Wound Healing Flashcards
regeneration v healing
requires intact tissue scaffolding. new cells tissues derived from stabile/stem cells restore tissues to normal state
occurs when scaffolding has been altered or destroyed. involves collagen deposition and results in scarring
cell proliferation regulated by
1 hormones
2 growth stimuli
3 pathology stimuli
cell division in stable cell populations governed by
1 soluble stimulatory and inhibitory factors
2 cell-to-cell contact
mechanisms for increasing proliferation
shortening cell cycle
pushing stable cells into cell cycle
stimulating stem cells to differentiate
soluble factors that interact w/ cells
growth factors- PI3 kinase/MAP kinase, IP3 kinase pathways
g-protein (chemokines)- cAMP pathways, Ca
Cytokine- JAK/STAT pathway
what are the broad processes that occur following injury
clotting and inflammation
removal of dead tissue
proliferation and migration of fibroblasts
angiogenesis and granulation tissue
ECM synthesis/collagen
tissue remodeling
wound contraction
wound strength
how does the ECM communicate w/ the cell
integrin proteins are attached to the ECM, and actin/cytoskeletal elements are attached to the integrin
disruption of the ECM causes changes in the cell via these anchors
ECM contents
collagen, elastin, fibrillin, elastic fibers
adhesive glycoproteins- fibronectin, laminin “glue”
matricellular proteins
proteoglycans- substances get anchored or use these to move
why doesnt collagen associate inside cells?
the subunits are capped- doesnt allow them to associate until they are removed extracellularly
what type of collagen is found in scar tissue? in basement membrane?
type 1, type 4
basement membrane components
laminin, collagen type 4, proteoglycans, intactin
laminin
cross structure- domain that binds cells, collagen type 4
gives cell polarity
fibronectin
has collagen 1, fibrin, integrin and heparan binding domains
important for beginning wound healing
in tissues that can regenerate, what determines whether the tissue fully recovers
if the basement membrane is preserved, the tissue will scar
mechanisms of wound healing
starts w/ hemostasis - causes clotting.
fibronectin, fibrin, and collagen start forming loose cross linked lattice. provides structure leukocytes can use to migrate and the initial tensile strength
platelets from initial injury release TGF-b and PDGF- causing proliferation of endothelium, fibroblasts and smooth muscle.
these generate granulation tissue and the beginning of a scar
PDGF also recruits PMNs and macrophages. produce collegenases and proteases to remove dead tissue
granulation tissue
earliest form of a scar. have new capillaries and collagen
cicatrix
scars, specifically after burns
what are the coagulation factors active in wound repair and what do they do?
hageman factor- permeability
bradykinin- dilation, permeability, pain
complement- leukocyte recruitment, permeability
fibrin- plug, growth factors, provisional matrix
role of platets in wound healing
plug vessels
vasoconstriction
growth factors- PDGF, TGF-b, FGF (fibroblast proliferation, angiogenesis)
macorphages in wound repair
decontamination via phagocytosis,
debridement (cleaning dead host tissue),
growth factor release
fibroblast functions in wound repair
growth factor production
proliferation- granulation tissue formation
ECM production
ECM contraction
epithelial cells in wound repair
growth factor production
migration and proliferation to reepithelialize
ECM production
endothelial cell in wound repair
thrombomodulin, prostacyclin, and plasminogen prevent thrombosis
metalloproteases-make hole in nearby blood vessel to form new branch to area of damage
growth factor
leukocyte diapedesis
ECM production
angiogenesis
healing by first intention/second intention
bring tissue close together to minimize the amount of scar tissue
second intention is lots of scar tissue
