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*Mammalian Physiology > Slide Set 10: Tissue, Bone Growth and Calcium Balance > Flashcards

Slide Set 10: Tissue, Bone Growth and Calcium Balance Flashcards

1
Q

What kind of tissue is bone?

A

connective tissue

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2
Q

Bone consists of

A

cells, fibers and extracellular matrix mater

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3
Q

Extracellular components of bone are

A

hard and calcified

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4
Q

What is the ratio of ECM and bone cells?

A

ECM is more abundant than cells and contains lots of collagen

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5
Q

ECM of bones are high in

A

collagen

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6
Q

What is the function of bones?

A
  • Support—bones form the framework-shape, alignment, and positioning
  • Protection—protect the structures they enclose
  • Movement—bones with joints function as levers that move
  • Mineral storage reservoir for calcium, phosphorus,
  • Hematopoiesis—blood cell formation
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7
Q

______ and ______ of bone allows it to serve its supportive and protective functions

A

Rigidity

strength

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8
Q

What are the types of bones?

A

A. Long bones
B. Short bones
C. Irregular bones
D. Flat bone

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9
Q

Compact bone is

A

dense and used for support

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10
Q

Spongy bone (cancellous) or trabecular bone forms

A

a calcified lattice

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11
Q

_____ is the end of a long bone.

A

Epiphysis

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12
Q

_______ is the site of bone growth

A

Epiphyseal plate

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13
Q

____ is the shaft of along bone.

A

Diaphysis

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14
Q

Diaphysis

A
  • Main shaft of long bone
  • Hollow, cylindrical shape and thick, compact bone
  • Function is to provide strong support without cumbersome weigh
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15
Q

Epiphysis

A
  • Both ends of a long bone, made of cancellous bone filled with marrow
  • Bulbous shape
  • Function is to provide attachments for muscles and give stability to joint
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16
Q

Articular cartilage

A

• Layer of hyaline cartilage that covers the articular surface of epiphyses

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17
Q

Hyaline cartilage

A

Elastic cartilage,

Function is to cushion jolts and blows

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18
Q

Periosteum

A
  • Dense, white, fibrous membrane that covers bone
  • Attaches tendons firmly to bones
  • Contains cells that form and destroy bone
  • Contains blood vessels important in growth and repair
  • Contains blood vessels that send branches into bone
  • Essential for bone cell survival and bone formation
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19
Q

What does periosteum contain?

A
  • Contains cells that form and destroy bone
  • Contains blood vessels important in growth and repair
  • Contains blood vessels that send branches into bone
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20
Q

Endosteum

A

thin epithelial membrane that lines medullary cavity

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21
Q

Medullary (or marrow) cavity

A
  • Tubelike, hollow space in diaphysis

* Filled with yellow marrow in adult

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22
Q

What are the layers of bones from superficial to deep?

A

Periosteum
Endosteum
Medullary (or marrow) cavity

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23
Q

Short, flat, and irregular bone features

A

 Inner portion is cancellous bone, covered on the outside with compact bone
 Spaces inside cancellous bone of a few irregular and flat bones are filled with red marrow
 Large amounts of red bone marrow are found in flat bones like those of the ribs, pelvis and skull

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24
Q

Large amounts of red bone marrow are found in _____ like those of the ribs, pelvis and skull

A

flat bones

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25
Q

The Extracellular Matrix of Bone is made up of ________ and ______

A

an Organic and an Inorganic component

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26
Q

Inorganic salts

A

–The hardness of bone results from the deposition of
–>Hydroxyapatite—highly specialized chemical crystals of calcium and phosphate
–Found in the spaces between the collagen
–Also about 10% calcium carbonate
–Slender, needle-like crystals are oriented to most effectively resist stress and mechanical deformation–Magnesium and sodium are also found in bone

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27
Q

Hydroxyapatite

A

highly specialized chemical crystals of calcium and phosphate

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28
Q

Inorganic salts are found in

A

the spaces between the collagen

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29
Q

Organic matrix

A

secreted by bone cells (osteoblasts, derived from mesenchymal stem cells). They become imprisoned in the matrix
• Collagenous fibers and a mixture of protein and polysaccharides which forms a gelatinous material termed ground substance
• Ground substance is also important in bone growth, repair and remodelling as it acts as a medium for the diffusion of nutrients, oxygen and metabolic waste. This organic matrix combines with large amounts of crystallized minerals. Mostly calcium to give bone its rigidity

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30
Q

Collagenous fibers

A

Collagenous fibers and a mixture of protein and polysaccharides which forms a gelatinous material termed ground substance

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31
Q

Ground substance

A

Ground substance is also important in bone growth, repair and remodelling as it acts as a medium for the diffusion of nutrients, oxygen and metabolic waste.

This organic matrix combines with large amounts of crystallized minerals. Mostly calcium to give bone its rigidity

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32
Q

Four types of structures make up each osteon:

A
  • Lamella
  • Lacunae
  • Canaliculi
  • Haversian canal
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33
Q

Lamella

A

concentric rings that are , islands of calcified matrix. Altered by growth. Think of Tree rings

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34
Q

Lacunae

A

small spaces containing tissue fluid in which bone cells (osteocytes) are located between hard layers of the lamella

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35
Q

Canaliculi

A

ultra small canals radiating from the osteocytes and connecting them to each other and to the Haversian canal (part of network that allows excretion and absorbtion of nutrients)

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36
Q

Haversian canal

A

extends lengthwise through the center of each osteon and contains blood vessels and lymphatic vessels

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37
Q

Structure of the Cancellous Bones

A

–There are no osteons in cancellous bone; instead, it has trabeculae-needle like bony spicules
–Nutrients are delivered and waste products removed by diffusion through tiny canaliculi(canals radiating from bone cells)
–Bony spicules are arranged along lines of stress, enhancing the bone’s strength

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38
Q

Difference in structure between cancellous bone and compact bone

A
  • Cancellous bone between compact bone (common in flat bones)
  • Cancellous bone found on the inner surface of long bone
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39
Q

What are the 4 types of bone cells?

A

Osteogenic cells
Osteoblasts
Osteocytes
Osteoclasts

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40
Q

Osteogenic cells

A

differentiate and develop into osteoblasts

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41
Q

Osteoblasts

A
  • synthesize and secrete the collagen in matrix
  • deposit calcium as they create new bone matrix
  • Bring about the formation of new bone
  • Facilitate the deposition and exchange of calcium
  • Determine osteoclast formation through the RANKL receptor ligand system
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42
Q

Osteocytes

A

Osteoblasts can become trapped in the matrix when it calcifies (mature bone cells)

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43
Q

Osteoclasts

A
  • stem from macrophages (not osteogenic cells)
  • break down bone matrix during bone resorption
  • Responsible for the active erosion of bone minerals
  • Formed by the fusion of several precursor cells multinucleated
  • Develop from stem cells in bone marrow
  • Attach to bone surface by integrins
  • Contain large numbers of mitochondria (energy) and lysosomes (enzymes to break down macromolecules)
  • Bring about the resorption of bone by secretion of collagenase, Matrix mettaloproteinases(MMPs) and the secretion of lactic and citric acids
  • MMPS destroy ECM such as collagen
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44
Q

MMPS destroy ______

A

ECM such as collagen

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45
Q

Osteoclasts develop from ______

A

stem cells in bone marrow

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46
Q

Osteoclasts attach to bone surface by ____

A

integrins

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47
Q

Osteoclasts contain _____

A

arge numbers of mitochondria (energy) and lysosomes (enzymes to break down macromolecules)

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48
Q

Osteoclasts bring about the resorption of bone by secretion of ______

A 
collagenase, 
Matrix mettaloproteinases(MMPs) and the secretion of lactic and citric acids
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49
Q

True/False

bone surfaces are covered with layer of cells mostly made of osteoclasts (bone reabsorbing), and less osteoblasts (bone building)

A

False

bone surfaces are covered with layer of cells mostly made of osteoblasts (bone building), and less osteoclasts (bone re-absorbing cells)

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50
Q

What is RANKL?

A

RANKL is on surface on osteoblast and bind its receptor RANK on osteoclast precursor cells.
This interaction leads to the differentiation of osteoclast precursor cells and the activation of osteoclasts to resorb bone

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51
Q

Stimulators of RANKL process are ______

A

Parathyroid hormone (released from thyroid to trigger release of Calcium)

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52
Q

Inhibitors of RANKL are ______

A

Inhibitors are estrogen acting vis osteoprotegrin

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53
Q

How do skeletal bones help the calcium homeostasis in the body?

A

Maintains and modulates blood calcium levels

  • Calcium is mobilized and moves into and out of blood during bone remodelling
  • During bone formation ca removed by Ob deposited in bone
  • During breakdown of bone, osteoclasts release calcium into blood and increase circulating levels
  • This process is controlled by : parathyroid hormone(parathyroid gland-posterior to the thyroid) calcitoninby the (thyroidgland) and by Vitamin D
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54
Q

What can affect Calcium Balance?

A
  • Age, disease, diet, medications
  • Children usually have a positive balance that allows bone to grow
  • In adults input and output should be the same
  • Post-menopausal women tend to have a negative calcium balance
  • Dietary intake is variable so the body must be able to adapt to raised or reduced levels
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55
Q

There are three major paths of calcium regulation:

A
  • Parathyroid hormone
  • Calcitonin
  • Vitamin D
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56
Q

Parathyroid hormone is released when ________

A

plasma Ca+ concentration is low

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57
Q

How does parathyroid hormone work in terms of calcium regulation?

A

 Mobilizes calcium from bone
 Enhances renal reabsorption of calcium
 Stimulates release of Calcitriol

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58
Q

What does calcitriol do?

A

Calcitriol increases intestinal calcium absorption

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59
Q

Calcium in the body is divided into three pools

A
  1. Extracellular calcium (0.1% of total)
  2. Intracellular calcium (0.9% of total)
  3. Calcium in bone matrix (99% of total)
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60
Q

How does calcitonin effect Ca+ homeostasis?

A

acts in opposite manner to PTH

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61
Q

When is calcitonin produced?

A

Produced in response to high blood calcium levels

Calcitonin(released when plasma Ca2+is high)

62
Q

How does calcitonin function?

A

 Decreases bone resorption

 Increases renal calcium excretion

63
Q

Where does Vitamin D (calcitriol) come from?

A
  • Vitamin D (Calcitriol) is absorbed by the small intestine as part of the diet
  • OR, is synthesized from exposure of skin to UV light converts 7-dehydrocholesterol to cholecalciferol—in the skin to a precursor of vitamin D
64
Q

How is Vitamin D (calcitriol) is produced from skin exposure to UV light?

A

converts
7-dehydrocholesterol –> cholecalciferol
—in the skin to a precursor of vitamin D

65
Q

Actions of Vitamin D on calcium regulation:

A

– Increased calcium reabsorption in the proximal and distal convoluted tubules of the kidney
–Vitamin D stimulates osteoblastactivity to increase bone mass and calcification
–In the intestine increases the synthesis of calcium binding proteins on intestinal cells
–Disorders of Vitamin D can cause weak bones (rickets in children or osteomalaciain adults)

66
Q

Vitamin D stimulates

A

osteoblastactivity to increase bone mass and calcification

67
Q

Disorders of Vitamin D can cause

A

weak bones (rickets in children or osteomalaciain adults)

68
Q

Calcification by

A

laying down of calcium salts (calcium and phosphorous)

69
Q

There are two mechanisms for bone formations

A
  1. Intramebranous
    some flat bones, no cartilage
  2. Endochondral
    cartilage, vascular, long and flat bones
70
Q

Intramebranous bone formation occurs when

A

occurs when fibrous membranes are replaced by bone tissue (less common)

71
Q

Where and how does intramebranous bone formation happen?

A

Flat bones, like the bones of the skull, sternum, and clavicle
–does not begin with a cartilage model.
–Instead, dense areas of mesenchymal cells (multipotent stem cells) differentiate and begin to lay down bone around themselves, forming early spicules.

72
Q

intramebranous bone formation does not begin with a cartilage model. Instead _______

A

dense areas of mesenchymal cells (multipotent stem cells) differentiate and begin to lay down bone around themselves, forming early spicules.

73
Q

in intramebranous bone formation dense areas of __________ (multipotent stem cells) differentiate and begin to lay down bone around themselves, forming early _______.

A

mesenchymal cells

spicules

74
Q

What are the 2 major steps of intramebranous bone formation

A
  1. Spongy bone tissue begins to develop at sites within the membranes called centers of ossification.
  2. Red bone marrow forms within the spongy bone tissue, followed by the formation of compact bone on the outside
75
Q

Intramembranous bone development occurs within a

A

connective tissue membrane

76
Q

Intramembranous bone development begins with

A

migration of mesenchymal stem cell which to the site of bone formation and differentiate into osteoblast

77
Q

How do osteoblasts act in intramembranous bone development

A

 Osteoblasts are clustered together in centers of ossification
 Osteoblasts secrete matrix material and collagenous fibrils (ground substance or osteod)

78
Q

How does mineralization occur in intramembranous bone formation

A

(calcium and phosphate) the organic strands once mineralized are called trabecula (little beam)

79
Q

Endochondral bone development

A

Most bones begin as a cartilage model, with bone formation spreading essentially from the center to the end

80
Q

How do mesenchymal cells act in endochondral bone formation?

A

Mesenchymal stem cell migrate to the site of eventual bone development

81
Q

in endochondrial bone formation mesenchymal cells are induced to become ____

A

These cell are induced to become chondrocytes (cartilage cells)

82
Q

In endochondrial bone formation chondrocytes differentiate into _____

A

very dense avascular mass

83
Q

Cartilage forms in the shape of _____

A

the bone

84
Q

Endochonral ossification

A

The cartilage is surrounded by periosteum (envelope of connective tissue) develops and enlarges

85
Q

In endochondral ossification, the cartilage is surrounded by ________ (envelope of connective tissue) develops and enlarges

A

periosteum

86
Q

In endochondral ossification, osteoblasts which differentiate from the __________ produce a ______

A

inner surface of the periosteum

collar of bone

87
Q

When does primary ossification site occurs in endochondral ossification?

A

Osteoblasts which differentiate from the inner surface of the periosteum produce a collar of bone

88
Q

Blood vessel enters the cartilage at the midpoint of the _______

A

diaphysis

89
Q

Bone grows in length as endochondral ossification progresses from the _____ toward ________

A

diaphysis

each epiphysis

90
Q

Bones elongate as __________

A

chondrocytes in cartilage of epiphyseal plate divide

91
Q

epiphyseal plate divisions –produce new cartilage within the _________

A

epiphyseal plate bordering the epiphyses.

92
Q

At the other end of the epiphyseal plate, bordering the diaphysis, older cartilage is broken down by __________

A

invading osteoclasts and eventually replaced by the expanding medullary cavity.

93
Q

Epiphyseal plate is composed of four layer

A
  • Zone of proliferation
  • Zone of hypertrophy
  • Zone of calcification
  • Ossification zone
94
Q

Zone of proliferation

A

cartilage cells (chondrocytes) undergoing active mitosis, causing the layer to thicken and the plate to increase in length

95
Q

Zone of hypertrophy

A

older, enlarged cells undergoing degenerative changes associated with calcium deposition

96
Q

Zone of calcification

A

dead or dying cartilage cells undergoing rapid calcification

97
Q

Ossification zone

A

matrix undergoes calcification

98
Q

When do Epiphyseal plate fuse?

A

around puberty

99
Q

Where does epiphyseal plate remain until bone growth in length is complete?

A

Epiphyseal plate remains between diaphysis and each epiphysis until bone growth in length is complete

100
Q

When does closing of the bone happen?

A

–Digits close early

–Arm, leg, and pelvis bones close later

101
Q

Why does closing happen in different times in women and men?

A

due to sex hormones

102
Q

Endochondral ossification step-by-step

A
  1. Chondrocytes at the center of the growing cartilage model enlarge and then die as the matrix calcifies.
  2. Newly derived osteoblasts cover the shaft of the cartilage in a thin layer of bone.
  3. Blood vessels penetrate the cartilage. New osteoblasts form a primary ossification center.
  4. The bone of the shaft thickens, and the cartilage near each epiphysis is replaced by shafts of bone.
  5. Blood vessels invade the epiphyses and osteoblasts form secondary centers of ossification.
103
Q

How do bones grow in diameter?

A

Bones grow in diameter by the combined action of osteoclasts and osteoblast

104
Q

How do osteoblasts and osteoclasts act in bone growth in diameter?

A
  • Osteoclasts enlarge the diameter of the medullary cavity

* Osteoblasts from the periosteum build new bone around the outside of the bon

105
Q

What is appositional bone growth and what happens in terms of osteoblast and osteoclast action?

A

• Enlargement in the diameter of bones occurs as it is growing in length

• Periosteum cells develop into osteoblasts
–Produce more matrix on the outer surface of the bone

• Osteoclasts erode the inner surface
–Enlarging the marrow cavity

106
Q

What are the symptoms of osteoporosis?

A

• symptoms include fractures of the vertebrae, wrists or hips, lower back pain, neck pain, bone pain or tenderness, loss of height over time, or stooped posture.

107
Q

What are the treatments for osteoporosis?

A
  • Use of drugs such, raloxifene, and calcitonin or through estrogen replacement therapy
  • Another recommended treatment for osteoporosis is exercise. Studies show that exercise can cause an increase in bone density
108
Q

What is the role of estrogen in bone formation and resorption? Explain the pathway

A
  • Estrogen acts on osteoblast to stimulates the production of TGF-beta,
  • TGF-βcauses the osteoblast cells to make osteoprotegerin (OPG)
  • OPG binds to RANKL and prevents it from binding to the RANK receptors on the preosteoclasts. This prevents them from becoming osteoclasts and thus limits bone resorption.
  • When there are low levels of estrogen, the levels of OPG decline, leaving RANKL to bind to RANK receptor and allowing differentiation of osteoclasts to proceed and bone resorption increases
109
Q

Bone remodelling in adults

A

–Osteocytes in lacunae continuously remove and replace surrounding calcium salts
–Maintain surrounding matrix
–Osteoblasts and osteoclasts remain active
–Remodelling bone, especially spongy bone

110
Q

Bone remodelling in young adults

A

–Remodeling is so rapid that about one-fifth of the skeletal mass is replaced each year

111
Q

Linear growth of long bones occurs at specialized regions called ________, located at each end of the bone shaft

A

epiphyseal plates

112
Q

The side of the plate closer to the end (epiphysis) of the bone contains continuously dividing columns of ________, collagen-producing cells of cartilage

A

chondrocytes

113
Q

What are the hormones that affect the bone growth?

A

The growth spurt of adolescent boys used to be attributed solely to increased androgen production but it now appears that estrogens play a significant role in pubertal bone growth in both sexes.

114
Q

The central region of the osteoclast secretes __

A

hydrochloric acid with the aid of carbonic anhydrase and an H+-ATPase. Osteoclasts also secrete protease enzymes that work at low pH. e combination of acid and enzymes dissolves the calci ed hydroxyapatite matrix and its collagen support. Ca2 + from hydroxyapatite becomes part of the ionized Ca2 + pool and can enter the blood.

115
Q

What is the importance of Ca2+ in the body?

A
  1. Ca2+ is an important signal molecule.
  2. Ca2+ is part of the intercellular cement that holds cells together at tight junctions.
  3. Ca2+ is a cofactor in the coagulation cascade.
  4. Plasma Ca2+ concentrations affect the excitability of neurons.
116
Q

Extracellular matrix Ca2++ function

A

• Cacified matrix of bone and teeth

117
Q

Extracellular fluid Ca2+

A
  • Neurotransmitter release at synapse
  • Role in myocardial and smooth muscle contraction
  • Cofactor in coagulation cascade
  • “Cement” for tight junctions
  • Influences excitability of neurons
118
Q

Intracellular Ca2+

A
  • Muscle contraction

* Signal in second messenger pathways

119
Q

When is PTH released? and What happens when PTH is released?

A

The stimulus for PTH release is a decrease in plasma Ca2+, monitored by a cell membrane Ca2+-sensing receptor (CaSR). The CaSR, a G protein–coupled receptor, was the first membrane receptor identified whose ligand was an ion rather than an organic molecule.

PTH acts on bone, kidney, and intestine to increase plasma Ca2 + concentrations. Increased plasma Ca2 + acts as negative feedback and shuts off PTH secretion.

120
Q

Parathyroid hormone raises plasma Ca2 + in three ways:

A
  1. PTH mobilizes calcium from bone.
    osteoclasts do not have PTH receptors instead, PTH effects are mediated by a collection of paracrines, including osteoprotegerin (OPG) and an osteoclast differentiation factor called RANKL.
  2. PTH enhances renal reabsorption of calcium.
    regulated Ca2 + reabsorption takes place in the distal nephron. PTH simultaneously enhances renal excretion of phosphate by reducing its reabsorption. The opposing effects of PTH on calcium and phosphate are needed to keep their combined concentrations below a critical level. If the concentrations exceed that level, calcium phosphate crystals form and precipitate out of solution. High concentrations of calcium phosphate in the urine are one cause of kidney stones.
  3. PTH indirectly increases intestinal absorption of calcium through its influence on vitamin D3
121
Q

Calcitriol is vitamin ____

A

D3

122
Q

3 hormones that are involved in calcium regulation

A

PTH
Calcitriol
Calcitonin

123
Q

Calcitonin is released when _____

A

plasma Ca2+ increases

124
Q

What is Paget’s disease

A

Calcitonin has been used medically to treat patients with Paget’s disease, a genetically linked condition in which osteoclasts are overactive and bone is weakened by resorption

125
Q

What is an alternative for HRT?

A

estrogen therapy alone increases the risk of endome- trial and possibly other cancers, and some studies suggest that combined estrogen/progesterone HRT might increase risk of heart attacks and strokes. A selective estrogen receptor modulator (SERM) called raloxifene has been used to treat osteoporosis.

126
Q

The 4 types of bone cells

A
  • osteogenic cells
  • osteoblasts
  • osteocytes
  • osteoclasts
127
Q

The layers of bone from superficial to deep

A

periosteum
endosteum
medullary/marrrow cavity

128
Q

give examples of short, flat and irregular bones

A

ribs
pelvis
skull

129
Q

The inner portion of short flat and irregular bones are ____ and covered with _____ on the outside

A

cancellous bone

compact bone

130
Q

osteoblasts are derived from

A

mesenchymal cells

131
Q

True/False

Osteons can be seen in cancellous bone

A

False

instead, trabecular needle like structure bony SPICULES

132
Q

Osteoclasts are attached to bone surface with ___

A

integrins

133
Q

Oc resort bone by secretion of ____

A

collagenase
Matrix metalloproteinase (MMP)
lactic acid
citric acid

134
Q

How does PTH regulate blood Ca+ levels

A

promotes OC activity
enhances renal resorption of calcium
stimulates calcitriol - increases intestinal absorption of calcium

135
Q

How is calcitriol stimulated

A

by PTH

136
Q

What is calcitriol’s function in regulating the blood calcium levels

A

increases intestinal absorption of calcium

137
Q

What is the role of calcitonin in regulation of blood calcium

A

lowers blood calcium levels and favours calcium storage in bone by decreasing bone resorption and renal excretion

138
Q

Name 2 enzymes that play opposite roles in regulating the blood calcium

A

calcitonin and PTH

139
Q

What is the role of vitamin D in regulation of blood calcium

A

deposits calcium in bone

stimulates OB

140
Q

How does vitamin D affect kidneys

A

increases Ca+ reabsorption in proximal and convoluted tubules in kidney

141
Q

Disorder of vitamin D can cause

A

rickets in children

osteomalacia in adults

142
Q

What is development of bone called

A

Osteogenesis

143
Q

What are the 2 mechanisms of bone formation?

A
  1. intramembranous

2. Endochondral

144
Q

What is the difference between intramembranous and endochondral bone formation?

A

intramembranous - no cartilage (flat bones)

endochondral - cartilage (long bones)

145
Q

What are the 2 major steps of intamembranous bone formation?

A
  1. spongy bone tissue develops - centers of ossification

2. red bone marrow forms within spongy bone and compact bone forms on the outside

146
Q

ground substance secreted by OB is also known as

A

collagenous fibrils

osteod

147
Q

mineralized strands are called

A

trabecula

148
Q

In endochondral bone formation the mesenchymal stem cells are induced to become

A

chondrocytes

149
Q

in endochondral bone formation the blood vessels enter the cartilage at ______

A

midpoint of the diaphysis

150
Q

Bone grows in length as endochondral ossification progresses from ____ toward ___

A

diaphysis –> epiphysis

151
Q

Epiphyseal plate is composed of 4 layers

A

zone of:

  • poliferation
  • hypertrophy
  • calcification
  • ossification
152
Q

What are the treatments options for osteoporosis?

A

Raloxifene
Calcitonin
ERT

*Mammalian Physiology (6 decks)

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