Control of Mineral Metabolism Flashcards

1
Q

roles of calcium

A

structural (bone), second messenger, exocytosis, neuronal/muscle excitability

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2
Q

hypocalcemia effect on neuronal/muscle excitability

A

increase excitability

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3
Q

hypercalcemia effect on neuronal/muscle excitability

A

decreases excitability– due to surface charge screening

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4
Q

why does hypercalcemia result in hypoexcitement

A

due to Ca in ECF, it binds the negative charges on the cell membrane of neurons/muscles, making the voltage gated channels sense less of a charge difference between inside/outside and less likely to fire

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5
Q

Roles of phosphate

A

Structure, energy currency, component of DNA/RNA, regulatory role (phosphorylation)

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6
Q

how well is Ca absorbed

A

not well, about 50% absorbed in gut; also lose about 325 from secretions in intestine, so net intake about 175 mg from diet of 1 g
- excrete about 825 in feces

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7
Q

Ca level set point

A

between 8 and 10

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8
Q

how is Ca in blood

A

50% bound to albumin,
about 40% as free Ca,
and 10% as salts (bicarbonate, phosphate)
- free Ca is regulated

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9
Q

how much Ca does kidney filter

A

about 10 g– retains most of it, excreting about 0.2 g excreted and retains about 9.8 g

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10
Q

main cell types in bone formation/degradation

A
  • Osteoblasts
  • complex canals filled with canalicular fluid–contains osteocytes
  • osteoclasts– phagocytic cells involved in matrix degradation
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11
Q

does blood or canalicular fluid have higher Ca

A

blood– this drives Ca into canalicular fluid

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12
Q

How does Ca get into bone

A

Ca pumped into canalicular fluid via surface osteoblasts and taken up by osteocytes and pumped out

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13
Q

how much Ca is exchanged between blood/canalicular fluid

A

10 g per day of Ca is rapidly exchanged

NOT Phosphate

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14
Q

Osteoclast role

A

degrade bone matrix to release Ca and Phosphate; slower than Ca exchange with blood and canalicular fluid

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15
Q

what processes contribute to serum Ca

A

fast exchange between blood and canalicular fluid and slower osteoclastic process exchanging both Ca and phosphate (net exchange of 280 mg Ca and 210 mg of phosphate every day)

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16
Q

is phosphate or Ca better absorbed

A

phosphate

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17
Q

how much phosphate taken up per day

A

1400 mg in diet – 1100 absorbed–200 lost in gut secretions

  • net uptake 900 mg, while 500 mg excreted in feces
  • 7g filtered through kidneys
  • 210 mg exchanged from osteoclast activity
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18
Q

Parathyroid hormone

A
  • peptide hormone
  • released by Ca dependent endocytosis by Chief cells of parathyroid
  • purpose: regulates Ca levels. If Ca lowers, PTH released to restore Ca back to set point
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19
Q

how is PTH stored

A

secretory vesicles;

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20
Q

why does decrease in serum Ca increases cytosolic Ca to release PTH

A
  • have Ca sensor on chief cells
  • normally bound with Ca– inactive
  • removal of Ca triggers receptor, which is a G protein coupled receptor (Gq) – produces IP3 – acts on IP3 receptors in ER to release Ca into cytosol, allowing vesicles of PTH release from vesicles
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21
Q

how does PTH act

A

on PTH receptors– G coupled protein receptors (Gs or Gq)– increase cAMP or IP3 levels in body

22
Q

function of PTH

A
  • mobilize sources of Ca to increase serum Ca back to set point
  • activate all processes leading to increased Ca in blood
    BONE
  • activates rapid Ca exchange so that equilibrium goes towards Ca release from bone
  • the slower osteoclast process activated – equilibrium shifted towards matrix breakdown and Ca going into blood (Phosphate will also be released here)
    KIDNEY
    -decreased reabsorption of phosphate but retention of Ca (so it doesn’t exceed solubility); also increases synthesis of 1,25 (OH)2 Vit D
    GUT
  • also increases Ca absorption via vitamin D
23
Q

if too much Ca phosphate

A

can have calcium-phosphate deposition

-

24
Q

high PTH

A

lots of Ca loss from bone – osteoporosis

- also can get kidney stones (lots of Ca retained can exceed solubility even if phosphate filtered out)

25
how does PTH increase Ca absorption
- through activation of vitamin D - vit D3 produced by skin (inactive) but activated by hydroxylation reactions in liver -- 25 hydroxy vit D3 -- 1,25-dihydroxy vit D3 in kidney - kidney also have enzyme to inactivate vit D3 -- becomes 24,25 - dihydroxyvitamin D3
26
what other deficiency would you have with PTH def
vitamin D deficiency
27
function of vitamin D
promotes absorption of Ca by increasing Ca binding protein Calbindin
28
Calbindin fxn
bind Ca and transfer form lumen of gut
29
2 hormones controlling Ca and phosphate in blood
PTH , vit D (absorption)
30
production/action of vitamin D regulated by what
parathyroid hormone
31
Causes of hyperparathyroid
usually tumors of parathyroid gland, and other tumors secreting peptides mimicking PTH
32
causes of hypoparathyroidism
surgical errors (thyroidectomy), pseudohypoparathyroidism
33
hyperparathyroid sxs
sluggish, low mental/muscle response, osteoporosis over time
34
sxs of hypoparathyroidism
Ca below set point-- tetany, seizures, retain more phosphate, Ca driven into bone
35
pseudohypoparathyroidism
glands nl, hormone nl, but receptors abnormal - can even have elevated hormone
36
how is phosphate transported in blood
85% free in ionized active form (as HPO4 and H2PO4) | - nl serum phosphate about 3-4 mg/dl
37
Calcitonin
produced by parafollicular 'C' Cells of thyroid | - secreted in response to elevated Ca and certain GI hormones (gastrin, cholescystokinin, secretin, glucagon)
38
function of calcitonin
acts on bone to decrease efflux of labile bone calcium
39
how is 1, 25 (OH)2 Vitamin D regulated
it acts in negative feedback look to negatively affect 1-hydroxylase - often 1-hydroxylase and 24-hydroxylase reciprocally regulated by influencing factors (i. e. high PTH positively affects 1-hydroxylase and negatively affects 24-hydroxylase; also leads to increase Ca via increased 1,25(OH)2 Vitamin D - cAMP thought to be involved in mediating influences of PTH/phosphate on 1 and 24 hydroxylase activity`
40
Short term regulation of blood Ca
mainly by PTH mobilizing Ca when levels are low; Calcitonin may help with increasing storage rate of acute Ca load
41
long term regulation of Ca balance
Vitamin D important in long-term regulation of Ca/phosphate via intestinal absorption
42
vitamin D deficiency
Rickets in children; osteomalacia in adults - rare in US due to milk supplementation; can be seen in certain liver diseases and renal dysfunction
43
Rickets: severe skeletal deformities
severe skeletal deformities
44
osteomalacia
vitamin D deficiency in adults; can include bone pain and pathologic findings
45
excess vitamin D
ingestion of lots of vitamin D-- hypercalcemia and pathological calcification of soft tissue
46
hyperparathyroidism
primary: increased PTH increases Ca levels in plasma and urine -- can cause renal stones secondary: any disorder where plasma Ca low (rickets/renal failure)
47
effects of hypercalcemia
vague/overt sxs of muscle weakness, depression and GI disorders; severe cases-- bone demineralization can cause bone pain/fractures
48
hypoparathyroidism
lack of PTH causing low calcitriol levles and decreased serum Ca levels as a result of less absorption in kidneys and intestines -increased neuromuscular excitability (cramps, seizures, mental changes)
49
test for hypoparathyroidism
tap facial nerve-- evokes facial muscle spasms called Chvostek's sign)
50
treat hypoparathyroidism
vitamin D and Ca supplements