7 - Regeneration and Repair Flashcards
What are the three processes involved in wound repair?
- Haemostasis: open vessels
- Inflammation: as tissue injury
- Regeneration (resolution/restitution) and repair
What is regeneration and when does it occur?
- Growth of cells and tissues to replace lost structures.
- Healed by primary intention, when there is a superficial abrasion. When there is an intact connective tissue scaffold, no harmful agent persisting
How are cells induced to regenerate?
- Growth factors in microenvironment
- Cell-to-cell communication
Where are the stem cells in:
- Epidermis
- Intestinal mucosa
- Liver
What is asymmetrical replication?
How stem cells replicate
What are some examples of unipotent and multipotent stem cells?
- Uni: Epithelia
- Multi: Haemopoietic stem cells
Can all tissue proliferate?
- No only labile and stable tissues
- Labile (e.g surface epithelia): short lived cells constantly dividing
- Stable/Quiescent (e.g liver, kidneys, pancreas) : low level of replication but cells can undergo rapid division in response to stimuli. Mature and stem cells replicate
- Permanent (e.g cardiomyocytes): left cell cycle and can’t divide
What happens if there is an injurty where the connective tissue scaffold is not in tact?
- Fibrous repair/ Organisation
- Healing by secondary intention leaving a scar
What is the time scale of a scar formation?
Outline the process of the fibrous repair.
What is granulation tissue and what is it’s function?
- Contains developing capillaries, fibroblasts, myofibroblast, chronic inflammatory cells
- Fills the gap, capillaries supply oxygen and nutrients, contracts and closes the hole
What is the function of fibroblasts in the granulation tissue?
- Produce the extracellular matrix, collagen
- Contract the wound
How is a scar matured?
- Remodelled due to collagen being remodelled slowly by collagenases
- Vaculature matures and shrinks so scar goes from being pink to white
Why do people with scurvy have an issue with bleeding?
- Fragile capillaries
- Old scars break down and open up as fresh wounds as collagen remodelling is resulting in weak collagen being incorporated to the scar
What is Alport syndrome?
- X-linked recessive
- Type IV Collagen abnormality
- Dysfunction in basement membrane in glomerular, cochlea or ear and lens of eye
- Present with haematuria as children that can progress to chronic renal failure. Often deafness and eye disorders
What factors control regeneration and repair?
- Cell to cell communication either directly or via local mediators/hormones
e. g growth factors
How do growth factors affect wound healing?
- Coded for by proto-oncogenes
- Bind to specific receptors that stimulate transcription of genes that cause the cell to enter into the cell cycle
- Causes cell proliferation for repair
(also involved in differentiation, angiogenesis, inhibiting division etc)
What are some examples of growth factors?
1. Epidermal GF: binds to EGFR. produced by macrophafes, keratinocytes, inflammatory cells. Used for epithelia, hepatocytes and fibroblasts
2. Vascular endothelial GF: vasculogenesis and angiogenesis in tumours
3. Platelet-derived GF: stored in platelet alpha granules and released on platelet activation. also produced by smooth muscle, tumours etc. cause migration and proliferation of fibroblasts, smooth muscle, monocytes
4. Tumour Necrosis Factor: induce fibroblast migration/proliferation and collagenase secretion
What is the importance of cell to cell contact in wound healing?
- Contact inhibition: cells replicate until they touch each other and then stop
- Integrins bind cells to x-cellular matrix and cadherins to other cells
- This mechanism is lost in malignancy, e.g breast cancer have no E-cadherins
What is the process of healing by primary intention?
- Occurs in incisional, closed, non-infected, clean wounds with opposed edges
- Disruption of basement membrane but only a few epithelial cells have died so small scar
What is the process of healing by secondary intention?
- Excisional wounds or wounds with tissue loss and separated edges or infection
- Open wound filled by abundant granulation tissue which grows in from wound margins. More intense inflammatory reaction and contraction to bring wound together as more necrotic tissue
- Shape of scar depends on original wound. Healing delayed in infection and new epidermis thinner
What are the two different types of skin grafts?
- Full thickness and split thickness
What is the process of healing after bone fracture?
What factors influence wound healing?
Local: Type/Size/Location of wound, mechanical stress, blood supply, local infection, denervation, foreign bodies, haematoma, necrotic tissue, protection, surgical techniques
General: Age, anaemia, obesity, diabetes, malignancy, genetic disorders (EDS), drugs like steroids, vitamin deficiency, malnutrition
