Lecture 18: Repair and regeneration Flashcards
What is regeneration?
Cells can regrow
Restoration of normal structure and function
What is repair?
Cells cannot regrow
Scar formation
Loss of function
After injury and acute inflammation, what pathways can be taken?
Regeneration
Repair
Chronic inflammation
Two most important factors determining outcome of injury?
- ability of the cells to replicate
- ability to rebuild complex architectural structures
What different cell types in the repair / regeneration of cells cycle?
- Continuously cycling labile cells
2 Permanent Cells - Quiescent stable cells
What different cell types in the repair / regeneration of cells cycle?
- Continuously cycling labile cells
2 Permanent Cells - Quiescent stable cells
What is the labile cell population and characteristics?
High normal turnover
Active stem cell population
Excellent regenerative capacity
Example: Epithelia
What is the stable quiescent cell population and characteristics?
Low turnover
(physiological)
Turnover can massively increase
(if needed)
Good regenerative capacity
Example: liver, renal tubules
What is the permanent cell population and characteristics?
No turnover
(physiological)
Long life cells
No regenerative capacity
Example: neurons, striated muscle cells
Stem cell characteristics?
Prolonged self-renewal
Asymmetric replication
Reservoirs in many adult tissues
How do Stem cells form?
- Terminal
differentiation
2.Differentiating
compartment
3.Amplifying cell
compartment
What is the population of Stem cells?
Present in many labile and stable cell populations
Located in specific areas (basal)
Survival = crucial to regeneration
Give an example of the rebuild of complex architectures which is limited?
Glomeruli, lung
An example of when survival of connective tissue is essential?
Cirrhosis
How does complete restitution occur?
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?
when cells cover defect proliferation stops
What is complex regeneration controlled by?
growth factors
cell-cell interactions
cell-matrix interactions
These mechanisms are lost in neoplasia
What does regeneration depend on?
tissue cell kinetics
architecture
stem cell survival
how does healing by regeneration affect specialised function?
Restitution of
specialised function
How does healing by repair affect specialised function?
Loss of specialised
function
What happens during repair of cells/tissues?
Normal structure cannot be replaced
Healing by non-specialised fibrous tissue (‘Scar’)
Functional consequences
What is Organisation?
the repair of specialised tissue by formation of a fibrous scar
What is an example of organisation?
Example = common consequence of pneumonia and infarction
Organisation characteristics?
Basic stereotyped pathological process
Production of granulation tissue (often on scaffold of fibrin)
Removal of dead tissue by phagocytosis
Granulation tissue contracts and accumulates collagen
Scar forms
Organised area = firm and puckered
What is Granulation tissue?
New capillary loops
Phagocytic cell (Neutrophils and Macrophages)
(Myo)fibroblasts
What does Endothelial cell proliferation include?
Buds
Canalisation
New vessels
What do phagocytes do?
Remove dead /
Damaged tissue
What is included in Proliferation and migration
of myofibroblasts?
Synthesise collagen
and ECM
Acquire myofibrils and
contractile ability
What decreases in maturation of granulation tissue?
- Vascularity
- Cellularity
What increases in Maturation of Granulation tissue?
Collagen, ECM wound strength.
What is involved in healing by first intention?
Clean, uninfected surgical wound
Good haemostasis
Edges apposed
What is involved by healing by second intention?
Extensive loss of tissue
Wound edges not apposed
Apposition not physically possible
Large haematoma
Infection
Foreign body
More florid granulation tissue reaction
More extensive scarring
Wound strength after a week?
10%
Wound strength after week 4- week 12?
70 - 80%
Local factors inhibiting healing?
Infection
Haematoma
Blood supply
Foreign bodies
Mechanical stress
Systemic factors inhibiting healing?
Age
Drugs (eg steroids)
Anaemia
Diabetes
Malnutrition
Catabolic states
Vitamin C deficiency
Trace metal deficiency
What is a haematoma?
Haemorrhage around and within the bone - haematoma
Is haematoma organised?
Yes - removal of necrotic fragments
Fracture healing pathway?
Osteoblasts lay down disorganised woven bone (callus)
Remodelling according to mechanical stress
Replacement by more orderly lamellar bone
Non- union of fractures?
Misalignment
Movement
Infection
Interposed soft tissue
Pre-existing bone pathology
‘pathological fracture’
How are neurons organised in the brain?
Terminally differentiated
Support tissue in the brain?
Glial cells
What do you get in the brain when damage tissues are removed?
Cysts
What happens in the brain rather than scarring?
Gliosis
For growth factor and function for control of healing:
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