Regulation of Ca, Pi, and Mg balance Flashcards

1
Q

What are the forms that calcium exists in the body?

A

ionized, bound to plasma proteins, complexed in non-ionized form

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2
Q

Where is calcium stored in the body?

A

99% in bone, 1% in ICF, 0.1% in ECF

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3
Q

What is the total plasma level of calcium?

A

5.0 mEq/L

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4
Q

What is the biologically active plasma calcium level?

A

2.4 mEq/L

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5
Q

What percent of calcium excretion is through the feces?

A

90%

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6
Q

What is the effect of hyoalbuminemia on calcium levels?

A

increases plasma Ca2+

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7
Q

What is the effect of hyperalbuminemia on calcium levels?

A

lowers plasma Ca2+

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8
Q

What is the effect of acidosis on calcium levels?

A

more free calcium in circulation

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9
Q

What is the effect of alkalosis on calcium levels?

A

more calcium bound to plasma proteins
predisposition to hypocalcemic tetany
acute alkalosis can induce symptoms mimicking hypocalcemia

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10
Q

What is the other name for vitamin D?

A

calcitriol

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11
Q

What does calcitriol act with on the bone?

A

PTH

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12
Q

What is the overall effect of calcitriol?
bone?
intestine?
kidney?

A

overall: increases serum calcium and phosphate
bone: promotes osteoid mineralization and osteoclast mediated bone resorption
intestine: increases calcium absorption (30% absorbed); increases phosphorus absorption
kidney: increases phosphate reabsorption; increases calcium reabsorption

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13
Q

What is the receptor for calcitriol?

A

Vitamin D receptor which is widely expressed

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14
Q

What is a calcitriol deficiency thought to contribute to?

A

chronic pain

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15
Q

What does calcitonin act on? What does it regulate?

A

bone and kidney

level of calcium

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16
Q

What does calcitonin inhibit?

A

bone resorption

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17
Q

What does calcitonin lower with high doses?

A

calcium and phosphate levels

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18
Q

What does calcitonin promote?

A

renal excretion of calcium and phosphate

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19
Q

What does calcitonin oppose?

A

PTH

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20
Q

What is calcitonin stimulated by?

A

hypercalcemia

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21
Q

What is the effect of calcitonin overall?
bone?
kidney?

A

overall: regulates Ca2+ and Pi concentrations
bone: inhibits osteoclast resorption
kidney: promotes calcium and phosphate excretion

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22
Q

What are pharmacologic doses of calcitonin used to treat?

A

osteoporosis
Paget’s disease
hypercalcemia

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23
Q

What is the effect of PTH overall?
bone?
intestines?
kidney?

A

overall: increases serum calcium and decreases serum phosphate
bone: increases osteoclastic resorption
intestine: increases calcium and phosphate absorption indirectly via calcitriol production
kidney: promotes reabsorption of calcium in DCT; decreases reabsorption of phosphate in PCT; decreases activity of Na+/H+ antiporter; decreases bicarbonate reabsorption

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24
Q

What can excess PTH cause?

A

hypercalcemia
hypophosphatemia
hypercholermic metabolic acidosis

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25
Q

What is the function of the calcium sensing receptor (CaSR)?

A

monitors calcium levels
when calcium levels are high, CaSR in the thick ascending limb senses this and is activated on the interstitial space side of the cell, which inhibits calcium reabsorption on the apical membrane (NKCC2 channels) which decreases calcium paracellular diffusion

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26
Q

What are the effects of decreased plasma calcium?

A

increased PTH

  - bone: increased resorption of calcium and Pi
  - kidney: increased Pi excretion, decreased Ca2+ excretion, increased calcitrol production
  - intestines: increased calcium and Pi absorption
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27
Q

What is the filtered load equation?

A

GFR x plasma concentration x filterability

28
Q

What is the filterability of calcium?

A

60%

29
Q

When is calcium not filterable?

A

plasma proteins

30
Q

What percent of calcium is reabsorbed in which parts of the nephron?

A

65-70% proximal tubule
~20% thick ascending limb
8% distal tubule

31
Q

Describe calcium reabsorption in the proximal tubule

A

most paracellular (follows Na+ and water)
some transcellular
-diffusion down gradient into cell
- exits cell via Ca2+-ATPase and Na-Ca2+ antiporter

32
Q

What is the effect of volume contraction on calcium reabsorption?

A

increases calcium reabsorption b/c calcium follows Na and water

33
Q

What is the effect of volume expansion on calcium reabsorption?

A

decreases calcium reabsorption

34
Q

Describe calcium reabsorption in the thick ascending loop (TAL)

A

paracellular (paralleling Na+)
dependent on TEPD (lumen positive voltage)
stimulated by ADH

35
Q

What does ADH do?

A
  1. increasing NaCl reabsorption via thick ascending limb –> increases hypertonicity of medullary interstitium
  2. regulates collecting duct water permeability allowing removal of water from the tubule fluid via diffusion
36
Q

How do loop diuretic work?

A

low yield
inhibits Na+ reabsorption by thick ascending loop
-reduces magnitude of lumen-positive transepithelial voltage
-reduces calcium paracellular reabsorption (increases calcium excretion)
-can treat hypercalcemia

37
Q

Describe calcium reabsorption in the distal tubule

A
  • DT has lumen negative transepithelial voltage
  • reabsorption is active transcellular transport
  • crosses apical membrane via TRPV5
  • crosses basolateral membrane via Na+-Ca2+ exchanger (NCE)
38
Q

Where is TRPV5?

A

distal tubule apical membrane

calcium reabsorption

39
Q

Where is NCE?

A

Na+-Ca2+ exchanger in the basolateral membrane of distal tubule

40
Q

How do thiazide diuretics work?

A

low yield
inhibit Na+ reabsorption in DT and stimulate Ca2+ reabsorption
-reduces calcium excretion in urine
-used to treat calcium containing kidney stones

41
Q

What stimulates calcium reabsorption?

A
PTH and calcitriol (vitamin D) (high yield)
thiazide diuretics (low yield)
42
Q

What do PTH and calcitriol do?

A

stimulate reabsorption of calcium

43
Q

What is the effect of acidemia on calcium?

A

increases calcium excretion by inhibiting TRPV5

44
Q

What is the effect of alkalemia on calcium?

A

decreases calcium excretion by stimulating TRPV5

45
Q

Is calcium secreted in the kidney?

A

NO

46
Q

How much plasma calcium is filtered at the glomerulus?

What percent of filtered calcium is reabsorbed?

A

60% filtered

99% reabsorbed

47
Q
What are the basic functions in regards to calcium:
PTH
vit D/calcitriol
calcitonin
decreased ECV
metabolic alkalosis
A

PTH: upregulates TRPV5, Na-Ca exchanger
vit D/calcitriol: upregulates TRPV5
calcitonin: opposes PTH, stimulated by hypercalcemia, decreases serum phosphorus and calcium concentrations
decreased ECV: increased sympathetics –> Na reabsorption in PCT; calcium reabsorption depends on transepithelial voltage and solvent drag, which depend on Na+ reabsorption
metabolic alkalosis: increases calcium reabsorption by acting on TRPV5/6

48
Q

What is the filterability of phosphate?

A

100%

49
Q

How much phosphate is reabsorbed by PT?

What is involved in the phosphate reabsorption in the PT?

A

80%

Na+-Pi symporter, PTH and Ca2+, FGF-23

50
Q

What is Na uptake across the apical membrane coupled with in the early proximal tubule?

A

SYMPORTERS: primarily HCO3-, glucose, amino acids, Pi, and lactate
ANTIPORTERS: reabsorbed in exchange for H+ or organic solutes

51
Q

How does Pi cross the basolateral membrane?

A

its own transporter; mechanism unknown

52
Q

How does Pi cross the apical membrane?

A

Na+-Pi symporter

53
Q

Describe FGF-23’s role in phosphate regulation

A

secreted by bone in response to PTH, calcitriol, and hyperphosphetemia
FGF-23 receptors on the basolateral membrane
inhibits NaPi symporters on apical membrane
promotes Pi excretion

54
Q

What is the effect of PTH on Pi?

A

inhibits NaPi symporter on apical membrane

promotes Pi excretion

55
Q

Where is calcitriol made?

A

proximal tubule epithelial cells

56
Q

What converst vitamin D to its active form?

A

renal 1alpha-hydroxylase

57
Q

What upregulates 1alpha-hydroxylase expression?

A

low calcium
low phosphate
high PTH

58
Q

What inhibits renal 1alpha-hydroxylase expression?

A

high calcium sensed by CaSR

59
Q

Is vitamin D filtered at the glomerulus?

A

some is filtered, but it is endocytosed by PT cells and reabsorbed

60
Q

What are the major regulatory factors of phosphate?

A

FGF-23 - fibroblast growth factor 23 released by bone to increase phosphate excretion
PTH - lowers serum phosphate by increasing renal excretion
1,25(OH)2D3 - increases serum phosphate by increasing intestinal phosphate absorption
insulin - loswers serum levels by shifting phosphate into cells
dietary - phosphate intake
renal function

61
Q

What is the most important hormone that regulates Pi excretion?

A

PTH

inhibits the NaPi transporters and NaH antiporter of PT cells

62
Q

What is the effect of chronic acidosis on Pi excretion?

chronic alkalosis?

A

chronic acidosis: increases Pi excretion

chronic alkalosis: decreases Pi excretion

63
Q

How much Mg2+ is reabsorbed in the PT?

A

20%

paracellular and follows Na and water

64
Q

How much Mg2+ is reabsorbed in the TAL?

A

70%

paracellular and depends on uptake of Na+ and K+ via NKCC2 which depends on lumen-positive voltage of TAL

65
Q

How much Mg2+ is reabsorbed in the distal tubule?

A

10%, site of fine-tuning

driven by electrical potential

66
Q

How does Mg2+ cross the apical border in the DT? basolateral border?

A

TRPM6; unknown mechanism

67
Q

Is magnesium reabsorption increased or decreased:
dietary depletion (60%; does not meet dietary requirements)
PTH
metabolic acidosis
metabolic alkalosis
ECF volume expansion
ECF volume contraction

A

dietary depletion (60%; does not meet dietary requirements): increased, promotes retention; increases paracellular permeability of Mg
PTH: increased
metabolic acidosis: decreased, decreased paracellular permeability of Mg
metabolic alkalosis: increased, enhances paracellular permeability of Mg
ECF volume expansion: decreased
ECF volume contraction: increased