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BRS > Regulation of calcium and phosphate > Flashcards

Regulation of calcium and phosphate Flashcards

1
Q

what is the most abundant metal in the body?

A

calcium

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2
Q

what is the recommended adult intake of calcium?

A

1000mg per day

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3
Q

what percentage of calcium is stored in the skeleton and teeth, and what form is it stored as?

A

99% calcium hydroxyapatite crystals

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4
Q

what is the average concentration of plasma calcium?

A

2.5mmol/L

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5
Q

what does plasma calcium consist of?

A

ionised (free) Ca2+ and bound Ca2+

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6
Q

what is bound Ca2+ bound to?

A

plasma proteins and anions eg. bicarbonate, phosphate, lactate

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7
Q

what is calcium important for?

A

muscle contraction bone strength intracellular 2nd messenger intracellular co-enzyme hormone/neurotransmitter stimulus-secretion coupling blood coagulation (factor IV)

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8
Q

what is phosphate used in?

A

high energy compounds eg. ATP 2nd messengers fundamental molecules eg DNA, RNA, phospolipids

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9
Q

what is the proportionality of extracellular phosphate to extracellular calcium? What does this mean?

A

inversely proportional both regulated by the same hormones

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10
Q

what percentage and concentrations of extracellular calcium is: a) free (ionised) b) i) bound to plasma proteins ii) associated with inorganic ions

A

a) 50% 1.25mM b) i) 45% 1.13mM ii) 5% 0.13mM

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11
Q

which factors increase calcium levels? Where do they act, mainly?

A

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

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12
Q

which factors decrease calcium levels? what happens if the parafollicular cells are removed?

A

calcitonin (secreted by thyroid parafollicular cells) reduce calcium acutely, but no negative effects if parafollicular cells are removed

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13
Q

what are the two sources and therefore forms of vitamin D?

A

diet - vitamin D2 (ergocalciferol) sunshine - vitamin D3 cholecalciferol

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14
Q

which initial chemical is converted to vitamin D3 in the skin by UVB light? What is the intermediate chemical?

A

7-dehydrocholesterol Pre-vitamin D3

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15
Q

vitamin D3 and D2 are transported in the blood to which organ before forming 25 (OH)cholecalciferol which enzyme is used to convert them?

A

liver 25-hydroxylase

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16
Q

25(OH)cholecalciferol is transported in the blood to which organ? which enzyme is used next? what is it converted into?

A

kidneys 1-alpha-hydroxylase 1,25(OH)2cholecalciferol (active form of vitamin D)

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17
Q

what is another name for 1,25(OH)2cholecalciferol?

A

calcitriol

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18
Q

when we are measuring someone’s vitamin D status in the body, which hormone do we measure in the serum?

A

inactive form of vitamin D: 25(OH)cholecalciferol

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19
Q

what happens to 1-alpha-hydroxylase once calcitriol is made?

A

the enzyme is switched off as a negative feedback mechanism to stop too much active vitamin D3 from being produced

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20
Q

what does calcitriol do in the kidney?

A

increases reabsorption of Ca2+ and PO43- into the blood

21
Q

what does calcitriol do in the gut?

A

stimulates absorption of Ca2+ and PO43-

22
Q

what does calcitriol do in the bones?

A

stimulates osteoblast activity

23
Q

where are parathyroid glands?

A

at the back of the thyroid glands left and right

24
Q

where is parathyroid hormone (PTH) made?

A

in the chief cells in the parathyroid gland

25
Q

how is PTH made?

A

cleaved from a long polypeptide chain precursor called pre-pro-PTH

26
Q

how is PTH secretion related to serum calcium level?

A

it is inversely proportional

27
Q

which receptor on which cell detects circulating calcium concentration?

A

G-protein coupled calcium receptors on chief cells

28
Q

what happens when calcium binds to the G protein coupled receptors on the chief cells in the parathyroid glands?

A

PTH secretion is inhibited

29
Q

what happens when there is a low concentration of circulating calcium?

A

less calcium binds to the receptor so more PTH is secreted

30
Q
  1. how does PTH increase circulating calcium levels in the kidney?
  2. how cause levels to increase in the gut?
A
  1. Increases Ca2+ reabsorption

stimulates excretion of phosphate

increases 1-alpha-hydroxylase activity which in turn

increases 1,25(OH)2D3 synthesis

  1. this leads to Ca2+ and phosphate absorption in the gut
31
Q

what does PTH do to the bone?

A

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

32
Q

osteoBlasts do what?

A

Build bone

33
Q

osteoClasts do what?

A

consume bone

34
Q

how does PTH stimulate osteoblasts to break down bone?

A
  • 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
35
Q
A
36
Q

what are the two negative feedback pathways which regulate PTH production?

A
  • 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
37
Q

where is calcitonin secreted?

what is its function?

what is its physiological role?

A

parafollicular (C) cells of thyroid gland

reduces serum calcium

unclear because removal of thyroid gland does not affect serum calcium

38
Q

how does calcitonin work?

A
  • increase in plasma Ca2+ stimulates parafollicular cells to secrete calcitonin
  • promotes Ca2+ excretion from kidney and reduces osteoclast activity
  • causing plasma Ca2+ to decrease
    *
39
Q

how does PTH affect phosphate reabsorption?

A

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

40
Q

which cells produce FGF23?

what is its function?

A

osteocytes in bone

  1. inhibits sodium phosphate co transporter in cuboidal epithelial cells of proximal tubule
  2. inhibits calcitriol production, resulting in less phosphate absorption from gut
41
Q
  1. what is HIGH serum calcium concentration called? how does it affect membrane exciteability?
  2. what is LOW serum calcium concentration called?
A
  1. hypercalcaemia - extracellular calcium blocks Na+ influx, so LESS membrane exciteability
  2. hypocalcaemia - enables greater Na+ influx, so GREATER membrane exciteability
42
Q

signs and symptoms of hypocalcaemia

A
  • paraesthesia (hands, mouth, feet, lips) - pins and needles
  • convulsions (seizures)
  • arrythmias - heart
  • tetany - muscles contract and can’t relax again

Mmemonic: CATs go numb

43
Q

Give 2 signs of hypocalcaemia you can test for

A
  • 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
44
Q

causes of hypocalcaemia

A
  • low PTH levels = hypoparathyroidism
  • neck surgery
  • auto-immune
  • magnesium deficiency
  • congenital (agenesis, rare)
  • vitamin D deficiency
45
Q

causes of vitamin D deficiency

A
  • adequate dietary intake/ malabsorption
  • insufficient sun exposure
  • liver disease
  • renal disease
  • vitamin D receptor defects (rare)
46
Q

consequences of vitamin D deficiency in children and adults

A

lack of mineralisation = soft bones

children - rickets (bowing of bones)

adults - osteomalacia (fractures, proximal myopathy)

47
Q

signs and symptoms of hypercalcaemia

A

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])
48
Q

causes of hypercalcaemia

A
  • 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)

BRS (19 decks)

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