L6 Repair and Regeneration

Question 1

The first response to injury is ____ ____?

Answer 1

acute inflammation

Question 2

Following injury, what is the aim of the acute inflammatory process?

Answer 2

• To remove the agents causing injury
• Protect against infection
• Allow immune system to access the area

Question 3

Following injury and acute inflammation, what are the possible outcomes?

Answer 3

1. Regeneration
   Damaging stimulus removed and cells regrow to restore normal structure and function
2. Repair
   Damaging stimulus is removed but cells cannot regrow. Scar formation and loss of function follow
3. Chronic inflammation
   Damaging stimulus is not removed

Question 4

What are the two most important factors in determining the outcome of injury?

Answer 4

1. The ability of the cells to replicate

2. The ability to rebuild complex architectural structures

Question 5

Continuously dividing cells, such as epithelium, are known as ____ cells.

Answer 5

labile

Question 6

Cells that can leave the cell cycle and then return and regenerate when required, such as hepatocytes, are known as ____ ( or ____) cells.

Answer 6

stable (or quiescent)

Question 7

Cells that leave the cell cycle after division and never return to divide again, such as neurons and cardiac myocytes, are known as ____ cells.

Answer 7

permanent

Question 8

Which cell population have the best regenerative capacity?

Answer 8

Labile

Question 9

Hepatocytes are an example of which cell population?

A) Labile
B) Quiescent
C) Permanent
D) None of the above

Answer 9

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.

Question 10

Neurons and striated muscle cells are examples which cell population?

A) Labile
B) Quiescent
C) Permanent
D) None of the above

Answer 10

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.

Question 11

Epithelium is made of which cell population?

A) Labile
B) Quiescent
C) Permanent
D) None of the above

Answer 11

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.

Question 12

Where are stem cells found?

Answer 12

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.

Question 13

How is the stem cell pool maintained in a tissue?

Answer 13

When a stem cell divides, one daughter cell remains in the stem cell compartment and the other enters the differentiating compartment.

Question 14

Define tissue regeneration and tissue repair.

Answer 14

Regeneration: Tissue returns to normal with restored specialised function.

Repair: Fibrosis and scarring heal the damaged tissue but it loses any specialised function.

Question 15

Why does damage to the glomeruli and alveoli usually result in fibrosis/scarring?

Answer 15

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.

Question 16

Why is it difficult for the body to regenerate when cirrhosis occurs?

Answer 16

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.

Question 17

How do labile cells repair a defect?

Answer 17

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.

Question 18

True or false: following MI, the myocardium can return to full functionality.

Answer 18

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)

Question 19

Regarding tissue damage, what is ‘organisation’?

Answer 19

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

Question 20

What is the process of granulation tissue formation?

Answer 20

1. Endothelial cell proliferation.
   Tissue is very vascular and cellular
2. Phagocytes.
   Removal of dead/damaged tissue
3. Myofibroblast proliferation.
   Collagen and extracellular matrix layed down. Myofibrils and ability to contract acquired
4. Wound contraction

Question 21

Clean uninfected surgical wounds heal by _____ intention.

Answer 21

first (or primary)

Question 22

When wound edges are apposed, do they heal by first or second intention?

Answer 22

First (primary) intention, provided there is good haemostasis.

Question 23

When wound edges are not apposed, does it heal by first or second intention?

Answer 23

Second (secondary) intention

Question 24

True or false: after suturing a wound, the sutures should be taken out when the tissue has returned to 70% strength.

Answer 24

False. Sutures would normally be removed around Day 7, when the tissue will only be at ~10% health.

Question 25

What local factors can inhibit wound healing?

Answer 25

Infection
Foreign bodies
Haematoma
Blood supply
Mechanical stress

Question 26

What systemic factors can inhibit wound healing?

Answer 26

Age
Drugs (steroids)
Anaemia
Diabetes
Malnutrition
Catabolic states
Vit C deficiency
Trace metal deficiency

Question 27

What is a Keloid Scar?

Answer 27

A scar that fails to regress. Instead it grows beyond the original wound margins due to proliferation of fibroblasts and excess production of collagen.

Question 28

Describe the process of fracture healing.

Answer 28

1. Haematoma forms around break and within bone
2. Haematoma is organised
3. Removal of necrotic fragments
4. Deposition of disorganised woven bone (callus) by osteoblasts
5. Remodelling according to mechanical stress
6. Replacement by more orderly ‘lamellar’ bone

Question 29

What are the consequences of non-union of fractures?

Answer 29

• Misalignment
• Infection (esp. compound #)
• Interposed soft tissue (interposed = positioned between to things)

Question 30

What are differences between normal tissue healing and healing in the brain?

Answer 30

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.