Tissue Healing/Repair Flashcards
Healing
Outcome of inflammation - regeneration or scarring
Cell growth in scarring vs. regneration
Regen - tissue’s own cells divide
Scar- fibroblasts and vascular endothelial cells divide
Liable cells
Continuously dividing
Short G0
Epithelial cells and hematopoietic cells
Stable cells
Low rate of cell division
Long G0
Re-enter cell cycle only under certain circumstances (healing)
Vascular endothelial cells, parenchymal cells of organs, mesenchymal cells
Permanent cells
Left cell cycle forever…will never undergo mitosis again
Neurons of CNS, cardiac muscle, skeletal muscle
3 conditions for healing by regeneration
Tissue composed of labile or stable cells
Area of injury has surviving cells capable of undergoing cell division
Connective tissue framework intact
Healing by scarring conditions
Tissue consists of permanent cells and/or no surviving cells remain and/or connective tissue framework is destroyed/disrupted
Growth factors
May promote cell proliferation by recruiting G0 cells into cell cycle…may inhibit cell proliferation…may influence other cell function
Epidermal growht factor family
EGF and TNF-alpha
EGF
Produced by several cells, including macrophages
Mitogenic for epithelial cells, hepatocytes and fibroblasts
Binds to ERB B1
TGF-alpha
Almost same to EGF, also binds to ERB B1
PDGF
Stored in alpha granules of platelets
Released when platelets activated
Also produced by macrophages, edothelial cells, smooth muscle, and some tumor cells
Mitogenic and chemitactic for fibroblasts, smooth muscle cells, and monocytes
FGF
Acidic and basic types
Produced by activated macrophages
Chemotactic and mitogenic for fibroblasts and endothelial cells
Induce angiogenesis
TGF-B
Produced by platelets, endothelial cells, lymphocytes, and activated macrophages
Generally mitogenic for fibroblasts but can inhibit grwoth of epithelial cells
Stimulates fibroblast chemotaxis, and stimulates production of collagen and fibronection (important for scars)
Fibrogenic cytokines
IL-1 and TNF
Mitogenic and chemotactic for fibroblasts
Stimulate collagen production by fibroblasts
Important in scar formation
Direct binding of what is critical for regeneration and scar formation?
Cell to the ECM
4 components of repair by fibrosis
Angiogenesis/neovascularization
Migration and proliferation of fibroblasts
Deposition of ECM components, including collagen
Organization of the fibrous tissue into a mature scar (remodeling)
In fibrosis, 24 hours after tissue injury
Fibroblasts and vascular endothelial cells proliferate
Granulation tissue
Formed by proliferation of fibroblasts and vascular endothelial cells
2 important features of granulation tissue
Angiogenesis and fibroblast proliferation
Angiogenesis - granulation tissue
New vessels originate from other blood vessels in the area
New vessels have leaky interendothelial junctions allowing exudate to form (tissue is edematous)
Need FGF and VEGF in order to grow
Fibroblast proliferation - granulation tissue
Triggered by EGF, TGF-B, PDGF, and others
TGF-B stimulates newly created fibroblasts to secrete collagen
Weeks to months after, how is granulation tissue turned into a scar?
Amount of collagen and other ECM proteins increases
Number of fibroblasts and other other vascularity decreases
Fully mature scare is practically avascular and has dense collagen
Healing of a surgical incision
Scalpel blade injures a number of epidermal cells and underlying connective tissue
Space fills with clotted blood
Neutrophils appear (24 hours)
By day 3, replaced with macrophages
At day 3, granulation tissue begins to form because of growht factors from platelets, macrophages, and endothelial cells…TGF-B stimulates production of collagen and other ECM proteins
Growth factors induce basal cells of the epidermis to regenerate
By day 5, granulation tissue has filled incisional space
During second week, collagen accumulates while leukocytes, edema, and increased vascularity begin to disappear
By then end of the first month, scar is formed and epidermis fully regenerated
It is then complete
