Podcast
Questions and Answers
What characterizes the healing process of primary intention?
What characterizes the healing process of primary intention?
Which of the following is a prominent feature of healing by secondary intention?
Which of the following is a prominent feature of healing by secondary intention?
Which factor can significantly impede the tissue repair process?
Which factor can significantly impede the tissue repair process?
What is the outcome in both primary and secondary intention healing regarding the strength of the healed skin?
What is the outcome in both primary and secondary intention healing regarding the strength of the healed skin?
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Which of the following statements about pathological aspects of repair is true?
Which of the following statements about pathological aspects of repair is true?
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What characterizes primary intention healing?
What characterizes primary intention healing?
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Which condition may prolong inflammation during the wound healing process?
Which condition may prolong inflammation during the wound healing process?
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Which condition is primarily associated with secondary intention healing?
Which condition is primarily associated with secondary intention healing?
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How does glucocorticoid medication affect wound healing?
How does glucocorticoid medication affect wound healing?
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What is a major factor influencing the tissue repair process in individuals with diabetes?
What is a major factor influencing the tissue repair process in individuals with diabetes?
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What distinguishes tertiary intention healing from primary and secondary intention healing?
What distinguishes tertiary intention healing from primary and secondary intention healing?
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What is a common feature of the healing response seen in secondary intention?
What is a common feature of the healing response seen in secondary intention?
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Which pathological aspect of wound healing can cause disruption to proper healing?
Which pathological aspect of wound healing can cause disruption to proper healing?
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Which type of scars results from excessive tissue repair and grows beyond the original wound boundary?
Which type of scars results from excessive tissue repair and grows beyond the original wound boundary?
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What is primarily responsible for wound dehiscence after surgery?
What is primarily responsible for wound dehiscence after surgery?
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Which form of ulcer is associated with poor oxygen delivery due to atherosclerosis?
Which form of ulcer is associated with poor oxygen delivery due to atherosclerosis?
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What defines healing by primary intention?
What defines healing by primary intention?
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Which phase of wound healing involves the proliferation of fibroblasts?
Which phase of wound healing involves the proliferation of fibroblasts?
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Which of the following statements is true regarding healing by secondary intention?
Which of the following statements is true regarding healing by secondary intention?
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Which factor influences the remodeling phase of wound healing?
Which factor influences the remodeling phase of wound healing?
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What is the primary characteristic of tertiary intention healing?
What is the primary characteristic of tertiary intention healing?
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What is typically involved in the inflammatory phase of wound healing?
What is typically involved in the inflammatory phase of wound healing?
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What characterizes the formation of granulation tissue?
What characterizes the formation of granulation tissue?
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What occurs if the reticulin/supporting framework of the liver is extensively damaged?
What occurs if the reticulin/supporting framework of the liver is extensively damaged?
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Study Notes
Regeneration and Repair
- Regeneration and repair are the two main processes of tissue repair, restoring tissue architecture and function after injury
- Regeneration involves the proliferation of surviving cells to replace damaged tissue
- Connective tissue deposition occurs when regeneration is not possible; fibrous connective tissue replaces damaged or lost tissue, resulting in fibrosis or scar formation
- Connective tissue supports other specialized tissues, providing structure, mechanical strength, and physical and metabolic support
- Connective tissue is made up of extracellular matrix (ECM) and supporting cells
Terminology
- Extracellular matrix (ECM): fibrous structural proteins (e.g., collagen), ground substance, and basement membrane
- Supporting cells: responsible for making ECM, such as fibroblasts
- Blood vessels, lymphatic vessels, and nerves provide nutrients and factors for tissue growth
Organ-Based Examples
- Skin (cutaneous organ): epidermis (epithelial layer) and dermis (connective tissue) have a mesh of elastin and collagen
- Liver (parenchymal/solid organ): hepatocytes (parenchymal cells) and reticulin (collagen fiber)
Tissue Repair
- Regeneration alone is not always practical for humans in most situations. In such cases, connective tissue deposition is crucial
- Several cell types proliferate during repair, including surviving functional cells and vascular endothelial cells
- Fibroblasts produce fibrous/scar tissue
- The ability of a tissue to repair itself is known as its intrinsic proliferative capacity
- The cell cycle phases affect a cell's proliferative capacity; different cells have different capacities for regeneration
Proliferative Capacity & the Cell Cycle
- A cell's intrinsic proliferation capacity depends on the part of the cell cycle in which it spends most time
- Active phases of the cell cycle are involved in active growth and division
- The resting /quiescent cell cycle phase, is known as G0
Three Main Tissue Types
- Labile tissue: continuously dividing cells (e.g., gastrointestinal epithelium, skin, oral mucosa, bone marrow)
- Stable tissue: cells with minimal proliferative capacity in a normal state, capable of entering G1 in response to injury (e.g., cells of connective tissue, smooth muscle cells, most solid organs such as kidney, pancreas, adrenal glands, and lung). There is an exception with the liver, which has a high capacity to regenerate
- Permanent tissue: cells incapable of proliferation (e.g., neurons, cardiac muscle cells)
Labile Tissues
- Labile tissues have the highest capacity for regeneration.
- Their cells continually renew themselves and have increased amounts of stem cells.
- They rapidly replace cells after injury
Stable Tissues
- Regeneration may occur, but is usually limited in stable tissues
- Cells of connective tissue and smooth muscle have a limited capacity for regeneration
- Most solid organs fall into this category
Permanent Tissues
- Permanent tissues are not capable of proliferation
- If tissue death occurs, the tissue relies on connective tissue deposition for repair
- This replaces functional cells with non-functioning scar tissue, potentially leading to reduced organ function
Regeneration
- A complex, multifaceted process involving interactions between growth signals and control mechanisms
- Cell replication is influenced by growth factors, hormones, cytokines, cell interactions with the extracellular matrix (ECM), mechanical support, and microenvironment maintenance
Example: Liver Regeneration
- Priming phase: Kupffer cells release cytokines (e.g., interleukin-6 (IL-6)) priming remaining hepatocytes to respond to growth factors
- Proliferation phase: growth factors (e.g., hepatocyte growth factor (HGF) and transforming growth factor alpha (TGF-α)) stimulate entry into the cell cycle in primed hepatocytes
Limitations of Regeneration
- Regeneration alone cannot repair severe or chronic injuries or injuries to non-dividing cells.
- In such cases, connective tissue deposition is more relevant for repair, which results in fibrous scarring. Liver regeneration has limitations as well, and depends on residual tissue's structural integrity
Limitations of Regeneration: Liver
- Regeneration occurs only if residual tissue is intact (e.g., after partial liver resection)
- Damaged liver tissue (e.g., by infection or inflammation) or damage to the reticulin/ supporting framework prevents sole regeneration, leading to scarring and eventual fibrosis
Repair by Connective Tissue Deposition
- Inflammatory phase: within 24 hours of injury, damaged tissue is removed and cytokines/growth factors initiate repair
- Proliferative phase: blood vessel growth (angiogenesis), new fibroblasts proliferate, collagen and other ECM components are produced -> creation of immature connective tissue (granulation tissue)
- Remodeling phase: scar tissue matures overtime, and matrix metalloproteinases degrade the ECM, including collagen
Cutaneous Wound Healing
- Divided into categories: primary, secondary, tertiary intentions; based on the degree of tissue injury
- Involves stages like blood clot formation, inflammatory response, granulation tissue formation, re-epithelialization, connective tissue deposition, wound contraction, and remodeling
Healing by Primary Intention
- Clean, uninfected, aligned wounds (e.g., sutured incision)
- Epithelial regeneration predominates, with minimal scar formation
- Dermal appendages lost.
Healing by Secondary Intention
- Large, infected, or chronic wounds (e.g., ulcers, infected surgical wounds)
- More extensive injury and repair
- Fibrosis predominates over epithelial regeneration, leading to larger scars
Wound Strength
- Healed skin is never as strong as original tissue. Strength increases over time in sutured wounds, beginning with minimal strength 7-10 days post-injury, increasing to more substantial strength within 3 months.
- Strength is never equal to original tissue's strength.
Pathological Aspects of Repair
- Complications categorized as inadequate or excessive tissue repair
- Inadequate repair: wound dehiscence, ulcers, poor oxygen delivery
- Excessive repair: hypertrophic scar, keloid scar, proud flesh, wound contractures, and desmoid tumors
Factors Influencing Tissue Repair
- Infection, foreign bodies, nutritional status, poor tissue perfusion, mechanical factors, diabetes, type of injury, and tissue type greatly affect the repair process
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