Regulation of calcium and phosphate Flashcards
what is the most abundant metal in the body?
calcium
what is the recommended adult intake of calcium?
1000mg per day
what percentage of calcium is stored in the skeleton and teeth, and what form is it stored as?
99% calcium hydroxyapatite crystals
what is the average concentration of plasma calcium?
2.5mmol/L
what does plasma calcium consist of?
ionised (free) Ca2+ and bound Ca2+
what is bound Ca2+ bound to?
plasma proteins and anions eg. bicarbonate, phosphate, lactate
what is calcium important for?
muscle contraction bone strength intracellular 2nd messenger intracellular co-enzyme hormone/neurotransmitter stimulus-secretion coupling blood coagulation (factor IV)
what is phosphate used in?
high energy compounds eg. ATP 2nd messengers fundamental molecules eg DNA, RNA, phospolipids
what is the proportionality of extracellular phosphate to extracellular calcium? What does this mean?
inversely proportional both regulated by the same hormones
what percentage and concentrations of extracellular calcium is: a) free (ionised) b) i) bound to plasma proteins ii) associated with inorganic ions
a) 50% 1.25mM b) i) 45% 1.13mM ii) 5% 0.13mM
which factors increase calcium levels? Where do they act, mainly?
parathyroid hormone (PTH) (secreted by parathyroid glands) vitamin D (synthesised by skin in response to UVB light or intake via diet) kidney, gut, and bone
which factors decrease calcium levels? what happens if the parafollicular cells are removed?
calcitonin (secreted by thyroid parafollicular cells) reduce calcium acutely, but no negative effects if parafollicular cells are removed
what are the two sources and therefore forms of vitamin D?
diet - vitamin D2 (ergocalciferol) sunshine - vitamin D3 cholecalciferol
which initial chemical is converted to vitamin D3 in the skin by UVB light? What is the intermediate chemical?
7-dehydrocholesterol Pre-vitamin D3
vitamin D3 and D2 are transported in the blood to which organ before forming 25 (OH)cholecalciferol which enzyme is used to convert them?
liver 25-hydroxylase
25(OH)cholecalciferol is transported in the blood to which organ? which enzyme is used next? what is it converted into?
kidneys 1-alpha-hydroxylase 1,25(OH)2cholecalciferol (active form of vitamin D)
what is another name for 1,25(OH)2cholecalciferol?
calcitriol
when we are measuring someone’s vitamin D status in the body, which hormone do we measure in the serum?
inactive form of vitamin D: 25(OH)cholecalciferol
what happens to 1-alpha-hydroxylase once calcitriol is made?
the enzyme is switched off as a negative feedback mechanism to stop too much active vitamin D3 from being produced
what does calcitriol do in the kidney?
increases reabsorption of Ca2+ and PO43- into the blood
what does calcitriol do in the gut?
stimulates absorption of Ca2+ and PO43-
what does calcitriol do in the bones?
stimulates osteoblast activity
where are parathyroid glands?
at the back of the thyroid glands left and right
where is parathyroid hormone (PTH) made?
in the chief cells in the parathyroid gland
how is PTH made?
cleaved from a long polypeptide chain precursor called pre-pro-PTH
how is PTH secretion related to serum calcium level?
it is inversely proportional
which receptor on which cell detects circulating calcium concentration?
G-protein coupled calcium receptors on chief cells
what happens when calcium binds to the G protein coupled receptors on the chief cells in the parathyroid glands?
PTH secretion is inhibited
what happens when there is a low concentration of circulating calcium?
less calcium binds to the receptor so more PTH is secreted
- how does PTH increase circulating calcium levels in the kidney?
- how cause levels to increase in the gut?
- Increases Ca2+ reabsorption
stimulates excretion of phosphate
increases 1-alpha-hydroxylase activity which in turn
increases 1,25(OH)2D3 synthesis
- this leads to Ca2+ and phosphate absorption in the gut
what does PTH do to the bone?
stimulates osteoclast activity in the bone which stimulate bone resorption - resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood
osteoBlasts do what?
Build bone
osteoClasts do what?
consume bone
how does PTH stimulate osteoblasts to break down bone?
- PTH receptor on osteoblast - binds
- osteoclast activating factors released which transform the osteoblasts into osteoclasts eg. RANKL, receptor activator of nuclear factor kappa-B ligand
what are the two negative feedback pathways which regulate PTH production?
- calcium binding to its G protein coupled receptors on the chief cells in the parathyroid gland, inhibiting PTH production
- calcitriol receptors on the chief cells detect calcitriol (active vitamin D3) which inhibits PTH production
where is calcitonin secreted?
what is its function?
what is its physiological role?
parafollicular (C) cells of thyroid gland
reduces serum calcium
unclear because removal of thyroid gland does not affect serum calcium
how does calcitonin work?
- increase in plasma Ca2+ stimulates parafollicular cells to secrete calcitonin
- promotes Ca2+ excretion from kidney and reduces osteoclast activity
- causing plasma Ca2+ to decrease
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how does PTH affect phosphate reabsorption?
inhibits Na+/PO43- co-transporter in cuboidal epithelia of proximal tubule, increasing excretion of phosphate in the urine due to less reabsorption into the blood
which cells produce FGF23?
what is its function?
osteocytes in bone
- inhibits sodium phosphate co transporter in cuboidal epithelial cells of proximal tubule
- inhibits calcitriol production, resulting in less phosphate absorption from gut
- what is HIGH serum calcium concentration called? how does it affect membrane exciteability?
- what is LOW serum calcium concentration called?
- hypercalcaemia - extracellular calcium blocks Na+ influx, so LESS membrane exciteability
- hypocalcaemia - enables greater Na+ influx, so GREATER membrane exciteability
signs and symptoms of hypocalcaemia
- paraesthesia (hands, mouth, feet, lips) - pins and needles
- convulsions (seizures)
- arrythmias - heart
- tetany - muscles contract and can’t relax again
Mmemonic: CATs go numb
Give 2 signs of hypocalcaemia you can test for
- Chvostek’s sign - tap facial nerve just below zygomatic arch - positive response = twitching of facial muscles - indicates neuromusculaer irritability
- Trousseau’s sign - inflation of BP cuff for several minutes induces carpopedal spasm
causes of hypocalcaemia
- low PTH levels = hypoparathyroidism
- neck surgery
- auto-immune
- magnesium deficiency
- congenital (agenesis, rare)
- vitamin D deficiency
causes of vitamin D deficiency
- adequate dietary intake/ malabsorption
- insufficient sun exposure
- liver disease
- renal disease
- vitamin D receptor defects (rare)
consequences of vitamin D deficiency in children and adults
lack of mineralisation = soft bones
children - rickets (bowing of bones)
adults - osteomalacia (fractures, proximal myopathy)
signs and symptoms of hypercalcaemia
stones, abdominal moans and psychic groans
reduced neuronal exciteability - 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 parathyroid gland adenoma
- no negative feedback - high PTH but high calcium
- Malignancy
- bony metastases produce local factors to activate osteoclasts
- certain cancers (eg. squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors
- vitamin D excess (rare)
