T2: Repair and Regeneration Flashcards
What are the 3 cell types in the cell cycle?
Labile cells continue to replicate so that lost cells are rapidly replaced. They have excellent regenerative capacity. They have a high normal turnover and an active stem, cell population located in specific areas of the epithelium.
Stable cells replicate infrequently under normal conditions. But when stimulated, stem cells differentiate to replace lost cells which re-enter the cell cycle. They are able to divide rapidly if required. It has a good regenerative capacity e.g. the liver and renal tubules.
In terms of permanent cells, have no or very little capacity to regenerate. These are long life cells. Examples include neurones and striated muscle cells.
What are stem cells? What is their role in regeneration?
These have a prolonged-self renewal. They replace cells lost through injury to at the end of the life cycle. They are present in many labile or stable cell populations. When a stem cell undergoes mitotic division, one of the daughter cells maintains the stem cell characteristics while the other undergoes differentiation. They are usually located in a specific compartment of reservoir in the adult tissue e.g. lower levels of the epidermis or in the bone marrow which can migrate to other areas and differentiate. Survival of stem cells crucial to regeneration e.g. vulnerable to radiation injury. Stem cells are vulnerable for example to radiation injury, having an impact upon healing.
Why is architecture important in terms of regeneration?
Rebuilding of complex architectures are limited e.g. glomeruli (leading to scarring and fibrosis as they cannot be regenerated) and the lung. Survival of connective tissue framework essential e.g. cirrhosis.
What is involved in the control of regeneration?
- Proliferation of stem cell / amplifying cell compartments
- Covering of defect
- Contact inhibition
- Complex control by growth factors, cell-cell and cell-matrix interactions
These mechanisms are lost in neoplasia
What is repair?
Occurs when normal structure cannot be replaced. Healing occurs by non-specialised fibrous tissue, also known as scar tissue. This can often have functional consequences.
What is mechanism of repair?
Organisation: The repair of specialised tissue by formation of a fibrous scar
It is the basic stereotyped pathological process. It results Production of granulation tissue (often on scaffold of fibrin) and removal of dead tissue by phagocytosis
Granulation tissue contracts and accumulates collagen, forming a scar. Organization is a common consequence of pneumonia and infarction. When the organized area heals it becomes firm and puckered.
Granulation tissue is formed by a mixture of new capillary loops - starts as buds which develop lumens and undergo canalisation. This is mixed with phagocytic cells which clear away debris. Fibroblasts also migrate to the damaged area which synthesise collagen and extracellular matrix.
Theses acquire myofibrils and contractile ability to contract the wound by up to 80% - reducing the volume of tissue to be repaired.
As granulation tissue matures it becomes less cellular and vascular. The wound becomes stronger as more collagen and extracellular matrix is laid down.
What is healing by first intention?
• Occurs in Clean, uninfected surgical wound
• Good haemostasis - no evidence of haematoma
Edges apposed e.g. with sutures or staples. This maximises the healing by primary intention.
If little or no skin is lost the edges of the incision are joined by a thin layer of fibrin. This is eventually replaced by a collagen scar covered by the epidermis. Coagulated blood forms the scab. The fibrin joint should not be disturbed - can be done by suturing or a plaster. The epidermis grows over the gap. They initially grow along the base before the contact each other and grow up. If the wound is gaping, some epidermal cells can grow into the defect. These usually stop growing and becoming absorbed however some do remain and form a keratin-filled cyst = implantation dermoid. After a matter of weeks, the only remaining defect is to reconstruct the elastic ability within the dermis.
The end result is a neat scar.
What is healing by second intention?
Healing by secondary intension Wound edges are not apposed This may be due to: • Extensive loss of tissue • Apposition not physically possible • Large haematoma • Infection • Foreign body Requires More florid granulation tissue reaction (“leaving a wound to granulate”) and leads to more extensive scarring.
It results in a larger defect which gets replaced by an area of granulation tissue. This eventually contracts and leaves a scar. As the weeks pass, the wound strength increases.
What factors inhibit healing?
Local: • Infection • Haematoma • Blood supply • Foreign bodies • Mechanical stress - such as when a bone is broken
Systemic: • Age • Drugs (e.g. steroids) • Anaemia • Diabetes • Malnutrition • Catabolic states • Vitamin C deficiency Trace metal deficiency
- Vitamin C is involved in collagen synthesis- scurvy leads to problems with wound healing.
- Protein malnutrition (dietary deficiency or loss) impairs wound healing
Steroids – immunosuppressive actions, and so interfere with formation of granulation tissue
What is keloid scarring?
Dermal injury is sometimes followed by excessive fibroblast proliferation and collagen production. This is genetically determined – Keloid.
What is the variation on the basic repair process in the brain?
- Neurons are terminally differentiated - cannot be replaced
- Supporting tissue is glial cells rather than collagen and fibroblasts etc. – these can proliferate. This is a process known as gliosis.
- Hence damaged tissue is removed, often leaving cyst
- Gliosis rather than scarring.
Intracerebral haemorrhage resolved by lysis and removal of blood components with residual staining, leaving a cyst surrounded by gliosis.
Cerebral infarct resolves leaving a cyst.
What is the variation on the basic repair process in bones?
- Haemorrhage around and within the bone - haematoma
- Haematoma is organized. It causes structure and a scaffold for repair.
- Removal of necrotic fragments
- Osteoblasts lay down disorganized woven bone (callus)
- Remodeling according to mechanical stress
Replacement by more orderly lamellar bone
Fractures can sometimes not heal properly. For example if the bones are misaligned. Unless the ends are put together, the area will not heal. Infection also delays healing and is much more common in compound fractures (when the skin is broken). There is a risk of osteomyelitis.
What is resolution?
The bodies initial reaction to injury is acute inflammation to clear way dead tissue, to protect against local infection and to allow the immune system into the damaged area. If the damaging stimulus is removed, the damaged area may be replaced by organized tissue identical in structure and function to the original. This is resolution and is the ideal outcome, but depends upon cells being able to regrow and for cell debris to be cleared form the site.
What is cirrhosis?
Cirrhosis – imbalance between hepatocyte regeneration and failure to reconstruct the architecture
What is ulceration?
Loss of the epidermis
