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Endocrinology and Reproduction > Regulation of Calcium and Phosphate Homeostasis I > Flashcards

Regulation of Calcium and Phosphate Homeostasis I Flashcards

1
Q

In a healthy adult, bone deposition approximates

A

Bone reabsorption

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2
Q

Bone must be strong and rigid, yet somewhat flexible. These characteristics are conferred by the mix of

A
  1. ) Cortical Bone (80%)

2. ) Trabeculated bone (20%)

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3
Q

Comprises the outer layer of all bones and the bulk of the interior of long bones

A

Cortical bone

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4
Q

Dense tissue that gives bone it’s strength and shape

A

Cortical Bone

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5
Q

Contains bone mineral, extracellular matrix, blood vessels, and canaliculi

A

Cortical Bone

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6
Q

Comprises the interior of bones and is especially prominent in the vertebral bodies

A

Trabecular bone

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7
Q

Which undergoes more remodeling, trabecular or cortical bone?

A

Trabecular

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8
Q

The rigidity of bone comes from its organic matrix, which is comprised of

A
  1. ) Collagen (90-95%)

2. ) Ground substance

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9
Q

A mixture of extracellular fluid and proteoglycans (hyaluronic acid and chondroitin sulfate)

A

Ground substance

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10
Q

The storage form of bone salts Ca2+ and PO4

A

Hydroxyapatite

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11
Q

Exist in supersaturating conditions within the ECF

A

Ca2+ and PO4

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12
Q

Under normal circumstances, precipitation of Ca2+ and PO4 is prevented in all tissues except bone by

A

Pyrophosphate

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13
Q

The freeing of Ca2+ and PO4 from bone

A

Reabsorption

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14
Q

The use of Ca2+ and PO4 to lay down new bone

A

Deposition

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15
Q

The cell type responsible for reabsorption of bone

A

Osteoclasts

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16
Q

The cell type that controls deposition of bone

A

Osteoblasts

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17
Q

Mediate various components of deposition and reabsorption

A

Osteocytes

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18
Q

Large multinucleate cells which are concentrated around the growth surfaces of bone

A

Osteoclasts

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19
Q

At any given moment, less than 1% of the surface of adult bone is undergoing

A

Reabsorption

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20
Q

To begin reabsorption, osteoclasts secrete acids such as citric and lactic acid which

A

Dissolves bone mineral

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21
Q

Osteoclasts also secrete a substance to hydrolyze the organic matrix proteins, this is called

A

Proteolytic enzyme

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22
Q

Micro particles of the bone matrix are then phagocytosed by

A

Osteoclasts

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23
Q

Secrete factors that promote proliferation of osteoclast precursor cells

A

Osteoblasts

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24
Q

What do osteoblasts produce that stimulates the differentiation of proteoclasts into osteoclasts

A

Receptor Activator for Nuclea Factor kB (RANK) ligand (RANKL)

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25
Q

Also functions to upregulate osteoclast activity

A

RANKL

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26
Q

Binds RANKL and lowers the local availability

-also produced by osteoblasts

A

Osteoprotegerin

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27
Q

Orchestrate aspects of bone reabsorption and deposition, illustrating that mineralization of bone in the adult depends on reabsorption

A

Osteoblasts

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28
Q

Communicate with one another, bone surface, and bone marrow via dendritic processes

-Derived from osteoblasts

A

Osteocytes

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29
Q

Shear stress is sensed by the dendritic processes of osteocytes and in response, osteocytes orchestrate cycles of

A

Reabsorption and deposition

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30
Q

Plasma Ca2+ levels are maintained by the concerted actions of

A

PTH and Calcitriol

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31
Q

PTH and calcitriol maintain plasma Ca2+ levels within a relatively narrow range of

A

9.0-10.3 mg/dL

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32
Q

Of this, approximately 45% s circulating as

A

Ionized Ca2+

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33
Q

It is this ionized form which is

A

Bioavailable

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34
Q

The majority of total plasma Ca2+ is bound to

A

Albumin

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35
Q

More bioavailable Ca2+ is actually present than the measured amount would indicate with

A

Hypoalbuminemia

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36
Q

We can compensate for this phenomenon with hypoalbuminemia by raising the plasma Ca2+ by

A

0.8 mg/dL per 1.0g/dL drop in albumin

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37
Q

Approximately 85% of PO4 is stored in bone with around 14% in cells and about 1% in

A

Serum and ECF

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38
Q

Serum PO4 is maintained within a narrow range of approximately

A

2.0-3.5 mg/dL

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39
Q

Serum PO4 is regulated by the actions of PTH, calcitriol, and

A

Fibroblast growth factor 23

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40
Q

Secreted by the chief cells located within the parathyroid glands

A

PTH

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41
Q

Causes an increase in serum Ca2+ and a decrease in serum PO4

A

PTH

42
Q

Recall that within the kidney, PTH suppresses the excretion of Ca2+ in urine, while increasing the excretion of PO4. These actions occur mainly in the

A

Distal tubules and collecting ducts

43
Q

PTH promotes the synthesis of calcitriol by increasing renal

A

1a hydroxylase (CYP27B1)

44
Q

Occurs during episodes of chronic elevation of PTH

-through an indirect mechanism involving osteoblasts

A

Bone reabsorption

45
Q

Osteoblasts express

-Osteoclasts DO NOT

A

PTH receptors

46
Q

As a result of chronic exposure to PTH such as would occur during the condition of hyperparathyroidism, osteoblasts secrete which 2 things?

A
  1. ) Protease which digests the bone matrix

2. ) Cytokines which promote osteoclasts differentiation and activity

47
Q

Impairs collagen synthesis by osteocytes

A

PTH

48
Q

Causes both a rapid and slow phase of Ca2+ and PO4 absorption

A

PTH

49
Q

The rapid phase of Ca2+ and PO4 absorption which involves the removal of hydroxyapatite from the bone matrix and bone surface

A

Osteolysis

50
Q

Within these regions of bone tissue, PTH has been shown to activate Ca2+ pumps that can mediate

A

Ca2+ absorption from bone

51
Q

Osteolysis co-dependent on

A

Calcitriol

52
Q

The slow phase of Ca2+ and PO4 absorption is mediated by

A

Osteoclasts and the interactions between osteoclasts and osteoblasts

53
Q

Involved in the enzymatic digestion of bone matrix and the subsequent freeing of Ca2+

A

Osteoclasts

54
Q

Increases osteoblast proliferation, blocks the onset of apoptosis in osteoblasts, and up-regulates Ca2+ channel activity in osteocytes

A

Acute elevations in PTH

55
Q

Upregulation of Ca2+ channel activity in osteocytes allows for the intracellular transfer of Ca2+ from osteocytes to

A

Osteoblasts

56
Q

Osteoblasts then pump this Ca2+ into the bone matrix enabling

A

Deposition

57
Q

This knowledge is clinically useful in that human recombinant PTH and PTH-related peptide (PTHrp) can be used to promote

A

Bone mineralization

58
Q

Parathyroid chief cells express

A

Calcium sensing receptors (CaSR)

59
Q

These plasma membrane receptors are coupled to a number of intracellular signaling cascades which collectively control the synthesis and secretion of

A

PTH as well as chief cell proliferation

60
Q

In the presence of normal or elevated plasma Ca2+ concentrations, CaSR tonically impair

A

PTH secretion and parathyroid cell proliferation

61
Q

When the extracellular Ca2+ concentration falls, change in CaSR-mediated signaling trigger the production and release of

A

PTH

62
Q

Note tht inactivating CaSR mutations induce

A

Chief cell hyperplasia and elevated PTH secretion

63
Q

Is also coupled to upregulating vitamin D receptor (VDR) expression in chief cells

A

CaSR

64
Q

Upregulates CaSR expression

A

Calcitriol

65
Q

Also expressed within the intestine, bone, kidneys, and calcitonin-secreting cells

A

CaSR

66
Q

Can detect changes in Ca2+ content within the forming urine as well as the renal interstitium

A

Renal CaSR

67
Q

Via CaSR activity, Ca2+ down-modulates proximal tubule expression of

A

CYP27B1

68
Q

Mediates aspects of mono- and divalent cation transport which affect JG cell function, the urine concentrating mechanisms, and urinary acidification

A

Renal CaSR

69
Q

Bioactive vitamin D (calcitriol) is biosynthesized from an inactive precursor that is produced in the

A

Skin (due to sunlight)

70
Q

The formation of calcitriol is primarily stimulated by

A

PTH and hypophosphatemia

71
Q

Functions to prevent hypocalcemia and hypophosphatemia

A

Calcitriol

72
Q

The primary function of calcitriol is

A

Ca2+ and PO4 absorption from intestines

73
Q

Intestinal Ca2+ and PO4 absorption are increased approximately 40% and 80%, respectively, in the
presence of

A

Calcitriol

74
Q

Stimulates Ca2+ reabsorption and blocks PO4 secretion within the proximal tubule

A

Calcitriol

75
Q

In the distal region of the nephron, calcitriol augments PTH-dependent

A

Ca2+ reabsorption

76
Q

It has been shown that calcitriol can block PTH secretion. This effect is likely mediated by

A

Fibroblast growth factor 23

77
Q

Secreted by the thyroid gland, and is a rapid-response hormone

A

Calcitonin

78
Q

Calcitonin is secreted by

A

Parafolicular (C) Cells

79
Q

Has been shown to exert an acute block in osteoclasts activity

A

Calcitonin

80
Q

Impairs renal tubule Ca2+ reabsorption

A

Calcitonin

81
Q

The Chronic actions of calcitonin appear to depress the formation of new osteoclasts, and this in turn blocks the differentiation of new

A

Osteoblasts

82
Q

It appears that long term effects of calcitonin do not result in significant changes in

A

Serum Ca2+

83
Q

Are there any long term pathologies associated with calcitonin excess in humans?

A

No

84
Q

Calcitonin (nasal salmon calcitonin spray) is approved for the treatment of

A

Osteoporosis

85
Q

You typically only use calcitonin spray for someone who can not tolerate

A

Antiosteoporotic agents (biphosphonates, estrogen replacement, and SERMs)

86
Q

Produced by osteocytes and is a major determinant of PO4 homeostasis

A

Fibroblast growth factor 23 (FGF23)

87
Q

A counter modulator of calcitriols effect on increasing plasma PO4

A

FGF23

88
Q

Stimulated by hyperphosphatemia and calcitriol

A

FGF23 secretion

89
Q

FGF23 binds to its cell surface receptor (FGFR), and binding of FGF23 to FGFR, as well as activation of FGFR are dependent upon in the presence of the co-receptor

A

Klotho

90
Q

Blocks CYP27B1 expression

A

FGF23

91
Q

Upregulates the activity of 24-hydroxylase

A

FGF23

92
Q

Proximal tubule enzyme which converts calcitriol into an active metabolite

A

24-hydroxylase

93
Q

Inhibits the proximal tubule PO4 pumps NaPi2a and NaPi2c

A

FGF23

94
Q

Accommodate PO4 reabsorption within the proximal tubule

A

NaPi2a and NaPi2c

95
Q

Lastly, FGF2 impairs secretion of

A

PTH

96
Q

Exerts a number of effects on Ca2+ homeostasis and within bone tissue that collectively promote bone mineralization

A

Estradiol-17B (E2)

97
Q

It has been demonstrated that E2 impairs PTH synthesis in post-menopausal women; however, parathyroid cells do not express either

A

ERa or ERB

98
Q

Thus, the inhibitory effects of E2 on PTH secretion are most likely mediated via

A

FGF23

99
Q

Recall that patients with chronic kidney disease can develop (secondary) hyperparathyroidism resulting in

A

Hyperphosphatemia

100
Q

Has been independently associated with LVH in some CKD patients

A

FGF23

Endocrinology and Reproduction (15 decks)

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