Wound Healing Flashcards
What are the main stages of wound healing?
+/- Haemostasis phase
Inflammatory phase
Proliferation Phase
Maturation/remodeling phase
What is the purpose of wound healing?
to restore normal function & structural integrity
What are the cellular components of wound healing?
platelets, neutrophils, monocytes, macrophages, endothelial cells, fibroblasts, myofibroblasts, keratinocytes
What are the non-cellular components of wound healing?
growth factors, cytokines, chemokines
What occurs during the inflammatory/debridement phase of wound healing?
Tissue disruption causes haemostais and inflammation. There is a disruption to the vascular endothelium. The endothelial cells release endothelin. Endothelin + Epinephrine/norepinephrine, and prostaglandins leads to vessel wall dilation and vasoconstriction.
When vessel dilation and vasoconstriction occur, what are the two cell types involved?
Phase I: neutrophils
Phase II: macrophages
How long does it take for neutrophils to react to a wound?
They arrive within the first 24-48 hours of a wound occurring
What cytokines/chemokines activate neutrophil infiltration to a wound site?
TGF-beta, Prostaglandins, TNF-alpha, IL-1, and bacterial products
What is the function of a neutrophil?
- Killing of bacteria via release of reactive oxygen species (ROS)
- Breakdown of ECM via release of proteolytic enzymes
- Phagocytosis of degraded bacteria & matrix debris
- Release of additional cytokines that prolong the inflammatory phase
What monocyte follows neutrophils to a wound site?
Macrophages
How does a monocyte become a macrophage?
The monocyte migrates through the vessel walls of the blood stream and matures into macrophages
After 48-96 hours post-wounding, what is the primary leukocyte found in the wound?
Macrophage (they have phagocytosed most of the neutrophils or the neuts have undergone apoptosis)
What is the function of a macrophage?
- wound debridement
- release of signalling molecules
- release of matric metalloproteinases
- secretion of proteases
- Phagocytosis of debris
- removal of bacteria
What signalling molecules from macrophages recruit other cell types?
Cytokines, IL-1/6/8, TNF-alpha
Growth factors: FGF, EGF, TGF-beta, PDGF
What macrophage matrix metalloproteinases (MMP) degrade provisional ECM to facilitate the movement of cells through a wound?
MMP - 1, 2, 3, 9
Thromboxane A2 and serotonin (activated platelets) lead to
vasoconstriction
What do activated platelets thromboxane A2 & serotonin do?
- Adhere to exposed subendothelial collagen
- Aggregate
- Degranulate
What platelet alpha-granules are degranulated by thromboxane A2 & serotonin?
PDGF, TGF-beta, EGF, VEGF, FGF
Following vasoconstriction at a wound site, what occurs next?
Activation of coagulation leading to the formation of thrombin.
What does thrombin do at the site of a wound?
Platelet activation & converts fibrinogen to fibrin
What is the second stage of wound healing?
the proliferation/reparative phase
What is the purpose of the proliferation/reparative phase?
To restore blood flow, ECM, and epithelial covering to a wound
What occurs during the proliferation phase of wound healing?
Capillary ingrowth, collagen production, wound contraction, wound coverage
What causes capillary ingrowth (aka angiogenesis) to a wound site?
Occurs as a result of capillaries sprouting from existing vasculature surrounding the wound
What growth factors and cells encourage angiogenesis at a wound site?
VEGF, Keratinocytes, FGF
What is the purpose of angiogenesis at a wound site?
the development of a microvascular network within the wound provides oxygen and nutrients to cells and becomes part of developing granulation tissue beds
Where do fibroblasts come from and what cell types encourage their proliferation?
Fibroblasts migrate from surrounding tissue and proliferate in response to factors from platelets & macrophages
What type of collagen is synthesised by fibroblasts in response to PDGF at a wound site?
Type III collagen
Macrophages release what growth factor during the proliferative phase of healing and what does this growth factor do?
TGF-beta
Increases synthesis of Type I collagen & decreases production of MMPs
How does TGF-beta influence fibroblasts at the site of healing?
It encourages fibroblasts in the wound to transform into myofibroblasts to form focal adhesions thus providing adequate mechanical leverage to cause wound contraction
What causes epithelial cells to begin proliferation into a wound site?
Epithelial cells respond to EGF and TGF-alpha
What is secreted by epithelial and endothelial cells to break down fibrin in the path of cell migration?
MMPs
What process stops the movement of endothelial cells when in a wound?
Contact inhibition
What are the predominant cell types in the proliferative phase of healing?
fibroblasts, epithelial cells, endothelial cells
What is the purpose of the maturation or remodelling phase of wound healing?
Reorganisation of collagen & return of some degree of pre-wound strength
Explain the process of the maturation/remodelling phase of wound healing.
- Remodelling & strengthening of collagen
- Collagen III converts to Collagen I
- Matrix becomes more rigid
- As tension on wound edges decreases secondary to collagen deposition, myofibroblasts regress, and collagen synthesis by fibroblasts is progressively decreased
- Collagen maturation may continue for 12-18 mos
- Collagen becomes reabsorbed and redeposited along lines of stress
Disruptions to the mucosa alone heal by…
epithelial cell proliferation & migration –> seals in about 3 days
Full thickness injuries to the GIT heal beginning w/
an inflammatory phase similar to skin healing
what occurs during the proliferation phase of healing in the GIT?
granulation tissue is formed at the wound site and collagen undergoes synthesis and lysis
Fibroblasts and smooth muscle cells synthesise what in the GIT healing phase?
collagen
How many types of collagen are present within the GIT and what are they?
3 types of collagen: Collagen I, II, III
What is the Lag phase of healing in the GIT?
Activity of collagenase during the first 1-2 days of healing
What is special about the healing of fascia?
restoration of the integrity of the fascia is prolonged as the inflammatory cells and fibroblasts have to migrate longer distances through normal tissues to reach avascular and acellular fascial wounds
What is special about fascia in the first 7 days of fascial wound healing?
Fascial incisions have no inherent strength and the integrity of the wound is dependent on suture material.
How long does it take skin to reach pre-wound strength? Fascia? Bladder?
Skin: 6 wks
Fascia: 14 wks
Bladder: 3 wks
How long does it take the bladder to re-epithelialize?
2-4 days
What causes the initial inflammatory reaction of bone healing?
pro-inflammatory cytokines
Growth factors
bone morphogenetic proteins (BMPs)
What do BMPs do?
stimulate undifferentiated mesenchymal cells to become chondroblasts & osteoprogenitor cells
Neurovascularization of bone occurs in response to
GF release
Capillary budding
Endothelial cell migration
Bone healing requires…
- Chondroblasts & osteoblasts to produce cartilage & osteoid
- Osteoclasts to degrade devitalised bone
What is the initial callus of bone created by when healing?
fibrous tissue, cartilage, loosely woven bone
The maturation phase of bone may last longer than
1 year
Between dogs and cats, what is different about first intention healing of linear wounds?
Breaking strength is less in cats & equivalent to only half that of dogs
Between dogs and cats, what is different about second intention healing?
Granulation tissue is observed faster and in higher quantity in dogs than cats
Between dogs and cats, which one has a faster mean time to completely cover a wound with granulation tissue?
Dogs
What are the major impediments to wound healing?
Local factors and Systemic factors
What local factors impede wound healing?
wound perfusion
tissue viability & wound fluid accumulation
wound infection
What systemic factors impede wound healing?
Primary immunodeficiencies & conditions that impair immune function
Cancer
Age
