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
What are some complications with fibrous repair?
- Fibrous adhesions: can block tubes
- Loss of function due to replacement of cells by non-functioning collage: e.g myocytes
- Disruption of tissue relationships in an organ: cirrhosis
- Overproduction of fibrous tissue: keloid, common in afrocarribbeans
- Excessive scar contraction: impair blood supply, disfigured scars, tubes and joints
How do each of the following tissues regenerate?
- Cardiac muscle
- Liver
- Peripheral Nerve
- Cartilage
- CNS
- Limited, leads to scar formation and loss of function
- If architecture not severely damage hepatocytes followed by non-parenchymal ells replicate. Regenerative nodules of hepatocytes with intervening fibrosis leads to cirrhosis
- Axons degenerate and they sprout and elongate from proximal stumps using Schwann cells 1-3mm/day
- Not well as no blood, lymph or nerves
- Permanent tissue, when damaged replaced by glial cells, gliosis.
What is the difference between a keloid scar and a hypertrophic scar?
- Keloid scars grow onto normal skin outside the range of the wound
- Hypertrophic remain in the boundaries of the wound
What is the most common complication of wound healing?
- Insufficient fibrosis: wound dehiscence, ulceration
- Elderly, obesity, malnutrition, steroids, EDS
What is traumatic neuroma and some of the symptoms?
When proximal and distal nerve fibres are not close together so the proximal fibres grow in tangles of connective tissue, forming lumps under the skin.
- Painful palpable nodule
- Parasthesia
- Fatigue
What is Walerian degeneration?
When a nerve fibre is crushed or cut the fibres distal to the cut is degenerated
What is proud flesh and how can it be treated?
- Hypergranulation leading to too much connective tissue and vessels in an open wound
- Trim away, silver nitrate dressing, cortisone cream
