Healing and Repair Flashcards
Where does complete restoration of tissues occur and where does greater tissue destruction occur?
acute inflammation
chronic inflammation
What is regeneration and what is repair?
replacement with functional differentiated cells
production of a fibrous scar and changes in tissue structure/architecture
What determines regeneration or repair?
severity and location of damage
What tissues cannot regenerate if damaged?
brain
heart
What are the cell types and what are their characteristics?
- Labile cells;
– Normal state is active cell division
– Rapid regeneration - Stable cells (conditional renewal cells); – variable rates of regeneration
– Rapid proliferation in response to injury - Permanent cells;
– unable to divide
– unable to regenerate
What cells are present in heart?
permanent cells
What are examples of labile cells?
epithelial cells
hematopoietic stem cells
Where are there stable cells?
liver
kidneys
What are the four stages of healing?
1- coagulation
2 - inflammation
3 - proliferation
4 - maturation
What happens in the coagulation phase (homeostasis)?
– Clot formation
– Mitosis of labile/stable cells (e.g., epithelial cells)
What happens in the inflammation phase?
– Macrophages/neutrophils phagocytose and degrade infectious agent
– Stimulation of certain cells (e.g., keratinocytes/fibroblasts) to start regenerating and/or repairing tissue
What happens in the proliferative phase?
– Formation of granulation tissue
– Fibroblasts are key players
– New connective tissue (rich in collagen)
– Angiogenesis (new blood vessels)
– Growth factors are essential
What are essential in the proliferative phase?
growth factors
What are the two phases of the granulation tissue?
1st - vascular granulation tissue
2nd - fibrous granulation tissue
What are the characteristics of vascular granulation tissue?
– Mix of proliferating capillaries, fibroblasts, immune cells
– New capillaries are relatively ‘leaky’ allowing cells and fluid into tissue
What are the characteristics of fibrous granulation tissue?
– Overtime capillaries regress and immune cells return to blood
– Mature fibroblasts lay down collagen
What is angiogenesis?
formation of new capillaries (blood vessels)
What are the two mechanisms in which blood vessels are formed?
sprouting (sprouting from existing vessels)
intussusceptive (splitting)
What growth factor is associated with angiogenesis?
vascular endothelial growth factor (VEGF)
What is VEGF produced by?
in extracellular matrix produced by epithelial cells, macrophages and fibroblasts
What occurs if there is a VEGF gradient?
endothelial cells move towards gradient (sprouting)
What occurs if there is no VEGF gradient?
lumen of existing blood vessel enlarges until central areas fuse together leading to splitting of vessel.
What do growth factors do?
- Promote or inhibit cell growth and
differentiation - Bind receptors on cell surfaces
What are the functions of growth factors?
- Promote cell survival
- Locomotion
- Contractility
- Differentiation
- Angiogenesis
What is fibrosis?
the extensive deposition of collagen and fibrous connective tissue
What is fibrosis driven by?
fibroblasts (and M2 macrophages)
What macrophage subtype is responsible for healing and repair?
M2 macrophages
What growth factors are produced during fibrosis by macrophages?
TFG - BETA
PDGF
What happens during maturation phase?
– Disorganized granulation tissue remodeled by remaining cells
– Collagen fibres are cross linked along tension lines
– Re-epithelization (growth factors)
– Regain of tensile strength (up 80% of
pre-injury strength)
– Fibrous scar remains (in repair)
– Tissue remodeling
What is the difference between primary and secondary intentions?
primary - regeneration
secondary - regeneration and repair
What intention causes a difference in tissue appearance?
secondary
What does the inflammatory stage (48 hours) of hard tissue repair include?
- Blood clot formation at fracture
- Acute inflammatory response
- Death of bone cells
What happens to bone cells in the inflammatory stage that are deprived of oxygens?
die off
What does the repairing stage 1 (weeks) of hard tissue repair include?
- Capillaries form into hematoma
- Fibroblasts produce collagen fibers and osteoblasts form spongy bone
- Granulation tissue forms and becomes the soft callus
What do osteoblasts form in repairing stage 1?
spongy bone
What does the repairing stage 2 (months) of hard tissue repair include?
- Chondrocytes and osteoblasts produce cartilage and bone
- Formation of hard bone callus at fracture site (known as Fracture Callus or woven bone)
What does the remodelling stage (months-years) of hard tissue repair include?
- Osteoclasts and osteoblasts remodel the hard bone callus (resorption vs deposition of bone)
- Cortical bone replaces woven bone.
- Angiogenesis essential in bone regeneration and repair
