Wound Repair Flashcards
definition of a wound
an acquired defect in the structural and functional integrity of tissue caused by physical or chemical insults
two subtypes of wound healing
regeneration & replacement
wound regeneration
restoration of lost tissue structures via cell division and growth of new parenchymal cells
wound replacement/repair
filling of the wound with less specialized connective tissue, principally collagen resulting in a scar
three types of regeneration
1) division of parenchymal cells in intact stroma
2) division of parenchymal cells in remaining structure
3) stem cell division and differentiation
labile cells
cells that can undergo high regeneration due to highly proliferative tissues (GI epithelium, epidermis, bone marrow)
stable cells
tissues that undergo limited regeneration bc they divide at low rates. (liver, kidney, vascular endothelium)
permanent cells
post-mitotic tissue (neurons, cardiac muscle)
chronic inflammation and wound repair
inhibits regeneration and therefore leads to replacement
milder injury & regeneration
when accompanied with persistence of underlying stromal framework, enables regeneration
severe injury & regeneration
destroys stromal framework precluding regeneration or triggering abnormal regeneration
characteristics of replacement of a wound with a scar
destruction of tissue stromal architecture, limited proliferation of tissue stem cells, chronic inflammation
primary union
straight wound, well apposed edges, clean. minimal scar formation. minimized formation of granulation tissue and scar formation.
secondary union
irregular wound, unappeased edges, dirty/infected, significant scar formation. extensive inflammation and granulation tissue, wound contraction. attempts to close via primary union can prevent infection from clearing.
tertiary union
wound that is allowed to begin healing by secondary union and is sutured after resolution of infection to allow further healing by primary union
5 steps in wound healing
- clot formation
- inflammatory cell recruitment
- proliferation/migration of parenchymal/stromal cells
- synthesis of ECM proteins
- remodeling
PDGF (platelet derived GF)
released by activated platelets and macrophages, stimulates proliferation of fibroblasts and vascular endothelial cells
FGF (fibroblast GF)
produced by macrophages and fibroblasts. potent activator of angiogenesis via stimulation of proliferation of endothelial cells and via directing their formation into tubular vessels
KGF (keratinocyte GF)
produced by fibroblasts, stimulates growth of keratinocytes during reepithelialization of the wound
VEGF (vascular endothelial GF)**
synthesis is stimulated by hypoxia, released from many cells including endothelial cells, fibroblasts, macrophages. stimulates endothelial cell proliferation and angiogenesis. also increases permeability of vessels
TGF-beta (transforming GF-beta)
produced by many cells including platelets, macrophages, fibroblasts, keratinocytes. regulates multiple target cells and all stages of wound healing
wound healing steps (simple version)
clot, inflammation, epithelialization, granulation, collagenization, maturation
clot phase of wound healing
initial coverage of the wound via clot, entry of acute inflammatory cells (PMNs) via leaky/damaged vessels, which release chemokines and GFs that attract cellular components of epithelialization
first line of defense against wound
clot
scab
superficial aspect of a clot that has become dehydrated
epithelialization phase of wound healing
keratinocytes migrate under the clot
granulation tissue phase of wound healing
epithelial regrowth has reached surface. underneath there is ingrowth of fibroblasts, new/leaky endothelial bus (create edema), macrophages
functions of fibroblasts in a wound
secrete ECM (collagen, glycoproteins, etc), secrete growth factors, contract to reduce size of wound
functions of endothelial cells in wound
migration and angiogenesis=leaky vasculature
collagenization phase of wound healing
replacement of granulation tissue with disorganized collagen (type 3)
maturation phase of wound healing
collagen deposition stops and it is reorganized into tensile bundles. vascularity and cellularity decrease, production of GF ceases
matrix metalloproteinases (MMPs)
key regulators of wound healing. set of 24 proteins that help keratinocyte migration, modulate chemokine activities, help remodel ECM,
principle components of granulation tissue
leaky capillaries and macrophages
examples of pathologic scarring
nodule formation in cirrhosis, contractures, keloids, strictures
keloids
growth of the scar beyond the boundaries of the original wound. over exuberant deposition of collagen and ECM
