Regulation of calcium phosphate Flashcards
What increases the concentration of serum calcium and phosphate and where are they synthesised
Parathyroid hormone: synthesised by parathyroid glands
Vitamin D: synthesised in skin or uptake by diet
What decreases the concentration of serum calcium and phosphate?
Calcitonin: secreted by parafollicular cells
what is serum 25-OH cholecalciferol
its a good indicator of Vitamin D status
biologically inactive
How is Vitamin D made into its active form?
From UV: ( in skin cells) 7-dehyrocholesterol -> pre vitamin D3 -> Vitamin D3
(in liver) Vitamin D3-> 25 OH cholecalciferol via 25 alpha hydroxylase
(in kidney) 25 OH cholesterol -> 1 25(0H)2 cholecalciferol via 1-alphahydroxylase
From diet: Vitamin D2 from diet -> Vitamin D3 -> liver and kidney bit repeated
how does 1, 25(OH)2 cholecalciferol regulate its own synthesis
Decreases transcription of 1-alpha-hydroxylase
Effects of calcitriol
increase calcium and phosphate reabsorption in the kidney
increase phosphate absorption in gut
increase calcium absorption in gut
increase calcium reabsorption in bones
Where are parathyroid hormones secreted from
chief cell in parathyroid gland
what is the PTH precursor
what detects change in Ca2+ conc to stimulate chief cell to produce PTH
what is the relationship between PTH and serum calcium
pre-pro-PTH
G-protein coupled receptors
inversely proportional
how does high serum calcium affect parathyroid cells (vice versa for low serum calc)
many calc bind to receptor on parathyroid cell
PTH secretion inhibited
Effects of PTH
Bones: increase calcium conc in blood from bone
Kidney: increase calcium reabsorption
phosphate excretion
increase 1 alpha hydroxylase activity
increases 1 25(OH)2 cholecalciferol
Gut: increase calcium and phosphate reabsorption ( due to increased 1 25(OH)2 cholecalciferol)
How does PTH impact bone
PTH binds to PTH receptor on Osteoblast
Osteoblast releases Osteoclast activating factors eg RANKL)
Osteoblasts activates osteoclast
increases bone resorption ( breakdown of bone to release calcium into the bloodstream
Effects of Calcitriol on bone for low and high serum calcium
Low serum calcium: calcitriol binds to calcitriol receptor on osteoblast increasing calcium reabsorption from bone to blood. Osteoclasts> osteoblasts
High serum calcium: Increases bone formation
Osteoblasts> osteoclasts
How is PTH regulated
increases calcium in plasma decreases secretion of PTH
increased calcium decreases 1 25 (OH)2 D3 synthesis, decreasing PTH conc
where is calcitonin secreted
what does it do
does its removal affect serum calcium
parafollicular cells of thyroid gland
reduces serum calcium
no
how does calcitonin work
Increases calcium conc detected in blood
increased secretion of calcitonin
In bone: decrease osteoclast activity
In kidney: increase calcium excretion in urine
decreases plasma Ca2+
what does FG23 do
how does it work
lowers phosphate
method 1: inhibits sodium phosphate transporter between proximal tubule and blood
cant reabsorb phosphate from urine as more phosphate lost in urine
method 2: Inhibits calcitriol
reduces phosphate reabsorption from gut
what is the term for high serum calcium
what is the term for low serum calcium
effects of high serum calcium (vice versa for low)
hypercalcaemia
hypocalcaemia
calcium blocks Na+ influx, less membrane excitability
how does Hypocalcaemia affect body
sensitises excitable tissues; muscle cramps, tetany , tingling
signs and symptoms:
Paraesthesia (hands, mouth, feet, lips)
convulsions
arrhythmias
tetany
what is Chvostek sign
what is trousseaus sign
when facial muscles twitch after tapping the facial nerve below the zygomatic arch
when inflation of BP cuff induces carpopedal spasm
both indicate neuromuscular irritability due to hypocalcaemia
Causes of Hypocalcaemia
Low PTH levels = hypoparathyroidism
Surgical – neck surgery Auto-immune Magnesium deficiency Congenital (agenesis, rare) Vitamin D deficiency
causes of vitamin D deficiency
dietary insufficiency
inadequate sun exposure
liver disease- no synthesis of compounds before calcitriol
renal disease- no 1-alphpa-hydroxylase action stimulated by PTH
Vit D receptor defects (rare)
consequences of vit D deficiency
Lack of bone mineralisation = ‘soft’ bones
In children – rickets (bowing of bones)
In adults – osteomalacia (fractures, proximal myopathy)
symptoms of hypercalcaemia
‘Stones, abdominal moans and psychic groans’
Reduced neuronal excitability – atonal muscles
Stones – renal effects
Nephrocalcinosis – kidney stones, renal colic
Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
Causes of hypercalcaemia
Primary hyperparathyroidism
- Too much PTH
- Usually due to a parathyroid gland adenoma
- No 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)
