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COT 1 (WPH) > 4.1 lect - connective tissue - Rushmore > Flashcards

4.1 lect - connective tissue - Rushmore Flashcards

1
Q

these stem cells are responsible for generating connective tissue within the body

A

mesenchymal stem cells

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2
Q

this type of collagen can be stronger than steel

A

type I collagen

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3
Q

collagen biosynthesis begins with…

A

transcription and translation of alpha chains

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4
Q

how many different collagen alpha chains are possible?

A

42

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5
Q

how many different collagen types are possible?

A

28 and counting

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6
Q

how are collagen types named?

A

by order of discovery

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7
Q

T/F collagen is a protien

A

true

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8
Q

every third amino acid in collagen I is __

A

glycine

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9
Q

collagen I contains large ratios of these three amino acids

A

glycine
proline
lysine

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10
Q

how often does glycine occur in collagen I ?

A

every third amino acid

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11
Q

after transcription and translation of alpha chains, what is next in collagen I biosynthesis?

A

post-translational modification in the ER

  • glycosylations
  • hydroxylations (hydrosyproline, hydroxylysine)
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12
Q

what are common post-translational modifications to collagen I ?

A

glycosylations
hydroxylations
-hydroxyproline
-hydroxylysine

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13
Q

when post-translational modifications in the ER is complete, the collagen I protein is called __

A

procollagen

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14
Q

how many alpha chains are in a procollagen molecule

A

3

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15
Q

why is procollagen called a triple helix?

A

it is composed of 3 alpha chains wound around each other

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16
Q

what is the role of glycine in procollagen?

A

allow tight winding

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17
Q

what is the role of hydroxyproline in procollagen?

A

bind alpha chains together

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18
Q

what regions make up the ends of procollagen?

A

propeptide regions (frayed rope)

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19
Q

after post-translational modification in the ER, what is next for procollagen?

A
  • secretion into extracellular space
  • cleavage of propeptide regions by procollagen peptidase
  • procollagen is now tropocollagen
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20
Q

where is procollagen formed?

A

in the ER

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21
Q

where is tropocollagen formed?

A

in the extracellular space

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22
Q

what does procollagen become in the extracellular space?

A

tropocollagen

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23
Q

this enzyme cleaves the propeptide regions from procollagen

A

procollagen peptidase

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24
Q

this enzyme turns procollagen into tropocollagen

A

procollagen peptidase

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25
Q

procollagen peptidase

A

cleaves propeptide regions from procollagen, turning it into tropocollagen in the extracellular space

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26
Q

how does procollagen become tropocollagen?

A

it is secreted into the extracellular space, where procollagen peptidase cleaves the propeptide regions from its ends, turning it into tropocollagen

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27
Q

what is the function of the propeptide regions of procollagen?

A

prevent polymerization intracellularly

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28
Q

after cleavage of procollagen into tropocollagen, what is next for the protein?

A

it polymerizes into collagen fibrils

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29
Q

the secondary folding structure of alpha collagen chains is __

A

helical

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30
Q

how is one alpha collagen chain associated with the other?

A

through hydroxyproline interactions

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31
Q

how does one tropocollagen protein associate with another?

A

through hydroxylizine interactions

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32
Q

the role of hydroxyproline in collagen I biosynthesis is to…

A

associate three alpha chains together

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33
Q

the role of hydroxylysine in collagen I biosynthesis is to…

A

polymerize tropocollagen proteins together

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34
Q

in two words or less per step, describe the biosynthesis of collagen I in 6 steps

A
  1. transcription/translation
  2. post-translational modification
  3. procollagen
  4. tropocollagen
  5. collagen fibrils
  6. collagen fibers
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35
Q

where do the following steps in the biosynthesis of collagen I take place?

  1. transcription/translation
  2. post-translational modification
  3. procollagen
  4. tropocollagen
  5. collagen fibrils
  6. collagen fibers
A
  1. nucleus / RER
  2. ER
  3. ER
  4. extracellular space
  5. extracellular space
  6. extracellular space
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36
Q

what do collagen I fibrils look like on LM?

A

collagen fibrils are not resolvable on LM, only fibers

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37
Q

what color do collagen fibers stain on H&E ?

A

pink - acidic / eosinophilic

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38
Q

what is the difference between a fibril and a fiber?

A

fibrils make up fibers

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39
Q

3 components of connective tissue are:

A
  • cells
  • fibers
  • ground substance
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40
Q

large cells that store lipids and often occur together in large masses

A

unilocular adipocytes

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41
Q

adipose tissue is composed of…

A

adipocytes

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42
Q

white fat cells are also called…

A

unilocular adipocytes

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43
Q

unilocular adipocytes are also called…

A

white fat cells

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44
Q

lipid storing cells specialized for heat production

A

multilocular adipocytes

brown fat cells

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45
Q

multilocular adipocytes are…

A

lipid storing cells specialized for heat production

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46
Q

another name for multilocular adipocyte

A

brown fat cell

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47
Q

another name for brown fat cells

A

multilocular adipocytes

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48
Q

this cell is responsible for the production, remodeling, and degradation of the extracellular matrix fibers and ground substance

A

fibroblasts

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49
Q

fibroblasts

A

produce, remodel, and degrade extracellular matrix fibers and ground substance

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50
Q

myofibroblasts

A

subtypes of fibroblasts that produce myosin in order to generate force

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51
Q

this is a myosin-producing subtype of fibroblast specialized to generate force

A

myofibroblast

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52
Q

what is the dominant fiber of connective tissue?

A

type I collagen

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53
Q

in what kinds of cells is procollagen synthesized?

A

fibroblasts

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54
Q

this type of collagen is synthesized as as triple-helix procollagen molecules within fibroblasts, then aligned and cross-linked extracellularly into fibrils

A

type I collagen

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55
Q

reticular fibers are made of this type of collagen

A

type III collagen

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56
Q

T/F type III collagen has a space filling function

A

false - type III collagen composes reticular fibers, which are small and do not have a space filling function (scaffolding function)

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57
Q

these fibers are found everywhere stretchiness is required

A

elastic fibers

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58
Q

elastic fibers are composed of…

A

elastin

fibrillin

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59
Q

elastin composes what type of connective tissue fiber?

A

elastic fibers (with fibrillins)

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60
Q

fibrillins compose what type of connective tissue fiber?

A

elastic fibers (with elastin)

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61
Q

what collagen types are associated with basement membranes and external membranes?

A

types IV and VII

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62
Q

type IV collagen is found…

A

forming a meshwork of dimers to form the basal lamina or external lamina

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63
Q

type VII collagen is found…

A

in the lamina retucularis, securing fibers of connective tissue (e.g. reticular fibers) to the basal lamina

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64
Q

this collagen type is crucial to the structure of cartilage

A

type II

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65
Q

type II collagen

A

is crucial to the structure of cartilage

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66
Q

this collagen type is found in the growth plates of bones

A

type X

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67
Q 
briefly describe the functions of the following types of collagen:
I
II
III
IV
VII
X
A 
I - tensile strength, space filler
II - cartilage
III - reticular fibers (scaffolding)
IV - meshwork of basal and external lamina
VII - secure ct fibers to basal lamina
X - growth plates
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68
Q

space between connective tissue cells and fibers is occupied by…

A

ground substance

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69
Q

ground substance consists of…

A

glycosaminoglycans (GAGs)
proteoglycans
glycoproteins
(highly hydrated complexes)

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70
Q

what is a proteoglycan

A

a core protein with one or more covalently attached GAG chains

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71
Q

the purpose of ground substance is to…

A

keep the ECM hydrated

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72
Q

classification and function of tissues are derived from…

A

the morphology of aggregated cells and their specializations

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73
Q

Connective tissues are comprised of…

A

cells surrounded by extracellular material

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74
Q

this tissue gives rise to all connective tissues of the adult

A

mesenchymal tissue

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75
Q

this is comprised of interconnected and multipotent cells derived from the mesoderm

A

mesenchymal tissue

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76
Q

T/F undifferentiated mesenchymal stem cells persist in the adult

A

true - they look like fibroblasts

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77
Q

3 classes of connective tissue proper

A

loose (areolar)
dense irregular
dense regular

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78
Q

areolar connective tissue is another name for

A

loose connective tissue

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79
Q

is loose connective tissue regular or irregular?

A

irregular

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80
Q

what is another name for connective tissue proper?

A

general connective tissue

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81
Q

what is another name for general connective tissue?

A

connective tissue proper

82
Q

these two types of connective tissue exist on the same spectrum

A

loose (areolar)

dense irregular

83
Q

how can you tell loose and dense irregular connective tissue apart?

A

according to fibrous content

  • loose: many cells, few fibers, much ground substance
  • dense: many fibers, few cells, little ground substance
84
Q

this connective tissue is characterized by tightly packed fibers organized in one direction

A

dense regular connective tissue

85
Q

3 examples of dense regular connective tissue include:

A

tendons - muscle to bone
ligaments - bone to bone
aponeuroses - muscle to muscle

86
Q

a tendon connects…

A

muscle to bone

87
Q

a ligament connects

A

bone to bone

88
Q

an aponeurosis connects…

A

muscle to muscle

89
Q

this connects bone to bone

A

ligament

90
Q

this connects bone to muscle

A

tendon

91
Q

this connects muscle to muscle

A

aponeurosis

92
Q

what does dense regular tissue look like in the longitutinal plane? transverse?

A
  • longitudinal: 1 directionally organized sometimes waivy rows of much fiber and relatively few cells / nuclei
  • transverse: fibers not especially apparent, just looks like regularly spaced nuclei in a plain eosinophilic fascilcle
93
Q

4 examples of specialized connective tissue include:

A

adipose tissue
blood
bone
cartilage

94
Q

the two larges divisions of connective tissues are:

A

connective tissue proper (general)

specialized connective tissue

95
Q

loose, dense irregular, and dense regular are subclasses of what larger class of connective tissue

A

connective tissue proper (general)

96
Q

adipose tissue, blood, bone, and cartilage are subclasses of what larger class of connective tissue?

A

specialized connective tissue

97
Q

what is the resident cell of loose connective tissue

A

fibroblast

98
Q

what is the resident cell of dense irregular connective tissue

A

fibroblast

99
Q

what is the resident cell of dense regular connective tissue

A

tendinocyte (a specialized fibroblast, more squished)

100
Q

the resident cell of adipose tissue

A

adipocyte

101
Q

the resident cell of bone

A

osteocyte

102
Q

the resident cell of cartilage

A

chondrocyte

103
Q

fibroblast

A

creates, elaborates, maintains, and degrades the ECM of loose and dense irregular connective tissue

104
Q

tendinocyte

A

creates, elaborates, maintains, and degrades the ECM of dense regular connective tissue

105
Q

adipocyte

A

creates, elaborates, maintains, and degrades the ECM of adipose tissue

106
Q

osteocyte

A

creates, elaborates, maintains, and degrades the ECM of bone

107
Q

chondrocyte

A

creates, elaborates, maintains, and degrades the ECM of cartilage

108
Q

when is connective tissue not made from fibroblasts or other connective tissue resident cells?

A
  • epithelial cells make basement membrane
  • smooth muscle cells in walls of blood vessels make ECM elements
  • Schwann cells make connective tissue elements in nervous tissue
109
Q

what kind of cell makes the basement membrane?

A

epithelial cells

110
Q

what kind of cells make connective tissue elements in nervous tissue?

A

Schwann cells

111
Q

what is the shape of a fibroblast?

A

fusiform and flattened nucleus

long cytoplasmic process

112
Q

what kinds of fibers can make up extracellular material?

A

collagen
reticular fibers
elastic fibers

113
Q

what does ground substance look like on LM?

A

empty space

114
Q

what does ground substance look like on EM?

A

spots / freckles

115
Q

what is the ~diameter of a collagen fiber?

A

2-10 microns

116
Q

how does the tensile strength of collagen compare to steel?

A

10x the strength

117
Q

reticular fibers provide…

A

a flexible scaffolding

118
Q

where are reticular fibers found?

A

in the stroma of regions and organs that change in volume e.g. lymph nodes, spleen, liver

119
Q

what is the ~diameter of reticular fibers?

A

<2 microns

120
Q

how does the diameter of reticular fibers compare to that of collagen fibers?

A

<2 microns vs 2-10 microns

121
Q

how do reticular fibers stain?

A

argyrophilic

black with silver salts

122
Q

which fiber stains argyrophobic black with silver salts?

A

reticular fibers

123
Q

elastic fibers are specialized to…

A

allow distensibility

stretching of tissues with subsequent return to original form

124
Q

this fiber is specialized to allow distensibility

A

elastic fiber

125
Q

of collagen, reticular, and elastic fibers, which is the thinnest?

A

elastic (0.2 - 1.5 microns)

126
Q

of collagen, reticular, and elastic fibers, which is the thickest?

A

collagen (2-10 microns)

127
Q

what are the ~diameters of the following fibers:

  • collagen
  • reticular
  • elastic
A

2-10 microns
<2 microns
0.2-1.5 microns

128
Q

elastic fibers selectively stain with…

A

deep purple with
Vaerhoeff’s stain or
resourcin-fuschin

129
Q

how to tell difference between silver and vaerhoeff’s stain?

A
  • silver reticular fibers hold cells together in a framework, scaffolding (highly cellular)
  • vaerhoeff elastic fibers do not associate with cells, merely hold together structures and permit stretching (fewer cells)
130
Q

you would expect highly cellular material with connective tissue consisting of this fiber

A

reticular

131
Q

you would expect few cells with connective tissue consisting of this fiber

A

elastin

132
Q

what do collagen fibrils look like on EM?

A

small cylindrical structures aggregated into a much larger fibers

133
Q

T/F type I collagen fibers are visible on LM

A

true

134
Q

type I collagen accounts for __% of all collagens

A

90%

135
Q

which connective tissue fiber is resistant to stretch?

A

type I collagen

136
Q

T/F type II collagen organizes into scattered fibers

A

false - type II collagen (cartilage) does not organize into fibers

137
Q

what is the composition of cartilage?

A

50% cartilage II

50% ground substance

138
Q

what does type II collagen look like on EM?

A

scattered little fibers – type II fibers do not organize into fibers but EM cannot make sense of their arrangement

139
Q

this fiber has a high number of glycosylated residues with adjacent hydroxylated groups

A

reticular fiber (collagen III)

140
Q

this fiber type allows the large changes in volume typical in tissues like adipose, hematopoeitc, and lympoid tissues

A

reticular fiber

141
Q

this collagen type forms a meshwork of dimers to form the external or basal lamina

A

type IV collagen

142
Q

this collagen type forms anchoring fibers in the lamina reticularis that secure fibers of connective tissue (e.g. reticular fibers) to the basal lamina

A

type VII collagen

143
Q

give 2 examples of collagenopathies

A

scurvy

ehlers-danlos syndrome

144
Q

how does scurvy arise?

A
  • not enough vitamin C ingested for proline and lysine hydroxylation
  • ulcers/disruption of epithelial surfaces, teeth fall out (regions of high collagen turnover most affected)
145
Q

what parts of the body does scurvey effect most?

A

regions of high collagen turnover (e.g. periodontal ligament)

146
Q

Ehles’ Danlos Syndrome is characterized by

A

prevalent dislocation, hyperextension

147
Q

this collagenopathy is characterized by prevalent dislocation and hyperextension

A

Ehler’s Danlos Syndrome

148
Q

elastic fibers usually occur with __ to prevent overstretching

A

collagen

149
Q

what is fibroelastic collagen?

A

elastic fibers occur with collagen fibers to allow stretching but prevent over stretching

150
Q

what is the structure of an elastic fiber?

A

an amorphous elastin core surrounded by microfibrils made of fibrillin

151
Q

are elastic fibers hydrophobic or hydrophilic?

A

hydrophobic - tendency to curl up together in water

152
Q

in elastic fibers, desmosine is a protein the functions to…

A

cross link elastic fiber molecules, regulating elasticity and providing structure

153
Q

marfan syndrome

A

genetic defect in fibrillin (FBN1) gene

  • affects eyes, heart, blood vessels
  • patients are tall with long fingers and limbs (lincoln, volleyball player w/ burst aorta)
154
Q

a genetic defect in the fibrillin (FBN1) gene causes this syndrome

A

marfan syndrome

  • affects eyes, heart, blood vessels
  • patients are tall with long fingers and limbs (lincoln, volleyball player w/ burst aorta)
155
Q

non-fibrillar extracellular substance in the ECM is…

A

ground substance

156
Q

T/F ground substance is comprised of materials that critically influence cell growth, movement, proliferation and differentiation

A

true

157
Q

ground substance is comprised of these:

A

GAGs
proteoglycans
adhesive glycoproteins

158
Q

T/F ground substance stains eosinophilic

A

false - it is typically washed out with standard histological preparative techniques

159
Q

what are the general molecular and chemical characteristics of GAGs?

A
  • long unbranched linear chains of <300 repeating disaccharide units
  • one unit is an amino sugar that is sulfated and carboxylated (1-2 negative charges per repeating subunit, massive amounts of electronegativity)
160
Q

what function to the dense negative charges of GAGs serve?

A

dense negative charges repel each other, making GAG matrix slippery, attracting water in hydration shells, making large and pliable volume resistive to compressive forces and allowing diffusion of nutrients and gases

161
Q

4 typical GAGs include…

A
  • dermatan sulfate
  • heparan sulfate
  • keratan sulfate
  • chondroiotin sulfate
162
Q

name 1 unique GAG, why is it unique?

A

hyaluronic acid
-non-sulfated
-can have up to 25000 repeates while other GAGs have no more than 300
spun from the cell membrane rather than synthesized within the cell like other GAGs

163
Q

this GAG is unique because
-it is non-sulfated
-can have up to 25000 repeates while other GAGs have no more than 300
spun from the cell membrane rather than synthesized within the cell like other GAGs

A

hyalurnonic acid

164
Q

the function of GAGs in ground substance

A
  • charges repel each other making GAG chains slippery
  • hydration shells cause large volume that enables a pliable medium to resist compressive forces
  • hydration allows diffusion of nutrients and gases
  • web of GAGs makes difficult for pathogens to navigate
  • permit use of signaling molecules
165
Q

one dermatan sulfate molecule attracts…

A

2 H2O
2 Na+
hydration shells cause large volume that enables a pliable medium to resist compressive forces and allows diffusion of nutrients and gases

166
Q

how do GAGs allow diffusion of nutrients and gases?

A

hydration of ECM

  • GAGs are carboxylated and/or sulfonated
  • charges repel each other making GAG chains slippery
  • hydration shells cause large volume that enables a pliable medium to resist compressive forces
  • hydration allows diffusion of nutrients and gases
167
Q

what is a proteoglycan?

A

a protein with one or more covalently attached GAG chains
-occupy large volumes relative to mass
-resist compressive forces
-hydrate matrix for gas and nutrient transport
-modifiable sieve that permits/restricts access to
substances based on charge and size
-permit use of signaling molecules

168
Q

what is the function of proteoglycans in ground substance?

A

same as that of GAGs:
-occupy large volumes relative to mass
-resist compressive forces
-hydrate matrix for gas and nutrient transport
-modifiable sieve that permits/restricts access to
substances based on charge and size
-permit use of signaling molecules

169
Q

how do neutrophils navigate proteoglycan tangles of ground substance?

A

secrete cathepsins and gelatinases to facilitate passage

170
Q

neutrophils secrete these two enzymes to facilitate passage through proteoglycan tangles of ground substance

A

cathepsins

gelatinases

171
Q

what type of cell secretes cathepsins and gelatinases to facilitate its passage through proteoglycan tangles of ground substance?

A

neutrophil

172
Q

how do pathogenic bacteria navigate proteoglycan tangles of ground substance?

A

secrete hyaluronidase to break down hyaluronic acid

173
Q

pathogenic bacteria can secrete this enzyme to facilitate passage through ECM

A

hyaluronidase

174
Q

what is the difference between glycoproteins and proteoglycans?

A

proteoglycans - unbranched, repeating GAG subunits that hydrate
glycoproteins - ‘glue’ cells to fibers and glycoproteins. branched subunit

175
Q

what is the function of glycoproteins in ground substance in the ECM?

A

‘glue’ together cells, fibers, and ground materials. sometimes help cells travel through matrix

176
Q

name 3 places we have seen glycoproteins

A
  • secretions (mucins)
  • glycocalyx
  • ground substance
177
Q

which have larger sugar chains, glycoproteins or proteoglycans?

A

proteoglycans - larger, linear sugar chains

178
Q

which have shorter sugar chains, glycoproteins or proteoglycans?

A

glycoproteins - smaller, branched sugar chains

179
Q

give an example of an adhesive glycoprotein in ground substance

A

fibronectin

  • attaches integrins of cell membranes to matrix elements (fibers and GAGs)
  • enables cells to travel through matrix
180
Q

fibronectin is an example of what element of ground substance?

A

a glycoprotein

  • attaches integrins of cell membranes to matrix elements (fibers and GAGs)
  • enables cells to travel through matrix
181
Q

describe the differential appearance of unilocular and multilocular adipocytes

A

unilocular - one big lipid droplet, eccentrically displaced nucleus
miltilocular - multiple lipid droplets, nucleus is more round and central, eosinophilic mitochondria

182
Q

what organelle and protein specialize multilocular adipocytes to generate heat?

A

mitochondria

thermogenin (uncoupling protein-1 (UCP-1))

183
Q

where / when are multilocular adipocytes usually found?

A
  • mostly found in human infants

- also found in human adults around scapulae and cervial/thoracic vertebral regions

184
Q

brown fat was discovered in adults when a radiolabeled marker that is taken up and trapped in tissues with high metabolic rates was observed in brown fat under what conditions?

A

normal to cold conditions - brown fat metabolically activated

185
Q

what kind of adipocytes give a “chicken wire” histological appearance?

A

unilocular adipocytes (white fat)

186
Q

T/F white adipose tissue is highly vascular

A

true

187
Q

what are 4 functions of white adipose tissue?

A
  • mechanical absorption
  • thermal insulation
  • energy storage
  • endocrine function
188
Q

adipocytes release chemical signals called…

A

adipocytokines

e.g. leptin and adiponectin

189
Q

leptin and adiponectin are examples of…

A

adipocytokines - chemical signals released by adipocytes

190
Q

adipocytokines are…

A

chemical signals released by adipocytes

191
Q

release of this adipocytokine is directly related to the amount of stored fat

A

leptin

192
Q

a cytokine is…

A

a chemical signal

193
Q

lipostatic theory of energy balance

A

signal from cell to brain says adipocytes are empty, need to eat more, increase apetite. When filled, cells signal brain to use energy. Thought if we could interfere with these cytokine signals we could decrease appetite and obesity. easier said than done because adipocytes are like little endocrine glands, secreting many signals

194
Q

adipocytes were originally thought to be generated….

A

during a specific post-natal period, after which few or no additional adipocytes are generated

195
Q

up to about 18-25% of BMI change are due to what kind of adipocytic growth

A

hypertrophic growth

196
Q

after about 18-25% BMI change, further changes are due to what kind of adipocytic growth

A

hyperplasia / hypercellularity

197
Q

what kind of obesity is associated with more severe symptoms, hypertrophic or hypercellular?

A

hypercellular

198
Q

how are adipocytes generated?

A

from mesenchymal stem cells

199
Q

what is the rate of adipocyte turnover?

A

about 10% / year die and are replenished by mesenchymal stem cells. this rate of turnover is constant

200
Q

what are 5 potential avenues for obesity treatment?

A
  • get UCP1 into white fat, converting it into brown fat and get it to burn itself off
  • modulate adipocytokine levels (complicated because of vast number of signals)
  • alter cell turnover rates
  • controlled diet and exercise
  • gut microbiota transplant

COT 1 (WPH) (25 decks)

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