Healing and repair Flashcards
What is meant by tissue repair (Healing)
Is the restoration of tissue architecture and function after an injury
- Repair: mainly used for parenchymal (internal organs) and connective tissue.
- Healing: mainly for surface epithelium
What are the different repair/healing mechanisms?
1) Regeneration:
- mild injury
-replacement of dead cells with healthy same-type cells (proliferation)
-goes back to normal
2) Scar formation:
-Severe injury
-replacement of dead cells with connective tissue (scar tissue)
-doesn’t fully go back to normal. (mainly maintains the structure of tissue only)
- ECM provides the necessary support for the regeneration of tissues, thus if the injury is severe enough that it affects the ECM then regeneration won’t be possible
What determines whether the tissue repair will occur by regeneration or healing?
- By their proliferative capacity
Labile tissue: Basically injured or not will always be proliferating. 🡪 regenerate easily
Stable tissue: only when injured do they proliferate to a limit, the liver has one of the best regenerative capacities in this type of tissue 🡪 (evidence) in a liver transplant, we cut a lobe of the liver and transplant it. This lobe will grow to become a functional liver after some time. (regeneration)
- Permanent tissue: as soon as the baby is born it will NOT proliferate.
When does regeneration fail to occur?
1) In permanent tissue (always scar formation)
2) Necrotic cells became permanent
3) The connective tissue framework of a tissue formed from stable cells has been destroyed
4) Extensive necrosis making no viable cells available
What are the steps in scar formation?
1) hemostatic plug formation (stops bleeding)
2) Early in inflammation, macrophages are the central players
3) at the inflammation site, fibroblasts and vascular endothelial cells begin proliferating
4) Angiogenesis: formation of new BV
5) Formation of granulation tissue
6) Remodeling (maturation and recognition of the fibrous tissue to produce a stable fibrous scar)
what is the difference between stem cells and fibroblasts?
Fibroblasts are more differentiated and limited
What are the factors that influence tissue repair (delay it)?
1) Infections
2) Bad nutrition (Vitamin C deficiency)
3) Mechanical stressors
4) Location of injury
5) Foreign bodies
6) Poor perfusion
7) Defects in cell growth and ECM production
What are the stages of cutaneous wound healing?
1) Inflammation
2) Cell proliferation
3) ECM deposition (remodeling)
What are the different classifications of wounds?
1) Based on gross appearance:
- Open: Exposed
- Closed
2) Based on bacterial load:
- Clean: not opened
- Clean-contained: Without the spillage of content
- Contaminated: with gross spillage of content, and inflammation
-Dirty: Traumatic wound, inflammation, fecal matter and pus
What are the classifications of wound closure?
1) Healing by primary intention:
- Surgical incision
- Edges are easily joined together
- Small amounts of granulation tissue
- Little fibrosis
- Wound strength 70-80% of normal by the third month
2) Healing by secondary intentions:
- Large wounds (may be infected)
- Edges are not brought close together
- Large amount of granulation tissue is formed
- Scar forms and contractures
What is the mechanism by which first-intention healing occurs?
- Epithelial regeneration is the principal mechanism
1st Day:
1) Neutrophil migration
2) Increased mitotic activity of basal cells
3) Epithelial in the edges migrates and proliferates
4) Deposition of basement membrane components
Day 3:
1) Neutrophils are replaced by macrophages
2) Granulation tissue invades the incision space
3) Collagen fibers are present vertically oriented
Day 5:
1) Granulation tissue fills the incisional space
2) Collagen fibrils become abundant and bridge the incision
Week 2:
1) Collagen continues to accumulate and fibroblasts proliferate
2) Leukocytes infiltrate, edema and vascularity are diminished
1st month:
The scar will consist of connective tissue, covered by normal epidermis
Describe the mechanism of healing by second intentions!
1) Tissue loss is more extensive, and involves a combination of regeneration and scarring
2) Inflammatory reaction is more intense
3) Abundant granulation tissue, with ECM accumulation and large scar formation
4) Wound contraction mediated by the action of myofibroblasts (remodeling)
How is the wound strength restored?
- Due to excess collagen synthesis over the collagen degradation during the first 2 months of healing, and later from structural modification and cross-linking
1) During the first week about 10% is restored
2) By the next 4 weeks strength increases rapidly
3) By the third month the wound reaches a plateau at 70-80% of the unwounded skin
What is the difference between healing by primary and secondary intentions?
Wounds healed by secondary intentions:
- Require more time to close
- Shows more inflammation
- Contains more granulation tissue
- wound contraction is (5-10% “myofibroblasts”)
How can a wound be complicated?
1) Excessive scarring
- Hypertrophic scar (excessive raised scarring that is within the borders “due to collagen accumulation”)
- Grows rapidly, containing abundant myofibroblasts
- Settles within 12 months
- Due to thermal/traumatic injury, which involves deep layers of the dermis
2) Keloids
- Scar tissue grows beyond the boundaries
- Does not regress
- Thick connective tissue deposition in the dermis (microscopic appearance)
- Some individuals, especially Africans are predisposed to scar formation
3) Exuberant granulation
- Excessive granulation tissue
- Protrudes above the skin level
- Blocks reepithelialization (proud flesh, must be removed by surgical excision)
4) Demoids/aggressive fibromatoses
- Excessive fibrous tissue
- Incisional scar/traumatic injuries followed by exuberant proliferation of fibroblasts and other Connective Tissues
5) Contractures
- Important for normal healing
- Exaggeration of this process results in deformities, due to the thickening and shortening of collagen fibers
- Occurs in palms, soles, and anterior aspect of the thorax after serious burn compromising joint mobility
