Term
| common themes of wound healing (5) |
|
Definition
angiogenesis
fibroblast formation
deposition of ECM
formation of granular tissue
maturation and reorganization of the fibrous tissue |
|
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Term
|
Definition
| generation of new vessels at periphery of injury |
|
|
Term
|
Definition
| fibroblast with a contractile phenotype to close wounds |
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|
Term
| granular tissue: composition, function |
|
Definition
immature vessels, immature collagen, mycofibroblast, elastin, growth factors
fills in large wound deficit that mycofibroblasts cannot close |
|
|
Term
| how can you tell if collagen is mature |
|
Definition
| mature collagen stains with trichrome blue |
|
|
Term
| explain what happens in the phase where there is maturation and reorganiation of fibrous tissue in wound healing |
|
Definition
vessels regress, collagen remains
excess collagen forms scar (fibrosis) |
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|
Term
| first 12-24 hours of wound repair (2) |
|
Definition
filled by clot
neutrophils invate and release growth factor and cytokines to initiate inflammatory response |
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|
Term
|
Definition
| platelets interacting with collagen that was exposed via wounding |
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|
Term
| what is nescessary for wound healing, in general |
|
Definition
|
|
Term
| next 3-7 days of wound healing (4) |
|
Definition
neutrophils have apoptosed
macrophages abudent
angiogenesis
fibroblasts come and form granular tissue |
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|
Term
| last 1-2 weeks of wound repair (4) |
|
Definition
wound fills with granular tissue
fibroblasts form into myofibroblasts
myofibroblasts contact
collagen deposits |
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|
Term
| define labile cell, give examples |
|
Definition
cells capiable of continous replication
epithelium. GI |
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|
Term
| define permanent cell, give examples |
|
Definition
cells that don't have the capacity to re-renter the cell cycle
cardial muscle and neurons |
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|
Term
| define quiescent cell, give examples |
|
Definition
cells that don't continously replicate but do have the abaility to be called back into the cell cycle on demand
kidney, hepatocytes |
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|
Term
|
Definition
| replace cells with same type |
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|
Term
|
Definition
| regenerating and replacement. fills with some of the origin cells and with granular tissue, collagen, ECM because the hole is too big |
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|
Term
| what regulates the cell cycle, how do they work |
|
Definition
growth factors
and
cyclin dependent kinase is produced consistuiently (always expressed) but is inactive
cyclins turn on CDK with phosphorlyation. CDK can then go phosphorlyate things that manage the cell cycle |
|
|
Term
| how does CDK and cyclins manage the cell cycle |
|
Definition
shorten the cycle (enhance cell proliferation)
recruit resting cells into the cycle |
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|
Term
| ECM mechanical functions(4) |
|
Definition
tensile and compressive strength and elasticity
turor in soft tissue
rigidity to bone
support for cell adhesion |
|
|
Term
| how does the ECM give rigidity to bone |
|
Definition
| it had the ability to sequester water |
|
|
Term
|
Definition
| buffers against extracellular changes and water rention |
|
|
Term
| how does the ECM function in organizing our tissues (5) |
|
Definition
control their behavior by holding onto growth factors and interacting with cell receptors
cell-cell communicationg
determine cell polarity
determination location of cell growth
contol cell differentiation |
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|
Term
| what does it mean when said that the ECM is dynamic |
|
Definition
| it is constantly remodeling |
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|
Term
| give 7 examples of how the ECM is specific |
|
Definition
plasma ECM is liquid
bone and tooth enamel is highly mineralized
tendon ECM is very elastic
coats for muscle and fat cells
forms glomerular filter in the kidney
wraps myelin sheath |
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|
Term
| what are the two types of ECM |
|
Definition
basement membrane (basal lamina)
interstitial matrix |
|
|
Term
| give some examples of where a basement mebrane is located (3) |
|
Definition
beneath epithelial cells
under endothelium in vessels
around smooth muscle cells |
|
|
Term
| how is basement membrane made |
|
Definition
| made by epithelium and mysenchymal cells (fibrobroblasts, chrondrocytes, osteoblasts) |
|
|
Term
| what are the two main function of the basement membrane, what is its consistancy |
|
Definition
hold the cells down
integrity is crucial for tissue regeneration
gel like |
|
|
Term
| what are the components of the basement membrane(3) |
|
Definition
type 4 or 7 collagen
laminin |
|
|
Term
| type 4 collagen: where is it located, what is its classification, why would it not be in it is location |
|
Definition
located in ECM basement membrane
amorphpous non-fibullar collagen
sometime collagen 4 is replaced by collagen 7. this occurs when you call the basement membrane a basal lamina in the stratified squamous epithelium |
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|
Term
|
Definition
an adhesive glycoprotein in the basemement membrane
can connect to other adhesive glycoproteins (like in the ECM to anchor cell) |
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|
Term
| interstitial matrix: give 3 examples of its location |
|
Definition
| between cells in the CT, between epithelium, between smooth muscle cells |
|
|
Term
| what makes the interstitial matrix, what is its consistancy |
|
Definition
made by mesenchymal cells (fibrobolasts)
amorphous gel |
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|
Term
| what are the compontents of the interstitial matrix (16) |
|
Definition
fibullar and non-fibullar collagen:1-4, 7, 9, 12
adhesive glycoproteins: fibronectin, nidogon
elastin
GAGs: hayluronan, chondrotin, dermatin, heparin, keratan
proteoglycans: herparin sulfate, syndecan, perlican
integrins |
|
|
Term
| collagen: general structure |
|
Definition
3 alpha chains in triple helix
GXY repeats (glycine-proline-hydroxy proline)
fibrullar and non-fibullar |
|
|
Term
|
Definition
|
|
Term
| collagen 2 location, function |
|
Definition
| tensile strength in tendons |
|
|
Term
|
Definition
| granulation tissue, embryonic tisssue, uterus, KELOIDS |
|
|
Term
| how is the structure of a fribullar collagen different from that of a non, which collagen are fribullar |
|
Definition
| collagen 1-3 form fibrils around the triple helix and laterally cross link the strands with covalent bonds made through lysyl oxidase and vitamin C |
|
|
Term
| collagen 9 and 12 function |
|
Definition
fibril associated collagen
link type 1 and 2 collagen together |
|
|
Term
| collagen 4 and 7 function |
|
Definition
form mesh networks
collagen 7 connects to basal lamina to epithelium |
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|
Term
| frbronectin: what is it, what are the functions (7) |
|
Definition
adhesive glycoprotein
fibroblasts, monocytes, endothelium use it for adhesion
Attaches to the ECM with integrins with a specil motif
forms firbillar aggregates during wound healing so fibrin in cloths has scaffolding
binds heparin, collagen, cells, and self |
|
|
Term
| what is the morif that fibronectin uses to bind to the ECM, what is its importance |
|
Definition
tripeptide argining-glycine-aspartic acid motif
without the motif fibronectin cant tell where itself is and will apototose. this is a letheal mutation |
|
|
Term
| what adhesive glycoproteins are in the interstitial matrix |
|
Definition
|
|
Term
| elastin: functions, how is it made, what is its structure |
|
Definition
gives ability to reocil
is important in vessel walls, uterus, skin, and ligaments
secreted as a tropeleasin precursor that is cross linked like collagen and coated with firbillin microfibrils |
|
|
Term
| what component of elastin can be deficient, what disease is this, what is the symptom |
|
Definition
| fibrillin 1 is deficient in marfan's syndome and causes weak elastic tissue |
|
|
Term
| GAGs: composition, chemical significance |
|
Definition
unbranched repeated disaccharides
negative charge attracts ions, espially Na which attracts water and causes GAG to puff up like a gel and fill lots of space while remaining light |
|
|
Term
| hyaluronan: composition, function, how it is made |
|
Definition
large mucopolysaccharide with no protein core
binds water forming a gel matrix and fills up space
sun out from cell membrane
not sulfated or anchored to proteins
removed after cell migration is complete |
|
|
Term
| GAGs other than hyaluronan: how are they made, where are they located, list 4 of them |
|
Definition
made intracellular, secreted, sulfated
covalently bound to proteoglycans
chondroitin, dermatin, heparin, keratan |
|
|
Term
| proteoglcans: function (6), composition |
|
Definition
compressible gel for resiliance and lubrication
reservior for growth factors
some are integral membrane proteins with role in proliferation, migration, and adhesion of cells
glycosamine and mucopolysaccharides linked to a protein back bone |
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|
Term
| heparin sulfate: what is it, what are its functions (3) |
|
Definition
proteoglycan
bind fibroblast growth factor in ECM and release it during injury
bind chemokines at inflammatory sites to prolong WBC chemotaxis
blind and block some proteases |
|
|
Term
| syndecan: what is it, what are its functions (2) |
|
Definition
transmembrane proteoglycan
interaction with FGF facilitating it with its receptors
important in epithelial sheath morphology via interaction with actin |
|
|
Term
| perlican: what is it, what is its structure |
|
Definition
main proteoglycan in the basal lamina
core protein with three heparin sulfates |
|
|
Term
| integrins: what are they, how do they work |
|
Definition
transmembrane adhesive membrane receptors
low affinity for their ligand but there are a lot of them
require Ca or Mg for lingand binding |
|
|
Term
|
Definition
link the ECM to fibronectin which is required for cell survival
helps leukocytes roll along vessels to get to inflammatory sites
involved in cell-cell attachments (hemidesmosomes and focal adhesions) |
|
|
Term
| why do cells apoptose when integrin isn't holding them to the ECM |
|
Definition
because failure to adhere can lead to metastasis
mutations can cause failure to apoptose leading to cancer |
|
|
Term
| what growth factors regulate wound healing (7) |
|
Definition
platelet derived growth factor
fibroblast growth factor
epidermal growth factor
vascular endothelial growth factor
insulin like growth factor I and II
transforming growth factor B |
|
|
Term
| platelet derived growth factor (PDGF): where does it come from, what is a drug that has it in it |
|
Definition
released from degranulating platelets upon injury
approved to treat skin ulcers |
|
|
Term
|
Definition
binds to transmembrane tyrosine kinase in epidermis, dermis, and granulation tissue
chemotactic: neutrophils, monocytes, fibroblasts
stimulates activation of fibroblasts |
|
|
Term
| what functions does PDGF tell fibroblasts to do (3) |
|
Definition
proliferate
produce ECM
contract collagen matrices (myofibroblasts) |
|
|
Term
| fibroblast growth factor (FGF): how does it work, where is it located |
|
Definition
sends signal through tyrosine kinase
sequestered in herparin sulfate proteogycans |
|
|
Term
| what is the benifit of FGF being sequestered in heparin sulfate (4) |
|
Definition
stabilizes it from thermal denaturization and proteolysis
limists diffusability
essential for receptor activation |
|
|
Term
|
Definition
stimulate proliferation of cells in ectoderm, mesoderm, and endoderm origins
cytosupportive: supports cells under stress
stimulates tissue repair |
|
|
Term
| epidermal growth factor (EGF): how does it work |
|
Definition
up-regulated early after injury
binds to high affinity receptors making dimers
EGF binds to EGFR (receptor) on tyrosine kinase on epithelial cells and fibroblasts |
|
|
Term
|
Definition
stimulate cell division
role in re-epithelialization |
|
|
Term
| vascular endothelial growth factor (VEGF): how does it work |
|
Definition
| binds to tyroskin kinase receptors on blood vessels and granulation tissues |
|
|
Term
|
Definition
| macrophages and keritnocytes |
|
|
Term
|
Definition
regulate vasculogenesis and angiogenesis development in wound healing
increase permeability of vessels increasing swelling
lymphangiogenesis: absence of lymph vessels in chronic wounds |
|
|
Term
| insulin like growth factor I and II (ILGF): where does it come from (3) |
|
Definition
| macrophages, epidermal cells, inflammatory cells |
|
|
Term
|
Definition
| mitogenic, promotes survival of cells, role in scaring, matrix deposition, re-epithelization, fibroplasia |
|
|
Term
| what does delayed expression of ILGF cause, where is this seen |
|
Definition
| in people with diabetes and glucocorticoid treatment it causes delayed wound healing |
|
|
Term
| transforming growth factor B (TGFb): how does it work, where does it come from |
|
Definition
released from platlets on woundiing
attaches to heterochromatic receptor complexes (serine-tyrosine kinase)
sequested in matrix in latent form allowing sustained release when proteolytic enzymes come along |
|
|
Term
|
Definition
development, homeostasis, disease and repair
chemoattractant for neutrophils, macrophages, fibroblasts
mitogenic for fibroblasts ***
inhibits proliferation of other cells**
stimulates ECM proteins and integrins**
implicated in the fibrosis elicted in chronic inflammatory states |
|
|
Term
| how has TGFb been used in wound treatment, what was the outcome |
|
Definition
treatment of wounds with B1 increases scaring
treatment of wounds with B1 and B2 reduces scaring |
|
|
Term
| what cytokines are used to regulate wound healing (9) |
|
Definition
| chemokines, TNFa, IL-1a, 1b, 6, 8, 10, lymphokines, interferons |
|
|
Term
| role of chemokines in wound healing |
|
Definition
| secreted proteins that stimulate chemotaxis and extravasion of leukocyes |
|
|
Term
| role of IL-8 in wound healing |
|
Definition
| chemoattractant for NEUTROPHILS in human blister in skin graft |
|
|
Term
| role of IL-6 in wound healing |
|
Definition
scaring
neutrophil chemoattractant
up-reglated in inflammatory phase
made by macrophages and neutrophils |
|
|
Term
| role of IL-1a, IL-1b, IL-6, TNFa in wound healing |
|
Definition
up-regulated in inflammatory phase
made by macrophages and neutrophils |
|
|
Term
| why don't fetuses get scars |
|
Definition
| they have different expression of IL-1a, 1b, 6, TNFa |
|
|
Term
| role of IL-10 in wound healing |
|
Definition
inhibits neutrophil and macrophage infiltration
inhibits scaring |
|
|
Term
|
Definition
| assembly of primitive vascular network from angioblasts in angeogenesis |
|
|
Term
| what are the supplies needed for angiogenesis |
|
Definition
endothelial progenitor cells
OR
pre-existing vessels |
|
|
Term
| what are the two ways angiogenesis can occur |
|
Definition
endothelial progenitor cells come from the marrow
OR
endothelial cells grow from pre-existing vessels |
|
|
Term
| explain the process of angiogenesis |
|
Definition
proteolysis of the ECM
migration and chemotaxis
proliferation
lumen formation, maturation, and inhibition of growth
increased permeability through gaps and transcytosis |
|
|
Term
| what stimulates the proliferation during angiogenesis |
|
Definition
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