Regeneration and repair Flashcards
what processes are involved in wound healing?
- haemostasis (repair of blood vessels)
- acute inflammation
- regeneration and/or repair
what are the basic principles of regeneration?
- regrowth of cells
- only possible with minor injuries
- regeneration is a physiological process that constantly occurs
where do new cells come from?
- stem cells can differentiated into other types of cells
- stem cells also self renew
what are the 3 types of stem cells?
- totipotent - can form any cell
- multipotent - can form several different cells
- unipotent - only produce one cell
where are stem cells found?
- in epidermis: found in basal layer
- in intestinal mucosa: found at bottom of crypts
- in liver: found between hepatocytes
what are the different types of tissue in relation to their ability to repair and regenerate?
- labile tissue - constantly replicate cells e.g. endothelial of skin
- stable tissue - low level of replication but can undergo periods of high replication in response to damage e.g. smooth muscle
- permanent tissue - never normally replicates e.g. brain, skeletal muscle
what is the relationship between the different tissue types and the cell cycle?
- labile tissues - constantly cycle
- stable tissue - leave cell cycle (in G0) but can re-enter
- permanent tissue - leave cell cycle and cant re-enter
what does regeneration rely on?
regeneration relies on their being an intact tissue architecture
(if damage is substantial then the tissue must undergo repair)
what is repair/fibrosis?
replacement of funcitoning tissue with a scar
how do we know if regeneration or repair will occur?
Tissue type:
* if damage is to permanent tissue then it will always undergo repair/fibrosis
* if damage is to labile or stable tissue then there are 2 possible outcomes:
1. if collagen architecture is intact then regeneration occurs
2. if collagen framework or chronic inflammation occurs then repair occurs
what are the different stages of repair?
- haemostasis - seconds to minutes
- inflammation - digestion of blood clot - mins to days
- proliferation - capillaries, fibroblasts, myofibroblasts - forms granulation tissue - days to weeks
- remodelling - maturation of scar - reduced cell population + increased collagen - weeks to years
what is the function of granulation tissue formation in the proliferation stage of scar formation?
- fills gap
- capillaries supply oxygen and nutrients
- contracts to close wound
what are the different cells involved in fibrous repair?
- neutrophils and macrophages - phagocytosis, release of mediators and acute inflammation
- lymphocytes - eliminate pathogens + co-ordinate other cells
- endothelial cells - proliferation stage of repair
- fibroblasts - secrete collagen + elastin to form extracellular matrix
- myofibroblasts - has intracellular actin so can contract allowing for wound contraction
how do fibroblasts appear under the microscope?
spindle shaped nucleus + cytoplasmic extensions
what are myofibroblasts?
cell somewhere between a fibroblast and smooth muscle cell
appears very similar to a fibroblast under microscope
what are the basic principles of collagen?
most abundant protein in humans
varying types
how is collagen synthesised?
- pre-pro collagen (a polypeptide alpha chain) is found in the ER of myo/fibroblasts
- undergoes vitamin C dependent hydroxylation
- pro collagen - alpha chains are cross linked to form a triple helix
- N + C terminals of pro collagen are cleaved - forms tropocollagen in cytoplasm
- tropocollagen is cross linked to form microfibrils, which are cross linked to form fibrils, which are cross linked to form collagen
what are the different diseases associated with defective collagen?
Acquired:
* scurvy
Inherited:
* Ehlers-Danlos syndrome
* osteogenesis imperfecta
* alport syndrome
what are the basics of scurvy?
vitamin C deficiency
pre-pro collagen cant undergo adequte vitamin C dependent hydroxylation
defective triple helix results in defective collagen
how do patients with inherited collagen defectives usually present?
- hypermobility
- bone weakness
- stretchy skin
- blue ring around the eyes
how are regeneration + repair controlled?
- cells communicate with one another to stimulate or inhibit proliferation
what is contact inhibition?
isolated cells replicate until they come in contact with another cell
the cadherins on the surface of both cells bind and inhibit further proliferation
(mutations in cadherins can cause cancer since they dont stop cell proliferation)
what are growth factors?
polypeptides that act on the cell surface
cause cells to enter cell cycle and proliferate
(defects in GF can cause excessive amounts of proliferation causing cancer)
how does skin heal?
Primary intention:
* incised wound
* apposed edges (sutures)
* minimal clot and granulation tissue
* epidermis regenerates
* dermis undergoes fibrous repair
Secondary intention:
* significant tissue loss
* unapposed edges - results in infection or ulcers
* abundant clot, inflammation + granulation tissue
* considerable wound contraction required (myofibroblast)
how does a fracture heal?
- haematoma forms - sorrounds injury + granulation tissue forms
- soft callus forms - fibrous tissue and collagen are layed down + woven bone begins to form
- hard callus forms - woven bone is organised into lamellar bone
- bone remodelling - lamella bone is remodelled to original outline of boe
what factors influence wound healing?
Local factors:
* size of wound
* location of wound
* how good the blood supply is?
* is wound infected
Systemic factors:
* age
* co-morbidities (anaemia etc)
* obesity
* diabetes
* drugs
* vitamin deficiency + malnutrition
what are complications with fibrous repair?
insufficient fibrosis: wound may reopen + this occurs in those who are:
* obese
* old
* malnurished
excessive fibrosis: keloid scar forms
inappropriate adhesions form: fibrous bands can cause obstruction of tubes
loss of function: specialised tissue replaced by fibrous tissue
excessive scar contraction - constriction of tubes
