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Biochem > Lecture 46- Calcium and Phosphate Homeostasis > Flashcards

Lecture 46- Calcium and Phosphate Homeostasis Flashcards

1
Q

what cellular functions are calcium ions critical in

A

-cell division/ cell adhesion
-plasma membrane integrity
- 2nd messenger in signal transduction
- muscle contractility
- neuronal excitability
- blood clotting
-skeletal development
- bone, dentin, enamel mineralization

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2
Q

what cellular functions is phosphorus critical in

A

-membrane composition
- intracellular signaling
- nucleotide structure
- skeletal development
- bone, dentin, enamel mineralization
- chondrocyte differentiation

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3
Q

what are the 3 major pools of calcium in the body

A

-bone calcium
-calcium in blood and extracellular fluid
- intracellular calcium

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4
Q

what is the hydroxyapatite mineralization of bone important for

A

mechanical and weight bearing properties of bone

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5
Q

what does bone hydroxyapatite serve as a reservoir for

A

calcium to maintain blood ionized calcium within normal range

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6
Q

what is the normal range for total serum calcium in the blood

A

8.5-10.5 mg/dL

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7
Q

what is the biologically active fraction of calcium

A

the ionized form

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8
Q

what are the forms of calcium in the blood

A

-ionized
- bound to albumin
- complexed with citrate or phosphate ions

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9
Q

what is the normal range of ionized calcium

A

4.4-5.4 mg/dL

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10
Q

describe the concentration of ionized calcium and total calcium

A

ionized calcium levels are relatively stable but total calcium can vary with changes in amounts of albumin or pH

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11
Q

how much calcium is ingested per day

A

1000mg

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12
Q

how much calcium is absorbed by the gut per day

A

200mg

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13
Q

how much calcium is filtered through the kidney daily

A

10g

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14
Q

how much calcium is excreted in urine daily

A

200 mg

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15
Q

how much calcium does the skeleton store

A

1Kg

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16
Q

how much calcium is released from bone per day due to normal bone turnover

A

500mg/day

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17
Q

how much calcium is deposited in bone due to bone formation

A

500mg/day

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18
Q

what is the concentration of extracellular calcium

A

1-2 mM

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19
Q

what is the concentration of intracellular calcium

A

0.0001 mM

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20
Q

what is phosphorus present as

A

free phosphate ions in solution - inorganic phosphate

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21
Q

where is the majority of body phosphate

A

in hydrozyapatite mineral phase of bone/teeth

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22
Q

where is the remainder of body phosphate

A

distributed between other tissues and extracellular fluid

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23
Q

where is phsophorus absorbed

A

in the gut

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24
Q

what is the adult serum phosphorus concentration

A

2.5-4.5 mg/dL

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25
Q

what is the function of the extracellular phosphate free in solution

A

buffer to maintain physiological pH

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26
Q

which serum level varies more: phosphate or calcium?

A

phosphate as it is not as tightly regulated

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27
Q

what organs are involved in calcium and phosphate homeostasis

A

gut, skeleton, kidney, and parathyroids

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28
Q

how are calcium and phosphate concentrations regulated in the gut

A

through absorption

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29
Q

how are calcium and phosphate concentrations regulated in the skeleton

A

bone turnover

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30
Q

how are calcium and phosphate concentrations regulated in the kidney

A

filtration and reabsorption

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31
Q

what are calcium and phosphate concentrations regulated in parathyroids

A

hormone secretion

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32
Q

what are the 3 steps in calcium uptake

A

-uptake of calcium from apical side of cell by ion channels belonging to TRP superfamily (transient receptor potential ion channels)
- transcellular transport of calcium - by calcium binding proteins (calbindins)
- extrustion of calcium on basal surface of cell by membrane transport proteins (Ca2_ ATPases or Na+ dependent Ca2+ exchangers)

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33
Q

what does the TRPV6 channel do

A

Ca2+ uptake on apical side of intestinal epithelial cell

34
Q

what does calbindin D9K do

A

transcellular transport of Ca2+ to basal side of cell

35
Q

what does Ca2+ ATPase1b do

A

pumps Ca2+ out of basal side of cell

36
Q

what happens during high dietary calcium intake

A

passive calcium uptake by a diffusional paracellular path of absorption occurs

37
Q

how is phosphate taken up into the cell

A

by phosphate transporter Na+ dependent Pi co-transporter type 2b on brush border of ileum

38
Q

what happens after intestinal absorption of calcium and phospate into blood

A

filtered in kidney glomerulus

39
Q

how much calcium and phosphate are reabsorbed in kidney tubules

A

99% of Ca2+ and 85-95% of Pi

40
Q

what are the 3 steps in Ca2+ uptake in renal reabsorption

A

-uptake
- transcellular transport
- extrusion

41
Q

what does Pi uptake look like in renal absorption

A

same mechanism as in gut but different isoforms of Na+ depended Pi co-transporter

42
Q

what hormones are involved in calcium homeostasis

A

-PTH
-calcitriol
- calcitonin

43
Q

what hormones are involved in phosphate homeostasis

A

PTH, calcitriol, FGF23, and DMP1/PHEX

44
Q

when is PTH released

A

when serum calcium is low

45
Q

how does the body increase calcium in the blood

A

increase calcium release from bone, increase calcium uptake in gut, increase calcium reabsorption in kidney

46
Q

what are serum calcium concentrations detected by

A

calcium sensing receptor expressed in the parathyroid gland

47
Q

what does high serum calcium do to CasR signaling

A

increases it

48
Q

describe PTH

A

84 amino acid peptide hormone produced by parathyroid glands

49
Q

what is the PTH receptor called

A

PTH1R

50
Q

what type of receptor is PTH1R

A

GPCR

51
Q

what are PTH actions mediated via

A

activation of adenylate cyclase/cAMP production

52
Q

what does CaSR signaling shut off do to PTH

A

leads to release of PTH

53
Q

what does PTH do

A

-increases bone resorption (releases Ca and Pi)
- increases calcium reabsorption in kidney
- opposite effect on phosphate reabsorption in kidney

54
Q

what does PTH stimulate in kidney

A

conversion of 25(OH)D3 to active form 1,25(OH)2D3

55
Q

what are the actions of 1,25(OH)2D3

A

-induces expression of calbindins and other components of calcium transport system
-induces expression of phosphate transporters

56
Q

what does the expression of calbindins and other components of calcium transport system result in

A

INCREASED:
-Ca2+ uptake in intestine
-Ca2+ reabsorption in the kidney tubules
- Ca2+ release into circulation from bone

57
Q

what does the expression of phsophate transporters result in

A

INCREASED:
- Pi uptake in the intestine
- Pi reabsorption in they kidney tubules
- Pi release into circulation from bone

58
Q

what do the combined actions of PTH and 1,25(OH)2D3 result in

A

increase serum calcium and phosphate back to normal range

59
Q

what happens when Ca2+ returns to normal

A

further production of PTH inhibited and inhibition by active Vit D3

60
Q

what is the homeostatic response to high serum calcium mediated through

A

modulation of expression of calcium transporter proteins

61
Q

when is calcitonin released and by what

A

released by thyroid gland in response to elevated serum calcium

62
Q

what does calcitonin oppose

A

PTH actions

63
Q

what is the major effect of calcitonin

A

inhibits osteoclast resorption in bone by causing retraction of osteoclast ruffled border

64
Q

what is the minor effect of calcitonin

A

inhibits renal reabsorption of Ca2+ and phosphate allowing them to be excreted in the urin

65
Q

why calcitonin NOW though to play a more minor role

A

thyroid tumors that secrete excessive amounts of calcitonin have normal serum calcium

66
Q

does the removal of the thyroid have a large affect on calcium homeostasis

A

NO

67
Q

what are the main regulators of phosphate homeostasis

A

-PTH,
active vitamin D 3
- FGF 23

68
Q

when is expression of FGF23 induced

A

when serum phosphate is too high

69
Q

what does PTH do w phosphate

A
  • increases phosphate relase from bone
  • decreases renal phosphate reabsorption
  • increases active vitamin D3 production by kidney
70
Q

what does 1,25(OH)2D3 do

A
  • increases phosphate release from bone
  • increases renal phosphate reabsorption
  • increases phosphate uptake in gut
71
Q

what is FGF 23 expression in osteocytes inhibited by

A

DMP-1 and PHEX

72
Q

what is a major source of endocrine FGF23 and regulate phosphate homeostasis

A

osteocytes

73
Q

what are FGF23 actions in the kidney

A

-decreases reabsorption of phosphate
- decreases production of active vit D3

74
Q

what is the overall effect of FGF23

A

lowers serum phosphate

75
Q

what is the main mechanism for rapid regulation of phosphate

A

kidney reabsorption

76
Q

where are NaPi2a and NaPi2c expressed

A

in proximal tubules

77
Q

how does PTH inhibit phosphate reabsorption

A

via inhibition of NaPi2a and Napi2c expression

78
Q

what results in the absence of PTH

A

increases phosphate reabsoprtion

79
Q

what produces FGF23 and when

A

osteocytes when serum phosphate is high

80
Q

what does FGF23 downregulate

A

NaPi2a and NaPi2c

Biochem (34 decks)

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