TISSUE REPAIR Flashcards
healing and repair
•Healing
-minimal/no residual defect
•Repair
- Occurs with tissue loss
- Restoration of tissue architecture & function after injury
Repair is by two reactions
- Regeneration by proliferation of residual cells
2. Maturation of tissue stem cells and deposition of connective tissue
Regeneration
- Components returning to normal state
* Occurs by proliferation of residual cells
Connective tissue deposition (Scar formation)
• Laying down of fibrous tissue that may result in a scar
• When tissue are incapable of complete restitution
• If supporting structures are severely damaged
• Fibrosis: extensive deposition of collagen as a consequence of chronic
inflammation: lungs, liver, kidney
• Organization: fibrosis in a tissue space occupied by an inflammatory
exudate.
Cell & Tissue Regeneration
• Cell proliferation • Growth factors • Critically dependent on: - Integrity of the extracellular matrix - Development of mature cells from stem cells • Intrinsic proliferative capacity
Repair: Tissue types
3 Groups
• Labile (continuously dividing)
• Stable (G0)
• Permanent
Labile tissues
(continuously dividing)
• E.g. Haemopoietic cells, surface epithelia
• Readily regenerative after injury
Stable tissues
- E.g. cells of solid organs like liver
* Proliferate only in response to injury or loss
Permanent tissues
(terminally differentiated)
• E.g.. Neurons/myocardium
• Injury is irreversible and results in scar
Signals of Cell Proliferation: Growth factors
• Multiple cell types/ cell-selective
• Produced by cells near the site of damage.
- Mainly Macrophages
- Epithelial & stromal cells
• Signaling pathways: proteins : cell cycle & release blocks on
checkpoints
Tissue stem cells
• Supplement proliferation of residual cells • Live in specialized niches • Triggered by injury • Differentiate into mature cells that repopulate the injured tissue
Repair by Connective Tissue Deposition (Scar formation)
• A response that “patches” rather than restores the tissue
• If repair cannot be accomplished by regeneration alone
• In combination with regeneration
• If the tissue injury is:
- Severe/chronic
- To parenchymal cells/epithelia + connective tissue framework
- In non-dividing cell
Steps in scar formation
• Angiogenesis
- Formation of new blood vessels,
- Supplying nutrients and oxygen: supporting repair
• Formation of granulation tissue:
- Pink, soft, granular gross appearance
- Migration + proliferation of fibroblasts
- Deposition of loose connective tissue, together with the vessels & leukocytes
- Remodeling of connective tissues
- Production of a stable fibrous scar
Deposition of connective tissue
• Two steps:
1. Migration & proliferation of fibroblasts : site of injury
2. Deposition of ECM proteins produced by these cells
• Orchestrated by: Cytokines & Growth factors
- TGF-β (Transforming growth factor-β): most important cytokine
- PDGF, FGF-2
Remodeling of Connective Tissue
• Outcome of repair: Synthesis Vs degradation of ECM proteins
• After its deposition, the connective tissue in the scar continues to be modified
and remodeled.
• The degradation of collagens & other ECM components
- Family of matrix metalloproteinases (MMPs),(metal ions (e.g. zinc)
- Produced: fibroblasts, macrophages, neutrophils, synovial cells, &
some epithelial cells)
- Synthesis & secretion: growth factors, cytokines & other agents.
Factors influencing tissue repair
- Infection
- Diabetes
- Nutritional status
- Glucocorticoids(steroids)
- Renal failure
- Haematological disorders
- Poor perfusion
- Foreign bodies
- Type and extent of tissue injury
- Location of injury
- Mechanical Factors/Movement
Two clinically significant types of repair:
- The healing of skin wounds (cutaneous wound healing)
* Fibrosis in injured parenchymal organs
Healing of Skin wounds
- First intention/primary union
* Second intention/secondary union
healing by first intension
The mechanism of repair when injury involves only the epithelial layer
- Clot formation
- 24 hrs- neutrophils clear debris/basal proliferation
- 3 days- macrophages infiltrate and granulation tissue invasion
- 5 days-peak neovascularisation
- 2 weeks- Collagen deposition & fibroblast proliferation
- Diminished inflammation and oedema - 1 month- cellular Connective Tissue scar
Healing by second intention
Extensive cell/tissue loss: large wounds, abscesses, ulceration and ischaemic
necrosis
1. Larger fibrin clot/more inflammation
2. More granulation tissue
3. Provisional matrix of fibrin, plasma, fibronectin and type III collagen
2 weeks-type 1 collagen: scaffold of pale, avascular scar-fibroblasts, dense collagen,
elastic tissue
4. 1 month-acellular CT covered by intact epidermis
5. Wound contraction
fibrosisi in Parenchymal Organs
• Excessive deposition of collagen & ECM components
• Internal organs in chronic diseases
• Same as scar formation
• Chronic infections & immunologic reactions
• Associated with loss of tissue
• It may be responsible for substantial organ dysfunction and even
organ failure.
• TGF-β: necrosis/apoptosis& reactive oxygen species
• Myofibroblasts
Abnormalities in Tissue Repair
- Inadequate formation of granulation tissue or formation of scar
• Wound dehiscence
• Ulceration - Excessive formation of components of repair
• Hypertrophic scars
• Keloids - Exuberant granulation
- Contractures
