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Path Tissue Repair
KYCOM Block 9
86
Pathology
Graduate
08/28/2013

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Cards

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
Term
angiogenesis definition
Definition
generation of new vessels at periphery of injury
Term
myoflbriblast function
Definition
fibroblast with a contractile phenotype to close wounds
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)
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
Term
what forms a blod clot
Definition
platelets interacting with collagen that was exposed via wounding
Term
what is nescessary for wound healing, in general
Definition
inflammatory response
Term
next 3-7 days of wound healing (4)
Definition
neutrophils have apoptosed
macrophages abudent
angiogenesis
fibroblasts come and form granular tissue
Term
last 1-2 weeks of wound repair (4)
Definition
wound fills with granular tissue
fibroblasts form into myofibroblasts
myofibroblasts contact
collagen deposits
Term
define labile cell, give examples
Definition
cells capiable of continous replication
epithelium. GI
Term
define permanent cell, give examples
Definition
cells that don't have the capacity to re-renter the cell cycle

cardial muscle and neurons
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
Term
define regeneration
Definition
replace cells with same type
Term
define healing
Definition
regenerating and replacement. fills with some of the origin cells and with granular tissue, collagen, ECM because the hole is too big
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
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
ECM protective function
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
Term
what does it mean when said that the ECM is dynamic
Definition
it is constantly remodeling
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
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
Term
what is laminin
Definition
an adhesive glycoprotein in the basemement membrane
can connect to other adhesive glycoproteins (like in the ECM to anchor cell)
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
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
collagen 1 location
Definition
skin, bone, tendon
Term
collagen 2 location, function
Definition
tensile strength in tendons
Term
collagen 3 location
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
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
fibronecting and nidogen
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
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
integrin functions (3)
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
PDGF: functions (3)
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
FGF: functions (3)
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
EGF functions (2)
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
VDGF: what makes it
Definition
macrophages and keritnocytes
Term
VEGF functions (3)
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
ILGF functions (6)
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
TGFb functions
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
define vasculogenesis
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
VEGF and some FGF
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