Session 4 - Regeneration and Repair

Question 1

What are the three processes that occur in wound healing?

Answer 1

• Haemostasis - as vessels are open
• Inflammation - due to tissue injury
• Regeneration and repair - as structures have been injured or destroyed

Question 2

What is regeneration also known as?

Answer 2

Resolution or restitution

Question 3

What is regeneration? What does it require to take place?

Answer 3

The growth of cells and tissues to replace lost structures. It requires an in tact tissue scaffold and therefore the damage must not be extensive.

Question 4

What induces regeneration?

Answer 4

• Growth factors in the environment
• cell to cell communication

Question 5

What is a labile tissue? List some examples.

Answer 5

a tissue that proliferates throughout life replacing cells that are destroyed.

Examples include

• epithelia
• columnar epithelia of the GI tract and uterus
• Haematopoietic tissues

Question 6

What is a stable tissue? Give some examples.

Answer 6

These are cells that normally have a low level of replication but cells in these tissues can undergo rapid division in response to stimuli - they have the ability to reconstruct the tissue of origin.

Examples include:

• Parenchymal cells of the liver, kidney and pancreas
• Mesenchymal cells such as fibroblasts, bone osteoclasts and smooth muscle cells.

Question 7

What is a permanent tissue? Give some examples:

Answer 7

These are tissues that have left the cell cycle (G0) and therefore cannot divide in postnatal life.

Examples:

• Neurones
• Skeletal and cardiac muscle cells.

Question 8

What are stem cells?

Answer 8

They are cells that have prolonged proliferative activity and show assymetric replication.

Question 9

What is assymetric replication?

Answer 9

This is when upon division one daughter cell will remain as a stem cell whilst the other is a mature non-dividing cell.

Question 10

What is the difference between an embryological stem cell and adult stem cell?

Answer 10

Embryological stem cells are totipotent and most adult stem cells are unipotent and some are multipotent.

Question 11

What are the three different types of stem cells and what are their definitions?

Answer 11

1. Totipotent - embryological stem cells. These kinds of cells can give rise to any cell type.
2. Unipotent - these are stem cells that cna give rise to only one cell type
3. Multipotent - these are stem cells that can give rise to multiple cell types (eg. haematopoietic stem cells).

Question 12

What happens in the healing process of permanent tissues?

Answer 12

Healing with a scar (fibrous repair) or in the case of the CNS the damaged space will be filled with glial cells.

Question 13

Why do scars quite often appear pale in pigmented skin?

Answer 13

This is because the regeneration of melanocytes is very slow if at all and therefore you will have lower levels of melanin in the skin causing the pale colour in the scar.

Question 14

Describe the regeneration capacity of:

• Smooth muscle
• Striated muscle
• Cardiac muscle

Answer 14

• Smooth muscle - very good regenerative capacity
• Striated muscle - limited, regeneration can occur from satellite cells
• Cardiac muscle - cannot regenerate

Question 15

Describe the regenerative capacity of

• Peripheral nerves
• CNS axons

Answer 15

• Peripheral nerves - can regenerate. They sprout axons at 1-3mm/day
• CNS axons - lost neurones cannot be replaced and severed CNS axons do not grow back.

Question 16

What is organisation? (In the context of healing)

Answer 16

Also known as fibrous repair - this is where fibrovascular tissue will grow into the area due to the loss of function of parenchymal cells due to extensive damage.

Question 17

Describe the process of organisation

Answer 17

1. Phagocytosis of necrotic tissue debris
2. The endothelial cells will proliferate resulting in angiogenesis
3. Fibroblasts will proliferate and some differentiate into myofibroblasts that synthesise collagen and cause wound contraction (due to the presence of actin in myofibroblasts).
4. Granulation tissue becomes less vascular and matures into a fibrous scar.
5. Scar matures and shrinks due to the contraction of fibrils within the myofibroblasts.

Question 18

What is scurvy? Describe some of the symptoms.

Answer 18

This is an acquired disease due to vitamin D deficiency. Vitamin C is required for hydroxylation of procollagen.

Symptoms include:

• Receding gums
• Tendency to bleed due to the weakness of the capillaries
• Wounds don’t heal properly
• Old scars can reopen.

Question 19

What is Ehlers-Danlos syndrome? Describe some of the symptoms.

Answer 19

Ehlers-Danlos is a group of 6 inherited disorders where the collagen fibres lack adequate tensile strength.

Symptoms:

• Skin is hyperextensible
• Thinning of the sclera
• Poor wound healing
• Patients have a predisposition to joint dislocation

Question 20

What is osteogenesis imperfecta? Describe some of the symptoms.

Answer 20

An autosomal dominant inherited disease that is also known as ‘brittle bone disease’. Symptoms include:

• Skeletal fragility - bones prone to breaking
• Blue sclera
• Hearing impairment
• Dental abormalities

Question 21

What is alport syndrome? Describe some of the symptoms:

Answer 21

An X-linked disease. Type IV collagen is abnormal and this results in dysfunction of the glomerular basement membrane, the cochlea of the ear and the lens of the eye.

• Haematuria
• Chronic renal failure
• Neural deafness
• Eye disorders

Question 22

What is the role of epidermal growth factor? Which cells produce it?

Answer 22

It is a mitogenic agent for

• epithelial cells
• hepatocytes
• fibroblasts

It is produced by

• keratinocytes
• macrophages
• inflammatory cells

Question 23

What is the role of vascular endothelial growth factor?

Answer 23

It promotes:

• vasculogenesis (blood vessel development)
• growth of new blood vessels (angiogenesis)
• Chronic inflammation
• Wound healing

Question 24

Which cells produce platelet derived growth factor?

Answer 24

• Macrophages
• endothelial cells
• smooth muscle cells
• tumour cells

Question 25

What is the role of platelet derived growth factor?

Answer 25

It causes migration and proliferation of fibroblasts, smooth muscle cells and monocytes.

Question 26

What is the role of tumour necrosis factor?

Answer 26

Induces fibroblast migration, fibroblast proliferation, and collagenase secretion (an enzyme released by neutrophils so they can undergo diapedesis).

Question 27

In what kind of wounds do healing by primary intention occur?

Answer 27

Incisional, closed, non-infected and sutured wounds - there is interruption to the basement membrane but death of only a few epithelial and connective tissue cells.

Question 28

Describe the process of healing by primary intention with the following steps: 1. seconds to minutes 2. minutes to hours 3. up to 48 hours 4. three days 5. seven to ten days 6. one month to two years.

Answer 28

1. seconds to minutes: haemostasis - this is where the severed arteries contract, the blood clots and forms a scab. 2. Minutes to hours - inflammation. Neutrophils appear at the margins of the incision. Inflammatory responses happen automatically. 3.

Question 29

What is healing by secondary intention?

Answer 29

It is seen in: * excisional wounds * wounds with separated edges * infected wounds

Question 30

What happens in healing by secondary intention?

Answer 30

* Abundant granulation tissue forms and grows in from the edges * Intense inflammatory condition. * wound contraction by shrinkage of the scab and also by myofibroblast contraction (after around a week)

Question 31

Describe the process of bone fracture healing?

Answer 31

* **Haematoma formation** * **Fibrin mesh** is formed followed by **granulation tissue**. * Platelets and inflammatory cells release cytokines activating osteoprogenitor cells, osteoclastic and osteoblastic activity * **Soft callus formation (at 1 week)** - fibrous tissue and cartilage within which woven bone begins to form. * **Hard callus (after several weeks)** - laid down by osteoblasts. * Formation of lamellar bone (stronger than the woven bone formed in the hard callus) * **Bone remodelling** - in response to mechanical stress.

Question 32

Name at least 3 complications of fibrous repair

Answer 32

1. Formation of fibrous adhesions compromising organ function or blocking tubes 2. Excessive scar contraction obstructing tubes, causing joint contractures and in severe cases impairing blood circulation 3. Overproduction of fibrous scar tissue cauisng a keloid scar. 4. Disruption of complex tissue relationships with an organ - distortion of architecture interfering with normal function (such as in liver cirrhosis).

Question 33

Name some factors that stimulate monocytes to form macrophages?

Answer 33

* Platelet derived growth factor * Interleukin 1 * TNF alpha

Question 34

Name some examples of factors that affect wound healing.

Answer 34

1. Infection 2. Foreign bodies (sutures) 3. steroids/immunosuppressants 4. diabetes 5. haematoma 6. lack of vitamin C 7. poor blood supply.