4.1 lect - connective tissue - Rushmore Flashcards
these stem cells are responsible for generating connective tissue within the body
mesenchymal stem cells
this type of collagen can be stronger than steel
type I collagen
collagen biosynthesis begins with…
transcription and translation of alpha chains
how many different collagen alpha chains are possible?
42
how many different collagen types are possible?
28 and counting
how are collagen types named?
by order of discovery
T/F collagen is a protien
true
every third amino acid in collagen I is __
glycine
collagen I contains large ratios of these three amino acids
glycine
proline
lysine
how often does glycine occur in collagen I ?
every third amino acid
after transcription and translation of alpha chains, what is next in collagen I biosynthesis?
post-translational modification in the ER
- glycosylations
- hydroxylations (hydrosyproline, hydroxylysine)
what are common post-translational modifications to collagen I ?
glycosylations
hydroxylations
-hydroxyproline
-hydroxylysine
when post-translational modifications in the ER is complete, the collagen I protein is called __
procollagen
how many alpha chains are in a procollagen molecule
3
why is procollagen called a triple helix?
it is composed of 3 alpha chains wound around each other
what is the role of glycine in procollagen?
allow tight winding
what is the role of hydroxyproline in procollagen?
bind alpha chains together
what regions make up the ends of procollagen?
propeptide regions (frayed rope)
after post-translational modification in the ER, what is next for procollagen?
- secretion into extracellular space
- cleavage of propeptide regions by procollagen peptidase
- procollagen is now tropocollagen
where is procollagen formed?
in the ER
where is tropocollagen formed?
in the extracellular space
what does procollagen become in the extracellular space?
tropocollagen
this enzyme cleaves the propeptide regions from procollagen
procollagen peptidase
this enzyme turns procollagen into tropocollagen
procollagen peptidase
procollagen peptidase
cleaves propeptide regions from procollagen, turning it into tropocollagen in the extracellular space
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
what is the function of the propeptide regions of procollagen?
prevent polymerization intracellularly
after cleavage of procollagen into tropocollagen, what is next for the protein?
it polymerizes into collagen fibrils
the secondary folding structure of alpha collagen chains is __
helical
how is one alpha collagen chain associated with the other?
through hydroxyproline interactions
how does one tropocollagen protein associate with another?
through hydroxylizine interactions
the role of hydroxyproline in collagen I biosynthesis is to…
associate three alpha chains together
the role of hydroxylysine in collagen I biosynthesis is to…
polymerize tropocollagen proteins together
in two words or less per step, describe the biosynthesis of collagen I in 6 steps
- transcription/translation
- post-translational modification
- procollagen
- tropocollagen
- collagen fibrils
- collagen fibers
where do the following steps in the biosynthesis of collagen I take place?
- transcription/translation
- post-translational modification
- procollagen
- tropocollagen
- collagen fibrils
- collagen fibers
- nucleus / RER
- ER
- ER
- extracellular space
- extracellular space
- extracellular space
what do collagen I fibrils look like on LM?
collagen fibrils are not resolvable on LM, only fibers
what color do collagen fibers stain on H&E ?
pink - acidic / eosinophilic
what is the difference between a fibril and a fiber?
fibrils make up fibers
3 components of connective tissue are:
- cells
- fibers
- ground substance
large cells that store lipids and often occur together in large masses
unilocular adipocytes
adipose tissue is composed of…
adipocytes
white fat cells are also called…
unilocular adipocytes
unilocular adipocytes are also called…
white fat cells
lipid storing cells specialized for heat production
multilocular adipocytes
brown fat cells
multilocular adipocytes are…
lipid storing cells specialized for heat production
another name for multilocular adipocyte
brown fat cell
another name for brown fat cells
multilocular adipocytes
this cell is responsible for the production, remodeling, and degradation of the extracellular matrix fibers and ground substance
fibroblasts
fibroblasts
produce, remodel, and degrade extracellular matrix fibers and ground substance
myofibroblasts
subtypes of fibroblasts that produce myosin in order to generate force
this is a myosin-producing subtype of fibroblast specialized to generate force
myofibroblast
what is the dominant fiber of connective tissue?
type I collagen
in what kinds of cells is procollagen synthesized?
fibroblasts
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
reticular fibers are made of this type of collagen
type III collagen
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)
these fibers are found everywhere stretchiness is required
elastic fibers
elastic fibers are composed of…
elastin
fibrillin
elastin composes what type of connective tissue fiber?
elastic fibers (with fibrillins)
fibrillins compose what type of connective tissue fiber?
elastic fibers (with elastin)
what collagen types are associated with basement membranes and external membranes?
types IV and VII
type IV collagen is found…
forming a meshwork of dimers to form the basal lamina or external lamina
type VII collagen is found…
in the lamina retucularis, securing fibers of connective tissue (e.g. reticular fibers) to the basal lamina
this collagen type is crucial to the structure of cartilage
type II
type II collagen
is crucial to the structure of cartilage
this collagen type is found in the growth plates of bones
type X
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
space between connective tissue cells and fibers is occupied by…
ground substance
ground substance consists of…
glycosaminoglycans (GAGs)
proteoglycans
glycoproteins
(highly hydrated complexes)
what is a proteoglycan
a core protein with one or more covalently attached GAG chains
the purpose of ground substance is to…
keep the ECM hydrated
classification and function of tissues are derived from…
the morphology of aggregated cells and their specializations
Connective tissues are comprised of…
cells surrounded by extracellular material
this tissue gives rise to all connective tissues of the adult
mesenchymal tissue
this is comprised of interconnected and multipotent cells derived from the mesoderm
mesenchymal tissue
T/F undifferentiated mesenchymal stem cells persist in the adult
true - they look like fibroblasts
3 classes of connective tissue proper
loose (areolar)
dense irregular
dense regular
areolar connective tissue is another name for
loose connective tissue
is loose connective tissue regular or irregular?
irregular
what is another name for connective tissue proper?
general connective tissue
what is another name for general connective tissue?
connective tissue proper
these two types of connective tissue exist on the same spectrum
loose (areolar)
dense irregular
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
this connective tissue is characterized by tightly packed fibers organized in one direction
dense regular connective tissue
3 examples of dense regular connective tissue include:
tendons - muscle to bone
ligaments - bone to bone
aponeuroses - muscle to muscle
a tendon connects…
muscle to bone
a ligament connects
bone to bone
an aponeurosis connects…
muscle to muscle
this connects bone to bone
ligament
this connects bone to muscle
tendon
this connects muscle to muscle
aponeurosis
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
4 examples of specialized connective tissue include:
adipose tissue
blood
bone
cartilage
the two larges divisions of connective tissues are:
connective tissue proper (general)
specialized connective tissue
loose, dense irregular, and dense regular are subclasses of what larger class of connective tissue
connective tissue proper (general)
adipose tissue, blood, bone, and cartilage are subclasses of what larger class of connective tissue?
specialized connective tissue
what is the resident cell of loose connective tissue
fibroblast
what is the resident cell of dense irregular connective tissue
fibroblast
what is the resident cell of dense regular connective tissue
tendinocyte (a specialized fibroblast, more squished)
the resident cell of adipose tissue
adipocyte
the resident cell of bone
osteocyte
the resident cell of cartilage
chondrocyte
fibroblast
creates, elaborates, maintains, and degrades the ECM of loose and dense irregular connective tissue
tendinocyte
creates, elaborates, maintains, and degrades the ECM of dense regular connective tissue
adipocyte
creates, elaborates, maintains, and degrades the ECM of adipose tissue
osteocyte
creates, elaborates, maintains, and degrades the ECM of bone
chondrocyte
creates, elaborates, maintains, and degrades the ECM of cartilage
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
what kind of cell makes the basement membrane?
epithelial cells
what kind of cells make connective tissue elements in nervous tissue?
Schwann cells
what is the shape of a fibroblast?
fusiform and flattened nucleus
long cytoplasmic process
what kinds of fibers can make up extracellular material?
collagen
reticular fibers
elastic fibers
what does ground substance look like on LM?
empty space
what does ground substance look like on EM?
spots / freckles
what is the ~diameter of a collagen fiber?
2-10 microns
how does the tensile strength of collagen compare to steel?
10x the strength
reticular fibers provide…
a flexible scaffolding
where are reticular fibers found?
in the stroma of regions and organs that change in volume e.g. lymph nodes, spleen, liver
what is the ~diameter of reticular fibers?
<2 microns
how does the diameter of reticular fibers compare to that of collagen fibers?
<2 microns vs 2-10 microns
how do reticular fibers stain?
argyrophilic
black with silver salts
which fiber stains argyrophobic black with silver salts?
reticular fibers
elastic fibers are specialized to…
allow distensibility
stretching of tissues with subsequent return to original form
this fiber is specialized to allow distensibility
elastic fiber
of collagen, reticular, and elastic fibers, which is the thinnest?
elastic (0.2 - 1.5 microns)
of collagen, reticular, and elastic fibers, which is the thickest?
collagen (2-10 microns)
what are the ~diameters of the following fibers:
- collagen
- reticular
- elastic
2-10 microns
<2 microns
0.2-1.5 microns
elastic fibers selectively stain with…
deep purple with
Vaerhoeff’s stain or
resourcin-fuschin
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)
you would expect highly cellular material with connective tissue consisting of this fiber
reticular
you would expect few cells with connective tissue consisting of this fiber
elastin
what do collagen fibrils look like on EM?
small cylindrical structures aggregated into a much larger fibers
T/F type I collagen fibers are visible on LM
true
type I collagen accounts for __% of all collagens
90%
which connective tissue fiber is resistant to stretch?
type I collagen
T/F type II collagen organizes into scattered fibers
false - type II collagen (cartilage) does not organize into fibers
what is the composition of cartilage?
50% cartilage II
50% ground substance
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
this fiber has a high number of glycosylated residues with adjacent hydroxylated groups
reticular fiber (collagen III)
this fiber type allows the large changes in volume typical in tissues like adipose, hematopoeitc, and lympoid tissues
reticular fiber
this collagen type forms a meshwork of dimers to form the external or basal lamina
type IV collagen
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
give 2 examples of collagenopathies
scurvy
ehlers-danlos syndrome
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)
what parts of the body does scurvey effect most?
regions of high collagen turnover (e.g. periodontal ligament)
Ehles’ Danlos Syndrome is characterized by
prevalent dislocation, hyperextension
this collagenopathy is characterized by prevalent dislocation and hyperextension
Ehler’s Danlos Syndrome
elastic fibers usually occur with __ to prevent overstretching
collagen
what is fibroelastic collagen?
elastic fibers occur with collagen fibers to allow stretching but prevent over stretching
what is the structure of an elastic fiber?
an amorphous elastin core surrounded by microfibrils made of fibrillin
are elastic fibers hydrophobic or hydrophilic?
hydrophobic - tendency to curl up together in water
in elastic fibers, desmosine is a protein the functions to…
cross link elastic fiber molecules, regulating elasticity and providing structure
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)
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)
non-fibrillar extracellular substance in the ECM is…
ground substance
T/F ground substance is comprised of materials that critically influence cell growth, movement, proliferation and differentiation
true
ground substance is comprised of these:
GAGs
proteoglycans
adhesive glycoproteins
T/F ground substance stains eosinophilic
false - it is typically washed out with standard histological preparative techniques
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)
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
4 typical GAGs include…
- dermatan sulfate
- heparan sulfate
- keratan sulfate
- chondroiotin sulfate
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
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
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
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
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
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
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
how do neutrophils navigate proteoglycan tangles of ground substance?
secrete cathepsins and gelatinases to facilitate passage
neutrophils secrete these two enzymes to facilitate passage through proteoglycan tangles of ground substance
cathepsins
gelatinases
what type of cell secretes cathepsins and gelatinases to facilitate its passage through proteoglycan tangles of ground substance?
neutrophil
how do pathogenic bacteria navigate proteoglycan tangles of ground substance?
secrete hyaluronidase to break down hyaluronic acid
pathogenic bacteria can secrete this enzyme to facilitate passage through ECM
hyaluronidase
what is the difference between glycoproteins and proteoglycans?
proteoglycans - unbranched, repeating GAG subunits that hydrate
glycoproteins - ‘glue’ cells to fibers and glycoproteins. branched subunit
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
name 3 places we have seen glycoproteins
- secretions (mucins)
- glycocalyx
- ground substance
which have larger sugar chains, glycoproteins or proteoglycans?
proteoglycans - larger, linear sugar chains
which have shorter sugar chains, glycoproteins or proteoglycans?
glycoproteins - smaller, branched sugar chains
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
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
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
what organelle and protein specialize multilocular adipocytes to generate heat?
mitochondria
thermogenin (uncoupling protein-1 (UCP-1))
where / when are multilocular adipocytes usually found?
- mostly found in human infants
- also found in human adults around scapulae and cervial/thoracic vertebral regions
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
what kind of adipocytes give a “chicken wire” histological appearance?
unilocular adipocytes (white fat)
T/F white adipose tissue is highly vascular
true
what are 4 functions of white adipose tissue?
- mechanical absorption
- thermal insulation
- energy storage
- endocrine function
adipocytes release chemical signals called…
adipocytokines
e.g. leptin and adiponectin
leptin and adiponectin are examples of…
adipocytokines - chemical signals released by adipocytes
adipocytokines are…
chemical signals released by adipocytes
release of this adipocytokine is directly related to the amount of stored fat
leptin
a cytokine is…
a chemical signal
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
adipocytes were originally thought to be generated….
during a specific post-natal period, after which few or no additional adipocytes are generated
up to about 18-25% of BMI change are due to what kind of adipocytic growth
hypertrophic growth
after about 18-25% BMI change, further changes are due to what kind of adipocytic growth
hyperplasia / hypercellularity
what kind of obesity is associated with more severe symptoms, hypertrophic or hypercellular?
hypercellular
how are adipocytes generated?
from mesenchymal stem cells
what is the rate of adipocyte turnover?
about 10% / year die and are replenished by mesenchymal stem cells. this rate of turnover is constant
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
