TBL6 Calcium Flashcards
Calcium is found in 3 forms in blood serum.
- Ionised calcium (free and bioactive)
- Bound to albumin
- Calcium complexed to serum constituents
Most calcium is found in bone as ________, thus it serves as a major reservoir.
hydroxyapatite crystals
Any changes in concentration of ________ affects the concentration of ionised calcium in the blood.
albumin
- changes in albumin causes changes in the amount of calcium bound to albumin, hence total calcium concentration.
Binding of calcium to albumin is pH-dependent. (Acidosis/alkalosis) increases calcium binding to protein.
Alkalosis increases calcium binding to protein
=> decreased ionised calcium proportion => increased neuromuscular excitability
(increased/decreased) ionised calcium concentration increases neuromuscular excitability.
Decreased ionised calcium concentration
- Calcium ions inhibits sodium transport. Thus, lower calcium levels will increase neuromuscular excitability, caused by increased sodium transport leading to depolarisation.
Clinical conditions that cause changes in total but not ionised calcium
- Hypo/hyperalbuminemia
2. Multiple myeloma - causes elevated calcium levels due to increased renal calcium reabsorption
Clinical conditions that causes changes to ionised calcium but not total calcium
- Acid-base disorders
- PTH disorders
- promotes bone resorption that increases blood serum ionised calcium levels - Hyperhosphataemia
- Phosphate complexes serum calcium, leading to lower levels of normal ionised calcium
Vitamin D3 (calcitriol) is acquired from 2 main sources.
- Diet
2. Skin (via UV radiation)
Vitamin D3 (Calcitriol) synthesis occurs in ________ where ________ is photoconverted to previtamin D3, which is then converted to Vitamin D3.
- occurs in skin keratinocytes
- 7-dehydrocholesterol (precursor) –> pre-vitamin D3 –> vitamin D3 (Calcitriol)
2-step reaction to convert inactive Vitamin D3 to active metabolite ____________.
- Hydroxylation reaction in the _____ to produce 25-hydroxyvitamin D
- Hydroxylation reaction in the _______ to produce the active metabolite.
active metabolite 1,25-dihydroxyvitaamin D/cholecalciferol
- Hydroxylation reaction in the liver
(Vitamin D3 –> 25-hydroxyvitamin D) - Hydroxylation reaction in the kidneys
(25-hydroxyvitamin D –> 1,25-dihydroxyvitamin D)
by enzyme 1a hydroxylase
In calcitriol synthesis, negative feedback occurs as 1,25-dihydroxyvitamin D inhibits _________ enzyme to reduce the production.
1,25-dihydroxyvitamin D inhibits 1a-hydroxylase enzyme (in the kidneys)
Calcitriol is a principal regulator of calcium. It mainly acts on _______ and bones.
Calcitriol
- mainly acts on intestines to increase intestinal calcium absorption
- acts on bones to increase bone resorption
=> increases total serum calcium levels
PTH is synthesised and secreted by the _______
chief cells of the parathyroid glands
The dominant regulator of PTH is _______.
plasma calcium
- High calcium levels inhibit PTH secretion.
How does calcium concentration affect PTH secretion?
- via membrane-bound calcium-sensing receptors (CASR) present on chief cells
- calcium binds, activating PLC and inhibiting adenylyl cyclase
- increases intracellular calcium concentration
=> prevents exocytosis of PTH-containing granules
The overall action of PTH is to (increase/decrease) plasma calcium levels and (increase/decrease) phosphate levels.
PTH:
- increase plasma calcium levels
- decrease plasma phosphate levels
Action of PTH:
- on bone
- on kidneys
- on intestines (indirectly)
- [bone] increases bone resorption by osteoclasts
- [kidneys] increases renal calcium reabsorption in the distal tubules and stimulate phosphate excretion
- [intestines] stimulate 1,25-dihydroxyvitamin D3 synthesis by stimulating 1a hydroxylase
=> intestinal effects of calcitriol
If excess 1,25-dihydroxyvitamin D3 is produced, _________ catalyses the 24-hydroxylation of calcitriol, inactivating it.
CYP24 (cytochrome P450 enzyme)
Calcitonin is synthesised and secreted by __________.
parafollicular cells of thyroid gland
Calcitonin is stimulated mainly by
increased plasma calcium levels
- the overall action of calcitonin is to decrease plasma calcium levels.
Main effects of calcitonin on:
1. bone
- inhibits osteoclast motility and inactivates them
=> inhibits bone resorption