Calcium and Phosphate Homeostasis Flashcards

1
Q

what is the biologically active form of calcium?

A

free, ionized Ca2+

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2
Q

What effect does aging have on calcium levels?

A

during aging, there are decreases in the amount of calcium absorbed from dietary intake and in dietary intake of calcium

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3
Q

What effect does the decreased calcium absorption/intake levels have in association with aging?

A

aging contributes to osteopenia or osteoporosis

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4
Q

what are the symptoms of hypocalcemia?

A

hyperreflexia, spontaneous twitching, muscle cramp, tingling and numbness

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5
Q

what two signs are associated with hypocalcium?

A

Chvostek sign and trousseau

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6
Q

what are the symptoms of hypercalcemia?

A

constipation, lack of appetite, polyuria, muscle weakness, hyporeflexia, lethargy

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7
Q

what effect does a low extracellular Ca2+ level have on the action potential?

A

it reduces the activation threshold for Na+–> so its easier to evoke an AP

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8
Q

what effect does a high extracellular Ca2+ level have on the acton potential?

A

it raises the activation threshold–> decreased the membrane excitability–> harder to evoke an action potential

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9
Q

the forms of Ca2+ in the blood can be altered by what?

A

changes in plasma protein concentration, changes in anion concentration, acid-base abnormalities

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10
Q

what is the ionized Ca2+ concentration going to look like in an acidemia situation?

A

free ionized Ca2+ concentration increases (because less Ca2+ is bound to albumin

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11
Q

what is the ionized Ca2+ concentration going to look like in an alkalemia situation?

A

free ionized Ca2+ concentration decreases (because less Ca2+ is bound to albumin)

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12
Q

To maintain Ca2+, what must the kidneys do?

A

they must excrete the same amount of Ca2+ that is absorbed by the GI tract

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13
Q

Ca2+ homeostasis involves the coordinated interaction of three organ systems. What are they?

A

Bone, kidney, intestine

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14
Q

Ca2+ homeostasis involves the coordinated interaction of 3 hormones. What are they?

A

PTH, calcitonin, and vitamin D

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15
Q

How is extracellular phosphate (Pi) related to extracellular free ionized Ca2+?

A

they are inversely related

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16
Q

what is the role of the Parathyroid glands?

A

they secrete PTH

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17
Q

what specific cell type in the parathyroid gland secretes PTH?

A

chief cells

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18
Q

What type of hormone is PTH?

A

peptide hormone

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19
Q

what is the stimulus for secretion of PTH?

A

low plasma Ca2+ levels

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20
Q

What senses the amount of extracellular Ca2+ levels?

A

Calcium-sensing receptor (CaSR)

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21
Q

when is the CaSR activated?

A

whenever there are high levels of extracellular Ca2+

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22
Q

what happens when the CaSR is activated?

A

there is going to be a downstream signaling pathway that either shuts down the production of PTH or it can also inhibit the PTH gene

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23
Q

What effect does vitamin D have on PTH production?

A

the active form of vitamin D is going to exert a negative feedback mechanism on the regulation of PTH

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24
Q

Chronic hypercalcemia causes what to PTH?

A

causes decreased synthesis and storage of PTH and increased breakdown of stored PTH

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25
Q

chronic hypocalcemia causes what to PTH?

A

causes increased synthesis and storage of PTH and hyperplasia of the parathyroid glands

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26
Q

what type of receptor is the PTH receptor?

A

it is a GPCR

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27
Q

what does recognition of PTH by the PTH GPCR lead to?

A

increased levels of cAMP through the activation of AC

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28
Q

where are PTH receptors mostly found?

A

in the bone and the kidney tubule

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29
Q

what is a byproduct of the activation of PTH?

A

cAMP

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30
Q

what is the significance of cAMP being a byproduct of activation of PTH?

A

you are going to see increased levels of cAMP in the urine, so therefore increased urine cAMP could indicate increased levels of PTH

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31
Q

what is the effect of PTH secretion on bone?

A

increased bone resorption

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32
Q

what is the effect of PTH secretion on the kidney?

A

decreased Pi reabsorption (phosphaturia), increased Ca2+ reabsorption, increased urinary cAMP

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33
Q

what is the effect of PTH secretion on the intestine?

A

increased Ca2+ absorption

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34
Q

What type of hormone is vitamin d?

A

steroid hormone

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35
Q

what is the stimulus for the production of the active form of vitamin D?

A

decreased levels of Ca2+, increased levels of PTH and decreased levels of Phosphate

36
Q

what is the main circulating form of vitamin D?

A

25-OH-cholecalciferol but it is inactive

37
Q

what converts 25-OH- cholecalciferol into its active form? and where does this occur?

A

CYP1 alpha (aka 1alpha-hydroxylase) and this occurs in the renal proximal tubule

38
Q

how is kidney 1alpha-hydroxylase enxyme tightly regulated?

A

at the transcriptional level

39
Q

where exactly on bones is the PTH receptor located?

A

on the osteoblasts

40
Q

what are the short-term actions of PTH on bone?

A

bone formation (via direct action on osteoblast)

41
Q

what are the long-term actions of PTH on bone?

A

increased bone resorption (due to indirect action on osteoclasts mediated cytokines released from osteoblasts)

42
Q

What is M-CSF?

A

it induces stem cells to differentiate into osteoclast precursors

43
Q

What is the primary mediator of osteoclast formation?

A

RANKL

44
Q

Where is RANK found?

A

it is a cell surface protein receptor on osteoclasts and osteoclast precursors

45
Q

What are the specific actions of PTH on bone formation and resorption?

A

increased RANKL and decreased OPG

46
Q

what is OPG?

A

produced by osteoblasts- inhibits RANKL/RANK interaction

47
Q

what are the specific actions of vitamin D on bone formation and resorption?

A

increased RANKL

48
Q

how does PTH cause phosphaturia?

A

by inhibiting the Na+ Phosphate transporter

49
Q

How does PTH stimulate the kidney?

A

it stimulates the 1alpha-hydroxylase activity

50
Q

what is the effect of vitamin D on the intestines?

A

it is going to promote calcium absorption as well as Pi absorption

51
Q

how does vitamin D promote calcium absorption in the intestines?

A

it promotes the protein synthesis of the TRPV6-Ca2+ channel

52
Q

what is the stimulus for calcitonin release?

A

high levels of Ca2+ in plasma

53
Q

where is calcitonin released from?

A

the parafollicular cell (c cells) in the thyroid gland

54
Q

what are the effects of calcitonin on bone?

A

it inhibits bone resorption

55
Q

where are calcitonin receptors found on bone?

A

osteoclasts

56
Q

what is the main effect of calcitonin on bone?

A

it promotes bone formation

57
Q

what would you expect the calcitonin levels to be after a thyroidectomy?

A

decreased, but no effect on Ca2+ levels

58
Q

what would you expect the calcitonin levels to be with a thyroid tumor?

A

increased levels, but no effect on Ca2+ levels

59
Q

what are the effects of Estradiol-17 B on the intestines and kidney?

A

it stimulates intestinal Ca2+ absorption and renal tubular Ca2+ reabsorption

60
Q

what is the most potent regulator of osteoblast and osteoclast function?

A

estradiol-17B

61
Q

what is the effect of estrogen on bone?

A

estrogen promotes the survival of osteoblasts and apoptosis of osteoclasts

62
Q

what is the affect of the adrenal glucocorticoids (cortisol) on bone, kidney, and intestines?

A

they promote bone resorption, renal Ca2+ wasting, and inhibit intestinal Ca2+ absorption

63
Q

patients treated with high levels of a glucocorticoid (aka a patient with addison disease) could develop what?

A

osteoporosis

64
Q

what is primary hyperparathyroidism?

A

adenoma of the parathyroid gland- over secretion of PTH

65
Q

what would expect to see with a patient with primary hyperparathyroidism?

A

stone, bones, and groans(constipation); hypercalciuria- leads to kidney stones; increased bone resorption

66
Q

what levels would you expect to see with a patient with primary hyperparathyroidism?

A

increased PTH, increased Ca2+, decreased Pi, increased Vitamin D

67
Q

what are some causes of low Ca2+ in the blood that could cause secondary hyperparathyroidism?

A

renal failure or vitamin d deficiency

68
Q

what levels would you expect to see in a patient with renal failure?

A

increased PTH, decreased Ca2+, increased Pi, decreased vitamin D

69
Q

what levels would you expect to see in a patient with vitamin d deficiency?

A

increased PTH, decreased Ca2+, decreased Pi, decreased vitamin D

70
Q

what do the symptoms of hypoparathyroidism resemble?

A

hypocalcemia

71
Q

What levels would you expect to see in a patient with hypoparathyroidism?

A

decreased PTH, decreased Ca2+, decreased vitamin D, increased Pi

72
Q

what is the treatment of hypoparathyroidism?

A

oral Ca2+ supplement and active form of vitamin D

73
Q

what is albright hereditary osteodystrophy?

A

an inherited autosomal dominant disorder where the Gs for the PTH receptor in the bones and kidneys is defective

74
Q

what is the result of albright hereditary osteodystrophy?

A

hypocalcemia and hyperphosphatemia

75
Q

what would you expect to the PTH levels to be in a patient with albright hereditary osteodystrophy?

A

high PTH levels (PTH resistance)

76
Q

what would the treatment of albright hereditary osteodystrophy with PTH result in?

A

it would produce no response and no increase in urinary cAMP

77
Q

what would you expect the levels to be in a patient with albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)

A

increased PTH levels, decreased Ca2+ levels, increased Pi levels, decreased vitamin D levels

78
Q

what is the phenotype of pseduohypoparathyroidism?

A

short stature, short neck, obesity

79
Q

some malignant tumors secrete what?

A

PTH-related peptide (PTH-rp)

80
Q

what would you expect the levels of PTH and vitamin D to be in humoral hypercalcemia of malignancy?

A

low

81
Q

what is familial hypocalciuric hypercalcemia (FHH)

A

a mutation that inactivates the CaSR in the parathyroid glands

82
Q

what does familial hypocalciuric hypercalcemia

A

decrease in urinary Ca2+ excretion (hypocalciuria) and increased serum [Ca2+] levels

83
Q

in children vitamin D deficiency causes what?

A

rickets

84
Q

what is rickets?

A

there is an insufficient amount of Ca2+ and Pi available to mineralize growing bones

85
Q

In adults vitamin D deficiency results in what?

A

osteomalacia

86
Q

What is osteomalacia?

A

new bone fails to mineralize, resulting in bending and softening of the weight-bearing

87
Q

what are two things you could use to treat osteoporosis?

A

estrogen and RANKL inhibitors (Denosumab)