5.4 Wound Healing and Repair Flashcards
What is necessary for healing by regeneration?
- Tissues composed of cells with proliferative capacity
AND
- The underlying structure of the tissue has not been too severely damaged
What is necessary for repair by scar formation?
- Tissues composed of cells with limited or no proliferative capacity
- The underlying structure of the tissue is lost
What are the three cases in which cell proliferation occurs?
What is the size of a cell population determined by?
- The size of a cell population is determined by
- Cell proliferation (mitosis)
- Cell death (apoptosis)
What is the replication of cells stimulated by?
- growth factors (pleiotropic)
- Promote cell cycle entry
- Relieving blocks in cell cycle arrest
- Preventing apoptosis
- Enhance biosynthesis
- signals from extracellular matrix
What is the proliferative capacity of labile tissue?
- Continuously lost and replaced
- Do not enter G0
- Maturation of stem cells or proliferation of mature cells
- Tissue can regenerate if stem cells reserved and tissue structure intact
- Eg Hematopoietic cells Epithelial cells (skin, GIT etc
What is the proliferative capacity of stable tissue?
- Quiescent
- Enter G0
- Reenter cell cycle if stimulated by loss of cells
- Limited capacity to regenerate (exception liver)
- Eg. Parenchyma of most solid organs (liver and kidney)
- Endothelial and smooth muscle cells, fibroblasts
What is the proliferative capacity of permanent tissue?
- Terminally differentiated
- Enter G0
- Cannot reenter the cell cycle
- Limited stem cell replication (not sufficient for regeneration)
- Eg. Neurons, cardiac muscle cells and skeletal muscle cells*
- *some regenerative capacity
What do organs and tissues consist of?
- Functional parenchyma cells - cells that are unique to that organ and perform its funciton
- Stroma-supporting connective tissue including the extracellular matrix (ECM)
What is the difference between the interstitial matrix and the basement membrane?
- Interstitial matrix is the spaces between
- Cell in connective tissue
- Epithelium and vasculature
- 3-D amorphous gel
- Basement membrane is highly organized structure formed around epithelium, endothelial cells and smooth muscle cells.
What are the three essential components of the extra cellular matrix?
- Fibrous structural proteins such as collagen and elastin provide tensile strength and recoil
- Water hydrated gels such as proteoglycans provide compressive resistance and lubrication
- Adhesive glycoprotein such as fibronectin connects elements to each other and cells. Also cell adhesion molecules such as cadherins, integrins, selectins initiate signalling cascades affecting cell locomotion, proliferation and differentiation
What are some of the functions of the extra cellular matrix?
- Dynamic, constantly remodeling
- Control of cell growth (signaling receptors)
- Mechanical support (anchorage, migration, polarity)
- Influences differentiation (via cell surface integrins)
- Provides scaffolding for tissue renewal (stroma and basement membrane)
- Boundaries (basement membrane)
- Storage (growth factors)
How does tissue regeneration occur in the liver?
- Regeneration occurs following most injury
- Resection or cell death (necrosis or apoptosis)
- Surgical removal (60%) restored in 4-6 weeks
- Quiescent hepatocytes become competent to enter the cell cycle in response to cytokines and growth factors.
- Replicate once or twice and then return to quiescence
How does the appearance of granulation tissue compare to scar tissue?
What are the two types of macrophages and their functions?
- Classical macrophage activation (M1)
- Secrete cytokines that stimulate inflammation
- Ingest and eliminate microbes and dead tissue
- Alternative macrophage activation (M2)
- Initiate the process of tissue repair
- Secrete growth factors that promote angiogenesis, activate fibroblasts and stimulate collagen synthesis
What happens in angiogenesis during injury healing?
- Capillary sprouts from existing blood vessel
- Provide collateral circulation at the site of injury
- Migration and proliferation of endothelial cells
- Inhibition of proliferation and remodeling
- Recruitment of periendothelial cells (pericytes and SMC) to form mature vessel
What is the role of fibroblasts in wound healing and injury repair?
- Recruitment and proliferation of fibroblasts
- Fibroblasts migrate towards the site of injury
- Proliferation in response to growth factors and cytokines
- Released by M2 macrophages
- Repair begins when macrophages predominate at the site of injury following acute inflammation
How does the deposition of extracellular matrix lead to scar formation?
- Stimulation of fibroblasts and synthesis of collagen (and other matrix protein)
- Inactive spindle shaped fibroblasts
- Vascular regression
How does collagen remodelling occur in a wound during repair?
- The replacement of granulation tissue with a scar involves changes in the composition of the ECM
- Balance between collagen synthesis and degradation
- Collagen synthesis is critical to strength of the wound
- Initial collagen type III is replaced by type I (larger diameter fibrils with greater tensile strength)
How does scab formation occur in healing by first intention?
- Thrombosis (scab)
- Barrier to invading organisms
- Prevents loss of tissue fluid
- Inflammation
- Neutrophils
- Exudate (pus)
How is regeneration seen in healing by first intention?
- Labile epithelial cells migrate and proliferate
- Form a thin epithelial layer beneath the scab
What is the role of neutrophils in healing by first intention?
- Neutrophils largely replaced by macrophages
- Macrophages
- Clear debris
- Elaborate mediators that facilitate repair
What is the role of granulation tissue in healing by first intention?
- Granulation tissue
- Angiogenesis
- Fibroblast recruitment and activation
- Form new stroma (ECM components- proteoglycans, glycoproteins, collagen type III)
How does scar formation occur in healing by first intention?
- Collagen accumulation
- Type I collagen (thicker and stronger)
- Leukocyte infiltrate and edema decrease
- Vascularity decreases
- Wound strength increases
What happens in healing by second intention?
- Larger clot
- More inflammation
- More granulation tissue
- Wound contraction
- Specialized granulation tissue
- Myofibroblasts
- Modified fibroblast with smooth muscle cell like properties
- Reduce the size of the wound
What are the characteristics of successful wound healing?
- Rapid resolution of local injury
- Localized transient scarring
- Restoration of function
