Cell Repair & Regeneration Flashcards
What is the body’s initial response to injury?
Acute inflammation
What are the main roles of acute inflammation?
- clear away dead tissue
- protect against local infection
- allow the immune system into the damaged area
If a damaging stimulus is removed, what may happen to the damaged tissue?
damaged tissue may be replaced by organised tissue that is identical in structure and function to the original tissue
What is cell regeneration dependent on?
cells being able to regrow and clearance of cell debris from the site of injury
What happens if damaged cells cannot regrow or the architecture of the tissue is destroyed?
REPAIR
Healing takes place by the formation of scar tissue
What are the 3 outcomes of acute inflammation?
- regeneration - cells regrow
- repair - cells cannot regrow
- chronic inflammation
What are the 2 most important factors in determining the outcome of cellular injury?
- the ability of cells to replicate
2. the ability to rebuild complex architectural structures
What are the 3 different types of cell populations?
- laible cells
- quiescent (stable) cells
- permanent cells
What is the turnover and regenerative ability of labile cell populations?
High normal turnover
Active stem cell population
Excellent regenerative capacity
What is an example of labile cell population?
epithelial cells
What is the turnover and regenerative ability of stable cell populations?
low physiological turnover
Turnover can massively increase if needed
Good regenerative capacity
What are examples of stable cell populations?
hepatocytes
What is the turnover and regenerative ability of permanent cell populations?
No physiological turnover
These are long life cells with no regenerative capacity
What are examples of permanent cell populations?
Neurones, striated muscle cells
Which types of cells will replace cells lost through injury?
Stem cell pools that are present in many labile and stable cell populations
What happens when stem cells undergo mitotic division?
one of the daughter cells retains stem cell characteristics
the other cell progresses along a differentiation pathway e.g. epidermis
Where are stem cell pools present in the body?
in many labile and stable cell populations
located in specific areas e.g. basal layers of epidermis
What is the main difference between regeneration and repair?
Tissue returns to normal in regeneration
Fibrosis and scarring leads to healing in repair
How does regeneration and repair affect function of cells?
Regeneration allows restitution of the specialised function
Repair leads to loss of specialised function
What is the main architectural consideration regarding repair and regeneration?
Rebuilding of complex architectures is very limited
e.g. the lung or glomerulus
What is essential when determining whether a body part can regenerate?
the survival of the connective tissue framework
What causes liver cirrhosis?
It is the end result of persistent long term damage to the liver by a noxious agent that persists over a long period
e.g. autoimmune damage, alcohol
Why can’t the regeneration of liver cells repopulate the normal architecture in cirrhosis?
there is collapse of the reticulin (connective tissue) framework of the liver
What is the result of the collapsed reticulin framework in a cirrhotic liver?
the formation of regenerative nodules divided by fibrous septa
What type of cell population are hepatocytes?
Hepatocytes are a stable cell population with excellent regenerative capacity
In a minor skin abrasion, can the cell population be restored?
The loss of labile cell population can be completely restored
What is meant by contact inhibition when labile cell populations are restored?
cells at the edge of the defect multiply to cover the defect
once the cells cover the defect, proliferation stops
this is when the cells touch each other
How does regeneration occur in a minor skin abrasion where there is limited loss of epidermis?
- cells at the margins proliferate and spread out as a thin sheet across the dermis
- once the defect is covered the stimulus for the cells proliferate and move is switched off by contact inhibition
- the epidermis then grows from the base upwards
What controls regeneration?
complex control by growth factors, cell to cell and cell to matrix interactions
In which condition are the mechanisms of regeneration control lost?
neoplasia
What type of tissue is involved in cellular repair?
What is the consequence of this?
Healing is by non-specialised fibrous (scar) tissue
This means that the normal structure cannot be replaced
What are the mechanical consequences of scar tissue developing in the interventricular septum after a myocardial infarction?
- loss of pumping capacity
2. if the scar is large it may cause cardiac failure
What are the electrical consequences of scar tissue developing in the interventricular septum after a myocardial infarction?
- a scar may be a focus of abnormal electrical activity
- it may lead to arrhythmia
- it might disrupt the cardiac conducting system if it is in a critical point (e.g. His bundles) - giving heart block
What are the 2 general processes that occur during fibrous scar formation?
- production of granulation tissue
2. removal of dead tissue by phagocytosis
What is granulation tissue usually produced on?
a scaffold of fibrin
What happens once granulation tissue has been produced?
the granulation tissue contracts and accumulates collagen, forming a scar
How will the organised area appear after scar formation?
firm and puckered
What cells/components are present in granulation tissue?
- new capillary loops
- phagocytic cells - neutrophils & macrophages
- (myo)fibroblasts
Why is wound contraction an important process?
It is important for reducing the volume of tissue for repair
What is the role of myofibroblasts within granulation tissue?
- they proliferate and migrate
- they synthesise collagen and ECM
- they acquire myofibrils and contractile ability
What is the role of the phagocytes within granulation tissue?
removal of dead and damaged tissue
What is the role of the capillary loops within granulation tissue?
They are needed for endothelial cell proliferation
They form buds, undergo canalisation and form new vessels
What happens to vascularity, cellularity and the wound strength as the granulation tissue matures?
- vascularity and cellularity decline
2. collagen, ECM and wound strength increase
What are the 2 types of healing that occur with skin wounds?
- healing by primary intention
2. healing by secondary intention
What type of wound will heal by first intention?
A clean, uninfected surgical wound that is closed at the end of a procedure
What are the first stages of healing by first intention if little or no skin is lost?
- the edges of the incision are joined by a thin layer of fibrin
- fibrin is replaced by collagen covered by surface epidermis
What actually forms the scab in healing by first intention?
coagulated blood
What helps to prevent the fibrin join from being disrupted?
Using a plaster or sutures
What happens to cell growth if the wound is gaping?
Epidermis grows over the defect
If the wound is gaping, epidermal cells can grow down into the defect
If the epidermal cells do not stop growing and do not get reabsorbed what happens?
they remain and grow to form a keratin-filled cyst
this is an implantation dermoid
What is the only residual defect associated with healing by first intention?
the inability to reconstruct the elastic network within the dermis
What is the main difference between healing by first and second intention?
In healing by second intention, the wound edges are not apposed
In first intention, the edges are apposed with sutures or staples
What prior events usually lead to the wound edges not being apposed?
- extensive loss of tissue
- large haematoma
- infection
- foreign bodies
What are 2 other differences between healing by first and second intention?
In healing by second intention:
- more florid granulation tissue reaction
- more extensive scarring
What is the process behind healing by second intention?
The process is fundamentally the same, but the tissue defect is larger
Wound is replaced by granulation tissue which eventually contracts leaving a scar
After how many days are sutures taken out?
after 7 days when the wound strength is 10%
After how many weeks is the wound 80% strong?
week 12
By which method would a chronic foot ulcer in a diabetic patient heal?
secondary intention
lots of granulation tissue will form a broad fibrous scar
What are the 2 broad categories of factors that inhibit healing?
Local and systemic factors
What are the 5 main local factors that inhibit healing?
- infection
- haematoma
- blood supply
- foreign bodies
- mechanical stress
What are the 6 main systemic factors that inhibit healing?
- age
- drugs e.g. steroids
- anaemia
- diabetes
- malnutrition
- Vitamin C or trace metal deficiency
What is the main malnutrition that impairs wound healing?
Protein malnutrition
Why does Vitamin C deficiency lead to problems with wound healing?
Vitamin C is involved in collagen synthesis
Why do steroids interfere with wound healing?
They have immunosuppressive actions so interfere with formation of granulation tissue
What is dermal injury sometimes followed by?
excessive fibroblast proliferation and collagen production
This is genetically determined
What are the stages in fracture healing?
- haemorrhage around and within the bone (haematoma)
- haematoma is organised
- removal of necrotic fragments
- osteoblasts lay down disorganised woven bone
- remodelling occurs according to mechanical stress
- replacement by more orderly lamellar bone
What is the disorganised woven bone that is laid down by the osteoblasts?
callus
How does the haematoma in the bone form?
Why is it important?
It is formed by haemorrhage within the bone from ruptured vessels in the bone marrow
It provides the framework/scaffold for repair
What are the 5 factors that can lead to non-union of fractures?
- misalignment
- movement
- infection
- interposed soft tissue
- pre-existing bone pathology
What are the consequences of misalignment in fractures?
It slows healing and prevents a good functional result
It increases the risk of degenerative disease in adjacent joints - osteoarthritis
What are the consequences of movement in fractures?
It causes pain and excess callus production
This prevents or slows healing
What are the risks of infection in fractures?
When is infection more likely to occur?
Infection delays healing
There is a risk of chronic osteomyelitis
It is more likely in compound fractures when the skin is broken
What steps may be required before a pathological fracture heals?
Treatment of an underlying pathological condition
What is the difference in healing when it is occurring in the brain?
Neurones are terminally differentiated
The supporting tissue is glial cells rather than collagen and fibroblasts - these can differentiate
What is the result of healing in the brain?
Damaged tissue is removed, often leaving a cyst
Gliosis occurs instead of scarring
What is meant by reactive gliosis?
proliferation of astrocytes
How is healing controlled?
it is tightly controlled by complex networks of cytokines
What is the role of epidermal growth factor (EDP) in healing?
It is mitogenic for keratinocytes and fibroblasts
It stimulates granulation tissue formation
What is the role of transforming growth factor (TFG-b) in healing?
it is chemotactic for phagocytes, fibroblasts and smooth muscle cells
It inhibits keratinocyte proliferation
What is the role of platelet-derived growth factor (PDGF) in healing?
It is chemotactic for phagocytes, fibroblasts and smooth muscle cells
It simulates angiogenesis
It is mitogenic for fibroblasts and endothelial cells
What is the role of keratinocyte growth factor (KGF) in healing?
It stimulates keratinocyte migration, proliferation and differentiation
What is the role of tumour necrosis factor (TNF) in healing?
It activates macrophages and regulates other cytokines
What is the role of vascular endothelial cell growth factor (VEGF) in healing?
it increases vascular permeability
it is mitogenic for endothelial cells
What is the role of transforming growth factor (TGF-a) in healing?
It stimulates replication of hepatocytes and most epithelial cells
