4.6 - Regulation of Calcium and Phosphate Flashcards
1
Q
What is calcium and how much is the recommended adult intake?
A
- most abundant metal in the body
- diet should make all requirements
- recommended adult intake is 1000 mg/day
2
Q
What is the calcium distribution in the body?
A
- 99% in skeleton and teeth as calcium hydroxyapatite crystals
- 1% intracellular
- 0.1% extracellular which is tightly regulated
2.5 mmol/L in plasma, where 45% is biologically active unbound ionised Ca2+ and 55% is bound Ca2+ - out of the bound Ca2+, 45% is bound to plasma proteins and 55% to anions like bicarbonate, phosphate, lactate
3
Q
What three hormones are responsible for regulating serum calcium and phosphate?
A
- parathyroid hormone (PTH) secreted by parathyroid glands - increases
- vitamin D synthesised in skin or intake via diet
- PTH and vitamin D are the main regulators of calcium and phosphate homeostasis via actions on kidney, bone and gut
- calcitonin secreted by thyroid parafollicular cells - can reduce calcium acutely but no negative effect if parafollicular cells are removed e.g. thyroidectomy = not a main player in regulation
4
Q
How is vitamin D3 made and both D2 and D3 metabolised?
A
- vitamin D is activated after undergoing both hydroxylation steps
- 1,25(OH)2 cholecalciferol = calcitriol = active form of vitamin D
- UVB –> 7-dehydrocholesterol –> previtamin D3 –> vitamin D3 –> 25-hydroxylase –> 25(OH)cholecalciferol –> 1-alpha-hydroxylase –> 1,25(OH)2 cholecalciferol
- OR vitamin D2 from diet –> vitamin D3
- serum 25-OH cholecalciferol (biologically inactive) is a good indicator of body vitamin D status, as calcitriol is difficult to measure in blood
5
Q
How does calcitriol regulate its own synthesis?
A
Decreases transcription of 1-alpha-hydroxylase - negative feedback
6
Q
What are the effects of calcitriol?
A
- bone - low serum calcium = increases Ca2+ reabsorption by binding to calcitriol receptors on osteoblasts which release OAFs which switch on osteoclasts (osteoclasts > osteoblasts)
- when normal serum calcium, calcitriol works to increase bone formation –> osteoblasts > osteoclasts
- kidney - increases Ca2+ and PO4(3-) reabsorption by kidney from urine
- gut - increases Ca2+ and PO4(3-) absorption from food / reabsorption from gut
7
Q
What secretes PTH?
A
- chief cells in parathyroid glands
- secreted as a large precursor (pre-pro-PTH) and cleaved to PTH
8
Q
How is PTH secretion related to calcium levels?
A
- PTH secretion is inversely proportional to serum calcium
- G-protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
- high ECF Ca2+ concentration = more Ca2+ binds to receptors on parathyroid cells = PTH secretion inhibited
- low ECF Ca2+ concentration = less Ca2+ binds to receptors on parathyroid cells = PTH secreted
9
Q
What are the effects of PTH?
A
- bone - increases reabsorption of Ca2+ from bone
- kidney - increases Ca2+ reabsorption from urine, increases PO4(3-) excretion, increases 1-alpha-hydroxylase activity (increases calcitriol synthesis)
- gut - through increase in calcitriol synthesis, there is an increase in Ca2+ and PO4(3-) absorption from gut (so PTH does not directly affect gut)
- overall increase in plasma calcium
- effects on phosphate is neutral - causes loss through kidney and gain through gut
10
Q
What specifically happens when PTH interacts with bone?
A
- PTH binds to PTH receptor on osteoblasts (cells that BUILD bone)
- stimulates osteoblasts to make osteoclast activating factors (OAFs) e.g. RANKL (receptor activator of nuclear factor kappa-B ligand)
- osteoclasts (cells that CONSUME bone) are switched on and dissolve bone, releasing calcium
11
Q
How is PTH regulated?
A
- PTH causes increase in plasma Ca2+ which has negative feedback as it binds to Ca2+ receptors on chief cells and decreases PTH secretion
- PTH also increases calcitriol synthesis by increasing the action of 1-alpha-hydroxylase –> chief cells also have calcitriol receptors and there is negative feedback again as high calcitriol levels cause decrease in PTH secretion
12
Q
Where is calcitonin secreted from and what does it do?
A
- secreted from parafollicular (C) cells of the thyroid gland
- reduces serum calcium
- physiological role in calcium homeostasis in humans unclear
- removal of thyroid gland does not affect serum calcium
13
Q
How does calcitonin work?
A
- increase in plasma Ca2+ is detected by parafollicular cells of thyroid
- leads to calcitonin release which decreases osteoclast activity in bone and increases Ca2+ excretion through urine
- this overall decreases plasma Ca2+
14
Q
How does phosphate reabsorption in the kidneys happen?
A
- phosphate reabsorbed via sodium-phosphate co-transporter - this also therefore results in less sodium excretion in urine (as Na+ also reabsorbed)
- increased phosphate loss in urine would lower serum phosphate levels
- PTH inhibits renal phosphate reabsorption by inhibiting sodium-phosphate cotransporters
- in primary hyperparathyroidism, serum phosphate is low due to increased urine phosphate excretion
15
Q
What is FGF23 and what does it do?
A
- fibroblast growth factor 23 is derived from bone
- also inhibits phosphate reabsorption in kidneys by inhibiting Na-PO4 transporters
- also inhibits calcitriol synthesis causing less phosphate absorption from gut from food
