Healing and repair Flashcards
What are the 2 main pathways a tissue can undergo following injury and inflammation?
Resolution or repair
- resolution = tissue essentially goes back to normal
- repair = once inflammation subsides tissues doesn’t go back to normal
What does healing require and what is it dependent upon?
Requires regrowth of cells and ECM Depends on: 1) type of tissue that is injured 2) nature of the injury 3) sufficient blood supply (angiogenesis)
What are the 3 main structural elements/junctions of the skin and what do they do?
Epidermis - contains stem cells in constant cell cycle
Dermo-epidermal junction- connects epidermis to dermis via hemidesmosomes, basement membrane and collagens
Dermis - comprises fibroblasts, blood vessels and abundant extracellular matrix
What are the roles of the collagen, proteoglycans and elastic fibres in the ECM of the dermis?
Collagen fibres - provide structural support
Proteoglycans - form a hydrated gel which resists compressive forces whilst permitting rapid diffusion of nutrients, metabolites and hormones
Elastic fibres - provide resilience by stretch and recoil functions - more important for stretching, not present in scar so therefore they are not as stretchy as normal skin
What are the 2 ways of wound healing in the skin?
Primary intention- most common, single incision during surgery allows this process to occur
Secondary intention - not possible to bring 2 ends of skin together e.g. leg ulcer - skin can heal but it takes longer as it has to heal up through the layers, the scar tissue is in the dermis and the epidermis is normal
What are the phases of clotting?
Fibrinogen to fibrin (monomer) to fibrin (polymer, unstable), to fibrin (polymer, stable)
Fibrin protects and provides structural support
Why is granulation tissue important?
“Provisional ECM” - much stronger than fibrin clot therefore provides support to defect to help support healing process
What are the stages of angiogenesis?
1) proteolysis of ECm
2) Migration and chemotaxis
3) Proliferation
4) Lumen formation, maturation and inhibition of growth
5) increased permeability through gaps ans transcytosis
What happens in fibroplasia?
Fibroblast proliferation and migration
Production of collagen, proteoglycans and elastin to re-form the ECM
- collagen forms the scar
What happens in re-epithelialisation?
Keratinocyte migration from edge of wound and skin appendages begins within 24 hours of injury (migrate along base of wound, covering it and then signal to move up and repair wound)
Keratinocyte proliferation is inhibited until migration is complete
Depends upon re-establishment of the dermo-epidermal junction
What occurs in wound contraction and scarring?
Complete re-epithelisation and dermal scarring
- collagen fibres orientate themselves parallel with cellular dermis
Fibroblasts develop properties of smooth muscle cells allowing contraction of the wound (myofibroblasts)
What stimulates epidermal and dermal healing?
Macrophages, fibroblasts and endothelial cells produce growth factors that stimulate healing
- integrins are major receptors for ECM and initiate growth factor signalling pathways
- MMPs are upregulated leading to remodelling of ECM - MMPs are inhibited by TIMPs
What systemic and local factors influence wound healing ?
Systemic- nutrition (malabsorption), metabolic status (diabetes), circulatory status, hormones
Local - local blood supply, infection, foreign body, mechanical factors
Wound strength
- 10% at 1 week
- 50-60% at 1 month
- 70-80% at 3 months - dermis is never as strong as before due to scarring
What is the ECM like in a normal liver?
Predominantly confined to the portal tracts with only a thin layer in contact with hepatocytes composed mainly of collagen
- sinusoids are lined by collagen
How does regeneration work in the liver following injury?
Hepatocytes stimulated out of Go into cell cycle
New ECM is deposited between hepatocytes
Angiogenesis establishes new sinusoids
