Case Study 4 - Wound Healing Flashcards
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
What could be causing the lymph nodes of her groin to be enlarged?
Reactive lymph node as a result of infection stimuli, tumoral lymph nodes as a result of malignancy (lymphoma or metastasis), ultraimmune lymph nodes as a result of an autoimmune response (rheumatoid arthritis)
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
What factors are important for successful wound healing? Does our patient have any factors
which may influence the healing of her groin wound?
Blood supply, tissue growth factor, infection control, nutrition, age, medications, intensity of injury, diabetes, vitamins, steroids
In the case of the 54-year-old woman, factors such as her age, smoking history, and diabetes may pose challenges to optimal wound healing. Smoking can reduce blood flow and impair the immune response, while diabetes can affect vascularization and overall tissue repair.
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
How do these factors influence wound healing at the cellular level?
Smoking:
Effect at Cellular Level: Smoking can lead to vasoconstriction, reducing blood flow to the wound site. Nicotine and other components in tobacco can also impair oxygen delivery to cells. This compromises the ability of cells to proliferate and function optimally.
Impact on Wound Healing: Reduced blood flow delays the inflammatory response, impairs immune cell function, and hinders the delivery of nutrients and oxygen needed for cellular activities during wound healing.
Infection:
Effect at Cellular Level: Infections introduce harmful microorganisms to the wound site, leading to an ongoing inflammatory response. Immune cells are recruited to fight the infection, but if the infection persists, it can become chronic and hinder the normal healing process.
Impact on Wound Healing: Chronic infections can result in prolonged inflammation, delaying subsequent phases of wound healing, including tissue repair and remodeling.
Vitamin C Deficiency:
Effect at Cellular Level: Vitamin C is essential for collagen synthesis, a crucial component of tissue repair. Deficiency in vitamin C can impair the formation of strong and functional collagen fibers.
Impact on Wound Healing: Inadequate collagen synthesis weakens the structural integrity of the wound, leading to delayed or compromised healing. This deficiency can result in poor wound closure and increased susceptibility to mechanical stress.
Steroids:
Effect at Cellular Level: Steroids can inhibit the activity of transforming growth factor-beta (TGF-beta), which plays a key role in the regulation of inflammation and fibroblast proliferation during wound healing.
Impact on Wound Healing: Reduced TGF-beta activity can impair the formation of granulation tissue and fibroblast proliferation, both crucial for tissue repair. This inhibition can result in delayed wound closure and increased risk of complications.
Poor Perfusion:
Effect at Cellular Level: Inadequate blood supply (poor perfusion) limits the delivery of oxygen and nutrients to the wound site, hindering cellular activities such as proliferation and metabolism.
Impact on Wound Healing: Cells require oxygen and nutrients to carry out their functions. Poor perfusion can lead to prolonged inflammation, delayed tissue repair, and increased susceptibility to infection.
Mechanical Factors:
Effect at Cellular Level: Mechanical stress on the wound can disrupt the delicate balance of cellular activities involved in healing, causing the wound edges to separate and impairing the formation of granulation tissue.
Impact on Wound Healing: Mechanical factors, such as excessive tension on the wound edges, can result in poor wound closure, increased scarring, and compromised overall healing.
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
What type of wound healing process will occur in the groin?
Yes, the wound healing process in the groin, where the edges are sutured closed, would typically follow the primary intention (also known as primary closure) pathway.
Primary Intention Healing:
This type of healing occurs when the wound edges are brought together and held in place, either through sutures, staples, or other means.
It is a more rapid and efficient process compared to secondary intention healing.
The reduced gap between wound edges allows for faster re-epithelialization and formation of granulation tissue.
Primary intention healing generally results in less scarring compared to secondary intention healing.
In the case of the groin wound after surgery, the fact that the surgeons sutured the wound closed indicates an intention to promote primary healing. This approach is often preferred for surgical incisions when feasible, as it reduces the risk of infection, promotes faster healing, and typically leads to better cosmetic outcomes.
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
Describe the 2 main types of wound healing and what happens during each process. What are the differences?
Primary Intention Healing:
Hemostasis:
Goal: Stopping bleeding and preventing excessive inflammation.
Process: Platelet aggregation forms a clot (hematoma), and cytokines (e.g., E1, A2, TA2) cause vasoconstriction.
Inflammatory Phase:
Cellular Response: Neutrophils are recruited to remove pathogens and cellular debris.
Cytokines Release: Various cytokines, including TNF, PBGF, TGF-beta, and FGF, mediate inflammation and immune response.
Proliferative Phase:
Cellular Activities: Cytokine-mediated proliferation of fibroblasts, leading to the formation of granulation tissue.
Growth Factors: VEGF supports angiogenesis, and various growth factors (TNF, PBGF, TGF-beta, FGF) contribute to collagen and extracellular matrix (ECM) production.
Remodeling Phase:
Process: Devascularization occurs, and apoptosis of fibroblasts takes place.
Resolution: Infection resolves, and continued deposition of collagen and proteins contributes to wound closure.
Secondary Intention Healing:
Inflammatory Phase:
Cellular Response: Similar to primary intention, involving neutrophils and an inflammatory response.
Cytokines Release: Release of various cytokines, contributing to the inflammatory cascade.
Proliferative Phase:
Granulation Tissue Formation: Granulation tissue starts from the bottom and fills the wound gradually.
Cellular Activities: Myofibroblasts, containing actin and myosin, contribute to wound contraction.
Growth Factors: Similar growth factors (VEGF, TNF, PBGF, TGF-beta, FGF) play a role in collagen and ECM production.
Remodeling Phase:
Process: Similar to primary intention, involving devascularization, apoptosis of fibroblasts, and continued collagen and protein deposition.
Contraction: Myofibroblasts contribute to wound contraction, aiding in reducing the wound size.
Differences:
Size of Wound:
Primary intention is used for smaller, clean wounds with well-apposed edges.
Secondary intention is employed for larger wounds with tissue loss or contamination.
Timeline:
Primary intention generally has a faster healing timeline due to the approximation of wound edges.
Secondary intention takes longer as the wound fills gradually with granulation tissue.
Scar Formation:
Primary intention often results in less scarring and better cosmetic outcomes.
Secondary intention may lead to more noticeable scarring due to the gradual filling of the wound.
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
What are fibroblasts and what is their function in wound healing?
Fibroblasts:
Fibroblasts are a type of cells found in connective tissue. They play a crucial role in wound healing and tissue repair. Here’s an overview of their function in wound healing:
Collagen Synthesis:
Fibroblasts are responsible for the synthesis and secretion of collagen, which is a key structural protein in connective tissues. Collagen provides strength and support to the wound, contributing to the formation of granulation tissue.
Granulation Tissue Formation:
During the proliferative phase of wound healing, fibroblasts migrate to the wound site and proliferate. They lay down the framework for the formation of granulation tissue, which is a temporary, highly vascularized tissue that fills the wound and supports further healing processes.
Extracellular Matrix (ECM) Production:
Fibroblasts produce various components of the extracellular matrix, including proteoglycans and glycoproteins. The ECM serves as a scaffold for cells involved in wound healing, providing structural and biochemical support.
Wound Contraction:
In addition to their role in collagen synthesis and granulation tissue formation, fibroblasts can differentiate into myofibroblasts. Myofibroblasts have contractile properties due to the presence of actin and myosin filaments. This contraction ability allows them to contribute to the closing of the wound during the remodeling phase.
Tissue Remodeling:
Fibroblasts participate in the remodeling phase of wound healing. This phase involves the maturation and reorganization of the newly formed tissue. Fibroblasts play a role in determining the strength and flexibility of the healed tissue.
Differentiation into Myofibroblasts:
Under certain conditions, fibroblasts can differentiate into myofibroblasts.
Myofibroblasts have contractile properties, allowing them to exert mechanical forces on the wound edges and contribute to wound contraction.
This contraction helps reduce the size of the wound and brings the edges closer together, promoting a more efficient healing process.
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
The patient experiences difficulty with the wound
healing process. A few months later, a repeat scan shows another enlarged lymph node. Instead of operating, the surgeons decide to apply
radiotherapy to the groin area. It treats the lymph
node, but the wound begins to break down
again.
What is radiotherapy and what effect does it have on tissues?
Radiotherapy:
Radiotherapy, also known as radiation therapy, is a medical treatment that uses high doses of ionizing radiation to target and kill or damage cancer cells. It is a common treatment modality for various types of cancer, including squamous cell carcinoma of the vulva. Radiotherapy can be delivered externally (external beam radiation) or internally (brachytherapy), depending on the type and location of the cancer.
Effect of Radiotherapy on Tissues:
The primary mechanism of action of radiotherapy is to damage the DNA within cells. While the main goal is to damage the DNA of cancer cells and prevent them from dividing and growing, normal healthy cells in the radiation field can also be affected. Here are some key effects of radiotherapy on tissues:
DNA Damage:
Ionizing radiation causes breaks in the DNA strands of cells, leading to damage. Cancer cells are more sensitive to this damage due to their increased rate of division.
Cell Cycle Arrest:
Radiation disrupts the cell cycle, preventing cells from progressing through the normal stages of growth and division. Cancer cells, being rapidly dividing, are particularly susceptible.
Apoptosis (Cell Death):
Severely damaged cells, both cancerous and normal, may undergo programmed cell death (apoptosis) as a protective mechanism to eliminate cells with extensive DNA damage.
Tissue Inflammation:
Radiation can induce inflammation in the treated area. This inflammatory response is part of the body’s natural healing process but can contribute to side effects such as pain and swelling.
Vascular Damage:
Blood vessels in the irradiated area can be damaged, affecting blood flow and oxygen delivery. This can contribute to tissue damage and delayed wound healing.
Effect on Wound Healing:
In the case of the patient undergoing radiotherapy to the groin area, the radiation likely had an impact on the healing process. The effects on normal healthy cells, including fibroblasts and blood vessels, can contribute to complications such as delayed wound healing and breakdown. The compromised vascular supply and cellular damage can hinder the normal tissue repair mechanisms, leading to difficulties in wound closure.
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
The patient experiences difficulty with the wound
healing process. A few months later, a repeat scan shows another enlarged lymph node. Instead of operating, the surgeons decide to apply
radiotherapy to the groin area. It treats the lymph
node, but the wound begins to break down
again.
The patient notices that the wound edges are becoming further apart and appear pale and
fibrotic. The base of the wound contains a red, spongy material. She isn’t sure what this is.
She goes to see her doctor who sends a sample of it to the pathologist.
What is the red, spongy material that the patient noticed? (1)
Image
A 54 year old woman has been diagnosed with a squamous cell carcinoma of the vulva. She has lost 2 stone in weight over the past 6 months. She has smoked 10 cigarettes a day for 15 years and is a diet-controlled diabetic. She undergoes major surgery to have the cancer removed. The surgeons also perform a groin dissection as a scan showed several enlarged lymph nodes which were suspicious. They suture
the wound closed and place a dressing over the top
The patient experiences difficulty with the wound
healing process. A few months later, a repeat scan shows another enlarged lymph node. Instead of operating, the surgeons decide to apply
radiotherapy to the groin area. It treats the lymph
node, but the wound begins to break down
again.
The patient notices that the wound edges are becoming further apart and appear pale and
fibrotic. The base of the wound contains a red, spongy material. She isn’t sure what this is.
She goes to see her doctor who sends a sample of it to the pathologist.
What important anatomical structures are found in the groin that could be vulnerable to injury?
nerves, ligaments, muscles, femoral artery
A 20 year old man suffers a severe burn over his left
hand and forearm whilst trying to put out a fire in
his kitchen. He goes to hospital and is told that he has third degree burns. He is surprised as he doesn’t feel very much pain.
Below is a picture of normal skin. Label it and
explain which layers are involved in a third degree burn. What is the difference between first,
second and third degree burns? (2)
Image
A 20 year old man suffers a severe burn over his left
hand and forearm whilst trying to put out a fire in
his kitchen. He goes to hospital and is told that he has third degree burns. He is surprised as he doesn’t feel very much pain.
Why is our patient not experiencing much pain from the burn?
nerve damage (no sensation of pain)
A 20 year old man suffers a severe burn over his left
hand and forearm whilst trying to put out a fire in
his kitchen. He goes to hospital and is told that he has third degree burns. He is surprised as he doesn’t feel very much pain.
How will his burn heal?
skin graft
for 3rd degree burn it heals by secondary intention because burn covers a large area
A 20 year old man suffers a severe burn over his left
hand and forearm whilst trying to put out a fire in
his kitchen. He goes to hospital and is told that he has third degree burns. He is surprised as he doesn’t feel very much pain.
What is scar tissue made of?
collagen fibres (scar tissue is fibrous tissue made from cross-linked fibres)
A 20 year old man suffers a severe burn over his left
hand and forearm whilst trying to put out a fire in
his kitchen. He goes to hospital and is told that he has third degree burns. He is surprised as he doesn’t feel very much pain.
What is meant by a ‘labile’ tissue type?
epithelial tissues of skin, bone marrow are examples of labile tissue as they’re constantly being replaced by maturation of cells or by proliferation of mature cells
A 20 year old man suffers a severe burn over his left
hand and forearm whilst trying to put out a fire in
his kitchen. He goes to hospital and is told that he has third degree burns. He is surprised as he doesn’t feel very much pain.
What is angiogenesis and how does it occur?
Angiogenesis is the process of forming new blood vessels from existing ones. This complex and highly regulated physiological process plays a crucial role in various normal and pathological conditions, including wound healing, development, and diseases such as cancer. While you’ve mentioned some aspects of angiogenesis, let’s break down the process in more detail:
Initiation:
Angiogenesis is often initiated in response to a stimulus, such as hypoxia (low oxygen levels) or tissue injury. In the case of a burn, the severe damage to the tissue can trigger the need for increased blood supply.
Vasodilation and Increased Permeability:
Nitric oxide and vascular endothelial growth factor (VEGF) are key molecules in the early stages of angiogenesis.
Nitric oxide causes vasodilation, increasing the diameter of existing blood vessels.
VEGF increases vascular permeability, allowing substances like growth factors and immune cells to move from the bloodstream to the surrounding tissue.
Activation of Angiogenic Factors:
Fibroblast Growth Factor 1 (FGF-1) is one of the angiogenic factors activated in response to the initial signals.
Activation of Endothelial Cells:
FGF-1 binds to receptors on endothelial cells, the cells that line blood vessels.
This binding activates the endothelial cells, initiating the process of angiogenesis.
Release of Proteases:
Proteases, such as matrix metalloproteinases (MMPs), are released. MMPs are enzymes that can break down components of the extracellular matrix.
Separation of Pericytes:
Pericytes are contractile cells that wrap around small blood vessels. They are involved in stabilizing and supporting the blood vessel.
Angiogenesis involves the separation of pericytes from blood vessels.
Degradation of Basement Membrane:
Proteases degrade the basement membrane, a specialized extracellular matrix that surrounds blood vessels.
Formation of Sprouts:
Endothelial cells at the site of angiogenesis form solid sprouts, extending into the surrounding tissue.
Connection to Neighboring Blood Vessels:
Sprouts connect with neighboring blood vessels, forming a network of capillaries.
Growth and Migration:
Endothelial cells migrate alongside each other, guided by various signals and adhesion molecules.
The sprouts continue to grow towards angiogenic stimuli.
Formation of Loops:
The sprouts undergo remodeling, and loops of capillary lumens are formed.
Maturation:
Pericytes and smooth muscle cells are recruited to stabilize and mature the new blood vessels.
