Physiology of Ca regulation

Question 1

Describe the Ca in blood

Answer 1

Ca bound to plasma proteins e.g., albumin - 40%
Ca in complexes e.g., citrate - 10%
Ionised/active Ca - 50%

Question 3

What hormones control Ca

Answer 3

Parathyroid hormone (PTH)
Caclitonin
Active Vitamin D3 (calcitriol)

Question 4

Where is PTH produced?

Answer 4

Chief cells of external and internal parathyroid glands

Question 5

Where is calcitonin produced?

Answer 5

Parafollicular (C-cells) of thyroid

Question 6

Label the cells of the parathyroid gland

Answer 6

Question 7

Describe the synthesis of PTH

Answer 7

Stimulated by hypocalcaemia
Preprohormone => prohormone => into secretory vesicles as PTH
First 34 amino acids (N-terminus) is active part
Short half life - 10 mins

Question 8

Describe PTH secretion

Answer 8

Secreted continuously
Increases as extracellular fluid iCa2+ levels decrease
Direct -ve feedback system
Membrane receptors on principal/chief cells
Receptors coupled to G protein which controls exocytosis of PTH containing vesicles

Question 9

What are the 4 actions of PTH?

Answer 9

Bone: fast phase gets calcium from bone fluid
Bone: slow phase gets calcium from bone
Kidney: reabsorption within tubules recovers Ca from filtrate
Intestine: indirect effect through activation of Vit D to get calcium from gut

Question 10

Describe the effect of PTH on bone - fast phase

Answer 10

Osteocytic osteolysis:
- PTH interacts with membrane receptors on osteocytes and osteoblasts
- increases permeability to Ca on bone fluid side of membrane
- increases Ca uptake from bone fluid (ATP powered pump)
- nearby calcium phosphate crystal replace Ca in bone fluid (osteolysis)
- begins in minutes and progressively increases for hours

Question 11

Where is bone fluid found?

Answer 11

Bone fluid is found between osteocytic-osteoblastic membrane and bone

Question 12

Describe the action of PTH on bone: slow phase

Answer 12

Osteoclastic osteolysis
- osteoclasts activated (indirectly by activated osteocytes and osteoblasts as osteoclasts have no PTH receptors) and new osteoclasts formed
- osteoclasts attach to bone and forms a resorption cavity
- bone is resorbed by release of organic acids and proteolytic enzymes
- released Ca and P transported across osteoclast to blood
- takes days to respond

Question 13

Describe the effect of PTH on this kidney

Answer 13

Increases Ca reabsorption in late distal tubules and collecting tubules => retention of Ca and Mg
Decreases phosphorus reabsorption in renal proximal tubule => rapid loss of phosphorous

Question 14

Describe the effect of PTH on vitamin D

Answer 14

Vit D from diet converted to 25-hydroxyvitamin D in liver
Converted to active vitamin D (calcitriol) in renal tubules
PTH activates enzyme 1-alpha-hydroxylase which catalyses calcitriol formation

Question 15

What is the effect of calcitriol on calcium?

Answer 15

Increases Ca absorption from intestine
Decreases Ca excretion by kidneys
Needed for normal bone function

Question 16

How does calcitriol increase intestinal calcium uptake?

Answer 16

Enters intestinal epithelial cells and increases synthesis of calcium-transport proteins => increases active transport of calcium
Takes ~48 hrs

Question 17

what calcium transport proteins are found in the intestine?

Answer 17

Calcium channel proteins on luminal surface
Calcium binding (calbindin) protein ferries Ca to pumps
Calcium ATPase pump on basolateral surface

Question 18

what is the effect of calcitriol on the kidney?

Answer 18

increased calcium and phosphorous reabsorption

Question 19

Describe the role of vitamin D in normal bone health

Answer 19

Without Vit D, bone is not reabsorbed in response to PTH (allows Ca transport across membranes)
Excess Vit D causes osseous proliferation (Ca deposition)

Question 20

What is the action of calcitonin?

Answer 20

Stimulated by hypercalcaemia
Lowers blood Ca
Opposite effects to PTH on bone:
- rapid phase: Ca into bone fluid by inhibiting osteoclast absorptive activity
- slow phase: Ca into bone by reducing formation of new osteoclasts

Question 21

What would plasma tCa look like in hypoproteinaemia?

Answer 21

Low total Ca
Ionised Ca unchanged
Low tCa doesn’t necessarily mean hypocalcaemia

Question 22

Describe the effects of PTH on phosphorous homeostasis

Answer 22

Increased release from bone and gut
Increased secretion from renal tubules