Calcuim Metabolism And Homeostasis

Question 1

Calcium

Answer 1

• total body 1-1.4kg, 99% in bones
• extracellular ionised calcium (blood)
• intracellular cytosolic

Question 2

Biological roles of calcium

Answer 2

• mineralisation of bones and teeth
• calcium ions in tracellar and extracellular fluid are essential to many biochemical processes
  • neuromuscular excitability and maintenance of membrane potential
  •blood clotting cascade
  •hormonal secret
  •enzymatic regulation
  •cell signalling

Question 3

Total body calcium distribution

Answer 3

The remaining 1% of 99% calcium
- 50% non bound ionised or free dialysable
-10% bound to anions
-40% blood calcium and protein bound

Question 4

Plasma calcium

Answer 4

2.2-2.6 mmol/L
- >2.6 hypercalcaemia
- <2.2 hypocalceamia

• free (unbound or ionised)
• bound to albumin
• complexed
• feedback mechanisms are regulated by the free faction- physiologically important
• measure total calcium = free plus bound plus complexed

Question 5

Plasma calcium in patient

Answer 5

• if patient has low albumin concentration. The total calcium will also be low but the free calcium may be quite normal

Question 6

adjusting calcium

Answer 6

-when the serum total calcium would have been if the albumin had been normal

Question 7

organs and molecules involved

Answer 7

• metabolic control
• parathyroid hormone (PTH)
• 1,25 dihydroxyvitamin D
  -organs involved
• parathyroid glands (calcium sensing receptors)
  *kidney
  *gut
  *bone

Question 8

calcium sensing receptor CaSR

Answer 8

-on parathyroid cells- minute to minute response to ionised Ca
-main physiological ligand is Ca
- serves as a calciostat for calcium homoestasis

Question 9

parathyroid hormone PTH

Answer 9

• a 84 amino acid polypeptide produced by the parathyroid glands
• secretion is regulated by free/ionised calcium, sensed by the calcium sensing receptors
  -measurement is by immunoassay

Question 10

vitamin d metabolism

Answer 10

-1,25(OH)2 cholecalciferol main effect to maintain serum calcium within normal limits
-Also inhibits proliferation and differentiation of cells
modulates immune system
enhances insulin secretion
down regulates renin/angiotensin system

-People of colour need longer sun exposure to make the same amount of vitamin D

> 70y produce 30% less vit D when exposed to sunlight compared to younger person

Latitude, season and time of day important. Can store surplus in fat
Sunscreen effect

Dietary sources –oily fish – salmon, mackerel, cod liver oil

25(OH) cholecalciferol – major circulating form – production poorly regulated and reflects cutaneous production and dietary supplies – a good indicator of sufficiency

Question 11

cholecalciferol

Answer 11

1,25(OH)2 cholecalciferol production tightly controlled by PTH directly and indirectly via hypophoshataemia
Biphasic effect on Ca absorption – 2 - 6h and 12-24h Also enhances PO4 absorption.
Where dietary calcium is inadequate for body’s requirements, 1,25(OH)2 cholecalciferol increases bone resorption – via VDR on osteoblasts. It also increases expression of ALP, OC, osteopontin etc.

Major function of 1,25(OH)2 cholecalciferol for mineralisation is maintenance calcium x PO4 product to allow passive mineralisation of osteoid matrix.

Question 12

calcium homeostasis

Answer 12

Extracellular calcium pool is in dynamic equilibrium with calcium entering and exiting through gut, bone and renal tubule.

Homeostasis of calcium ( and Mg and Po4) achieved by coordinated action of
intestine – site of net absorption
Kidney – site of net excretion
Bone - largest repository of these ions

Kidney – ionised and complexed (but not protein bound) fractions filtered

Question 13

calcuim homeostasis simplified

Answer 13

in response to decrease in ionised Ca, PTH:
- stimulates calcium reabsorption in renal tubule
-stimulates formation of 1,25 DHCC in kidney, which enhances calcium absorption from gut and bone resorption
- promotes bone resorption