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Questions and Answers
What characterizes regeneration in tissue response to injury?
Which of the following factors does NOT impair wound healing?
Which type of cells are categorized as labile cells?
What best describes healing by primary intention?
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What is the main difference between repair and regeneration?
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Which of the following characteristics is NOT true about wound healing by secondary intention?
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What condition is associated with excessive scar formation?
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Which of the following is considered a local factor influencing wound healing?
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In the nervous system, gliosis is a type of repair associated with which area?
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Which of the following nutrients is specifically mentioned as important for collagen formation?
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What is the role of stem cells in tissue healing?
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Which type of cells are classified as permanent cells?
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What is the primary function of polypeptide growth factors?
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What is the significance of extracellular matrix (ECM) in tissue?
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What is a primary characteristic of the inflammatory phase of wound healing?
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During the proliferative phase of wound healing, which occurs?
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How does scar remodeling occur during wound healing?
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What does Walker's Law state regarding wound strength?
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Which of the following describes a wound healing process characterized by primary intention?
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When is wound strength at only 10% of unwounded skin?
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What is the correct definition of repair in the context of tissue response to injury?
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Which group of cells is characterized by a complete inability to divide and regenerate?
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What is the primary distinction between regeneration and repair in wound healing?
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What factor does NOT significantly contribute to poor wound healing outcomes?
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Which phase of wound healing is characterized by the removal of cell debris and prevention of infection?
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What is a significant consequence of healing by secondary intention compared to primary intention?
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Which factor has the least impact on local wound healing processes?
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What type of scar formation is associated with a genetic predisposition?
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Which chronic condition is specifically noted for impairing wound healing due to metabolic factors?
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For which tissue is fibrosis an expected healing outcome after injury?
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What primarily defines the nature of permanent cells during tissue repair?
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Which phase of wound healing involves neovascularization and granulation tissue formation?
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What is the primary function of the extracellular matrix (ECM) in wound healing?
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In wound healing, what is the role of metalloproteinases during the remodelling phase?
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How does the process of scar remodeling affect collagen in the wound?
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How does the presence of supporting stroma influence healing by regeneration?
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What distinct characteristic sets stable cells apart from labile cells?
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What ultimately determines the strength of a wound according to Walker's Law?
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What initiates the inflammatory phase of wound healing following an injury?
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What role do polypeptide growth factors play in the healing process?
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Study Notes
Tissue Response to Injury
- Initial response to injury is acute inflammation
- Resolution: No tissue destruction, removal of damaging agent and debris, tissue returns to pre-injury state - e.g., mild heat injury.
- Regeneration: Replacement of lost tissue with the same type, requires intact supporting framework, tissue returns to pre-injury state.
- Repair: Replacement of destroyed tissue with fibrous scar, occurs when there is destruction to parenchymal cells and stromal framework, and death of permanent cells.
Factors Affecting Healing
- Efficiency of: Removal of causative agent, clearance of inflammatory debris, degree of architectural damage, proliferative capacity of tissue, and extent of extracellular matrix damage.
Proliferative Capacity
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Ability of tissues to regenerate is dependent on proliferative capacity and presence of stem cells.
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Categorization of tissues:
Labile Cells
- Continuously dividing cells
- Epidermis, mucosal epithelium, GI tract epithelium
- Cells derived from stem cells
- Injury heals by regeneration if supporting stroma is intact.
Stable Cells
- Normally low level of replication.
- Hepatocytes, renal tubular epithelium, pancreatic acini
- Can be stimulated to divide
- Healing by regeneration if supporting stroma and regenerative stem cells are intact.
Permanent Cells
- Non-dividing cells
- Neurons, cardiac myocytes, skeletal muscle
- No regeneration, replaced by connective tissue.
Polypeptide Growth Factors
- Affect cell growth
- Present in serum or produced locally
- Exert pleiotropic effects: proliferation, cell migration, differentiation, tissue remodeling
- Regulate growth by controlling expression of genes involved in cell proliferation.
Extracellular Matrix
- Not just a scaffold for cells
- Regulates cell growth, motility, and differentiation
- Consists of:
- Fibrous structural proteins: collagen, elastin
- Adhesive glycoproteins that link ECM components and cells.
- Proteoglycans
Repair by Connective Tissue
- Involves production of granulation tissue
- Angiogenesis (formation of new blood vessels)
- Fibrosis - proliferation of fibroblasts and deposition of ECM
- Scar remodeling: Collagen type III replaced with type I collagen.
Phases of Wound Healing
- Inflammatory Phase: Acute inflammatory response to initial injury (haematoma formation, neutrophil and macrophage infiltration).
- Proliferative Phase: Epithelial cell proliferation, granulation tissue formation, new vessel development, and fibroblast proliferation (ECM synthesis).
- Remodeling Phase: Replacement of granulation tissue with fibrous tissue, remodeling of parenchymal elements to restore function, remodeling of connective tissue to achieve wound strength.
Wound Healing Types
- Primary Intention: Edges are approximated, healing is faster.
- Secondary Intention: Edges are not approximated, granulation tissue fills the gap, slower, more scarring.
Stages of Wound Healing by Primary Intention
- Day 1: Wound filled with blood clot, acute inflammation, epithelial cell proliferation.
- Day 2: Macrophages, epithelial cells covering surface.
- Day 3: Granulation tissue formation.
- Day 5: Collagen deposition.
- Day 7: Sutures removed.
Wound Strength
- At one week, wound strength is 10% of unwounded skin.
- By 3 months, wound strength is 80% of unwounded skin.
- Walker's Law: Wound strength is proportional to collagen content.
Stages of Wound Healing by Secondary Intention
- Similar to primary intention but with granulation tissue filling the gap.
- Slower, more intense inflammatory reaction, wound contraction, and more scarring.
Pathologic Aspects of Wound Healing
- Deficient Scar Formation: Wound rupture.
- Excessive Scar Formation: Keloid (genetic predisposition).
- Contracture Deformity:
- Malignant Transformation: Extremely rare.
Examples of Healing in Various Tissues
- Mucosal Surfaces: Erosion heals by regeneration, ulceration by regeneration and fibrosis.
- Liver: Single short-lived injury heals by regeneration, chronic injury by cirrhosis.
- Nervous System: Central nervous system - gliosis (repair), peripheral nerves - regeneration.
- Muscle: Cardiac muscle - fibrosis, skeletal muscle - fibrosis.
Factors Influencing Healing
- Local Factors: Poor vascular supply, infection, foreign material, excessive movement, poor approximation, size, site, and type of injury.
- Systemic Factors: Age, nutrition (proteins, vitamin C, copper, zinc), metabolic status (DM), hormones (steroids), malignancy, chemotherapy, radiotherapy.
Tissue Response to Injury
- Initial response to injury is acute inflammation
- Resolution - No tissue destruction, damaging agent and cell debris are removed, tissue returns to its pre-injury state (e.g., mild heat injury)
- Regeneration - Replacement of lost tissue by tissue of the same type, supporting framework must be intact, tissue is returned to its pre-injury state.
- Repair - Replacement of destroyed tissue by a fibrous scar, occurs when there is destruction to parenchymal cells and stromal framework, death of permanent cells.
Factors that Affect Healing
-
Efficiency of:
- Removal of the causative agent
- Clearance of inflammatory debris
- Degree of architectural damage
- Proliferative capacity of tissue
- The extent of extracellular matrix damage
Proliferative Capacity
- The ability of tissues to regenerate is dependent on their intrinsic proliferative capacity and/or the presence of tissue stem cells
- Labile Cells - Continuously dividing cells (e.g., epidermis, mucosal epithelium, GI tract epithelium), derived from stem cells, injury to such tissue can easily heal by regeneration if the supporting stroma is intact.
- **Stable Cells ** - Normally low level of replication (e.g., hepatocytes, renal tubular epithelium, pancreatic acini), can be stimulated to divide, healing by regeneration if the supporting stroma and the regenerative stem cells are intact.
- Permanent Cells - Non-dividing cells (e.g., neurons, cardiac myocytes, skeletal muscle), no regeneration, replaced by connective tissue.
Extracellular Matrix
- It is not just a scaffold for cells to grow on
- Regulates cell growth, motility and differentiation
- Consists of:
- Fibrous structural proteins
- Collagens
- Elastin
- Adhesive glycoproteins
- Proteoglycans
Repair by Connective Tissue
- Involves production of granulation tissue - fibroblasts (and myofibroblasts) and capillary buds
- Angiogenesis - New vessels budding from old
- Fibrosis, consisting of emigration and proliferation of fibroblasts and deposition of ECM (type III collagen)
- Scar remodeling type III collagen is replaced by type I collagen (collagenase- requires zinc)
Phases of Wound Healing
- Inflammatory Phase - Induction of acute inflammatory response by initial injury (e.g., haematoma formation, infiltration by neutrophils, infiltration by macrophages)
- Proliferative Phase - Epithelial cell proliferation, granulation tissue, formation of new vessels, proliferation of fibroblasts (synthesis of ECM proteins)
- Remodeling Phase - Replacement of granulation tissue by fibrous tissue, remodeling of parenchymal elements to restore tissue function, remodeling of connective tissue to achieve wound strength, degradation of excessive extracellular matrix (metalloproteinases)
Types of Wound Healing
- Primary Intention - Wound edges are approximated (e.g., surgical incision)
- Secondary Intention - The edges of the wound are not approximated (e.g., large wounds, pressure sores)
Stages of Wound Healing by Primary Intention
- Day 1: Wound filled with blood clot, acute inflammation in the surrounding tissue, Proliferation of epithelial cells.
- Day 2: Macrophages, epithelial cells cover the surface.
- Day 3: Granulation tissue formation.
- Day 5: Collagen deposition.
- Day 7: Sutures removed
Wound Strength
- After sutures are removed at one week, wound strength is only 10% of unwounded skin
- By 3 months, wound strength is about 80% of unwounded skin
- Walker's Law - Wound strength is directly proportional to the amount of collagen present within the wound.
Stages of Wound Healing by Secondary Intention
- The process is similar to healing by primary intention
- The edges are not approximated
- Granulation tissue fills the gap
- Slower
- More intense inflammatory reaction
- Wound contraction (myofibroblast)
- More scarring
Pathologic Aspects of Wound Healing
- Deficient scar formation - Wound rupture
- Excessive scar formation - Keloid-type III collagen, genetic predisposition
- Contracture deformity
- Malignant transformation (extremely rare)
Examples of Healing in Various Tissues
-
Mucosal surfaces:
- Erosion is healed by regeneration
- Ulceration by regeneration and fibrosis
-
Liver:
- Single short-lived injury is healed by regeneration
- Chronic injury by cirrhosis
-
Nervous system:
- Central nervous system gliosis (repair)
- Peripheral nerves Regeneration
-
Muscle:
- Cardiac muscle Fibrosis
- Skeletal muscle Fibrosis
Factors Influencing Healing
-
Local factors:
- Poor vascular supply
- Infection
- Foreign material
- Excessive movement
- Poor approximation
- Size, site and type of injury
-
Systemic factors:
- Age
- Nutrition (proteins, Vitamin C- collagen formation, copper- cross-linking of collagen, Zinc- conversion of type III to type I collagen)
- Metabolic status (DM)
- Hormones (steroids)
- Malignancy
- Chemotherapy/radiotherapy
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Description
This quiz explores the various stages of tissue response to injury, including acute inflammation, regeneration, and repair. It also examines factors that influence healing such as the proliferative capacity of different cell types. Understanding these concepts is essential for comprehending tissue recovery processes.
