7. Regeneration And Repair Flashcards
What process are involved in wound healing?
Injury
Haemostasis
Inflammation
Regeneration or repair
What is regeneration?
Regrowth of cells
Minimal evidence of injury
Only possible with minor injuries (e.g. superficial skin incision/abrasion)
Where do new cells come from?
Stem cells - can differentiate into other cell types and self-renew
Replace dead/damaged cells
What are the types of stem cell?
Totipotent - produce all cell types (embryonic stem cells)
Multipotent - reduce several cell types (haematopoietic stem cells)
Unipotent - produce one cell type (epithelial stem cells)
Which tissue types can regenerate?
Labile tissue - continuous replication of cells
Stable tissue - normally low level of replication but can undergo rapid proliferation if required
Which tissue types cannot regenerate?
Permanent tissue - cells do not replicate (neurons, skeletal tissue, cardiac muscle)
Describe the tissue types in the cell cycle
Labile cells - continuously cycling
Stable cells - left cell cycle but can re-enter
Permanent cells - left cell cycle and cannot re-enter
What does tissue regeneration require?
An intact connective tissue architecture (collagen and elastin)
What is fibrous repair?
The replacement of functioning tissue with a scar - fibrogenesis
What can lead to fibrous repair instead of regeneration?
Necrosis of permanent tissues
Necrosis of labile or stables tissues if collagen framework is destroyed or there is on-going chronic inflammation
What are the 4 stages of a scar forming?
Bleeding
Inflammation
Proliferation
Remodelling
What happens in bleeding and haemostasis in scar formation?
Prevention of blood loss
Seconds to minutes
What happens in inflammation in scar formation?
Acute then chronic
Digestion of blood clot
Minutes to days
Removal of necrotic tissue, infection, foreign body
What happens in proliferation during scar formation?
Proliferation of: - capillaries (angiogenesis) - fibroblasts - to make collagen and elastin - myofibroblasts - extracellular matrix Leads to formation of granulation tissue Days to weeks
What are the functions of granulation tissue?
Fills the gap
Capillaries supply oxygen and nutrients
Contracts and closes the defect
What happens in remodelling during scar formation?
Maturation of scar: - reduced cell population - increased collagen (tightly packed) - myofibroblasts contract Leads to fibrous scar Weeks to years
What cells are involved in fibrous repair?
Neutrophil and macrophage for phagocytosis and release of mediators
Lymphocytes to eliminate pathogens and co-ordinate other cells
Endothelial cells for proliferation and angiogenesis
Describe fibroblasts
Spindle shaped nucleus
Cytoplasmic extensions
Secrete collagen and elastin
Form extracellular matrix
Describe myofibroblasts
Between a fibroblast and smooth muscle
Very similar appearance to fibroblasts
Expresses intracellular actin - can contract leading to wound contraction
Describe collagen
Provides extracellular framework
29 different types
Type 1 - bones tendon, ligaments skin, sclera, vessels
Type 4 - basement membrane, lens, glomerular filtration
What happens in collagen synthesis?
Pre-pro collagen is formed - polypeptide alpha chain in ER of (myo)fibroblasts
Undergoes vitamin C dependent hydroxylation
Pro collagen is formed - alpha chains cross-linked, formation of triple helix in cytoplasm
Tropocollagen formed - C and N terminals of procollagen cleaved in extracellular space
Tropocollagen crosslinked to form microfibirls, fibrils and collagen fibres
What are diseases of defective collagen?
Acquired - scurvy
Inherited - Ehlers-Danlos syndrome, osteogenesis imperfecta, Alport syndrome
How are regeneration and repair controlled?
Cells communicated with each other to produce a proliferative response
By: direct cell-cell/cell-stroma contact, local mediators, hormones
What are growth factors?
Polypeptides that act on cell surface
Causes cell to enter cell cycle and proliferate
E.g. epidermal GF, vascular endothelial GF, platelet derived GF, tumour necrosis factor
