Wound Healing Flashcards
T/F: During normal homeostasis, hair follicles contribute to the epithelia.
False - normally do NOT, but during wound healing they do
What is a foam dressing?
polyurethane or silicone foam; vapor permeable but provide thermal insulation to the wound; hydrophilic wound contact layer and a hydrophobic backing – highly absorbent
What is the function of granulocyte/macrophage colony stimulating factor in wound healing?
stimulates proliferation and differentiation of osteoblasts; synergizes with Epogen in proliferation of BM progenitor cells; strong chemoattractant for neutrophils
What is an alginate?
produced from the calcium and sodium salts of alginic acid found in seaweeed; partially dissolved on contact with wound fluid –> forms a hydrophilic gel; can absorb 15-20 times their weight in fluid – excellent for highly exudative wounds
What is the purpose of semi-permeable films?
impermeable to fluids and bacteria but permeable to air and water vapor
What are differences between equine exuberant granulation tissue and keloids?
Exuberant granulation tissue lacks epithelial cover (keloids have); TGF-beta1 is increased –> induces general protein synthesis
What is the role of prostaglandins in wound healing?
increased vascular permeability, sensitize pain receptors, increased synthesis of glycosaminoglycans
What is the function of platelets that form the initial clot during wound healing?
maintain hemostasis, provide a matrix for migration of cells involved in wound healing, secrete cytokines to direct wound healing
What role does hypoxia play in wound healing?
activates fibroblasts and endothelial cells, stimulates macrophages to release angiogenic factors (TGF-beta1)
Indications for a semipermeable film (wound dressing)?
flat, shallow wounds with medium exudate; may be left in place for several days; useful secondary dressing; no cushion; provides moist environment and doesn’t adhere to wound
T/F: Migrating keratinocytes cannot bind to denatured collagen or denatured fibrin.
True - results in wound dissection and peeling off of the eschar
What cytokines and growth factors do activated platelets release?
platelet-derived growth factor, transforming growth factor beta-1 (TGF-beta-1), platelet activating factor, platelet-derived epidermal growth factor, fibronectin and serotonin
What are the processes that occur in scar tissue formation and tissue remodeling?
1) Fibrinolysis, 2) Removal of excessive extracellular matrix, 3) Contraction/scar formation, 4) Remodeling the collage and vasculature and further effects of matrix metalloproteinases
______ is new vascular tissue in granular form on an ulcer or the healing surface of a wound.
granulation tissue
What proteins do activated platelets release?
adenosine diphosphate (ADP), fibrinogen, fibronectin, thrombospondin; von Willebrand factor VIII
What is the function of platelet-derived growth factor in wound healing?
fibroblast proliferation, chemotaxis and collagen metabolism; angiogenesis; A & B isoforms are potent mitogens for fibroblasts, arterial smooth muscle cells, chondrocytes and epithelial cells; potent chemoattractant for hematopoietic and mesenchymal cells, fibroblasts and muscle cells, stimulates chemotaxis toward a gradient of PDGF; activates TGF-beta, stimulates neutrophils and macrophages, mitogenesis of fibroblasts and smooth muscle cells, collagen synthesis, collagenase activity and angiogenesis
What type of collagen is increased during neovascularization and in highly vascular hypertrophic scars?
collagen V
characteristics of hypertrophic scars
non-invasive, decreased collagen lysis –> abundance of collagen I, problem with remodeling phase
What is the role of kinins (e.g. bradykinin) in wound healing?
increased vascular permeability (through activation of complement cascade)
How are neutrophils removed from the wound?
with the wound eschar or are phagocytosed by activated tissue macrophages
What phenotypic changes occur in keratinocytes to allow migration to take place?
retract tonofilaments; dissolve desmosomes and hemidesmosomes; increase gap junctions (enhanced cellular communication); peripheral actin filaments and formation of lamellipodia (motor apparatus); express keratin 5, 14, 6, 16; express serine proteases and matrix metalloproteinases; express integrins that allow attachment to provisional matrix
What is the function of tumor necrosis factor in wound healing?
promotes inflammation
Migrating cells use what type of receptors that recognize the matrix components of the provisional matrix (fibrin, fibrinonectin, vitronectin)?
integrin receptors (mostly beta-2 integrins)
What is the second provisional matrix in wound healing?
granulation tissue
What is the most important growth factor in angiogenesis? What cell(s) release(s) it?
fibroblast growth factor - released by macrophages (and keratinocytes)
Why are neutrophils present in the wound earlier and in greater numbers than macrophages?
are present in the circulation in greater numbers
Indications for antimicrobial dressings?
can be used in all locally infected wounds
T/F: After wound healing, a scar reaches its original tissue strength.
False - only reaches 70% of original tissue strength
characteristics of keloids
invasive, abundance of collagen III, problem with proliferative phase (stuck in proliferative phase)
What are the known receptors for hyaluronic acid?
1) CD44 – involved with attachment, uptake and breakdown of HA, 2) RHAMM - found on macrophages and fibroblasts
What is the function of histamine in wound healing?
causes increased vascular permeability
Where are the most macrophages present in granulation tissue (what zone)?
zone of capillary sprouts and arches
What is the function of keratinocyte growth factor in wound healing?
keratinocyte proliferation - most potent growth factor for keratinocytes, playing a role in tissue repair following skin injuries; promotes wound healing via proliferation, differentiation, angiogenesis and cell migration; mitogen for many epithelial cells but not for fibroblasts and endothelial cells
In full thickness wounds, where does epithelialization start from?
wound’s edge
What is present in granulation tissue that gives wounds a “glisteny” appearance?
hyaluronic acid
Indication for a low adherent dressing?
flat, shallow wounds with low exudate
What are the primary collagens involved in wound repair?
Collagen III (present first) and then collagen I
What is the role of complement in wound healing?
increased vascular permeability, increased phagocytosis, enhanced bacterial lysis, mast cell and basophil activation
What is the function of connective tissue growth factor in wound healing?
fibroblast proliferation, chemotaxis and collagen metabolism; induces proliferation, migration, and tube formation of vascular endothelial cells and angiogenesis; potent stimulator for the proliferaiton and differentiation of osteoblasts, stimulates the matrix mineralization
What is the function of plasminogen activator in clot formation?
limits the clot formation by activating plasmin (converts plasminogen to plasmin) – plasmin causes clot lysis
What is a major chemoattractant for monocytes in wound healing?
TGF-beta-1
What replaces hyaluronic acid as a wound matures?
glycosaminoglycans
What cells are involved in coagulation/inflammation?
1) Platelets (coagulation), 2) Neutrophils (inflammation), 3) Growth factors (coagulation & inflammation), 4) Fibrin clot (coagulation), 5) Matrix metalloproteinases (coagulation & inflammation)
_____ refers to a reorganization of the tissue to accommodate the processes of healing.
Remodeling
What cytokine is thought to be involved in the development of keloids?
IL-6
How are macrophages removed from the wound?
apoptosis
What is a hydrogel?
matrix of insoluble polymers with up to 96% water content –> can donate water molecules to the wound surface; facilitate natural autolysis
What are the processes that occur during coagulation/inflammation?
1) Bleeding with resultant tissue hypoxia, 2) Platelet activation/aggregation and coagulation, 3) Recruitment of leukocytes, 4) Debridement of damaged tissue, 5) Formation of first provisional matrix = fibrin clot
What is the orientation of vessels in granulation tissue to the wound surface?
perpendicular
What is the first provisional matrix in wound healing?
fibrin clot
What is the function of IL-1 in wound healing?
fibroblast proliferation; proinflammatory; inhibits the growth of endothelial cells and hepatocytes
What is a hydrocolloid?
colloids such as sodium carboxymethylcellulose, gelatin, pectin, elastomers, and adhesives bonded to a carrier of a semi-permeable film on a foam sheet –> produces a flat, occlusive adhesive dressing that forms a gel on the wound surface. Water and air impermeable and used to rehydrate dry, necrotic eschar and promote autolytic (self) debridement
What cells are involved in tissue formation (migration/proliferation)?
macrophages, fibroblasts, keratinocytes, integrins, growth factors, enzymes (serine proteases and matrix metalloproteinases)
What cells would CD18 deficient mice lack in their wounds?
neutrophils – CD18 is a marker for integrins (needed for diapedesis of neutrophils)
What is the primary enzyme involved in collagen lysis?
matrix metalloproteinase-1 (collagenase-1) - ZINC depedent
How soon after the initial wound do macrophages replace neutrophils as the predominant cell type?
within 24-48 hours
What is the function of vascular endothelial growth factor in wound healing?
angiogenesis; vascular permeability; macrophage chemotaxis; induces synthesis of metalloproteinase – which degrades interstitial collagen types I, II, III
What do mast cells produce that lead to nerve stimulation?
histamine, serotonin, nerve growth factor
What effect would blocking plasminogen have on wound healing?
knockout mice show delayed re-epithelialization; plasminogen is converted to plasmin, which helps to limit the size of the clot that is formed
What is the function of epidermal growth factor in wound healing?
keratinocyte proliferation and migration; stimulates the proliferation of epidermal and epithelial cells, fibroblasts, and embryonic cells; chemoattractant for fibroblasts and epithelial cells; stimulates re-epithelialization, augments angiogenesis; influences the synthesis and turn-over of extracellular matrix
T/F: Scar tissue and grafts regain the innvervation of the original tissue
FALSE - healing wounds are associated with HYPERinnervation
What cells are involved in scar tissue formation and tissue remodeling?
myofibroblasts, enzymes (serine proteases and matrix metalloproteinases), growth factors
What is the function of insulin-like growth factor 1 in wound healing?
keratinocyte proliferation and differentiation; growth factor for normal fibroblasts; promotes the synthesis of collagenase and prostaglandin E2 in fibroblasts; stimulates collagen and matrix synthesis by bone cells, regulating metabolism of joint cartilage
What cleaves fibrinogen into fibrin?
thrombin
What do keratinocytes need to be in contact with in the provisional matrix in order to migrate?
collagen I, III or V, fibronectin, fibrin, tenascin, or vitronectin
What is the function of fibroblast growth factor in wound healing
fibroblast and epithelial cell proliferation; matrix deposition, wound contraction; angiogenesis
What is the purpose of a low-adherent dressing?
allow exudate to pass through a secondary dressing while maintaining a moist wound bed – designed to prevent the dressing form adhering to the wound
What is the role of serotonin in wound healing?
stimulates fibroblast proliferation, involved in cross-linking of collagen molecules
Indications for alginates (wound dressing)?
for highly exudative undermined wounds. Highly absorbent and needs a secondary dressing
Indications for a hydrocolloid (wound dressing)?
Sheets: cavity or flat, shallow wounds with low-medium exudate; absorbent; comfortable; good in difficult area; Paste: debriding agent - can cause maceration; Hydrofiber: like sheets but can handle higher exudate; can be left in place for several days but needs secondary dressing
T/F: Histology of keloids and hypertrophic scares usually reveals mast cell hyperplasia.
True - this is in contrast to normal rapid disappearance of perilesional mast cells
What is the function of IL-8 in wound healing?
supports angiogenesis, mitogenic for epidermal cells
What do mast cells produce after exposure to fibronectin and type III collagen that break down the extracellular matrix
proteases chymase and typtase
Why does fetal repair result in no scarring?
lack of inflammatory response
T/F: Endothelial cells produce their own extracellular matrix and basement membrane.
True- extracellular matrix is fibronectin and proteoglycans
What are the components of intrinsic blood clotting?
surface activation of Hageman Factor XII, tissue procoagulant released from damaged cells, coagulation factors expressed on activated platelets and endothelial cells
What are the processes that occur during tissue formation (migration/proliferation)?
1) Granulation tissue formation (second provisional matrix), 2) Cell migration and proliferation, 3) Final extracellular matrix production, 4) Fibroplasia/angiogenesis
Migrating keratinocytes contain what products normally found in the stratum corneum?
involucrin and transglutaminase
What cell(s) release vascular endothelial growth factor?
platelets, keratinocytes, macrophages, neutrophils
On what type of wound should semi-permeable films NOT be used?
highly exudative wounds
Hypertrophic scars and keloids result from persistance of what cell type?
fibroblasts (myofibroblasts)
What are chemoattractant factors for neutrophils?
IL-8, kallikrein, Gro (growth-related oncogene-alpha), fibrinogen degradation products, fibrinopeptides, cytokines released by activated platelets
What is the primary signal that stops keratinocyte migration?
reconstitution of laminin within the BMZ
What is the function of the complement cascade in clot formation?
results in release of anaphylatoxins C3a and C5a –> increase vessel permeability and attract neutrophils and monocytes to site of injury
Lymphocyte function associated-antigen, a beta-2 integrin present on activated neutrophils, binds to what on endothelial cells to facilitate neutrophil diapedesis?
I-CAM
In partial thickness wounds, where does epithelialization start from?
both the wound edge and from adnexal structures within the wound bed
Why could bandaging an equine leg increase the amount of granulation tissue produced?
bandaging results in a condition of hypoxia –> leads to stimulation of fibroblasts, endothelial cells, macrophages
What is the function of hepatocyte growth factor in wound healing?
keratinocyte proliferation
Where are the most neutrophils present in granulation tissue (what zone)?
Zone of necrotic debris
T/F: Hair follicles are not necessary to close a wound, only to initiate rapid re-epithelialization.
TRUE
What is the function of IL-10 in wound healing?
fibroblast proliferation; anti-inflammatory
What proteoglycans are important in wound healing?
serglycine (produced by mast cells and endothelial cell membranes –> involved in coagulation); chondroitin-4-sulfate and dermatan sulfate (produced by mature scar fibroblasts –> structural components); versican (promotes cell migration by decreasing adhesion); decorin (inhibits growth of cells in vitro); syndecan family
What is the primary role of neutrophils in the wound site?
phagocytosis and intracellular killing o fcontaminating bacteria
What is the most important storage factor for transforming growth factor beta-1 (TGF-beta-1)?
platelets
What are the four zones of granulation tissue?
Deepest –> superficial: 1) Zone of mature connective tissue, 2) Zone of capillary proliferation, 3) Zone of capillary sprouts and arches, 4) Zone of necrotic debris (“scab” or “crust”)
What is the function of transforming growth factor-beta in wound healing?
fibroblast proliferation, chemotaxis and collagen metabolism; angiogenesis; immunomodulation; decreases dermal scarring;
______ is the formation of granulation tissue and subsequent re-collegenation of the dermal matrix.
fibroplasia
What are the phases of wound healing?
1) Coagulation, 2) Inflammation, 3) Migration/Proliferation, 4) Remodeling
What is the function of transforming growth factor-alpha in wound healing?
keratinocyte proliferation and migration; resembles EGF (binds to the same receptor); stimulates mesenchymal, epithelial, and endothelial cell growth, endothelial chemotaxis, controls the epidermal development; stimulates the proliferaiton of endothelial cells (more potent than EGF); promotes the generation of osteoblasts - influencing them to lay down bone matrix during osteogenesis; affects bone formation and remodeling by inhibition fo the synthesis of collagen and release of calcium
Indications for foam dressings?
sheets: flat, shallow wounds - gives some cushioning. Can be left in for 2-3 days, needs secondary dressing; cavity foam: for medium to highly exudative cavitated wounds
What growth factors do macrophages release?
transforming growth factor beta-1; fibroblast growth factor; platelet-derived growth factor; vascular endothelial growth factor; hepatocyte growth factor
Indications for hydrogels (wound dressing)?
moisturizes dry, flat, cavitated or sinus wounds; good for necrotic, sloughing wounds - but can cause maceration. Needs a secondary dressing
