L6 - Repair and Regeneration Flashcards
what is repair?
- normal structure cannot be replaced
- healing by non-specialised fibrous tissue (‘scar’)
- functional consequences
what is regeneration?
Restoration of normal structure and function
cell can grow back
what are the 2 most important factors when determining the outcome of an injury?
- ability of cells to replicate
- ability to rebuild complex architectural structures
features of labile cell populations?
- continuously cycling
- usually seen in epithelial structures
- high turn over
- active stem cell population
- excellent regenerative capacity
features of stable (quiescent) cell populations?
- leave the cell cycle but can re-join and regenerate at
anytime - low turnover but can increase if needed
- good regenerative capacity
eg liver, renal tubules
features of permanent cell populations?
- divided and left the cell cycle and therefore cannot divide anymore - no turnover - long life cells - no regenerative capacity
eg, neurones, striated muscle cells
features of stem cell populations?
- prolonged self-renewal
- asymmetric replication
- reservoirs present in adult tissues
- stem cell pools present in labile and stable cell populations
- specific areas eg basal layers of epidermis or bottom of intestinal crypts
- crucial to regeneration
What is complete restitution?
- Loss of labile cell population can be completely restored e.g. minor skin abrasion
- Cells at edge of defect multiply to cover defect.
what is contact inhibition?
Once the cells at the edge cover defect, proliferation stops
what are the implications are scar tissue forming to replace myocardium?
- decrease contractility, resulting in heart failure
- electrical conductivity problems, resulting in arrhythmias
what is organisation?
The repair of specialised tissue by formation of a fibrous scar
features of organisation?
- Production of granulation tissue (often on scaffold of fibrin)
- removal of dead tissue by
phagocytosis - Granulation tissue contracts and accumulates collagen, forming a scar
- Organised area – firm and puckered
features of granulation tissue?
- New capillary loops
- Phagocytic cells (Neutrophils, Macrophages)
- (Myo)fibroblasts [which contract]
when is granulation tissue the most vascular?
Initially, the granulation tissue is very vascular and cellular.
over time, the vascularity and cellularity are lost and the wound becomes
much stronger because of the formation of collagen and ECM
features of healing by primary intention?
- clean, unaffected surgical wound
- good haemostats (not lots of bleeding)
- edges apposed (eg with staples or sutures)
Process of healing by primary intention?
- little or no skin loss
- coagulated blood forms fibrin join (scab)
- scab replaced my collagen that is covered by the epidermis growing over
features of healing by secondary intention?
- extensive loss of tissue
- apposition not possible
- large haematoma
- infection
- foreign body
which healing method (by primary or secondary intention) results in ore florid granulation tissue reaction and more extensive scarring?
secondary
how long does it take a wound to become 70-80% of its normal strength?
3 months
which healing intention do ulcers heal by? (primary/secondary)
secondary
local factors that could inhibit healing?
infection haematoma blood supply foreign bodies mechanical stress
systemic factors that could inhibit healing?
age drugs anaemia diabetes malnutrition catabolic states vitamin C deficiency Trace metal deficiency
how do steroids affect the healing process?
steroids interfere with formation of granulation tissue and are immunosuppressive
how does a vitamin C deficiency affect the healing process?
vitamin C deficiency affects collagen synthesis
what is a keloid scar?
When there’s damage to underlying dermis of the skin, it can be followed by
an excessive fibroblast proliferation and formation of collagen
NB: genetically determined process
features of a keloid scar?
- difficult to treat
- tough heaped up scar that rises above rest of skin
- tend to enlarge progressively unlike normal scars
- do not regress over time
Normally:
- shiny
- hairless
- raised
- hard and rubbery
- red or purple at first before becoming brown or pale
- painless
healing process of a fracture?
- haemorrhage around and within bone (haematoma)
- phagocytosis of necrotic fragments
- osteoblasts lay down disorganised bone (callus)
- remodelling and replacement by more orderly bone (lamellar)
non-union of fractures slows down healing and prevents functional results, can lead to arthritis and degenerative diseases.
Why does non-union of fractures occur?
misalignment
movement
infection
interposed soft tissue
pre-exisitng bone pathology e.g tumour
what is gliosis?
proliferation or hypertrophy of several different types of glial cells
where does gliosis occur and why?
occurs in the brain as a response to CNS damage (instead of scarring)
why do cysts form in the brain after CNS damage?
- Neurons are terminally
differentiated - Supporting tissue is glial
cells rather than collagen
and fibroblasts etc –
these can proliferate - Hence damaged tissue is
removed, often leaving
cyst
what secretes EGF?
platelets
macrophages
saliva
plasma
function of EGF?
stimulates granulation tissue formation
what secretes TGF-β?
platelets t-lymphocytes macrophages endothethial cells keritnocytes smooth muscle cells fibroblasts
what is the function of TGF-β?
- chemotactic stimulates; TIMP synthesis, angiogenesis, fibroplasia, - inhibits production of MMPs and keratinocyte proliferation
what secretes PDGF?
platelets macrophages endothelial cells keratinocytes SMC
what is the function of PDGF?
- stimulates angiogenesis
- stimulates production of MMPs and fibronectin
what secretes KGF?
fibroblasts
what is the function of KGF?
stimulates keratinocyte migration, proliferation, and differentiation
what secretes TNF?
macrophages
mast cells
T lymphocytes
what is the function of TNF?
activates macrophages
regulates other cytokines
what is the function of VEGF?
increases vascular permeability
mitogenic for endothelial cells
what is mitogenesis?
Mitogenesis is the induction (triggering) of mitosis, typically via a mitogen.
what is the function of TGF-α?
similar to EGF; stimulates replication of hepatocytes and most epithelial cells
which growth factor stimulates replication of hepatocytes?
TGF-α
which growth factor increases vascular permeability?
VEGF
which growth factor stimulates keratinocyte migration, proliferation and differentiation?
KGF
which growth factor is mitogenic for fibroblasts, endothelial cells and SMC?
PDGF
which growth factor is mitogenic for keratinocytes and fibroblasts?
TGF-β
which growth factors are mitogenic?
TGF-β
PDGF
which growth factor stimulates granulation tissue formation?
TGF-β
which growth factors are secreted by macrophages?
EGF TGF-β PDGF TNF TGF-α
Which growth factors are secreted by fibroblasts?
KGF
TGF-β
which growth factors are secreted by keratinocytes?
TGF-β
TGF-α
Which growth factors are secreted by platelets?
EGF
TGF-β
PDGF
Which growth factors are secreted by T-lymphocytes?
TGF-α
TNF
TGF-β
how is regeneration controlled?
- proliferation of stem cells
- covering of defect
- contact inhibition
- growth factors
what is ulceration?
loss of the surface epithelium or the mucosa (full loss of mucosa)
