Calcium and Phosphate Homeostasis Flashcards
Which 5 tissues regulate calcium and phosphate homeostasis
Parathyroid glands
Kidney
Gut
Thyroid
Bone
What is the role of parathyroid glands in Ca2+ and PO4 homeostasis?
Detect levels of plasma Ca2+ amd PO4
Make parathyroid hormone (PTH)
What is the role of the kidney in Ca2+ and PO4 homeostasis?
Site of Ca2+ and PO4 reabsorption
Site of vitamin D activation
What is the role of the gut in Ca2+ and PO4 homeostasis?
Site of Ca2+ and PO4 uptake
What is the role of the thyroid in Ca2+ and PO4 homeostasis?
Site of calcitonin synthesis
Detects serum Ca2+ levels
What is the role of bone in Ca2+ and PO4 homeostasis?
Body store of Ca2+ and PO4
Mike fibroblast growth factor 23 (FGF-23)
List the 6 physiological roles of calcium
Bone formation (growth and remodelling) and teeth
Muscle contraction
Nerve function
Enzyme co-factor
Intracellular second messenger
Stabilisation of membrane potentials
What is added to blood tubes to stop the blood from clotting?
EDTA - chelates calcium
What is the range for plasma Ca2+?
2.12-2.6
What % of plasma calcium is bound calcium?
Bound Ca2+ = 55%
Ionised Ca2+ = 45%
How is bound Ca2+ distributed, i.e. what is it bound to and in what
Bicarbonate, phosphate - 10%
Albumin - 80%
Globulins - 20%
Most of the bound Ca2+ in plasma is bound to albumin
What will an increase in albumin do to the plasma levels of Ca2+?
Increased albumin will increase the total plasma levels of Ca2+
Albumin binds to calcium
Ionised Ca2+ (the active portion of plasma Ca2+) will be unaffected
Describe normal Ca2+ homeostasis
Low serum Ca2+ stimulates the parathyroids to secrete PTH
An increase in PTH has 3 actions:
- increase bone resorption and increase Ca2+ release
- acts on the kidneys to increase Ca2+ reabsorption
- alters the enzyme 1a-OHase which converts inactive vitamin D (calcidiol) to active vitamin D (calcitriol). Calcitriol increase reabsorption in the kidney, and increases absorption of Ca2+ from the GI tract
An increase in serum Ca2+ and vitamin D switches off PTH secretion
An increase in serum Ca2+ causes the thyroid to produce calcitonin which inhibits reabsorption of Ca2+ in the bone and kidneys
How many parathyroid glands are there and where are they located?
4 parathyroid glands
Located on the posterior surfaces of the thyroid gland
Why is it important that the parathyroid glands have a separate blood supply?
Because a thyroidectomy should leave the parathyroid glands in tact and working
Which cells within the parathyroid glands synthesis and secrete parathyroid hormone?
Chief cells
What does PTH bind to?
What else can bind to this receptor?
PTHR1 - a G-protein coupled receptor
PTH-related peptide (PTHrP) can also bind to PTHR1
What does a sustained release of PTH require?
Gene expression
Proliferative activity of PT cells
Increase in gland and cell size
Describe how a HIGH level of Ca2+ is detected and PTH is regulated
High Ca2+ levels are detected by calcium-sensing receptor (CaSR) in the parathyroid gland
This increases activation of a G protein coupled receptor
This activates PLC, which increase IP3 levels, which DECREASES PTH release from the parathyroid hormone
Activation of the G protein coupled receptor also inhibits a pathway that increases cAMP and increases PTH, leading to a further reduction in PTH
Describe how a LOW level of Ca2+ is detected and PTH is regulated
Low serum Ca2+ levels means there is less binding to CaSR
This leads to less activation of the G protein coupled receptor
Which leads to less inhibition of adenylate cyclase, therefore increases levels of cAMP leading to an INCREASE in PTH
How can a malignancy cause hypercalcaemia?
Can cause a loss of Ca2+ from the bone due to osteolytic metastases
OR
the malignancy can produce parathyroid hormone-related peptide (PTHrP), which mimics exactly the action of PTH
What does parathyroid hormone related peptide (PTHrP) NOT increase?
Why is this useful?
Does not increase vitamin D levels
Good for diagnosis - can distinguish between PTH and PTHrP hypercalcaemia
Where is most of our calcium absorbed?
Duodenum and upper jejunum
How is calcium absorption facilitated in the GI tract?
By vitamin D
Vitamin D up-regulates luminal Ca2+ channels (TRPV6)
It also increases the amount of calcium binding protein (CaBP)
Name the 3 ways Ca2+ is moved out of the basolateral surface of the epithelial cell in the GI tract?
How else can Ca2+ be absorbed by the GI tract
Ca2+ ATP transporter
Ca2+ 3 Na+ exchanger
Endocytosis and exocytosis of Ca2+ -CaBP complex
Paracellular transport
How is Ca2+ up-taken by the brush border?
By TRPV6 calcium transporter
How is Ca2+ moved through the cell?
CaBP
Ca2+ binding protein
When is calcitonin used?
When there is excess Ca2+
Where is calcitonin synthesised?
Synthesised by C cells in the thyroid gland