Regulation of Calcium and Phosphate Homeostasis I

Question 1

In a healthy adult, bone deposition approximates

Answer 1

Bone reabsorption

Question 2

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

Answer 2

1. ) Cortical Bone (80%)

2. ) Trabeculated bone (20%)

Question 3

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

Answer 3

Cortical bone

Question 4

Dense tissue that gives bone it’s strength and shape

Answer 4

Cortical Bone

Question 5

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

Answer 5

Cortical Bone

Question 6

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

Answer 6

Trabecular bone

Question 7

Which undergoes more remodeling, trabecular or cortical bone?

Answer 7

Trabecular

Question 8

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

Answer 8

1. ) Collagen (90-95%)

2. ) Ground substance

Question 9

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

Answer 9

Ground substance

Question 10

The storage form of bone salts Ca2+ and PO4

Answer 10

Hydroxyapatite

Question 11

Exist in supersaturating conditions within the ECF

Answer 11

Ca2+ and PO4

Question 12

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

Answer 12

Pyrophosphate

Question 13

The freeing of Ca2+ and PO4 from bone

Answer 13

Reabsorption

Question 14

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

Answer 14

Deposition

Question 15

The cell type responsible for reabsorption of bone

Answer 15

Osteoclasts

Question 16

The cell type that controls deposition of bone

Answer 16

Osteoblasts

Question 17

Mediate various components of deposition and reabsorption

Answer 17

Osteocytes

Question 18

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

Answer 18

Osteoclasts

Question 19

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

Answer 19

Reabsorption

Question 20

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

Answer 20

Dissolves bone mineral

Question 21

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

Answer 21

Proteolytic enzyme

Question 22

Micro particles of the bone matrix are then phagocytosed by

Answer 22

Osteoclasts

Question 23

Secrete factors that promote proliferation of osteoclast precursor cells

Answer 23

Osteoblasts

Question 24

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

Answer 24

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

Question 25

Also functions to upregulate osteoclast activity

Answer 25

RANKL

Question 26

Binds RANKL and lowers the local availability -also produced by osteoblasts

Answer 26

Osteoprotegerin

Question 27

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

Answer 27

Osteoblasts

Question 28

Communicate with one another, bone surface, and bone marrow via dendritic processes -Derived from osteoblasts

Answer 28

Osteocytes

Question 29

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

Answer 29

Reabsorption and deposition

Question 30

Plasma Ca2+ levels are maintained by the concerted actions of

Answer 30

PTH and Calcitriol

Question 31

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

Answer 31

9.0-10.3 mg/dL

Question 32

Of this, approximately 45% s circulating as

Answer 32

Ionized Ca2+

Question 33

It is this ionized form which is

Answer 33

Bioavailable

Question 34

The majority of total plasma Ca2+ is bound to

Answer 34

Albumin

Question 35

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

Answer 35

Hypoalbuminemia

Question 36

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

Answer 36

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

Question 37

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

Answer 37

Serum and ECF

Question 38

Serum PO4 is maintained within a narrow range of approximately

Answer 38

2.0-3.5 mg/dL

Question 39

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

Answer 39

Fibroblast growth factor 23

Question 40

Secreted by the chief cells located within the parathyroid glands

Answer 40

PTH

Question 41

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

Answer 41

PTH

Question 42

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

Answer 42

Distal tubules and collecting ducts

Question 43

PTH promotes the synthesis of calcitriol by increasing renal

Answer 43

1a hydroxylase (CYP27B1)

Question 44

Occurs during episodes of chronic elevation of PTH -through an indirect mechanism involving osteoblasts

Answer 44

Bone reabsorption

Question 45

Osteoblasts express -Osteoclasts DO NOT

Answer 45

PTH receptors

Question 46

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

Answer 46

1. ) Protease which digests the bone matrix | 2. ) Cytokines which promote osteoclasts differentiation and activity

Question 47

Impairs collagen synthesis by osteocytes

Answer 47

PTH

Question 48

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

Answer 48

PTH

Question 49

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

Answer 49

Osteolysis

Question 50

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

Answer 50

Ca2+ absorption from bone

Question 51

Osteolysis co-dependent on

Answer 51

Calcitriol

Question 52

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

Answer 52

Osteoclasts and the interactions between osteoclasts and osteoblasts

Question 53

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

Answer 53

Osteoclasts

Question 54

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

Answer 54

Acute elevations in PTH

Question 55

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

Answer 55

Osteoblasts

Question 56

Osteoblasts then pump this Ca2+ into the bone matrix enabling

Answer 56

Deposition

Question 57

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

Answer 57

Bone mineralization

Question 58

Parathyroid chief cells express

Answer 58

Calcium sensing receptors (CaSR)

Question 59

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

Answer 59

PTH as well as chief cell proliferation

Question 60

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

Answer 60

PTH secretion and parathyroid cell proliferation

Question 61

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

Answer 61

PTH

Question 62

Note tht inactivating CaSR mutations induce

Answer 62

Chief cell hyperplasia and elevated PTH secretion

Question 63

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

Answer 63

CaSR

Question 64

Upregulates CaSR expression

Answer 64

Calcitriol

Question 65

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

Answer 65

CaSR

Question 66

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

Answer 66

Renal CaSR

Question 67

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

Answer 67

CYP27B1

Question 68

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

Answer 68

Renal CaSR

Question 69

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

Answer 69

Skin (due to sunlight)

Question 70

The formation of calcitriol is primarily stimulated by

Answer 70

PTH and hypophosphatemia

Question 71

Functions to prevent hypocalcemia and hypophosphatemia

Answer 71

Calcitriol

Question 72

The primary function of calcitriol is

Answer 72

Ca2+ and PO4 absorption from intestines

Question 73

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

Answer 73

Calcitriol

Question 74

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

Answer 74

Calcitriol

Question 75

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

Answer 75

Ca2+ reabsorption

Question 76

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

Answer 76

Fibroblast growth factor 23

Question 77

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

Answer 77

Calcitonin

Question 78

Calcitonin is secreted by

Answer 78

Parafolicular (C) Cells

Question 79

Has been shown to exert an acute block in osteoclasts activity

Answer 79

Calcitonin

Question 80

Impairs renal tubule Ca2+ reabsorption

Answer 80

Calcitonin

Question 81

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

Answer 81

Osteoblasts

Question 82

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

Answer 82

Serum Ca2+

Question 83

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

Answer 83

No

Question 84

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

Answer 84

Osteoporosis

Question 85

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

Answer 85

Antiosteoporotic agents (biphosphonates, estrogen replacement, and SERMs)

Question 86

Produced by osteocytes and is a major determinant of PO4 homeostasis

Answer 86

Fibroblast growth factor 23 (FGF23)

Question 87

A counter modulator of calcitriols effect on increasing plasma PO4

Answer 87

FGF23

Question 88

Stimulated by hyperphosphatemia and calcitriol

Answer 88

FGF23 secretion

Question 89

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

Answer 89

Klotho

Question 90

Blocks CYP27B1 expression

Answer 90

FGF23

Question 91

Upregulates the activity of 24-hydroxylase

Answer 91

FGF23

Question 92

Proximal tubule enzyme which converts calcitriol into an active metabolite

Answer 92

24-hydroxylase

Question 93

Inhibits the proximal tubule PO4 pumps NaPi2a and NaPi2c

Answer 93

FGF23

Question 94

Accommodate PO4 reabsorption within the proximal tubule

Answer 94

NaPi2a and NaPi2c

Question 95

Lastly, FGF2 impairs secretion of

Answer 95

PTH

Question 96

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

Answer 96

Estradiol-17B (E2)

Question 97

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

Answer 97

ERa or ERB

Question 98

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

Answer 98

FGF23

Question 99

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

Answer 99

Hyperphosphatemia

Question 100

Has been independently associated with LVH in some CKD patients

Answer 100

FGF23