Calcium Homeostasis Flashcards
Calcium
Most abundant mineral in the body
The body of a young adult human contains ~ 1100g (27.5mol)calcium
99% present in the skeleton, 1% in blood and other tissues
Total plasma calcium is ~ 2.5mmol/L (range 2.2-2.6mmol/L)
Distribution of Calcium in The Blood
Protein bound calcium- 41%
Complexed calcium- 9%
Free ionized calcium-50%
only ionized calcium is physiologically active
Functions of Calcium
Nerve function
Muscle contraction
Blood clotting
Skeletal mineralization
Cellular metabolism
Cell signaling
Calcium metabolism in the adult human
more calcium needed for pregnancy and nursing
Calcium Homeostasis
calcium homeostasis 9-11mg/100ml
rising blood levels increases calcium levels
falling blood levels decreases calcium levels
Calcium Homeostasis: Hormonal Regulation
3 hormones
calcitriol
calcitonin
parathyroid hormone
Parathyroid Hormone (PTH)
Produced by the chief cells of theparathyroid gland(x4) of the m
Single chain polypeptide (84aa) witha molecular weight of9500
Derived from the largerprecursorpeptides pre-proPTHandproPTH
Normal plasma level PTH (1-84)10-55pg/ml; t1/210 min
Regulation of PTH Secretion
Minute to minute:
Ca2+acting via the G protein coupledcalcium sensing receptor(CaSR)
↓ inionized (free)plasma Ca2+causes an ↑ in PTH secretion
Long-term:
Calcitriol acts directly on the parathyroid gland to decreasepreproPTHmRNA
Regulation of Calcium by PTH
decrease of plasma cal
increase PTH
if it goes to bone
increase bone reabsorption
increases plasma ca back to normal
if it goes to kidney
decrease in phosphate reabsorption
increase in ca reabsorption
increases plasma ca back to normal
if it goes via intestines
calcium absorption increase
ncreases plasma ca back to normal
Actions of PTH
increases plasma Ca2+ (and decreases plasma PO43-) via several actions:
Kidney
- Stimulates Ca2+ reabsorption in the distal tubule
- Inhibits PO43- reabsorption in the proximal tubule
- Increases activity of 1a-hydroxylase and decreases 24-hydroxylase
(net effect is a gradual increase in renal production of calcitriol)
Bone
- Stimulates rapid efflux of Ca2+ from freely exchangeable calcium pool
(an effect on osteocytes and bone-lining cells)
- Increases the number and activity of osteoclasts via action on osteoblasts
gradual increase in bone resorption (Ca2+ and PO43- release)
(GI Tract)
Stimulates absorption of Ca2+ and PO43-
Effect is delayed (≥ 24 hr) & indirect (increased renal production calcitriol)
Calcitriol -1a,25-dihydroxyvitamin D3
Active metabolite of vitamin D3
A secosteroid (open B ring)
Regulation of Calcitriol Production
Vitamin D3is rapidly converted in the liver to calcidiol
Plasma levels of calcitriol are determined by:
Rate of conversion of calcidiol to calcitriol (activation step)
Rate of conversion of calcitriol to calcitroic acid (inactivation step)
Actions of Calcitriol
increases plasma Ca2+
GI Tract (Main)
- Stimulates absorption of Ca2+ (principally in the duodenum)
- Stimulates absorption of PO43- (jejunum and ileum)
Bone Increases the number and activity of osteoclasts - Leads to an increase in bone resorption and hence Ca2+ and PO43- release Kidney Facilitates Ca2+ reabsorption (DCT
Calcitonin
Single chain polypeptide (32 aa) with a molecular weight of 3500
Secreted by the parafollicular ‘C’ cells of the thyroid gland
Secretion is regulated by Ca2+
IncreasedCa2+ increased calcitonin secretion
Actions of Calcitonin
Actions lead to fall in plasma Ca2+– opposite effect to PTH
Acts onboneto decrease release of Ca2+and PO43-
Decreases rapid efflux across the bone membrane
Acts directly onosteoclaststo inhibit bone resorption
Acts on thekidneyto decreasetubular reabsorptionofCa2+and PO43-
No significant effect on Ca2+absorption in the small intestine
