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
2
Q
this type of collagen can be stronger than steel
A
type I collagen
3
Q
collagen biosynthesis begins with…
A
transcription and translation of alpha chains
4
Q
how many different collagen alpha chains are possible?
A
42
5
Q
how many different collagen types are possible?
A
28 and counting
6
Q
how are collagen types named?
A
by order of discovery
7
Q
T/F collagen is a protien
A
true
8
Q
every third amino acid in collagen I is __
A
glycine
9
Q
collagen I contains large ratios of these three amino acids
A
glycine
proline
lysine
10
Q
how often does glycine occur in collagen I ?
A
every third amino acid
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)
12
Q
what are common post-translational modifications to collagen I ?
A
glycosylations
hydroxylations
-hydroxyproline
-hydroxylysine
13
Q
when post-translational modifications in the ER is complete, the collagen I protein is called __
A
procollagen
14
Q
how many alpha chains are in a procollagen molecule
A
3
15
Q
why is procollagen called a triple helix?
A
it is composed of 3 alpha chains wound around each other
16
Q
what is the role of glycine in procollagen?
A
allow tight winding
17
Q
what is the role of hydroxyproline in procollagen?
A
bind alpha chains together
18
Q
what regions make up the ends of procollagen?
A
propeptide regions (frayed rope)
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
20
Q
where is procollagen formed?
A
in the ER
21
Q
where is tropocollagen formed?
A
in the extracellular space
22
Q
what does procollagen become in the extracellular space?
A
tropocollagen
23
Q
this enzyme cleaves the propeptide regions from procollagen
A
procollagen peptidase
24
Q
this enzyme turns procollagen into tropocollagen
A
procollagen peptidase
25
procollagen peptidase
cleaves propeptide regions from procollagen, turning it into tropocollagen in the extracellular space
26
how does procollagen become tropocollagen?
it is secreted into the extracellular space, where procollagen peptidase cleaves the propeptide regions from its ends, turning it into tropocollagen
27
what is the function of the propeptide regions of procollagen?
prevent polymerization intracellularly
28
after cleavage of procollagen into tropocollagen, what is next for the protein?
it polymerizes into collagen fibrils
29
the secondary folding structure of alpha collagen chains is __
helical
30
how is one alpha collagen chain associated with the other?
through hydroxyproline interactions
31
how does one tropocollagen protein associate with another?
through hydroxylizine interactions
32
the role of hydroxyproline in collagen I biosynthesis is to...
associate three alpha chains together
33
the role of hydroxylysine in collagen I biosynthesis is to...
polymerize tropocollagen proteins together
34
in two words or less per step, describe the biosynthesis of collagen I in 6 steps
1. transcription/translation
2. post-translational modification
3. procollagen
4. tropocollagen
5. collagen fibrils
6. collagen fibers
35
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
1. nucleus / RER
2. ER
3. ER
4. extracellular space
5. extracellular space
6. extracellular space
36
what do collagen I fibrils look like on LM?
collagen fibrils are not resolvable on LM, only fibers
37
what color do collagen fibers stain on H&E ?
pink - acidic / eosinophilic
38
what is the difference between a fibril and a fiber?
fibrils make up fibers
39
3 components of connective tissue are:
- cells
- fibers
- ground substance
40
large cells that store lipids and often occur together in large masses
unilocular adipocytes
41
adipose tissue is composed of...
adipocytes
42
white fat cells are also called...
unilocular adipocytes
43
unilocular adipocytes are also called...
white fat cells
44
lipid storing cells specialized for heat production
multilocular adipocytes
| brown fat cells
45
multilocular adipocytes are...
lipid storing cells specialized for heat production
46
another name for multilocular adipocyte
brown fat cell
47
another name for brown fat cells
multilocular adipocytes
48
this cell is responsible for the production, remodeling, and degradation of the extracellular matrix fibers and ground substance
fibroblasts
49
fibroblasts
produce, remodel, and degrade extracellular matrix fibers and ground substance
50
myofibroblasts
subtypes of fibroblasts that produce myosin in order to generate force
51
this is a myosin-producing subtype of fibroblast specialized to generate force
myofibroblast
52
what is the dominant fiber of connective tissue?
type I collagen
53
in what kinds of cells is procollagen synthesized?
fibroblasts
54
this type of collagen is synthesized as as triple-helix procollagen molecules within fibroblasts, then aligned and cross-linked extracellularly into fibrils
type I collagen
55
reticular fibers are made of this type of collagen
type III collagen
56
T/F type III collagen has a space filling function
false - type III collagen composes reticular fibers, which are small and do not have a space filling function (scaffolding function)
57
these fibers are found everywhere stretchiness is required
elastic fibers
58
elastic fibers are composed of...
elastin
| fibrillin
59
elastin composes what type of connective tissue fiber?
elastic fibers (with fibrillins)
60
fibrillins compose what type of connective tissue fiber?
elastic fibers (with elastin)
61
what collagen types are associated with basement membranes and external membranes?
types IV and VII
62
type IV collagen is found...
forming a meshwork of dimers to form the basal lamina or external lamina
63
type VII collagen is found...
in the lamina retucularis, securing fibers of connective tissue (e.g. reticular fibers) to the basal lamina
64
this collagen type is crucial to the structure of cartilage
type II
65
type II collagen
is crucial to the structure of cartilage
66
this collagen type is found in the growth plates of bones
type X
67
```
briefly describe the functions of the following types of collagen:
I
II
III
IV
VII
X
```
```
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
```
68
space between connective tissue cells and fibers is occupied by...
ground substance
69
ground substance consists of...
glycosaminoglycans (GAGs)
proteoglycans
glycoproteins
(highly hydrated complexes)
70
what is a proteoglycan
a core protein with one or more covalently attached GAG chains
71
the purpose of ground substance is to...
keep the ECM hydrated
72
classification and function of tissues are derived from...
the morphology of aggregated cells and their specializations
73
Connective tissues are comprised of...
cells surrounded by extracellular material
74
this tissue gives rise to all connective tissues of the adult
mesenchymal tissue
75
this is comprised of interconnected and multipotent cells derived from the mesoderm
mesenchymal tissue
76
T/F undifferentiated mesenchymal stem cells persist in the adult
true - they look like fibroblasts
77
3 classes of connective tissue proper
loose (areolar)
dense irregular
dense regular
78
areolar connective tissue is another name for
loose connective tissue
79
is loose connective tissue regular or irregular?
irregular
80
what is another name for connective tissue proper?
general connective tissue
81
what is another name for general connective tissue?
connective tissue proper
82
these two types of connective tissue exist on the same spectrum
loose (areolar)
| dense irregular
83
how can you tell loose and dense irregular connective tissue apart?
according to fibrous content
- loose: many cells, few fibers, much ground substance
- dense: many fibers, few cells, little ground substance
84
this connective tissue is characterized by tightly packed fibers organized in one direction
dense regular connective tissue
85
3 examples of dense regular connective tissue include:
tendons - muscle to bone
ligaments - bone to bone
aponeuroses - muscle to muscle
86
a tendon connects...
muscle to bone
87
a ligament connects
bone to bone
88
an aponeurosis connects...
muscle to muscle
89
this connects bone to bone
ligament
90
this connects bone to muscle
tendon
91
this connects muscle to muscle
aponeurosis
92
what does dense regular tissue look like in the longitutinal plane? transverse?
- 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
4 examples of specialized connective tissue include:
adipose tissue
blood
bone
cartilage
94
the two larges divisions of connective tissues are:
connective tissue proper (general)
| specialized connective tissue
95
loose, dense irregular, and dense regular are subclasses of what larger class of connective tissue
connective tissue proper (general)
96
adipose tissue, blood, bone, and cartilage are subclasses of what larger class of connective tissue?
specialized connective tissue
97
what is the resident cell of loose connective tissue
fibroblast
98
what is the resident cell of dense irregular connective tissue
fibroblast
99
what is the resident cell of dense regular connective tissue
tendinocyte (a specialized fibroblast, more squished)
100
the resident cell of adipose tissue
adipocyte
101
the resident cell of bone
osteocyte
102
the resident cell of cartilage
chondrocyte
103
fibroblast
creates, elaborates, maintains, and degrades the ECM of loose and dense irregular connective tissue
104
tendinocyte
creates, elaborates, maintains, and degrades the ECM of dense regular connective tissue
105
adipocyte
creates, elaborates, maintains, and degrades the ECM of adipose tissue
106
osteocyte
creates, elaborates, maintains, and degrades the ECM of bone
107
chondrocyte
creates, elaborates, maintains, and degrades the ECM of cartilage
108
when is connective tissue not made from fibroblasts or other connective tissue resident cells?
- 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
what kind of cell makes the basement membrane?
epithelial cells
110
what kind of cells make connective tissue elements in nervous tissue?
Schwann cells
111
what is the shape of a fibroblast?
fusiform and flattened nucleus
| long cytoplasmic process
112
what kinds of fibers can make up extracellular material?
collagen
reticular fibers
elastic fibers
113
what does ground substance look like on LM?
empty space
114
what does ground substance look like on EM?
spots / freckles
115
what is the ~diameter of a collagen fiber?
2-10 microns
116
how does the tensile strength of collagen compare to steel?
10x the strength
117
reticular fibers provide...
a flexible scaffolding
118
where are reticular fibers found?
in the stroma of regions and organs that change in volume e.g. lymph nodes, spleen, liver
119
what is the ~diameter of reticular fibers?
<2 microns
120
how does the diameter of reticular fibers compare to that of collagen fibers?
<2 microns vs 2-10 microns
121
how do reticular fibers stain?
argyrophilic
| black with silver salts
122
which fiber stains argyrophobic black with silver salts?
reticular fibers
123
elastic fibers are specialized to...
allow distensibility
| stretching of tissues with subsequent return to original form
124
this fiber is specialized to allow distensibility
elastic fiber
125
of collagen, reticular, and elastic fibers, which is the thinnest?
elastic (0.2 - 1.5 microns)
126
of collagen, reticular, and elastic fibers, which is the thickest?
collagen (2-10 microns)
127
what are the ~diameters of the following fibers:
- collagen
- reticular
- elastic
2-10 microns
<2 microns
0.2-1.5 microns
128
elastic fibers selectively stain with...
deep purple with
Vaerhoeff's stain or
resourcin-fuschin
129
how to tell difference between silver and vaerhoeff's stain?
- 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
you would expect highly cellular material with connective tissue consisting of this fiber
reticular
131
you would expect few cells with connective tissue consisting of this fiber
elastin
132
what do collagen fibrils look like on EM?
small cylindrical structures aggregated into a much larger fibers
133
T/F type I collagen fibers are visible on LM
true
134
type I collagen accounts for __% of all collagens
90%
135
which connective tissue fiber is resistant to stretch?
type I collagen
136
T/F type II collagen organizes into scattered fibers
false - type II collagen (cartilage) does not organize into fibers
137
what is the composition of cartilage?
50% cartilage II
| 50% ground substance
138
what does type II collagen look like on EM?
scattered little fibers -- type II fibers do not organize into fibers but EM cannot make sense of their arrangement
139
this fiber has a high number of glycosylated residues with adjacent hydroxylated groups
reticular fiber (collagen III)
140
this fiber type allows the large changes in volume typical in tissues like adipose, hematopoeitc, and lympoid tissues
reticular fiber
141
this collagen type forms a meshwork of dimers to form the external or basal lamina
type IV collagen
142
this collagen type forms anchoring fibers in the lamina reticularis that secure fibers of connective tissue (e.g. reticular fibers) to the basal lamina
type VII collagen
143
give 2 examples of collagenopathies
scurvy
| ehlers-danlos syndrome
144
how does scurvy arise?
- 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
what parts of the body does scurvey effect most?
regions of high collagen turnover (e.g. periodontal ligament)
146
Ehles' Danlos Syndrome is characterized by
prevalent dislocation, hyperextension
147
this collagenopathy is characterized by prevalent dislocation and hyperextension
Ehler's Danlos Syndrome
148
elastic fibers usually occur with __ to prevent overstretching
collagen
149
what is fibroelastic collagen?
elastic fibers occur with collagen fibers to allow stretching but prevent over stretching
150
what is the structure of an elastic fiber?
an amorphous elastin core surrounded by microfibrils made of fibrillin
151
are elastic fibers hydrophobic or hydrophilic?
hydrophobic - tendency to curl up together in water
152
in elastic fibers, desmosine is a protein the functions to...
cross link elastic fiber molecules, regulating elasticity and providing structure
153
marfan syndrome
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
a genetic defect in the fibrillin (FBN1) gene causes this syndrome
marfan syndrome
- affects eyes, heart, blood vessels
- patients are tall with long fingers and limbs (lincoln, volleyball player w/ burst aorta)
155
non-fibrillar extracellular substance in the ECM is...
ground substance
156
T/F ground substance is comprised of materials that critically influence cell growth, movement, proliferation and differentiation
true
157
ground substance is comprised of these:
GAGs
proteoglycans
adhesive glycoproteins
158
T/F ground substance stains eosinophilic
false - it is typically washed out with standard histological preparative techniques
159
what are the general molecular and chemical characteristics of GAGs?
- 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
what function to the dense negative charges of GAGs serve?
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
4 typical GAGs include...
- dermatan sulfate
- heparan sulfate
- keratan sulfate
- chondroiotin sulfate
162
name 1 unique GAG, why is it unique?
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
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
hyalurnonic acid
164
the function of GAGs in ground substance
- 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
one dermatan sulfate molecule attracts...
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
how do GAGs allow diffusion of nutrients and gases?
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
what is a proteoglycan?
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
what is the function of proteoglycans in ground substance?
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
how do neutrophils navigate proteoglycan tangles of ground substance?
secrete cathepsins and gelatinases to facilitate passage
170
neutrophils secrete these two enzymes to facilitate passage through proteoglycan tangles of ground substance
cathepsins
| gelatinases
171
what type of cell secretes cathepsins and gelatinases to facilitate its passage through proteoglycan tangles of ground substance?
neutrophil
172
how do pathogenic bacteria navigate proteoglycan tangles of ground substance?
secrete hyaluronidase to break down hyaluronic acid
173
pathogenic bacteria can secrete this enzyme to facilitate passage through ECM
hyaluronidase
174
what is the difference between glycoproteins and proteoglycans?
proteoglycans - unbranched, repeating GAG subunits that hydrate
glycoproteins - 'glue' cells to fibers and glycoproteins. branched subunit
175
what is the function of glycoproteins in ground substance in the ECM?
'glue' together cells, fibers, and ground materials. sometimes help cells travel through matrix
176
name 3 places we have seen glycoproteins
- secretions (mucins)
- glycocalyx
- ground substance
177
which have larger sugar chains, glycoproteins or proteoglycans?
proteoglycans - larger, linear sugar chains
178
which have shorter sugar chains, glycoproteins or proteoglycans?
glycoproteins - smaller, branched sugar chains
179
give an example of an adhesive glycoprotein in ground substance
fibronectin
- attaches integrins of cell membranes to matrix elements (fibers and GAGs)
- enables cells to travel through matrix
180
fibronectin is an example of what element of ground substance?
a glycoprotein
- attaches integrins of cell membranes to matrix elements (fibers and GAGs)
- enables cells to travel through matrix
181
describe the differential appearance of unilocular and multilocular adipocytes
unilocular - one big lipid droplet, eccentrically displaced nucleus
miltilocular - multiple lipid droplets, nucleus is more round and central, eosinophilic mitochondria
182
what organelle and protein specialize multilocular adipocytes to generate heat?
mitochondria
| thermogenin (uncoupling protein-1 (UCP-1))
183
where / when are multilocular adipocytes usually found?
- mostly found in human infants
| - also found in human adults around scapulae and cervial/thoracic vertebral regions
184
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?
normal to cold conditions - brown fat metabolically activated
185
what kind of adipocytes give a "chicken wire" histological appearance?
unilocular adipocytes (white fat)
186
T/F white adipose tissue is highly vascular
true
187
what are 4 functions of white adipose tissue?
- mechanical absorption
- thermal insulation
- energy storage
- endocrine function
188
adipocytes release chemical signals called...
adipocytokines
| e.g. leptin and adiponectin
189
leptin and adiponectin are examples of...
adipocytokines - chemical signals released by adipocytes
190
adipocytokines are...
chemical signals released by adipocytes
191
release of this adipocytokine is directly related to the amount of stored fat
leptin
192
a cytokine is...
a chemical signal
193
lipostatic theory of energy balance
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
adipocytes were originally thought to be generated....
during a specific post-natal period, after which few or no additional adipocytes are generated
195
up to about 18-25% of BMI change are due to what kind of adipocytic growth
hypertrophic growth
196
after about 18-25% BMI change, further changes are due to what kind of adipocytic growth
hyperplasia / hypercellularity
197
what kind of obesity is associated with more severe symptoms, hypertrophic or hypercellular?
hypercellular
198
how are adipocytes generated?
from mesenchymal stem cells
199
what is the rate of adipocyte turnover?
about 10% / year die and are replenished by mesenchymal stem cells. this rate of turnover is constant
200
what are 5 potential avenues for obesity treatment?
- 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
