Wound Healing Flashcards
explain wound healing
Bleeding (sometimes not needed):
This is the initial response to injury. In some cases, bleeding may not occur, especially in very small wounds or in situations where bleeding is quickly controlled. However, in many cases, bleeding is an essential part of the healing process as it helps clean the wound and initiate the inflammatory phase.
Inflammatory Phase:
The inflammatory phase is the immediate response to tissue injury. It involves the activation of the body’s defense mechanisms, including the immune system, to fight off any potential pathogens and remove debris from the wound site.
Key components during this phase include the release of inflammatory mediators, recruitment of white blood cells (such as neutrophils and macrophages), and the removal of dead cells and foreign material.
Proliferation Phase:
In this phase, the body starts to repair the damaged tissue. It involves the growth of new blood vessels (angiogenesis) and the proliferation of various cell types, including fibroblasts, which are responsible for producing the extracellular matrix (collagen) needed for tissue repair.
Epithelial cells at the wound edges begin to migrate and cover the wound. This phase helps reconstitute and rebuild the damaged tissue.
Remodeling Phase:
The final stage of wound healing, the remodeling phase, can take place over a more extended period. It involves the reorganization and realignment of collagen fibers, making the newly formed tissue stronger and more functional.
This phase may last for months or even years, and the final result is the formation of a scar, which is composed of collagen and other proteins.
explain the initial stages of wound healing, known as the “Inflammatory Phase”
The initial stages of wound healing, known as the “Inflammatory Phase,” start immediately after an injury and typically last for about 2 to 5 days. During this phase, the body’s response is geared towards achieving hemostasis (preventing excessive bleeding) and initiating the inflammatory process. This phase can be broken down into two main processes:
A. Haemostasis:
Haemostasis is the process of stopping bleeding and involves several key steps:
Constriction of damaged blood vessels: Immediately after injury, the blood vessels constrict, or narrow, to reduce blood flow and limit bleeding.
Formation of a platelet plug: Platelets in the blood adhere to the exposed collagen at the site of injury and aggregate to form a plug that helps seal the wound.
Activation of intrinsic and extrinsic clotting pathways: These pathways are involved in forming a stable blood clot. The intrinsic pathway is initiated inside the blood vessel, while the extrinsic pathway is triggered by external trauma.
Formation of an initial fibrin matrix: Fibrin, a protein formed as a result of the clotting cascade, reinforces the platelet plug, creating a stable blood clot.
B. Inflammation:
The inflammatory phase involves the body’s immune response to the wound. Key processes include:
Recruitment of inflammatory cells by chemo-attractants: In response to the injury, the body releases chemical signals known as chemo-attractants, which attract white blood cells, such as neutrophils and macrophages, to the wound site.
These white blood cells are critical for removing foreign material, dead cells, and pathogens. They also help to control and limit the spread of infection.
The inflammatory phase sets the stage for subsequent stages of wound healing, including the proliferation phase and remodeling phase, which are essential for the formation of new tissue and the eventual closure of the wound.
explain the continuation of the inflammatory phase of wound healing
C. Neutrophils:
Neutrophils are white blood cells that play a crucial role in the early stages of the inflammatory response. They are responsible for:
Phagocytosis: Neutrophils engulf and digest dead tissue, cellular debris, and pathogens, helping to clean the wound site.
Preventing infection: By consuming bacteria, neutrophils contribute to preventing or limiting infections at the wound site.
D. Monocytes and Macrophages:
Monocytes are another type of white blood cell that enters the wound site during the inflammatory phase. They eventually differentiate into macrophages, which are specialized phagocytic cells.
Phagocytosis: Both monocytes and macrophages continue the cleaning process by phagocytosis, removing dead cells, debris, and remaining pathogens.
Release of growth factors: Macrophages also play a vital role in tissue repair and healing by releasing growth factors and cytokines that stimulate the proliferation of fibroblasts and other cells necessary for the repair and regeneration of tissue.
E. Lymphocytes (T and B cells):
Lymphocytes, which include T cells and B cells, arrive at the wound site during the later stages of the inflammatory phase and play different roles in wound healing:
T cells: T cells are involved in regulating the immune response and can help control inflammation to prevent excessive tissue damage.
B cells: B cells are responsible for antibody production, which can be important in defending against infections that may have entered the wound.
These immune cells work together in a coordinated manner during the inflammatory phase to not only remove debris and prevent infection but also to initiate the processes that will eventually lead to tissue repair and healing. The transition from the inflammatory phase to the proliferation phase, where tissue regeneration and repair occur, is a critical step in the overall wound healing process.
explain the “Proliferation Phase” of wound healing
Granulation Tissue Formation:
Granulation tissue is a type of connective tissue that begins to fill in the wound. It is rich in blood vessels, fibroblasts, and other cells necessary for tissue repair. This tissue provides a scaffold for further healing processes
Angiogenesis:
Angiogenesis is the formation of new blood vessels. During this phase, new blood vessels sprout from existing ones and infiltrate the granulation tissue. This is essential to supply nutrients and oxygen to the healing tissue.
Contraction of Wound Edges:
In some cases, the edges of the wound may contract, bringing the wound closer together. This can be particularly important in cases of large wounds or open wounds to reduce the size of the defect.
Epithelialization:
Epithelialization is the process of forming a new epithelial layer (skin) over the wound. This occurs as a result of the following processes:
Macrophages release cytokines: These signaling molecules attract fibroblasts, lymphocytes, and other cells to the wound site.
Growth factors: Growth factors like PDGF (Platelet-Derived Growth Factor), EGF (Epidermal Growth Factor), TGF (Transforming Growth Factor), and IL-1 (Interleukin-1) instruct mesenchymal stromal (stem) cells to generate new structures and promote healing. Fibroblasts: Fibroblasts play a central role in the proliferation phase by creating new connective tissue and aiding in the synthesis of collagen. Muscle cell formation: If the wound involves muscle tissue, new muscle cells can also form to aid in restoration.
Replacement of fibrin matrix: The initial provisional fibrin matrix, formed during the inflammatory phase, is gradually replaced by more mature collagen, often Type III collagen.
The proliferation phase is a dynamic period during which the wound gradually fills with new tissue, blood vessels, and an epithelial covering.
explain the timeline of how the strength of the healing tissue progresses following a wound
7 Days After Wounding:
At this stage, the skin has only about 10% of the strength of unwounded skin. The tissue is relatively weak due to the early stages of tissue repair, which includes the formation of granulation tissue and the synthesis of collagen.
4 More Weeks (Approximately 7 Weeks Post-Wound):
Following the initial 7-day period, strength increases rapidly over the next 4 weeks. This rapid increase in strength is due to the ongoing collagen synthesis, maturation of the extracellular matrix, and the healing of the wound. The tissue gradually gains structural integrity and tensile strength.
3 Months After Wounding:
The rate of strength increase slows down at around 3 months post-wound. By this point, the majority of the tissue repair and remodeling processes have occurred. The wound area may still be undergoing some fine-tuning in terms of tissue composition and strength.
Final Strength:
The final strength of the healed tissue is approximately 90% of the original, unwounded skin. While the tissue regains a significant portion of its strength, it may not reach 100% of the original strength. Scar tissue, which often replaces the original tissue, is typically not as strong or flexible as the original skin, which can account for the difference in strength.
It’s important to note that the timeline and final strength can vary depending on several factors, including the type and location of the wound, the individual’s overall health, and the quality of wound care and management. Scar tissue, while serving to repair the wound, may be less elastic and prone to hyperpigmentation compared to the original skin. Rehabilitation, such as physical therapy, can also be essential for regaining full functionality, especially for wounds involving muscles and joints.
explain angiogenesis
Angiogenesis is indeed the process of constructing or reconstructing blood vessels. It plays a crucial role in various physiological and pathological processes, including wound healing, tissue repair, and the growth of new blood vessels to supply oxygen and nutrients to tissues. Here are some key points regarding angiogenesis:
Stimulation by Hypoxic and Acidic Conditions: Angiogenesis is often stimulated in response to areas of low oxygen (hypoxia) and high acidity (low pH). When tissues experience inadequate oxygen and nutrients, they release signaling molecules that promote angiogenesis as a means to increase blood supply and improve tissue perfusion.
EGF-1 (Epidermal Growth Factor-1) as an Angiogenic Stimulant: EGF-1 is indeed a potent angiogenic stimulant. It is a growth factor that can promote the growth and development of new blood vessels. EGF-1 plays a significant role in several physiological and pathological processes, including wound healing.
Heparin as a Cofactor: Heparin is a naturally occurring anticoagulant that can act as a cofactor in angiogenesis. It can help to stabilize and enhance the activity of angiogenic growth factors and cytokines, such as EGF-1.
TGF-alpha and TGF-beta in Angiogenesis: Transforming Growth Factor-alpha (TGF-alpha) and Transforming Growth Factor-beta (TGF-beta) are growth factors that also contribute to angiogenesis. They play roles in the regulation of cell proliferation, differentiation, and tissue repair. TGF-beta, in particular, has complex effects on angiogenesis, as it can promote or inhibit blood vessel formation depending on the context.
Prostaglandins in Angiogenesis: Prostaglandins are lipid compounds that can have both pro-angiogenic and anti-angiogenic effects. Prostaglandins play a role in mediating inflammation, and certain prostaglandins can promote angiogenesis by influencing vascular growth factors and signaling pathways.
explain the process of wound contraction during the wound healing phases
Timing: Wound contraction usually initiates after about 4 or 5 days post-injury. This delay allows for the initial inflammatory and proliferation phases to set the stage for tissue repair.
Significance in Large Wounds: Wound contraction is generally more pronounced in larger wounds. This process is an essential mechanism to reduce the size of the wound defect and promote faster healing.
Centripetal Movement: Wound contraction involves the centripetal movement of the surrounding tissue towards the center of the wound. This helps to close the wound and reduce its size.
Maximum Contraction: The maximum rate of wound contraction typically occurs during the initial 2 weeks following injury and can progress at a rate of 0.6 to 0.75 mm per day. This rate may vary based on the specific circumstances and location of the wound.
Fastest Contraction on Lax Tissues: Wound contraction tends to occur more rapidly in areas with lax, or loose, tissue. Lax tissue allows for greater mobility and stretching, which facilitates the closure of the wound.
Square Wounds vs. Round Wounds: Interestingly, square wounds tend to contract faster than round wounds. This phenomenon is attributed to the geometry of the wound and the mechanical forces involved in the contraction process.
Continued Contraction in Open Wounds: If a wound is still open, wound contraction may continue at a smaller scale. The contraction process remains active as long as the wound has not completely closed or epithelialized.
Wound contraction is an important part of wound healing, particularly in cases where there is a significant loss of tissue. It helps to minimize the size of the wound, which can lead to better cosmetic outcomes and functional recovery. The process involves the coordinated actions of fibroblasts and myofibroblasts, which generate contractile forces within the wound bed, drawing the surrounding tissue toward the center.
explain the key components and processes associated with the provisional basement membrane and epithelial cell proliferation
Composition of the Provisional Basement Membrane:
The provisional basement membrane is made up of various components, including:
Fibronectin: Fibronectin is a glycoprotein that helps anchor cells to the extracellular matrix and facilitates cell migration.
Collagen Type I: Collagen Type I is a major component of the extracellular matrix and provides structural support to the wound.
Collagen Type III: Collagen Type III is another collagen type found in the provisional matrix. It helps maintain the structural integrity of the tissue during the early stages of repair.
Epithelial Cell Proliferation:
Epithelial cells, which are crucial for skin and tissue repair, play a central role in the proliferation phase of wound healing.
The provisional basement membrane provides a substrate for these cells to adhere to and migrate across the wound area.
As epithelial cells migrate and proliferate, they gradually cover the wound surface.
Contact Inhibition Chemicals:
Contact inhibition refers to the phenomenon in which cells stop dividing when they come into contact with neighboring cells. This mechanism helps prevent excessive cell proliferation and tissue overgrowth.
During wound healing, when the edges of the wound start to come together and epithelial cells meet, contact inhibition signals are released.
These signals can include chemical factors and cell-to-cell communication, which instruct nearby cells to halt their proliferation once the wound is adequately covered.
The provisional basement membrane, in conjunction with the proliferation of epithelial cells, plays a crucial role in wound closure. Once the epithelial cells have covered the wound and the provisional basement membrane is no longer needed, the tissue gradually transitions to the remodeling phase, where collagen synthesis and organization continue, ultimately leading to the maturation of the healed tissue.
explain the “Remodeling Phase” of wound healing
Collagen Formation for Tensile Strength:
During the remodeling phase, the focus is on the formation of collagen, primarily Type I collagen. This collagen is essential for providing tensile strength to the healed tissue, making it more robust and resilient.
Increased Cross-Links Between Fibers:
The number of inter-molecular cross-links between collagen fibers increases dramatically during the remodeling phase. These cross-links enhance the structural integrity and stability of the tissue.
Type 3 Collagen Replaced by Type 1:
Type 3 collagen, which is initially present in the early days of wound healing (part of the provisional matrix), gets gradually replaced by Type 1 collagen. Type 1 collagen is the primary collagen in healed tissue and contributes to its strength.
Gradual Remodeling Over 12 Months:
Remodeling continues for an extended period, often around 12 months or more. This slow and gradual process involves the ongoing reorganization, realignment, and maturation of collagen fibers and other extracellular matrix components.
Neat Scar Color Changes from Red to White:
Scars typically undergo a transformation in color during the remodeling phase. Initially, scars can appear red or pink, but over time, they often lighten and mature, ultimately becoming white or closer to the color of the surrounding skin.
Additional Information about Types of Collagen:
Type 1 collagen is the most abundant and is found in various tissues, including skin, tendons, bone, and blood vessels. It provides strength and support to these tissues.
Type 3 collagen is present in early wound healing and is gradually replaced by Type 1 collagen. It is also found in organs like the liver and plays a role in tissue repair.
Type 2 and Type 11 collagen are primarily found in cartilage and are important for cartilage structure and function.
Type 4 collagen is a major component of basement membrane
explain the key growth factors and their functions
Platelet-Derived Growth Factor (PDGF):
Promotes the migration and proliferation of fibroblasts, which are important for producing extracellular matrix (ECM) components.
Acts as a chemotactic factor for monocytes, recruiting them to the wound site to help in tissue repair and inflammation.
Epidermal Growth Factor (EGF):
Promotes the growth and proliferation of several cell types, including endothelial cells (important for blood vessel formation), epithelial cells (for wound closure), and fibroblasts.
Fibroblast Growth Factor (FGF):
Promotes the synthesis of ECM proteins, such as fibronectin.
Acts as a chemotactic factor for fibroblasts and endothelial cells.
Stimulates angiogenesis, which is the formation of new blood vessels, helping to improve blood supply to the wound.
Vascular Endothelial Growth Factor (VEGF):
Specifically promotes angiogenesis, playing a critical role in the development of new blood vessels.
Other Factors (Macrophage-Derived Growth Factor, IL-1, TNF, etc.):
These growth factors and cytokines often promote the proliferation of fibroblasts and endothelial cells, which are essential for tissue repair and wound healing.
The coordinated action of these growth factors helps orchestrate the various phases of wound healing, from inflammation and tissue repair to the formation of new blood vessels. They are involved in cell recruitment, proliferation, and the synthesis of extracellular matrix components, ultimately contributing to the successful healing of a wound.
give an overview of systemic and local factors that affect wound healing
Systemic Factors:
Nutrition:
Adequate nutrition is crucial for wound healing. Essential nutrients like protein, vitamins (particularly vitamin C and vitamin A), minerals (such as zinc and iron), and calories are required for the body to build new tissue and maintain overall health. Malnutrition can significantly impair wound healing.
Metabolic Health:
Metabolic conditions, such as diabetes, can negatively affect wound healing. Poorly controlled blood sugar levels can lead to impaired circulation and a compromised immune response, making it more challenging for wounds to heal.
Circulatory Status:
A strong blood supply is necessary for delivering oxygen and nutrients to the wound site. Conditions that affect circulation, like peripheral artery disease, can hinder the wound healing process.
Presence of Some Hormones:
Hormones, such as cortisol, play a role in regulating the body’s response to stress and inflammation. Chronic or excessive cortisol levels can slow down the healing process. Hormones related to growth and development, like growth hormone and insulin-like growth factor (IGF-1), also influence healing.
Local Factors:
Presence of Infection:
Infection is a significant impediment to wound healing. Bacterial, fungal, or viral infections can delay the natural healing process and may require medical intervention.
Motion:
Excessive mechanical stress or motion around the wound can disrupt the formation of new tissue, especially in weight-bearing areas or joints. Immobilization or support may be necessary to promote healing.
Foreign Material:
The presence of foreign material, such as debris, splinters, or foreign bodies within the wound, can create an obstacle to healing and may require removal.
Size, Location, and Type of Wound:
The size and location of a wound can impact the healing process. Larger wounds typically take longer to heal. Wounds in areas with less blood supply may heal more slowly. The type of wound, such as surgical incisions, traumatic wounds, or pressure
explain the potential consequences of deficient scar formation
Wound Dehiscence:
When a wound heals with a deficient or weak scar, there is an increased risk of wound dehiscence. Wound dehiscence refers to the separation or reopening of a previously closed surgical or traumatic wound. It can occur due to the inability of the fragile scar tissue to withstand mechanical stresses, such as tension, pressure, or stretching.
Wound dehiscence is a serious complication that can lead to delayed wound healing, increased risk of infection, and the need for additional medical intervention, including wound re-closure.
Ulcer Formation:
In some cases, deficient scar formation can lead to the development of chronic ulcers. These are open sores or wounds that fail to heal properly. A fragile scar may not provide the necessary structural support, leading to continuous breakdown and poor wound closure.
Chronic ulcers, such as pressure ulcers (bedsores) or diabetic foot ulcers, can result in prolonged pain, risk of infection, and impaired quality of life. Managing and treating these ulcers can be challenging.
To minimize the risk of deficient scar formation, wound care and management should focus on promoting robust and organized wound healing. This includes optimizing nutrition, managing any underlying medical conditions (such as diabetes), minimizing mechanical stress on the healing wound, and implementing appropriate wound care strategies.
explain the excessive formation of repair components in the wound healing process
Keloid or Hypertrophic Scar:
Keloids and hypertrophic scars are raised, thickened, and often reddish or purplish scar tissue that can extend beyond the boundaries of the original wound. They result from an overproduction of collagen and other extracellular matrix components during the wound healing process.
Keloids are more severe and extend well beyond the boundaries of the initial wound. They are more common in people with darker skin and tend to recur after treatment.
Hypertrophic scars are raised but remain within the boundaries of the original wound. They can be less severe than keloids but may still cause cosmetic and functional issues.
Exuberant Granulation or Proud Flesh:
Exuberant granulation, often referred to as “proud flesh,” occurs when there is an excessive and abnormal growth of granulation tissue in a wound. Granulation tissue is necessary for healing, but when it proliferates too much, it can impede wound closure and lead to raised, fleshy, and often painful tissue.
Proud flesh is a term commonly used for exuberant granulation in horses but can also describe similar excessive granulation tissue in humans.
The development of keloids, hypertrophic scars, or exuberant granulation/proud flesh is influenced by various factors, including an individual’s genetics, the size and location of the wound, and the overall management of the wound during the healing process. Prevention and treatment strategies for these issues may involve methods like pressure garments, silicone gel sheets, corticosteroid injections, surgical excision, or other specialized wound care approaches.
explain the two different types of wound healing processes
Primary Intention Healing:
This type of wound healing occurs when the wound edges are closely approximated or joined together. It is typically seen in small, clean surgical incisions or wounds with minimal tissue loss.
The key steps in primary intention healing include:
The wound edges are held together, often with sutures, staples, or adhesive strips.
A fibrin plug forms at the site of the wound, helping to seal it initially.
Basal epidermal cells start regrowing quickly.
The fibrin plug is eventually lysed, and re-epithelialization occurs, leading to the restoration of the skin to its intact state.
Primary intention healing generally results in minimal scarring and faster wound closure.
Secondary Intention Healing:
This type of wound healing occurs when there is a significant tissue loss or a wound with irregular or gaping edges, making it unable to be closed by simple approximation.
The key steps in secondary intention healing include:
The wound is left open to heal from the inside out.
A fibrin clot fills the wound, and the wound bed is gradually filled with granulation tissue.
New blood vessels and fibroblasts grow from the surrounding dermis into the fibrin, helping to establish a vascularized and connective tissue base.
Collagen is laid down by granulation tissue fibroblasts, which gradually restores the integrity of the wound.
As the collagen matures, it provides structural support and allows for the regrowth of the epidermis over the newly formed tissue.
Secondary intention healing often results in larger scars and a longer overall healing process.
The choice between primary and secondary intention healing depends on factors such as the size and type of wound, the risk of infection, and the available wound care resources. While primary intention is preferable for smaller, clean wounds, secondary intention is used for larger or more complex wounds that cannot be easily closed. Both methods aim to restore tissue integrity and promote wound healing, but the timing and approach differ significantly.
