Bone Formation and Growth Hormone Flashcards

0
Q

Where does REABSORPTION occur?

A

Kidneys (tube–>blood)

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1
Q

Where does ABSORPTION occur?

A

Intestines

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2
Q

Where does RESORBTION occur?

A

Bone

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3
Q

What are two classifications of bone formation?

A
  • Intramembranous

- Endochondral

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4
Q

When does intramembranous ossification begin?

A

In the embryo at week 8

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5
Q

Mesenchymal cells condense and differentiate into _____ via the transcription factor _____

A

osteoblasts; CBFA1 (core binding factor alpha)

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6
Q

True/False: Bone forms via a cartilage model

A

FALSE!!! Bone forms directly from mesenchyme NOT via a cartilage model

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7
Q

What do osteoblast secrete? What does it do?

A

osteoid (bone matrix); calcifies

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8
Q

Osteoblasts within the matrix become which type of cell following mineralization?

A

osteocytes

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9
Q

What type of bone, also called primary bone, forms with incoming blood vessels?

A

Woven bone

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10
Q

Vascularized mesenchyme condenses on the external face of the woven bone to become what?

A

periosteum

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11
Q

What type of bone replaces woven bone?

A

Lamellar bone (secondary bone)

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12
Q

What makes up lamellar bone?

A

Compact and spongy bone

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13
Q

What are some specific bones that are formed from lamellar bone?

A
  • Flat bones of the skull (cranial vault)
  • Facial bones (zygomatic, maxilla, and mandible)
  • Central part of the clavicle (collarbone)
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14
Q

____________ just deep to the periosteum thicken, forming a woven bone collar that is later replaced with what type of bone?

A

Traceculae; mature lamellar bone

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15
Q

Spongy bone (diploe), consisting of distinct trabeculae, persists internally and its vascular tissue becomes what?

A

Red marrow

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16
Q

What is the first step in endochondral ossification?

A

Fetal hyaline cartilage model develops.

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17
Q

In formation of the cartilage model, mesenchymal cells condense and form what?

A

The perichondrium, a CT layer

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18
Q

During the first stage of endochondral ossification, perichondrial cells differentiate into which type of cells and what do they produce?

A

chondroblasts; cartilage matrix

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19
Q

Which two things stimulate perichondrial cells to differentiate into chondroblasts?

A
  • Fibroblast growth factor (FGF)

- Bone morphogenic protein (BMP)

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20
Q

The cartilage model develops by which two processes?

A

Interstitial growth and appositional growth

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21
Q

The cartilage model develops by interstitial and appositional growth, chondroblasts become which type of cells?

A

Chondrocytes

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22
Q

What is the second stage of endochondral ossification?

A

Cartilage calcifies and bone collar forms around diaphysis (shaft)

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23
Q

During the process of cartilage calcification, perichondrium is invaded by _________ and becomes __________.

A

Vessels; periosteum

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24
Q

During cartilage calcification, which cells in the periosteum lay down collar of bone around the diaphysis?

A

Osteoblasts

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25
Q

During cartilage calcification (stage 2), what happens to chondrocytes?

A

They hypertrophy and die.

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26
Q

During cartilage calcification, blood vessels grow toward __________, carrying which type of cells?

A

cartilage; osteoblasts (from oseoprogenitors)

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27
Q

What is the third step of endochondral ossification?

A

Primary ossification center forms in the diaphysis

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28
Q

Where does the primary ossification center form?

A

diaphysis

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29
Q

What is the fourth stage of endochondral ossification?

A

Secondary ossification centers form in the epiphysis

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30
Q

Where does secondary ossification centers form?

A

epiphyses

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31
Q

When does secondary ossification occur?

A

Just before birth (some form postnatally)

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32
Q

When do secondary ossification centers close?

A

During puberty (up to early 20’s)

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33
Q

What is the fifth step in endochondral ossification?

A

Cartilage is replaced by bone

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34
Q

What is an exception of the fifth stage of endochondral ossification? (Where is cartilage NOT replace by bone?)

A

Articular cartilage and the epiphyseal plate

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35
Q

What is the sixth, and last factor of enchondral ossification?

A

Epiphyseal plate is site of bone elongation, but then ossifies.

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36
Q

What forms the epiphyseal line?

A

Ossification of the epiphyseal plate

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37
Q

When does ossification of epiphyseal plates take place?

A

Between 10-25

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38
Q

Which bones have epiphyseal plates that are the last to ossify?

A

Clavicle

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39
Q

Which two areas fuse together when the epiphyseal plate ossifies?

A

the diaphysis and the epiphysis

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40
Q

After ossification of the epiphyseal plate, bone lengthening ceases, so any further growth is _________ at the ____________.

A

appositional; periosteum

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41
Q

Epiphyseal plate is the site of bone enlargement, which undergoes expansion ___________.

A

interstitially

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42
Q

Degeneration, calcification, and replacement by bone occurs nearer to which area of bone?

A

ossification centers

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43
Q

Interstitial growth occurs as _____________ undergo rapid mitosis and move into what formation?

A

chondrocytes; stack up in columns (bone lengthens)

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44
Q

Once interstitial growth ceases, chondrocytes stop dividing, undergo ____________ and form ____________

A

hypertrophy; lacunae

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45
Q

Where are hydroxyapatites found?

A

In the matrix of the cartilage

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46
Q

How is cartilage calcified?

A

Hydroxyapatite, along with alkaline phosphate, form crystal mineralization from inside the matrix

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47
Q

How do cartilage cells die?

A

apoptosis

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48
Q

True/False: Capillaries vascularize the calcified cartilage.

A

True

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49
Q

These cells, from osteoprogenitor cells, do this, in the function of replacing cartilage.

A

osteoblasts; deposit bone matrix

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50
Q

Osteoblasts continue calcification by secreting what material?

A

alkaline phosphate

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51
Q

Bone stores Ca++ and PO4- by ____________ collagen fibers with _______________.

A

mineralizing; hydroxyapetite

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52
Q

Hydroxyapetite consists of which 7 compounds?

A

Ca10, (PO4)6, (OH)2

Mg, Na, K, and carbonate

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53
Q

Ca++ and PO4- are at near saturation levels, but are kept in which state by which enzyme?

A

solubilized; NPP1 (pyrophosphohydrolase)

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54
Q

How does NPP1 (pyrophosphohyrolase) keep Ca++ and PO4- soluable?

A

Hydrolyzes ATP and combines PO4- groups into pyrophosphate, PPi.

55
Q

Which cells release alkaline phosphatase (ALP or TNAP)?

A

Osteoblasts

56
Q

Osteoblast release of alkaline phosphate breaks down PPi to ____ which permits what?

A

PO4-; binding with Ca++

57
Q

In non-bone tissue, hydroxyapetite formation is inhibited by…

A

pyrophosphate

58
Q

Deficit of pyrophosphate, or excess of Ca++ and PO4- can cause mineralization of what?

A
soft tissues (arteries & veins)
degenerating tissues (blood clots)
59
Q

Osteoblasts secrete matrix vesicles that contain what two compounds?

A

Ca++ and alkaline phosphatase (TNAP)

60
Q

Secretion of matrix vesicles, containing Ca++ and TNAP allow for what process?

A

Cleavage of PPi, which permits crystallization

61
Q

Matrix vesicles rupture, permitting precipitation of Ca++ and phosphate in which areas?

A

along collagen fibers in localized areas of bone

62
Q

Limb bones develop solely via …

A

endochondral ossification

63
Q

In limb bone development, mesenchymal cells in center of limb condense into _______ _______.

A

precartilaginous aggregates

64
Q

What do cartilagenous cells (chondroblasts) secrete?

A

BMP (bone morphogenetic protein)

Ihh (Indian hedgehog)

65
Q

What does BMP (bone morphogenetic protein) facilitate?

A

growth

66
Q

What does Ihh (Indian Hedgehog) induce?

A

Further secretion of BMP (positive feedback)

67
Q

In endochondral ossification of vertebrae, scleretomal cells differentiate into which cell type?

A

chondroblasts

68
Q

In endochondral ossification of vertebrae, chondrification around the neural tube forms _____ _____?

A

cartilage models

69
Q

In endochondral ossification of vertebrae, cartilage is replaced with bone which leaves ______ ______ between ossification centers (fuse during puberty)

A

cartilage plates

70
Q

Primary ossification centers form vertebral sections that fuse between what ages?

A

3-5 years

71
Q

Secondary ossification centers form on vertebral periphery during which phase of life?

A

Puberty

72
Q

Growth of the body, especially bone, depends on which growth hormones? Secreted from which area of the body?

A

GH & IGF-1; secreted from the anterior pituitary gland

73
Q

In general, hormones are secreted from the pituitary gland by actions from which area?

A

hypthalamic neurons

74
Q

Pituitary gland extends down from the _________ and consists of which two portions?

A

hypothalamus; anterior & posterior

75
Q

Hypothalamic neuro-secretory cells emit what onto local capillaries?

A

releasing hormones (RH)

76
Q

When releasing hormones reach the anterior pituitary, it stimulates which cells to release anterior pituitary hormones into general circulation?

A

local endocrine cells (somatotrophs)

77
Q

Growth hormone is released into the body by…?

A

hypthalamic - pituitary - GH axis

78
Q

Growth Hormone Releasing Hormone (GHRH) is transported from the ___________ via which veins into the anterior pituitary?

A

hypothalamus; portal veins

79
Q

GHRH Somatostatin from which two parts of the hypothalamus have which effect on the release of GH from the pituitary?

A

periventricular & arcuate; INHIBITS

80
Q

Alternation of GHRH and SS stimulates a pulsatile release of Growth Hormone (GH) into circulation in what frequency?

A

every 3-4 hours

81
Q

GH is released from cells of which area? Where does it go?

A

anterior pituitary cells; goes into circulation and targets various organs and structures

82
Q

Growth hormone (GH) stimulates formation and release of which factor and from which locations?

A

Insulin-like Growth Factor (IGF-1); from liver and other tissues

83
Q

What does IGF-1 mediate?

A

Growth promoting action of GH

84
Q

What is the negative feedback on GH release?

A

GH and IGF-1

85
Q

What are the two main areas of action?

A

Growth and metabolism

86
Q

GH stimulates what type of growth and development both directly and indirectly through IGF-1?

A

Postnatal somatic growth

87
Q

True/False: GH generates IGF-1 in very specific areas of the body.

A

FALSE!! GH generates IGF-1 throughout the entire body

88
Q

IGF-1 is secreted from the liver as ________ or is generated within local structures as an _______ or ________.

A

Endocrine; autocrine/paracrine

89
Q

IGF-1, induced by GH, stimulates development of which two systems, and which two types of tissue?

A

Nervous and immune; cartilage and adipose tissue

90
Q

IGF increases organ size and function by stimulating what two things? Which organs are the exception?

A

protein synthesis and cell proliferation; (exception: gonads and brain)

91
Q

GH/IGF promotes linear growth in bone and cartilage by stimulating what two processes of chondrocytes in endochondral ossification?

A

differentiation and proliferation

92
Q

In metabolism, GH helps maintain what two things in adults?

A

normal lean body mass and bone mass

93
Q

Metabolism is regulated in the short term by ______, and _____ in the long term.

A

insulin; GH/IGF

94
Q

In metabolism, GH acts directly on what three tissues to shift the body’s energy source from glucose to lipids, maintaining an adequate blood glucose reserve for the brain?

A

adipose, muscle, and liver

95
Q

In metabolism, GH enhances muscle mass by enhancing which two processes?

A

amino acid absorption and protein synthesis

96
Q

In metabolism, GH reduces adiposity and releases fatty acids by enhancing what process?

A

the lipolytic activity of endocrines such as norepinephrine

97
Q

In metabolism of adipose, obesity _______ basal and stimulated GH secretion.

A

decreases

98
Q

In metabolism in the liver, GH stimulates the synthesis and release of _____ and decreases _________ ________.

A

IGF; carbohydrate (i.e. glycogen) utilization

99
Q

What are factors that upregulate GH?

A

Fasting, stress, sympathetic system

100
Q

What factors down regulate GH?

A

Malnutrition and illness

101
Q

What factors suppress GH?

A

obesity, cortisol, and FFA

102
Q

GH enhances bone growth by initiating cell division among which type of cells?

A

prechondrocytes

103
Q

When enhancing cell growth, GH stimulates synthesis and release of IGF-1 in which type of cells as paracrines or autocrines?

A

progenitor cells

104
Q

What factor increases further replication of chondroblasts causing the tissue to grow?

A

IGF-1

105
Q

Other endocrines facilitate bone growth; what does vitamin A facilitate?

A

Osteoblast formation

106
Q

Other endocrines facilitate bone growth; what does thyroid hormone enhance?

A

Chondrocyte proliferation and hypertrophy

107
Q

Estrogen induces pubertal growth spurt by what process?

A

Stimulation of the GH-IGF axis

108
Q

Later in puberty, estrogen accelerates what?

A

growth plate senescence

109
Q

What happens during growth plate senescence?

A

It slows cartilage proliferation leading to early closure

110
Q

Glucocorticoids (cortisol) slows longitudinal bone growth by inhibiting what 3 processes?

A

chondrocyte proliferation, hypertrophy, and cartilage matrix synthesis

111
Q

What are disorders of GH secretion often related to?

A

Dysregulation in the pituitary

112
Q

What issue is a result of a GH deficiency?

A

Dwarfism (some cases due to decreases in IGF)

113
Q

What two conditions are a result of GH excess?

A

Gigantism (youth)

Acromegaly (in adult)

114
Q

Growth accelerated prior to epiphyseal closure is a result of what condition?

A

Gigantism

115
Q

Increased bone thickness (esp. hands, feet, and membranous bones of head) is a result of what condition?

A

Acromegaly

116
Q

Bone remodeling is due to differential deposition of bone by ________ and resorption of bone by __________

A

osteoblasts; osteoclasts

117
Q

Osteoblasts are derived from which type of cell?

A

Osteoprogenitor cells

118
Q

Osteoclasts are derived from what type of cells?

A

mononuclear hemopoietic progenitor cells

119
Q

Osteoblasts activate osteoclast precursors with _______

A

RANKL

120
Q

RANKL is a cytokine from which two types of cells?

A

Osteoblasts and marrow stromal cells

121
Q

RANKL is inhibited by _____ from osteoblasts

A

OPG

122
Q

What are the 3 cycles of bone remodeling?

A
  • Initiation (bone resorption)
  • Transition
  • Bone Formation
123
Q

How are monocytes recruited by osteoclast precursors?

A

Signals from osteocytes as a result of a reduction in mechanical loading or microdamage in bone

124
Q

Once monocytes are recruited by the osteoclast precursors, they are differentiated into osteoclasts by ________ from osteocytes (from osteoblasts ONLY in development)

A

RANKL

125
Q

After osteoclasts excavate a resorption cavity, how is resorption terminated?

A

Osteoclast apoptosis

126
Q

During the transition cycle of bone remodeling, osteoprogenitor cells enter from ________ .

A

marrow

127
Q

Entry of osteoprogenitor cells from the marrow is regulated by which factors? And they are liberated from which area?

A
IGF-1
TGF
FGF
BMP
All liberated from resorbed bone matrix
128
Q

During bone formation osteoblasts deposit _____ for the process of _______

A

osteoid; mineralization

129
Q

What are the 3 fates of osteoblasts during bone formation?

A
  • apoptosis
  • become bone lining cells
  • become osteocytes within matrix
130
Q

There is alternation between bone resorption and deposition. During this process osteoblasts and osteoclasts release signaling factors that have what effect on each other’s actions during remodeling?

A

They inhibit each other’s actions

131
Q

True/False: Bone is remodeled by selective deposition and resorption of bone from opposing surfaces.

A

True

132
Q

At the epiphyseal plates, diaphyseal bone is resorbed _________ and deposited _______ for what purpose?

A

internally; externally; to maintain shape of the bone

133
Q

In the face, the maxilla grows by ____ _____ in the posterior as well as upward and downward directions

A

net growth

134
Q

What is a common site of hip breakage in the elderly (osteoporosis)?

A

Compression and tension trabeculae in the femoral neck.