Skin and wound healing Flashcards
What are the 2 possible outcomes of repair?
Regeneration and scarring
What is the defintion for regeneration?
Replacement of damaged tissue components and return to a normal state.
What cell types contribute to regeneration and how does this work?
- Proliferation of differentiated cells that have survived the injury and retain the capacity to proliferate
- Presence of tissue stem cells and their progenitors contribute to the restoration of tissues
TRUE/FALSE?
mammals have limited capacity for regeneration
TRUE
What is a scar?
Deposition of fibrous connective tissue
(occurs if tissues are incapable of regeneration)
What are 3 things required for repair?
- Cell proliferation
- Cell-cell interactions
- Cell- extracellular matrix interactions
What is the name for continuously dividing tissues?
Labile tissues
Give examples of labile cells.
haematopoietic cells in bone marrow and the majority of surface epithelia
What type of tissues have cells that are quiescent and have only minimal proliferative activity in normal state?
Stable tissues
Give examples of stable tissues.
- parenchyma of most solid tissues
(e.g liver, kidney and pancreas) - Endothelial cells
- Fibroblasts
- Smooth muscle cells
What type of tissue is made up of cells that are considered to be terminally differentiated and non-regenerative in post-natal life?
Permanent tissues
Give examples of permanent cells.
- Neurons
- Cardiomyocytes
What is the function of the ECM?
- Mechanical support (cell anchorage, polarity and migration).
- Regulator of cell proliferation (binding and displaying growth factors)
- Scaffolding for tissue renewal
- Foundation for establishment of tissue microenvironments
What are the 2 forms of ECM?
- Interstitial matrix
- Basement membrane
Where is the interstitial matrix loacted?
In spaces between stromal cells in CT
What is the interstitial matrix synthesised by?
Mesenchymal cells
(such as fibroblasts, oesteoblasts and chondroblasts)
Where is the basement membrane located?
Situated around epithelial cells, endothelial cells and smooth muscle cells
What are the main constituents of the basement membrane?
Laminin and collagen type IV
What are the 3 basic components of the ECM?
- Fibrous structural proteins (e.g collagen and elastin) for tensile strength and recoil
- Water-hydrated gels (proteoglycans and hyaluronan) for compressive resistance and lubrication
- Adhesive glycoproteins to connect ECM elements to one another and to cells
What are the 3 phases of repair?
- Acute inflammatory phase
- Proliferative phase
- Remodelling phase
How long does the inflammation phase last?
96 hours or longer
How long does the proliferation phase last?
4 weeks or longer
What happens during the proliferative phase?
- Formation of granulation tissue
- Angiogenesis (neovascularisation)
- Fibroplasia/ Desmoplasia
When does granular tissue formation form by?
2-5 days
What is granular tissue?
New connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process
What are the 5 stages involved in angiogenesis during wound repair?
- Proteolysis of ECM
- Migration and chemotaxis
- Proliferation
- Lumen formation, maturation and inhibition of growth
- Increased permeability through gaps and transcytosis (oedema)
When does collagen synthesis begin?
day 3-5 and continues for weeks
What are the 2 steps involved in deposition of connective tissue?
- Migration and proliferation of fibroblasts into the site of injury
- Deposition of ECM proteins produced by fibroblasts
What is deposition of CT orchestrated by?
Locally produced cytokines and growth factors
(including PDGF, FGF-2 and TGF-B)
What is involved in the remodelling phase of wound repair?
- Maturation and reorganisation of CT to produce stable scar tissue.
- Progressive vascular regression
- Remodelling of ECM by MMPs
- Increase in collagen which is deposited along tension lines (increase in tensile strength
What factors influence tissue repair?
- Infection
- Nutritional status
- Age
- Glucocorticoids
- Mechanical factors
- Poor perfusion
- Foreign bodies
- Type and extent of tissue injury
- Underlying neoplasia
- Location of injury
What layer of the skin is the bulk of ECM located?
Dermis
When would healing by first intention occur?
Only focal disruption of the epithelial basement membrane and death of only few epithelial and mesenchymal cells.
Give examples of wounds that would heal by first intention.
Injury only involves epithelial layer or is a clean, uninfected surgical incision approximated by sutures.
Within 24 hours what has happened if a wound is healing by first intention?
- Neutrophils migrate to the clot and release proteolytic enzymes which clear the debris
- Basal cells exhibit mitotic activity
What happens between 24 and 48 hours in a wound healing by first intention?
Epithelial cells from both sides migrate and proliferate and deposit basment membrane as they progress
What happens at day 3 in a wound healing by first intention?
- Neutrophils replaced by macrophages
- Granulation tissue formation commences (angiogenesis and ECM formation)
- Epithelium continues to proliferate
What happens at day 5 in a wound healing by first intention?
- Peak of oedematous granulation tissue
- Increase of collagen
- Epidermis at normal thickness and starts to mature
What happens during week 2 in a wound healing by first intention?
- Continued fibroblast proliferation and collagen formation
- Decrease of inflammtion, odema and vascularity (“blanching”)
- Sutures removed at 10 days
By the end of the first month what would usually be seen in a wound that has healed by first intention?
- Normal epidermis
- Collagenous scar
- No inflammation
Give examples of wounds that would heal via second intention.
- Ulcerations
- Lacerations
- abscesses
- ischemic necrosis
What are features that are seen in a wound that is healing by second intention?
- More intense inflammation
- Abundant granulation tissue, acumlation of ECM and formation of a large scar
- The wound contracts via myofibroblasts
- Poor tensile strength
- Wound may remain ulcerated
What is a myofibroblast?
Modified fibroblast that contains smooth muscle cells
Describe the CT in a wound that has healed by second intention.
Haphazardly formed and arranged (also lacks adnexa), which can also delay or prevent migration of epithelial cells
By the end of the first month what is granulation tissue replaced by in a wound that has healed by second intention?
Acellular fibrous tissue devoid of inflammation which is covered by intact epidermis
Upon the removal of sutures what % of strength is the wound compared to normal skin?
10%
What is fibrosis?
Excessive deposition of collagen
What is the major cytokine involved in fibrosis?
TGF-beta
What is fibrosis associated with?
loss of tissue
What is fibrosis a consequence of?
Persistent injurious stimuli
e.g chronic inflammation of infectious or immune mediated origin
What can fibrosis lead to?
Organ dysfunction or even failure
What is “proud flesh”?
Exuberant granulation tissue
What animal is “proud flesh” typically seen and in what body part is it located?
Legs of horses
What animal is more reliant on wound contraction from the edges of the wound?
cat
What animal is more reliant on central pull and epithelialisation during wound healing?
Dogs
Describe the initial inflammatory phase in horses.
- Weaker
- persists for longer
- Excessive granulation tissue
- Lower inital production of inflammatory mediators
True/ False?
Differences between horses and ponies are more significant with limb wounds than body wounds.
TRUE
How long should sutures remain in reptiles for?
4-6 weeks
What wound heals faster in reptiles?
wounds orientated cranial to caudal or transverse wounds.
Transverse wounds
True/False?
Ecdysis impairs healing.
FALSE
it promotes healing
