Wound healing Flashcards
Name the 4 phases of wound healing
1) Hemostasis
2) Inflammatory
3) Repair
4) Remodeling/maturation
What is the first cell to arrive in the hemostasis phase of wound healing?
Platelets
What structures become exposed when a wound is created, starting the clotting cascade?
Collagen
Tissue factor
What is released from platelet dense granules to cause vasoconstriction?
Thromboxane A2
Serotonin
What is released from platelet alpha granules to stimulate platelet aggregation?
VWF
fibrinogen
factor V
What enzyme converts fibrinogen to fibrin to form a fibrin clot?
Thrombin
What provides a matrix scaffold for cell attachment and serves as a growth factor reservoir during wound healing?
Fibrin clot
What clotting factors are part of the intrinsic pathway of clotting?
Factors XII
Factor XI
Factor IX
Factor VIII
What clotting factor is independently activated by the extrinsic and intrinsic pathways?
Factor X
What activates the extrinsic pathway of the clotting cascade?
Tissue factor
What activates the intrinsic pathway of the clotting cascade?
Collagen exposure
What clotting factors are part of the extrinsic pathway of the clotting cascade?
Factor VII
Factor III (tissue factor)
What factors are part of the common pathway of the clotting cascade?
Factor I (fibrinogen)
Factor II
Factor V
Factor X
Factor XIII
What components make up the fibrin clot?
Fibronectin
Activated factor XIII
Fibrin (factor Ia)
What cells are the first to arrive during the inflammation phase of wound healing?
Neutrophils
What factors are released by platelets to cause chemoattraction during the inflammatory phase of wound healing?
PDGF
VEGF
TGF-b
What platelet structure houses PDGF, VEGF, and TGF-b?
Alpha granules
How soon after an injury to leukocytes enter?
Within a few hours
What is present on the neutrophil surface to allow them to interact with the ECM?
Integrin receptors
What do neutrophils release to kill microbes and debride the wound bed?
Proteases
ROS
What cytokines are released by neutrophils to stimulate macrophages, KCs, and fibroblasts?
IL-1
IL-6
TNF-a
IGF
What cells are the most important producers of growth factors in wound healing?
Macrophages
How long does it take the inflammatory phase of wound healing to be completed?
72 hours
What is the function of M1 macrophages?
Kill bacteria
Scavenge debris
What is the function of M2 macrophages?
Suppress immune system
Tissue repair
What type of macrophage predominates in the repair phase of wound healing?
M2
What are 4 major cell types present during the repair phase of wound healing?
M2 macs
Keratinocytes
Fibroblasts
Endothelial cells
What is usually present within 72 hours of the onset of wound healing?
Granulation tissue
What is another name for the repair phase of wound healing?
Proliferation phase
What are 3 major events during the repair phase of wound healing?
Angiogenesis
Re-epithelialization
Fibroplasia
What structural proteins are released by fibroblasts when they enter a wound?
Collagen
Elastin
What adhesive protein is produced by fibroblasts when they enter a wound?
Fibronectin
What is the predominant type of collagen produced by fibroblasts early in wound healing?
Collagen III
What type of collagen replaces collagen III in wound repair?
Collagen I
What protein allows fibroblasts to bind to the ECM?
Fibronectin
What are the functions of fibroblasts during wound healing?
Protein synthesis
Cross-linking collagen
MMP production to removed damaged matrix
What do fibroblasts secrete to allow for collagen cross-linking during wound healing?
Lysyl oxidase
What MMPs are essential in wound healing?
Stromelysins
Gelatinases
Collagenases
In addition to collagen I, what other collagen is produced at the same time and serves to regulate the dermal matrix assembly?
Collagen VI
During wound healing, what proteinases are released during angiogenesis to break down old vessels and ECM, and what cells release them?
MMPs
Heparinase
Released by endothelial cells
What factors can stimulate angiogenesis during wound healing?
Macrophage-released cytokines
Low oxygen tension
Lactic acid
growth factors
What 2 growth factors are important for angiogenesis during wound healing?
Fibroblast growth factor (FGF)
VEGF
What is the function of TIMP in wound healing?
Inhibits MMPs
What cytokine is important for synthesis of TIMP?
IL-6
What 3 factors serve to inhibit angiogenesis during wound healing?
Endostatin
Angiostatin
Antithrombin III
What do keratinocytes form during wound healing to allow them to migrate into a wound?
Lamellipodia
What is the dominant factor that acts on endothelial cells during angiogenesis in wound healing?
VEGF
How long after wounding is re-epithelialization usually seen?
4-5 days
What process allows keratinocytes to stop migrating into a wound once they have reached the proper site?
Contact inhibition
What protein degrades the KC basement membrane and allows it to move towards the wound center during wound healing?
MMP-1 (collagenase)
In what part of a wound is the proliferation index the highest?
Center
During wound healing, what collagen helps re-form the basement membrane of KCs after re-epithelialization?
Collagen IV
What cells play an integral role in wound contraction during wound healing?
Myofibroblasts
List the mediators in wound healing that allow for keratinocyte proliferation and migration during re-epithelialization
EGF
FGF
HGF (hepatocyte growth factor)
IGF
TGF-a
TGF-b
IL-1
IL-6
TNF-a
What factor stimulates dermal fibroblasts to differentiate into myofibroblasts during wound healing?
TGF-b
What intracellular component within myofibroblasts interacts with fibronectin and collagen in the wound matrix?
Actin
When does wound contraction peak?
2 weeks after wound onset
What are the hallmarks of the maturation/remodeling phase of wound healing?
Apoptosis of endothelial cells
Collagen remodeling
What is the final strength of the scar after wound healing?
70-80% the strength of normal tissue
What is the major component of the scar formed at the end of wound healing?
Collagen I
What factor is most important during the remodeling stage of wound healing?
TGF-b
How do pigs typically heal wounds?
Re-epithelialization
How to rats and mice heal wounds?
Contraction
How does the wound healing of ponies and horses differ?
Ponies tend to heal via wound contraction
Horses tend to heal via re-epithelialization
Why do horse wounds tend to heal more poorly compared to other species?
1) Haphazard organization of myofibroblasts –> poor contraction
2) Weak but prolonged inflammatory responses
3) Excessive ECM production due to increased angiogenesis, lower MMP-1 concentrations, and disorganized collagen
What are the main contributors to excessive granulation tissue formation in horses?
1) Prolonged inflammatory response
2) Extended presence of fibroblasts and TGF-b
How does wound healing in dogs differ from that of cats?
1) Dogs produce more substantial early inflammatory response
2) Cutaneous angiosomes differ between species
3) Granulation tissue forms at bottom of wound in dogs and at periphery in cats
4) Indolent pocket wound formation in cats
What are known risk factors for surgical site infections of open wounds?
1) Hypothermia
2) Hypotension
3) Poor tissue oxygenation
What factors would lead you to suspect a biofilm has formed in a wound?
1) Delayed healing >3 weeks
2) Friable granulation tissue
3) Foul odor with minimal signs of infection
What cells critical to wound healing are most likely to be affected by chemotherapeutics?
Fibroblasts (i.e. any rapidly-dividing cells)
What are the effects of corticosteroids on wound healing?
1) Decreased cytokine expression
2) Reduced neutrophil adhesion/migration
3) Reduced macrophage infiltration
4) Inhibition of fibroblast migration and deposition of collagen
What medication/supplement has been reported to reverse the effects of corticosteroids on wound healing?
Vitamin A
What serum protein level is associated with poor wound healing?
<2 g/dl
What are the effects of vitamin A on wound healing?
1) Improved inflammatory response
2) Increased EGF receptors
3) Increased collagen synthesis
What are the components of the TIME principle in wound evaluation?
T=Tissue
I=Inflammation/infection
M=Moisture
E=edge of wound
How long should the inflammatory phase of wound healing typically last?
3 days
What type of wound would a calcium alginate dressing be used for?
Highly exudative wound
What component of a wound ECM gives a glistening appearance to the wound?
Hyaluronic acid
What cells serve as the most important storage location for TGF-b?
Platelets
What adhesion molecule is upregulated after wounding to allow neutrophils to adhere to endothelial cells?
E/P selectin
What integrins on neutrophils adhere to E- and P-selectin to allow for leukocyte adhesion?
CD11/CD18
What growth factors are released by macrophages during wound healing?
PDGF
FGF
TGF-b1
What occurs to vessels immediately following a wound?
Vasoconstriction followed by vasodilation
What receptor is normally expressed in inactive fibroblasts at rest?
Collagen integrin receptor a2
What integrin subunits are expressed by fibroblasts when exposed to provisional ECM, PDGF, and TGF-b?
Integrin receptor units a3 and a5
What types of ECM are present in a healing wound?
1) Fibrin clot
2) Fibronectin
3) Hyaluronan
4) Proteoglycans
5) Collagen
Which glycosaminoglycan supports movement and cell proliferation during wound healing?
Hyaluronan
Besides cytokines released from neutrophils, what else attracts macrophages into a wound?
Collagen fragments
Fibronectin
Elastin
TGF-B
When do lymphocyte numbers peak within a wound?
6 weeks after wound
What cytokines are released by lymphocytes during wound healing?
IL-6
TGF-B1
TGF-B2
What factor stops the proliferation of epithelial cells during wound healing?
TGF-B1
What are the chemoattractants for endothelial cells?
VEGF
TGF-a
Fibronectin
Heparin
What type of dressing serves as a useful secondary dressing?
Semipermeable films (i.e. Tegaderm)