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81 Cards in this Set
- Front
- Back
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What is the sole purpose of wound healing?
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To re-establish an epithelial shield (skin).
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Why do we have skin?
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Protection against foreign material and organisms, Protection against bacterial/viral/fungal infection, Maintenance of homeostasis (prevent water loss, conserve heat)
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True or False: The phases of wound healing are discrete events without overlap.
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FALSE: Wound healing is a continuum and the events overlap.
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4 Stages of Wound Healing
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Inflammation, Debridement, Repair, Maturation
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When does inflammation start?
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As soon as the surface cellular barrier is broken.
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How long does inflammation last?
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Day 0 to 3... But this can be prolonged and overlap with later stages (ex. Proud flesh in horses)
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At which stage of wound healing can a vet exert the greatest influence on later wound healing?
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Inflammation - important for initiating the repair process and protecting against infection
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Inflammation has two main mechanisms/components. What are they?
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Vascular and cellular component
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Describe the vascular component of the inflammatory stage.
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1. Initial hemorrhaging cleans wound bed --> 2. Vasoconstriction (5-10 min) --> 3. Vasodilation of small venules --> cells, fluid and protein pass into wound space --> 4. Clot formation: Thromboplastin released from injured cells --> activation of extrinsic coagulation system --> clot formation and platelet aggregation --> scab formation --> 5. Lymphatics plugged with fibrin
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Vasoconstriction is mediated by?
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Catecholamines, serotonin, bradykinin and histamine.
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Why is clot formation so important?
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Ensures patient doesn't bleed to death, and provides the scaffold for future cell migration.
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Why is factor XIII important?
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Activated factor XIII causes fibronectin to covalently crosslink with fibrin to form the provision extracellular matrix that acts as an early barrier to infection, and a scaffold for future wound healing.
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Why are lymphatics plugged with fibrin
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To prevent spread of inflammation and "glue" wound edges together.
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Describe the cellular component of the inflammatory stage.
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1. Platelets exposed to basement membrane --> 2. Platelets become active and release chemoattractants and growth factors --> initiation and amplification of wound repair.
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Name 3 chemoattractants/growth factors released by activated platelets during inflammation.
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Epidermal growth factor, platelet growth factor, transforming growth factors (alpha and beta)
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What causes the scab to slough off, along with underlying dead inflammatory cells and bacteria, as healing proceeds?
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Plasmin
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What stage of wound healing is this injury in? |
Inflammation |
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What is the second stage of wound healing and when does it typically occur? |
Debridement - Day 0 to 3 |
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TRUE OR FALSE: Inflammation and debridement stages of wound healing can occur simultaneously. |
True. |
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What are the two main leukocytes of the debridement stage? |
Neutrophils and macrophages
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When would we start seeing neutrophils at the wound site? |
6 hours post injury, and peak numbers 1-2 days after injury |
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TRUE OR FALSE: Neutrophils are essential to infected wound healing. |
TRUE. However, neutrophils ARE NOT essential to NON-INFECTED wound healing (ex. a sterile surgical incision) |
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The main role of neutrophils |
Seek and destroy debris and bacteria by phagocytosis, and subsequent degradation with enzymes and oxygen radical mechanisms. |
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What is pus? |
Combination of wound fluid, tissue debris and neutrophils. |
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The role of macrophages |
Carry out the debridement, microbial killing, and coordination of later stages of repair (by synthesis and secretion of cytokines). |
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When can macrophages be found in a wound and how long do they stay? |
Monocytes emigrate into the wound at 12 hours and change into macrophages 24-48 hours later. Macrophages remain in the wound for a few weeks. |
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Which cell is KEY to the reparation of the tissue? |
MACROPHAGES! (not neutrophils) |
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True or False: Both neutrophils and macrophages secrete collagenases, debride foreign material and sloughing tissue. |
True. |
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Why are macrophages key to tissue reparation? |
They secrete growth factors important for initiating, maintaining and coordinating the formation of granulation tissue. |
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Examples of growth factors secreted by macrophages. |
Platelet derived GF, transforming GF (alpha and beta), fibroblast GF and interleukin-1 |
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Other actions of macrophages in the wound bed |
Recruit mesenchymal cells, stimulate angiogenesis and modulate matrix production. |
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When does the repair stage of wound healing occur? |
After day 2-5 |
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What are the three main components of wound repair? |
Fibroplasia, angiogenesis and epithelialization. |
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Name the stage of wound healing this injury is in. |
Repair Stage |
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What are fibroplasia, angiogenesis and epithelialization? |
Fibroplasia - formation of granulation tissue Angiogenesis - formation of blood vessels Epithelialization - formation of skin |
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What are the three main elements of granulation tissue? |
Macrophages, fibroblasts, new blood vessels. |
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What type of tissue replaces the fibrin-containing clot during wound healing? |
Granulation tissue |
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Important role of granulation tissue |
Acts as a physical barrier to infection and provides a surface for cells to migrate across. |
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What is the general appearance of granulation tissue? |
Pink, smooth, shiny tissue usually starting as a light pink rim around the edge of the wound. |
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Describe granulation tissue formation |
Inflammatory cells signal fibroblasts to migrate to wound and proliferate --> fibroblasts produce protein to replace provisional/immature matrix (ex. Type III collagen) with mature matrix (type 1 collagen) --> increasing tension on the wound --> fibers orient parallel to wound margin --> granulation tissue |
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What happens to fibroblasts following deposition of the granulation matrix? |
They undergo apoptosis, OR transform into myofibroblasts that contribute to wound contraction. |
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What is proud flesh? |
Proud flesh is excess formation of granulation tissue (scar tissue) associated mostly with horses. |
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True or false: A nerve block must be administered prior to surgical removal of proud flesh on a horse. |
False; proud flesh is excess granulation tissue, which means it is highly vascularized (will see bleeding), but contains no nerve endings. |
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What is thought to be the cause of proud flesh? |
In horses, the signal to down-regulate collagen deposition as the wound repairs is prolonged, leading to an imbalance between collagen degradation and synthesis, causing the formation of excessive scar tissue. |
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What stage of wound healing is this? What mechanism of that stage is clearly shown? |
Repair, granulation tissue formation |
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What stage of wound healing is this? How do you know? |
Inflammatory; fresh blood is clearly flowing from the injury. NOT angiogenesis! |
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What is angiogenesis and what is its role in the repair of tissue? |
Angiogenesis is the formation of capillary blood vessels form existing ones. It's role is to vascularize and support the newly forming granulation tissue as it is formed by fibroblasts. |
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What are some factors that initiate angiogenesis? |
Angiogenic inducing agents are usually released in response to macrophage mitogenic factors, low oxygen tension and increased lactic acid. Ex. Fibroblastic growth factor and vascular endothelial growth factor. |
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Steps of angiogenesis: |
1. Increased microvascular permeability 2. Release of proteinases fro activated endothelial cells --> degrade basement membrane of old vessel. 3. Capillary bud formation 4. Endothelial cell proliferation |
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What is a capillary bud? |
Migration and sprouting of new endothelial cells in the interstitum. |
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What is the appearance of unhealthy granulation tissue? |
White with a high fibrous content and minimal capillaries. The wound should brighten to red as new capillaries, fibroblasts and fibrous tissue appear in the wound. |
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True or false: Lymphatic vessels develop rapidly during early healing and facilitate lymphatic drainage. |
False: Lymphatic vessels develop more slowly and so lymphatic drainage is more poor during early healing. |
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When does epithelialization of a wound occur? |
Epithelial migration starts 24-48 hours after wounding, and not visibly seen as a pink rim at the edges until 4-6 days later (this is highly variable based on the species and site and size of the wound) |
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True or false: Epithelialization is accelerated in partial thickness wounds (intact basement memrbane) compared to full thickness wounds. |
True: In full thickness wounds, granulation tissue must form first (and act as a scaffold) in order for epithelial cells to migrate across the wound. |
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Epithelium can grow from the edge of the wound at a rate up to______ per day. |
1mm per day |
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What is "contact inhibition" and why is it important for wound healing? |
The cessation of epithelial cell migration of across a wound when the cells make contact with one another on all sides. |
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What stage of wound repair is occurring here? Specifically, what mechanism is seen? |
Repair stage, epithelialization (can see that the wound has been completely covered by a layer of pink granulation tissue; white epithelialization layer can be seen advancing from the edges. |
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When does the maturation stage of wound healing occur? |
After day 17 post-trauma |
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What are the two components of wound maturation? |
1. Contraction 2. Matrix remodeling |
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What stage of wound healing is portrayed here? How do you know? |
Maturation stage; Scartissue, contraction and mature granulation are present, along with tissue remodeling. |
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What is the main cell type responsible for wound contraction? |
Myofibroblasts |
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Why is good wound contraction important? |
1. Smaller scar 2. Prevention of re-injury (less tissue involved in newly formed epithelium) |
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What is wound contraction? |
Dermis and epidermis brought together centripetally. |
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What are the 3 phases to wound contraction? |
1. Lag phase 2. Rapid Contraction phase 3. Slow Contraction phase |
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During wound contraction, what happens in the lag phase and how long does it last? |
Lag Phase: Wound increases in size due to swelling and centripetal forces by surrounding intact skin. Fibroblastic invasion. Lasts 5 to 10 days. |
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During wound contraction, what happens in the fast conduction phase and how long does it last? |
Fast conduction phase: Wound contracts at 0.6-0.8mm per day |
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During wound contraction, what happens in the slow conduction phase and how long does it last? |
Slow conduction phase: Wound is fully epithelialized and myofibroblasts return to being fibroblasts or undergo apoptosis. |
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What happens if myofibroblasts persist in a wound past the time they are required? |
Pathologic contracture - permanent disfiguring fibrosis of a joint or body orifice. |
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What are the three rules of contraction (stopping)? |
1. Wound edges meet (contact inhibition) 2. Tension in surrounding skin greater/equal to contractile force by myofibroblasts. 3. Low myofibroblast development or function (chronic poorly healing, pale wounds) |
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What is matrix remodelling and when do we typically see it? |
Conversion of extracellular matrix (ECM) from granulation tissue into scar tissue. Occurs as the last step of tissue maturation when there is adequate collagen in the wound (>17 days post-injury) |
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Deposition of collagen in the wound during matrix remodeling increases its tensile strength. How long does this take to occur for primary wound repairs? Second intention healing? |
Primary wound repairs: 7 days Second intention healing: More than 17 days |
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Describe matrix remodeling during the maturation phase of wound healing. |
Adequate collagen in wound --> deposition and aggregation of Type 1 collagen (mature) fibers --> net increase in collagen deposition and tensile strength of wound --> collagen synthesis and degradation --> fibers realign along lines of tension and cross link to original tissue --> no net increase in collagen content --> rearrangement and organization of fibers for YEARS to come. |
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Collagen degradation depends on what substances? |
Proteolytic enzymes (mainly matrix metalloproteinases) released from inflammatory and mesenchymal cells. |
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True or false: Wound remodeling can occur for years after injury. |
True. |
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The normal skin ratio of type I to type III collagen? |
4:1 (mature:immature collagen) |
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At max strength, scar tissue will be ________% weaker than surrounding tissue. |
15-20% weaker |
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What are the 3 main categories of factors that affect wound healing? |
1. Wound factors 2. Host factors 3. External factors |
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List examples of wound factors that can affect wound healing. |
Exposed tissues, foreign material, mechanical trauma, blood supply, moisture, temperature, communication with synovial spaces, biofilm |
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List examples of host factors that can affect wound healing. |
Age, nutritional status, hydration, disease (hepatic, renal), obesity, duration of anesthesia, cats vs. dogs, horses vs. ponies. |
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List examples of external factors that can affect wound healing. |
Radiation therapy, corticosteroids, chemotherapy. |
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This was a metal plate that was surgically placed into the patient. Based on this image, what factors can be seen to be affecting wound healing? |
The wound is infected (swollen, red and nasty). Will likely NOT heal until the plate is taken out. Plate has a biofilm and is acting as the source of contamination. (ie. Wound factors: foreign object, biofilm) |
