++

Intestine

Kidney

Bone

Ca++

Ca++

PTHChief cells of Parathyroid gland84 a.a- 9,500 MW1st 34 Biological Activity

Transcription

Translation

Pre Pro PTH Pro PTH PTH

6 10Serum Ca++

PTH

Mode of Action of PTH

BoneOsteoclast number

Receptor for PTH on osteoblasts

PTH

Secrete FactorsOsteoclast differentiating Factor

Stimulate Osteoclasts

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

osteoblasts(In the presence of preosteoclasts)

(RANKL)

Parathyroid hormone gene related peptide

PTHrP

Isolated from

Lung tumorsKidney tumors

Responsible for the hypercalcemia of malignancy

Calcitonin

32 aa3,000 mwC cells of thyroid.

Main effect onBone

Inhibits osteoclastic bone resorption

Osteoclasts shrink in size

Vitamin D Metabolism

24,25(OH)2D3

(inactivemetabolite)

24(OH)ase *

Mechanisms of Action of Steroids

1,25(OH)2D3

Intestine calcium binding proteincalbindinepithelial calcium channel TRPV6intestinal calcium absorption(also phosphate absorption)

Bone stimulates osteoclastic activityintracellular 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

(also phosphate absorption)

Urinary calcium excretion (only at supra-physiological concentration)

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 SHRINKSosteoclasts

No effect (inhibits gastric secretion from stomach)

Vitamin D #osteoclasts Enhances action of PTH on calcium at the distal tubule

Calcium absorption