CP3: Healing and Tissue Repair Flashcards
1. What is regeneration and repair 2. General features of wound healing: haemostasis, inflammation, angiogenesis, fibrosis (granulation tissue to scar) 3. Healing of skin and bone 4. Healing disorders
Name the 4 stages from injury to repair
- haemostats
- inflammation
- proliferation
- remodelling
What are the possible outcomes of tissue loss/destruction
- inflammation always occurs
- regeneration of tissue
- repair of tissue with fibrosis
- persistence of cavity/gap
- permanent loss of tissue
What is regeneration
the replacement of injured cells with cells of the same type by parenchymal cells via proliferation
What is resolution
the complete return to normal structure and function after injury
What is restitution
return of normality due to a combination of regeneration and resolution
What is repair
the replacement of lost tissue by fibrous scar tissue
Briefly outline haemostats
- vasoconstriction occurs
- endothelial cell activation
- platelets adhere, become activated and aggregate
- coagulation cascade forms a fibrin clot around platelet plug
What changes occur to blood vessels during inflammation and what can this result in
Initial constriction followed by immediate vasodilation
- this increases blood flow to injury site
- permeability of vessels increases and become leaky
- this means fluid moves out and can build up
- this causes swelling and oedema
What are the three cellular changes occurring in inflammation
- migration of cells
- phagocytosis
- neutrophils and macrophages
What are labile parenchymal cells
Ones that continue to proliferate throughout life to replace those constantly being destroyed
What are stable parenchymal cells
Ones that turn over at a low level under normal circumstances and are capable of rapid replication if needed
What are permanent parenchymal cells
these are incapable of mitotic division or organised proliferation
Where are labile parenchymal cells found
- skin
- gut mucosa
- bone marrow
Where are stable parenchymal cells found
- kidney
- liver
- endocrine glands
- bone
Where are permanent parenchymal cells found
- cardiac muscle
- neurones
- striated/skeletal muscle
What do tissues require in order for regeneration
Most need an intact basement membrane
If this is not available, fibrosis will occur (thickening due to scar tissue formation)
Only liver, bone and bone marrow can regenerate all constituents
What are embryonic stem cells
can generate all cell lines
What are multipotent stem cells
can generate most cells (narrower range)
What are somatic (adult) stem cells
they undergo transdifferentiation (this means they don’t undergo the pluripotent state or progenitor cell types)
What is granulation tissue
Tissue comprised of new connective tissue and tiny blood vessels that form the surfaces of a wound during healing. This is why the following are abundant
- fibroblasts
- myofibroblasts
- macrophages
What is angiogenesis
Formation of new blood vessels from pre-existing ones
How does angiogenesis occur
- Enzymatic degradation of basement membrane of parent vessels
- Migration of endothelial cells towards stimulus
- Proliferation of endothelial cells into cords
- Maturation and lumen formation (these are initially leaky)
- Differentiation into arterioles, capillaries and venules which acquire vasomotor nerves for dilation
What is the purpose of fibroblasts in granulation tissue
- synthesise extracellular matrix and collagen
- proliferate and chemotactic in response to mediators§
What is the purpose of macrophages in granulation tissue
- clear debris
- secrete growth factors
- stimulate endothelial cells
- stimulate fibroblasts
Briefly outline remodelling
- macrophages remove debris
- increased amounts of collagen are laid down
- vessels disappear
- fibrous tissue forms
- collagen cross-linking
- contraction of myofibroblasts
- fibrous scar
Hoe does fracture healing occur
- bleeding
- clot
- periosteal disruption and inflammation
- granulation tissue
- cartilage formation from chondrocytes in granulation tissue to bridge the gap = provisional callus
- calcification and ossification by osteoblasts = fibrocartilagenous callus then bony callus
- remodelling by osteoclasts/blasts
- woven bone becomes lamellar
When does granulation tissue lead to regeneration
Only in fracture healing (otherwise it will lead to repair with fibrosis)
What are the complications of repair
- exuberant granulation tissue (proud flesh)
- raised keloid scarring
- loss of function
- contractures
- stretching
- adhesions causing obstruction
What are contractures
This is where a normally elastic tissue is replaced by non-elastic fibrous tissue and so may inhibit movement and function (this is a complication of repair)
What are the general features of wound healing with escape of blood
- Haemostasis /clotting
- Inflammation
- Removal of debris by macrophages
- Cell regeneration if possible
- Micro vessel growth /angiogenesis
- Fibroblasts move in, proliferate and lay down collagen
- Scar
What is the primary intention of wound healing
Initial bleeding and inflammation can bring edges together easily
Epithelial cells proliferate and meet on surface while granulation tissue forms the underlying clot
Scar formation
Primary union
What is the secondary intention of wound healing
Edges cannot be approximated so there is more bleeding and inflammation and granulation tissue
Granulation tissue is on the surface as epithelium takes time to cover this
The process is the same but wound contraction occurs
What controls repair
- Growth factors: influence movement and cell cycle, proliferation of fibroblasts, angiogenesis and epithelial cell regeneration
- Cell-cell/ cell-matrix interactions
- ECM synthesis collagenisation
Systemic factors affecting healing
Age, nutrition, DM, steroids, chronic illness e.g. renal failure, haematological disorders
Local factors affecting healing
Infection, foreign material, blood supply, type of tissue, extent of injury, mobility, radiation
