Session 4 - Healing and Repair

Question 1

What is resolution in terms of healing and repair?

Answer 1

The temination of inflammation whereby the tissues return to being fully functional as they were previously

Question 2

What is regeneration?

Answer 2

The replacement of dead or damaged cell by functional, differentiated cells

Question 3

What are differentiated cells derived from, and what is this derivation controlled by?

Answer 3

Derived from stem cells, under the control of hormones and growth factors

Question 4

What is the purpose of stem cell division?

Answer 4

Self-renewal or differentiation

Question 5

What are three types of stem cell differentiation?

Answer 5

Unipotent - Can produce only one type of differentiated cell
Multipotent - Can produce several types of differntiated cell
Totipotent - can produce any type of differntiated cell

Question 6

What is fibrous repair?

Answer 6

Replacement of a functional tissue by scar tissue

Question 7

What are labile tissues?

Answer 7

Normal state is active cell division, which usually proliferate rapildy epithelia)

Question 8

What is a stabile tissue?

Answer 8

Not normally dividing at a significant rate. Speed of regeneration variable.
(hepatocytes, osteoblasts, fibroblasts)

Question 9

What is a permenant tissue?

Answer 9

Unable to divide

Unable to regenerate (neurones)

Question 10

What are two types of wond repair?

Answer 10

Healing by primary intention and healing by secondary intention

Question 11

When does healing by primary intention take place?

Answer 11

When edges are opposed

Question 12

What occurs in healing by primary intention?

Answer 12

There is minimal clot and granulation tissue formation
Epidermis regenerates
Dermis undergoes fibrous repair
Maturation of scar continues up to 2 years
Risk of trapping infection > abcess

Question 13

When does healing by secondary intention take place?

Answer 13

Unopposed wound edges, the healing of which causes large clot to form.

Question 14

How does secondary intention healing progress?

Answer 14

• Epidermis regenerates beneath
• Repair process produces much more granulation tissue
• Longer process – produces a larger scar
• Late contraction by myofibroblasts to reduce the volume of defect

Question 15

What are three key factors involved in wound repair?

Answer 15

Cell migratiom
Angiogenesis
Extracellular matrix production and remodelling

Question 16

What occurs in cell migration in wound repair?

Answer 16

Inflammatory cells, endothelial cells and myofibroblasts all play a role

Question 17

What do inflammatory cells do in the cell migration stage of wound repair?

Answer 17

Neutrophils & Macrophages phagocytose debris

Lymphocytes and macrophages chemically mediate wound repair

Question 18

What do endothelial cells do in the cell migrate stage of wound repair?

Answer 18

Angiogenesis

Question 19

What do myofibroblasts do in the cell migration phase of cell repair?

Answer 19

Produce extracellular matrix proteins, and are responsible for wound contraction

Question 20

Why is adequate blood supply vital to wound healing?

Answer 20

Provide access to the wond for inflammatory cells and fibroblasts
Delivers oxygen and other nutrients

Question 21

What is the proliferation of blood vesels in angiogenesis induced by?

Answer 21

Growth factors such as vascular endothelial growth factor (VEGF)

Question 22

What is the process of angiogenesis in wound repair?

Answer 22

1. Endothelial proteolysis of basement membrane
2. Migration of endothelial cells via chemotaxis
3. Endothelial proliferation, maturation and tubular remodeling
4. Recruitment of periendothelial cells

Question 23

What is the function of extracellular matrix production & remodelling

Answer 23

• Supports and anchors cells
• Separates tissue compartments e.g. basement membrane
• Sequesters growth factors
• Allows communication between cells
• Facilitates cell migration

Question 24

What is the structure of type 1 collagen?

Answer 24

• Triple alpha helix: gly-x-y structure
• x and y usually hydroxy-proline or hydroxy-lysine – hydrogen bonding promotes strength
• Glycine is the only amino acid small enough to fit at the centre of the helix

Question 25

What is the function of type 1 collagen?

Answer 25

• Non-elastic
• Strong
• Rigid
• Found in abundance in connective tissue

Question 26

What types of factors can effect the efficacy of healing and repair?

Answer 26

Local factors and general factors

Question 27

Give 6 local factors affecting the efficacy of local factors

Answer 27

• Type, size and location of wound
• Apposition, lack of movement e.g. keep ends of frature immobile and apposed
• Blood supply: arterial and venous – hastens healing and repair
• Infection: gangrene, suppuration (formation of abcesses)
• Foreign material
• Radiation damage e.g. during chemotherapy

Question 28

Give 6 general factors which effect efficacy of healing and repair?

Answer 28

• Age
• Drugs, e.g. steroids – inhibit inflammatory response & hormones
• General dietary deficiences e.g. protein – reduced immune response
• Specific dietary deficiences e.g. vit C – scurvy
• General state of health
• General CVS status

Question 29

What two factors can defective repair establish itself as?

Answer 29

Insufficient fibrosis

Excessive fibrosis

Question 30

What can cause insufficient fibrosis?

Answer 30

o Wound dehiscence, hernia, ulceration

o Due to obesity, age, steroids, malnutrition etc

Question 31

What can cause excessive fibrosis?

Answer 31

o Cosmetic scarring

o Keloids

o Cirrhosis

o Lung fibrosis

o Contractures: fibrous healing which produces distortion or limitation of movement of the tissues and is most often seen in patients with full thickness burns

• Skin graft and splinting helps prevention

Question 32

Describe the healing process of cardiac muscle

Answer 32

• Cardiac myocytes are permanent cells

* Damaged repaired by fibrosis

Question 33

Describe the healing process of bone

Answer 33

• Damage is not replaced by scar tissue but by bone
• Haematoma > macrophages and osteoclasts (procallus) > proliferation of fibroblasts > cartilage forms callus > cartilage reabsorbed and replaced by osteoblasts

Question 34

Describe the healing process of the liver

Answer 34

• Only organ in the body capable of regeneration
• Hepatocytes can re-enter the cell cycle and undergo mitosis
• Evidence of stem cells, ovalocytes which can differentiate into hepatocytes

Question 35

Describe the healing process of nerve cells

Answer 35

• Severed nerve can be repaired by Wallerian Regeneration
  1. Schwann cells line up in the basement membrane tube
  2. Synthesise growth factors
  3. GFs attract axonal sprouts formed at the proximal terminal of the damaged axon
  4. Basement membrane tube provides passage for the nerves which will innervate the muscle and skin