7. Repair and Regeneration Flashcards
what is a scar?
an area of fibrous tissue, a manifestation of healing by repair
what is a stem cell niche?
a microenvironment within the specific anatomical location of stem cells, which interacts with stem cells o regulate cell fate
what does the mechanism of healing depend upon?
whether or not cells can regrow
how do cells heal if they can be replaced?
regeneration and restitution of specialised function
how do cells heal if they cannot be replaced?
fibrosis and scarring - loss of specialised function
what are the different types of cell populations
labile
stable/quiescent
permanent
what are the characteristics of a labile population?
high normal turnover
active stem cell population
excellent regenerative capacity
eg. epithelia
what are the characteristics of a stable population?
low physiological turnover but can be massively increased if needed
good regenerative capacity
eg. liver, renal tubules
what are the characteristics of a permanent population?
no physiological turnover long life cells no regenerative capacity very specialised structure and function eg. neurons, muscle cells
what does regeneration depend on?
the structure that needs to be built, since it is not only the epithelium that gets damaged. epithelium cannot regenerate the rest of the functional tissue
what are the characteristics of stem cells?
prolonged self renewal
asymmetric replication
reservoirs present in many adult tissues
survival is crucial to regenration
what are the mechanisms in place for the control of regeneration?
- proliferation of stem cell components
- covering of defect
- contact inhibition
- complicit control by growth factors, cell-cell and cell-matrix interactions
what is repair?
when the normal structure is not replaced, healing bu non-specialised fibrous tissue
what does the granulation tissue contain?
new capillary loops
phagocytic cells
myofibroblasts which synthesise collagen and ECM. acquire myofibrils and contractile ability, leading to wound contraction
what happens as the granulation tissue matures?
vascularity and cellularity decrease, collagen, ECM and wound strength increase
what local factors inhibit healing?
infection haematoma blood supply foreign bodies mechanical stress
what is a haematoma?
a solid swelling of clotted blood within tissues
what systemic factors inhibit healing?
age drugs anaemia diabetes malnutrition catabolic states Vit. C deficiency trace metal deficiency
what is the criteria for healing by first intention?
wound edges need to be apposed to one another
good haemostats
clean and uninfected wound
what is the process of healing by first intention?
- formation of initial fibrinous clot, which heals by a process of organisation
- formation of a fibrous scar by granulation occurring and maturing
- fibrous union, contraction. scar aimed to be as small and neat as possible
when doe wounds heal by second intention?
when wound edges are not apposed due to:
- extensive loss of tissue
- apposition not physically possible
- large haematoma
- infection
- foreign body oresent
what is the consequence of healing by second intention?
more floris granulation tissue reaction and more extensive scarring
fundamentally similar reaction
when does non-union of fractures occur?
- misalignment
- movement
- infection
- interposed soft tissue
- pre-existing bone pathology
how do wounds in the brain heal?
supporting tissue in the brain is glial cells rather than collagen and fibroblasts, therefore damaged tissue is removed, leaving a cyst, and healing takes place by gliosis rather than scarring
how is healing controlled?
complex networks of cytokines
what is the function of epidermal growth factor (EGF)?
stimulates granulation tissue formation
what is the function of transforming growth factor beta (TGF-B)?
stimulates TIMP synthesis, angiogenesis and fibroplasia, inhibits production of MMPs and keratinocyte proliferation
what is the function of platelet derived growth factor (PDGF)?
activates PMNs, macrophages and fibroblasts. mitogenic for fibroblasts, endothelial cells and smooth muscle cells. stimulates angiogenesis
what is the function of keratin growth factor (KGF)?
stimulates keratinocyte migration, proliferation and differentiation
what is the function of tumour necrosis factor (TNF)?
activates macrophages, regulates other cytokines
what is the function of vascular endothelial cell growth factor (VEGF)?
increases vascular permeability, mitogenic for endothelial cells
what is the function of transforming growth factor alpha (TGF-A)?
similar to EGF, stimulates replication of hepatocytes and most epithelial cells