Regeneration And Repair Flashcards
Processes involved in wound healing
Injury —> haemostasis, —> inflammation —> regeneration —> repair
Only possible with minor injuries
E.g. superficial skin incision/abrasion
Regeneration
Can be physiological - e.g. production of white cells in bone marrow
Where do new cells come from - Stem cells - cells that can differentatiate into other cell types - and self renew - relapse and reject dead/damaged cells
Types of stem cell -
Totipotent - produce all cell types e.g. embryonic stem cells
Multipotent - produce some cell types in a cell lineage - e.g. haematopoietic stem cells
Unipotent - produce one cell type - e.g. epithelial stem cells
Where are the stem cells:
Epidermis - present in the basal layer
Intestinal mucosa - present right at the bottom of the intestinal crypts
Liver - between hepatocytes
What types of tissue can regenerate?
Labile tissue - continuous replication of cells e.g. epithelium, haematopoietic tissue
Stable tissue - normally low level of replication - but can undergo rapid proliferation if stimulated e.g. liver, pancreas, bone, kidneys
Permanent - cells do not replicate - e.g. neurons, skeletal muscle, cardiac muscle
What tissue types can regenerate:
Labile cells - continuously cycling
Stable cells - are in G0 (left cell cycle) - if stimulated can re-enter cycle
Permanent cells have left cell cycle and cannot re-enter (apart from specific circumstances)
The tissues that can repair need an intact connective tissue architecture
Fibrous repair - The replacement of functioning tissue with a scar
How does a scar form
1) bleeding and haemostasis - prevention of blood loss - occurs in seconds
2) inflammation - acute, then chronic - for digestion of blood clot - minutes to days
3) proliferation - of capillaries, fibroblasts, myofibroblasts and ECM —> granulation tissue*
4) remodelling - maturation of scar - reduced cell population, increased collagen and myofibroblasts contract —> fibrous scar (weeks to years)
* granualtion tissue - fills the gap of the damage - capillaries supply oxygen and nutrients - it can also contract and close the defect due to myofibrils
Cells involved in fibrous repair
Neutrophils and macrophages - both phagocytose and release mediators
Lymphocytes - eliminated pathogens and coordinate other cells
Fibroblast - spindle shaped nucleus, cytoplasmic extensions (cant usually see as fibroblasts interdigitate), secrete collagen and elastin, form ECM
Myofibroblast - between a fibroblast and smooth muscle - very similar in appearance to fibroblast
Express IC actin which can contract, leading to wound contraction
Collagen and collagen synthesis
Most abundant mammalian protein Provides extracellular framework
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Disease of defective collagen
Acquired - Scurvy
Inherited - Ehlers-Danlos Syndrome, Osteogenesis Imperfecta and Alport Syndrome
Scurvy - Vitamin C deficiency
Historically came about during long journeys
Inadequate hydroxylation of pre-pro collagen
Defective triple helix = defective collagen
Unable to heal wounds, therefore tendency to bleed and old scars to tear open and Tooth loss
How are regeneration and repair controlled
Cells communicate with each other to produce a prolierative response using -
Direct cell-cell contact
Local mediators
hormones
Growth factors - Polypeptides that act on cell surface
Causes cell to enter cell cycle and proliferate
Helpful for healing
Different types of skin healing
Primary Intention - Incised wound withApposed edges (sutured) - can be a deep cut but the width of the cut is small - produces little scaring
Minimal clot and granulation tissue
Epidermis regenerates Dermis undergoes fibrous repair
Secondary Intention - Significant tissue loss with Unapposed edges (Infection/ulcer/abscess) - width of cut is large
Abundant clot, inflammation and granulation tissue
Considerable wound contraction required (Myofibroblasts needed for actin and collagen)
Dermis requires significant repair Epidermis regenerates from edges - takes longer for skin to fully heal
Fracture healing
1) Haematoma surrounds the injury - Granulation tissue forms
2) Soft Callus (1 week) - Fibrous tissue and cartilage - Woven bone begins to form
3) Hard Callus (several weeks) - Woven bone gradually organized into lamellar bone
4) Remodeling (months – years) - Lamellar bone remodeled to original outline of bone
Factors influencing wound healing and complications of fibrosis repair
Factors -
Local - Size, Location , Mechanical stress, Blood supply Local infection, Foreign bodies
Systemic:Age, Anaemia hypoxia, hypovolaemia, Obesity, Diabetes, Drugs, Vitamin deficiencies, Malnutrition
Complications of fibrosis repair:
Insufficient fibrosis - wound dehiscence
Occurs in obesity, elderly, malnutrition, steroid use
Excessive fibrosis - keloid scar
Adhesions - fibrous bands - can cause obstruction of tubes
Loss of function - replacement of specials tissue by fibrosis tissue e.g. in MI, cardiac myocytes are replaced - heart doesn’t pump properly
Disruption of architecture - e.g. cirrhosis of the liver
Excessive scar contraction - leads to constriction of tubes —> flexed flexion deformities
