Physiology of Ca regulation Flashcards
Describe the Ca in blood
Ca bound to plasma proteins e.g., albumin - 40%
Ca in complexes e.g., citrate - 10%
Ionised/active Ca - 50%
What hormones control Ca
Parathyroid hormone (PTH)
Caclitonin
Active Vitamin D3 (calcitriol)
Where is PTH produced?
Chief cells of external and internal parathyroid glands
Where is calcitonin produced?
Parafollicular (C-cells) of thyroid
Label the cells of the parathyroid gland
Describe the synthesis of PTH
Stimulated by hypocalcaemia
Preprohormone => prohormone => into secretory vesicles as PTH
First 34 amino acids (N-terminus) is active part
Short half life - 10 mins
Describe PTH secretion
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
What are the 4 actions of PTH?
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
Describe the effect of PTH on bone - fast phase
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
Where is bone fluid found?
Bone fluid is found between osteocytic-osteoblastic membrane and bone
Describe the action of PTH on bone: slow phase
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
Describe the effect of PTH on this kidney
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
Describe the effect of PTH on vitamin D
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
What is the effect of calcitriol on calcium?
Increases Ca absorption from intestine
Decreases Ca excretion by kidneys
Needed for normal bone function
How does calcitriol increase intestinal calcium uptake?
Enters intestinal epithelial cells and increases synthesis of calcium-transport proteins => increases active transport of calcium
Takes ~48 hrs
what calcium transport proteins are found in the intestine?
Calcium channel proteins on luminal surface
Calcium binding (calbindin) protein ferries Ca to pumps
Calcium ATPase pump on basolateral surface
what is the effect of calcitriol on the kidney?
increased calcium and phosphorous reabsorption
Describe the role of vitamin D in normal bone health
Without Vit D, bone is not reabsorbed in response to PTH (allows Ca transport across membranes)
Excess Vit D causes osseous proliferation (Ca deposition)
What is the action of calcitonin?
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
What would plasma tCa look like in hypoproteinaemia?
Low total Ca
Ionised Ca unchanged
Low tCa doesn’t necessarily mean hypocalcaemia
Describe the effects of PTH on phosphorous homeostasis
Increased release from bone and gut
Increased secretion from renal tubules
