Regulation Of Calcium And Phosphate Flashcards
Where did we get calcium from?
All dietary
Most abundant metal in body
We need 1000mg a day
How is calcium distributed round the body?
99% is is skeleton and teeth as calcium hydroxyapatite crystals
Extracellular calcium is tightly regulated
Unbound ionised calcium is biologically active
What are the hormones involved In Increasing serum calcium and phosphate?
Parathyroid hormone (PTH)
Vitamin D
These both mainly act on the kidney, bone and gut
What is the hormone involved in decreasing serum calcium and phosphate?
Calcitonin (parafolicular cells of thyroid)
But doesn’t have as strong effect. Nothing much happens if you remove the parafollicular cells
What are the sources of vitamin D?
The diet - vitamin D2 (ergocalciferol)
Skin synthesis, UVB - vitamin D3 (cholecalciferol)
What is the active form of vitamin D?
Calcitriol (1,25(OH)2 cholecalciferol)
How does vitamin D metabolism work (to make calcitriol)?
Skin: UVB rays incident in the skin make 7-dehydroxycholesterol
This goes to pre-vitamin D3
Then Vitamin D3
Then into the blood
Vitamin D2 from the diet is also present in the blood
Vitamin D —> 25(OH)cholecalciferol (in the liver using 25-hydroxylase)
25(OH)cholecalciferol —> 1,25(OH)2 cholecalciferol (in the kidney using 1 alpha-hydroxylase)
So vitamin D must be hydroxylated twice to be made into the active form
Btw we use 25(OH)cholecalciferol to indicate how much Vitamin D we have as it is more reliable
How is calcitriol synthesis regulated?
By itself
Presences of calcitriol creates a negative feedback loop which decreases transcription of 1 alpha-hydroxylase (that makes calcitriol)
What are the effects of calcitriol?
Bone: increAses Ca2+ reabsorbtion
Kidney: increases Ca2+ and phosphate reabsorbtion
Gut: increases calcium and phosphate absorption (into blood)
The calcium from the gut is what is taken into the bones and kidney
Where and how does parathyroid hormone come from?
Chief cells in the parathyroid glands
It is secreted as pre-pro-PTH and then undergoes cleavage
G protein coupled receptors on chief cells detect change is circulating calcium concentration
PTH secretion is inversely proportional to serum calcium
(High ECF Ca2+ conc - calcium binds to receptors - this inhibits PTH secretion)
(Low ECF Ca2+ - less calcium binding - more PTH secreted)
What are the actions of PTH?
Bone: increases Bone reabsorbtion
Kidney: increases Ca2+ reabsorbtion, increases phosphate excretion, increases 1-alpha-hydroxylase activity
Increases 1,25(OH)2cholecalciferol (calcitriol) synthesis
Gut: increases calcium and phosphate absorption (through calcitriol)
Both increase plasma Ca2+
How does PTH work in the bone?
Binds to receptors on osteoblasts (these build bone)
These release osteoclast activating factors
Osteoclasts (which consume bone) then cause bone resorption
What do the effects of calcitriol on the bone depend on?
Serum calcium
Low: osteoclasts>osteoblasts so more calcium reabsorption from bone
Normal: osteoblasts>osteoclasts so bone formation increases
How is parathyroid hormone regulated?
Increased calcium, decreased PTH (inversely proportional)
Inhibited by synthesis of calcitriol
What is calcitonin and where does it come from?
Parafollicular cells of thyroid
Reduces serum calcium But not all that much
What are the actions of calcitonin?
Detects increased serum calcium
Bone: decreases osteoclast activity
Kidney: increases calcium excretion
Decreases plasma calcium (with limited effect)
What does fibroblast growth factor 23 do?
Regulates serum phosphate
It inhibits the sodium/phosphate cotransporter in the proximal convoluted tubule
This stops reabsorbtion of phosphate so it is excreted in Urine (PTH also does this)
FGF23 also weakly inhibits calcitriol, this means less phosphate is absorbed in the gut
It decreases phosphate
What is the difference between hypo and hyper calcaemia in terms of excitability?
Hyper (high calcium) - more calcium ions surrounding neurones, more resistance to the influx of Na required for an action potential. So less excitability
Hypo (low) - more sodium influx, so more membrane excitability
What are some symptoms of hypocalcaemia?
Paraesthesia - pins and needles
Convulsions
Arrythmias
Tetany (muscle contraction but no relax)
CATs go numb
May show Chvosteks sign. Tap the facial nerve just below zygomatic arch. Positive response is twitching of facial muscles. This indicates excitability due to hypocalcaemia
May also show trousseaus sign. Inflation of BP cuff for several minutes, induces carpopedal spasm
What causes hypocalcaemia?
Low PTH (hypo parathyroidism) - neck surgery, auto immune, magnesium deficiency (used for PTH synthesis), congenital (rare)
Vitamin D deficiency - not enough sun, malabsorption or dietary insufficiency, liver disease, renal disease, vitamin D receptor defects
What does a vitamin D deficiency cause?
Lack of bone mineralisation - soft bones
Children- rickets
Adults - osteomalacia (fractures, proximal myopathy)
What are some symptoms of hypercalcaemia?
Stones, abdominal groans and psychic groans
Reduces neuronal excitability
Stones- nephrocalcinosis - kidney stones
Moans- anorexia, nausea, dyspepsia, constipation, pancreatitis
Groans- fatigue, depression, impede concentration, coma
What causes hypercalcaemia?
Primary hyperparathyroidism - too much PTH (usually due to a parathyroid gland adenoma). Lack of negative feedback, high PTH but high calcium
Malignancy - bony metastases produce local factors to activate osteoclasts, increasing calcium reabsorption from bone
Vitamin D excess - rare
