Regulation of calcium and phosphate Flashcards
1
Q
What is the recommended daily amount of calcium for adults?
A
- 1000mg/day
- Diet should meet all requirements
- Calcium most abundant metal in body
2
Q
Describe the distribution of calcium in the body:
A
- 99% resides in skeleton and teeth as calcium hydroxyapetite crystals
- Extracellulat calcium (tiny amount) is tighty regulated
- ‘Unbound’ ionised calcium is biologically active component
3
Q
What hormones are involved with regulating serum calcium & phosphate?
A
Increase:
- Parathyroid hormone (PTH) secreted by parathyroid glands
- Vitamin D synthesised in skin or taken in via diet
- Main regulators of calcium & phosphate homeostasis via actions of kidney, bone, gut
DECREASE:
- Calcitonin secreted by thyroid parafollicular cells
- Can reduce calcium acutely, no negative effect if parafollicular cells removed (thyroidectomy)
4
Q
What are the steps in Vitamin D metabolism?
A
1) Sunlight UVB -> Pre-vitamin D3 -> Vitamin D3 -> blood stream -> liver
2) Vitamin D2 from diet -> Vitamin D3 in bloodstream -> liver
From liver:
- 25-hydroxylase catalyses hydroxylation of Vitamin D3 to 25(OH)cholecalciferol
- 1 alpha-hydroxylase catalyses hydroxylation of 25(OH)cholecalciferol to 1,25(OH)2cholecalciferol
- CALCITRIOL (acive form of vitamin D) regulates own synthesi sby decreasing transcription of 1 alpha hydroxylase
- Serum 25-OH cholecalciferol biologically inactive and good indicator of body vitamin D status
5
Q
What are the effects of calcitriol?
A
- Increases calcium in bloodstrean: causes reabsorption of calcium from bone, kidney and gut
- Increases phosphate reabsorption from kidney and gut
6
Q
Describe how parathyroid hormone is seecreted:
A
- Chief cells in parathyroid glanfs secrete large precursor pre-pro-PTH, which is cleaved to PTH
- Parathyroid glands found at back of thyroid glands
- G-protein coupled calcium sensing receptor on chief cells detects change in circulating calcium concentration
- PTH secretion inversely proportional to serum calcium
7
Q
How is PTH secretion regulated?
A
- High ECF [Ca2+] : Ca2+ binds to receptors on parathyroid cells - PTH secretion inhibited
- Low ECF [Ca2+] : Less Ca2+ binding to receptors on parathyroid cells - PTH secreted
8
Q
What are the actions of PTH? in the gut ?
A
- Increase calcium reabsorption from bone, gut, kidney
- PTH increase gut reabsorption of calcium by activatinf gormation of calcitriol active vitamin d
- PTH stimulates 1-alpha-hydroxylase step in kidney so more formation of calcium
- PTH has neutral effect on phosphate : through effect on calcitriol formation, PTH has stimulated absorption of phosphate from gut but PTH stimulating excretion of phosphate via urine - so neutral effect
9
Q
Describe PTH action in the bone:
A
- PTH binds to receptors on OSTEOBLAST (b=build bone)
- Stimulates osteoblast -> osteoclast
- Osteoclast activating factors (e.g. RANKL; receptor activator of nuclear factor kappa-B ligand)
- OSTEOCLAST (c-consume) -> bone resorption
10
Q
Describe effect of calcitriol in bone:
A
- Depends on serum calcium
- Low serum calcium : calcitriol increases calcium reabsorption from bone (osteoclasts>osteoblasts)
- Normal serum calcium : calcitriol works to increase bone formation (osteoblasts>osteoclasts)
(calcitriol binds to osteoblast to form osteoclast)
11
Q
How is PTH regulated?
A
- Decrease of calcium in bloodstream sensed by receptors on parathyroid cells - make more PTH
- PTH works directly on bone stimulating osteoclast formation to increase calcium release
- PTH works directly on kidney to increase calcium absorption from urine
- PTH works indirectly on gut by stimulating synthesis of 1,25(OH)2D3 (calcitriol) synthesis - calcitriol increases calcium reabsorption from gut
- Increase in plasma calcium, negative feedback switches off PTH, switch off calcitriol formation
12
Q
How does calcitonin function?
A
- Secreted from parafollicular (C) cells of thyroid gland
- Reduces serum calcium
- Physiological role in calcium homeostasis in humans unclear
- Removal of thyroid gland does not affect serum calcium
- Calcitonin promotes increase in calcium loss via urine so kidney excretes more calcium
- Switches off osteoclast activity
13
Q
A
14
Q
How does FGF23 regulate serum phosphate?
A
- FGF23 (hormone from bone) lowers phosphate
- Cotransporters in kidney cells in proximal convoluted tubule that brings in from urine to cell, sodium and phosphate. Sodium and phosphate flow through , excrete less phosphate in ruine and reabsorb more
- FGF23 lowers in 2 ways:
- Inhibits sodium /phosphate cotransporter so excrete more in urine
- Inhibits calcitriol (active form of vitamin D) which reabsorbs calcium from gut
15
Q
What happens when there is abnormal amount of calcium in serum?
A
- High serum calcium = HYPERCALCAEMIA
- Low serum calcium = HYPOCALCAEMIA
- Action potential generation in nerves/skeletal muscles require NA+ influx across cell membrane
- High extracellular calcium (hypercalcaemia) : Ca2+ blocks Na+ influx so less membrane excitability
- Low extracellular calcium (hypocalcaemia) : enables greater Na+ influx, so more membrane excitability
