L6 Repair and Regeneration Flashcards
Describe the phases of healing in a surgical wound Outline examples of why this system of healing can fail Describe what variations on the basic repair process occur in brain and bone Outline the cell biology of inflammation and repair in relation to targets for drug therapy
The first response to injury is ____ ____?
acute inflammation
Following injury, what is the aim of the acute inflammatory process?
- To remove the agents causing injury
- Protect against infection
- Allow immune system to access the area
Following injury and acute inflammation, what are the possible outcomes?
- Regeneration
Damaging stimulus removed and cells regrow to restore normal structure and function - Repair
Damaging stimulus is removed but cells cannot regrow. Scar formation and loss of function follow - Chronic inflammation
Damaging stimulus is not removed
What are the two most important factors in determining the outcome of injury?
- The ability of the cells to replicate
2. The ability to rebuild complex architectural structures
Continuously dividing cells, such as epithelium, are known as ____ cells.
labile
Cells that can leave the cell cycle and then return and regenerate when required, such as hepatocytes, are known as ____ ( or ____) cells.
stable (or quiescent)
Cells that leave the cell cycle after division and never return to divide again, such as neurons and cardiac myocytes, are known as ____ cells.
permanent
Which cell population have the best regenerative capacity?
Labile
Hepatocytes are an example of which cell population?
A) Labile
B) Quiescent
C) Permanent
D) None of the above
B) Quiescent
Also known as ‘stable’, quiescent cell populations have a low physiological turnover but this can be massively increased if required. The liver and the renal tubules are made up of these cell populations. These tissues have good regenerative capacity.
Neurons and striated muscle cells are examples which cell population?
A) Labile
B) Quiescent
C) Permanent
D) None of the above
C) Permanent
These cells have developed and then ceased dividing. They have no physiological turnover and cannot reenter the cell cycle. They have a long life-span and form tissues that have no regenerative capacity.
Epithelium is made of which cell population?
A) Labile
B) Quiescent
C) Permanent
D) None of the above
A) Labile
Labile cell populations have a high physiological turnover with an active stem cell population. These tissues have excellent regenerative capacity and are found in the skin and linings of the gut.
Where are stem cells found?
Many adult tissues contain stem cell pools, usually in specific areas (e.g. basal layers, intestinal crypts).
Many labile and stable cell populations contain stem cell pools.
How is the stem cell pool maintained in a tissue?
When a stem cell divides, one daughter cell remains in the stem cell compartment and the other enters the differentiating compartment.
Define tissue regeneration and tissue repair.
Regeneration: Tissue returns to normal with restored specialised function.
Repair: Fibrosis and scarring heal the damaged tissue but it loses any specialised function.
Why does damage to the glomeruli and alveoli usually result in fibrosis/scarring?
These are complex structures and are difficult to construct. Healing of these structures is generally repair rather than regeneration. Regeneration relies heavily on a connective tissue framework, which is not really present with these structures.
Why is it difficult for the body to regenerate when cirrhosis occurs?
Cirrhosis is scarring of the liver due to persistent damage. It causes a collapse of the tissue framework.
Although hepatocytes have good regenerative potential, they cannot form normal structure due to the loss of connective tissue framework.
This results in regenerative nodules.
How do labile cells repair a defect?
Without an adjacent cell to inhibit them, the cells at the edge of the defect proliferate to cover the defect. Once the defect is covered, the cells inhibit one another (contact inhibition) and proliferation stops.
True or false: following MI, the myocardium can return to full functionality.
False.
The myocardium is made of permanent cells, and so they can only repair as opposed to regenerate. The formation of scar tissue leads to decreased contractility (heart failure) and conductivity problems (arrhythmias)
Regarding tissue damage, what is ‘organisation’?
The repair of specialised tissue by formation of a fibrous scar.
- Production of granulation tissue (on scaffold of fibrin) and removal of dead tissue by phagocytosis.
- Contraction of GT and accumulation of collagen, forming a scar
- Organised area - firm and puckered
What is the process of granulation tissue formation?
- Endothelial cell proliferation.
Tissue is very vascular and cellular - Phagocytes.
Removal of dead/damaged tissue - Myofibroblast proliferation.
Collagen and extracellular matrix layed down. Myofibrils and ability to contract acquired - Wound contraction
Clean uninfected surgical wounds heal by _____ intention.
first (or primary)
When wound edges are apposed, do they heal by first or second intention?
First (primary) intention, provided there is good haemostasis.
When wound edges are not apposed, does it heal by first or second intention?
Second (secondary) intention
True or false: after suturing a wound, the sutures should be taken out when the tissue has returned to 70% strength.
False. Sutures would normally be removed around Day 7, when the tissue will only be at ~10% health.
What local factors can inhibit wound healing?
Infection Foreign bodies Haematoma Blood supply Mechanical stress
What systemic factors can inhibit wound healing?
Age Drugs (steroids) Anaemia Diabetes Malnutrition Catabolic states Vit C deficiency Trace metal deficiency
What is a Keloid Scar?
A scar that fails to regress. Instead it grows beyond the original wound margins due to proliferation of fibroblasts and excess production of collagen.
Describe the process of fracture healing.
- Haematoma forms around break and within bone
- Haematoma is organised
- Removal of necrotic fragments
- Deposition of disorganised woven bone (callus) by osteoblasts
- Remodelling according to mechanical stress
- Replacement by more orderly ‘lamellar’ bone
What are the consequences of non-union of fractures?
- Misalignment
- Infection (esp. compound #)
- Interposed soft tissue (interposed = positioned between to things)
What are differences between normal tissue healing and healing in the brain?
Neurons are terminally differentiated and are supported by glial cells instead of collagen and fibroblasts.
Gliosis, rather than scarring.
Damaged tissue is removed, leaving a cyst (hollow cavity). The space is filled by proliferating or hypertrophic glial cells, a process called gliosis.
