4. Healing and Repair

Question 1

What is regeneration?

Answer 1

The replacement of dead or damaged cells by functional, differentiated cells derived from stem cells.

Question 2

What is the key difference between regeneration and repair?

Answer 2

In regeneration, the normal structure is restored, in repair, the normal structure is permanently altered.

Question 3

What is repair?

Answer 3

Response to injury involving both regeneration and scar formation.

Question 4

Define unipotent.

Answer 4

Can only produce one type of differentiated cell, like epithelia.

Question 5

Define multipotent.

Answer 5

Can produce several types of differentiated cell, like haematopoietic.

Question 6

Define totipotent.

Answer 6

Can produce any type of cell, like embryonic stem cells.

Question 7

Where are the two checkpoints in the cell cycle and what do they check for?

Answer 7

Between G1 and S - checks that there’s no DNA damage.

Between G2 and M - checks no DNA rampage after synthesis.

Question 8

What are labile cells?

Answer 8

Normal state is active cell division. Usually has rapid proliferation.

Question 9

What are stable cells?

Answer 9

Resting state is G0 but it can enter the cell cycle so its speed of regeneration is variable.

Question 10

What are permanent cells?

Answer 10

Unable to divide as permanently in G0. They therefore can’t regenerate.

Question 11

Are the following cells labile, stable or permanent?

a. epithelia
b. cardiac myocytes
c. hepatocytes
d. osteoblasts
e. neurones
f. fibroblasts
g. haematopoietic cells

Answer 11

a. labile
b. permanent
c. stable
d. stable
e. permanent
f. stable
g. labile.

Question 12

What are the key features controlling regeneration?

Answer 12

Growth factors, and contact between basement membrane and adjacent cells

Question 13

How do growth factors control regeneration?

Answer 13

They promote proliferation in the stem cell population and expression of genes controlling cell cycle.

Question 14

How does contact between basement membrane and adjacent cells control regeneration?

Answer 14

Signalling through adhesion molecules. It inhibits proliferation in intact tissue - contact inhibition. Loss of contact promotes proliferation, this happens in a deranged way in cancer.

Question 15

What is fibrous repair?

Answer 15

The replacement of functional tissue by scar tissue.

Question 16

What are the key components of fibrous repair?

Answer 16

Cell migration, blood vessels (angiogenesis), and extracellular matrix production and remodelling.

Question 17

What are the cell types and their roles in fibrous repair?

Answer 17

Inflammatory cells: neutrophils and macrophages - phagocytosis of debris, lymphocytes and macrophages - chemical mediators.
Endothelial cells: angiogenesis.
Fibroblasts/myofibroblasts: collagen - extracellular matrix proteins, wound contraction.

Question 18

Why is angiogenesis needed in fibrous repair?

Answer 18

For wound healing, provides access to the wound for inflammatory cells and fibroblasts, also delivers oxygen and other nutrients.

Question 19

What initiates angiogenesis?

Answer 19

Proangiogenic growth factors like VEGF (vascular endothelial growth factor).

Question 20

What is the process of angiogenesis?

Answer 20

Endothelial proteolysis of basement membrane.
Migration of endothelial cell via chemotaxis.
Endothelial proliferation.
Endothelial maturation and tubular remodelling.
Recruitment of periendothelial cells.

Question 21

What is the function of extracellular matrix in fibrous repair?

Answer 21

Supports and anchors cells, separates tissue compartments, sequesters growth factors, allows communication between cells, and facilitates cel migration.

Question 22

What are the fibrillar collagen types?

Answer 22

I-III. Uninterrupted triple helices.

Question 23

What are the amorphous collagen types?

Answer 23

IV-VI. Triple helical domains are interrupted and have breaks, so they form sheets instead of fibrils.

Question 24

How are fibrillar collagens synthesised?

Answer 24

Polypeptide alpha chains synthesised in ER.
Enzymatic modification steps, vitamin C dependent hydroxylation.
Alpha chains align and cross link to form procollagen triple helix.
Soluble procollagen is secreted.
Procollagen cleaved to tropocollagen.
Tropocollagen polymerises to form fibrils.
Bundles of fibrils form fibres.
Slow remodelling by specific collagenases.

Question 25

What are four defects of collagen synthesis?

Answer 25

Vitamin C deficiency in scurvy. Means vitamin C dependent hydroxylation is defective so helix formaiton is defective. So collagen lacks strength, particularly in supporting blood vessels.
Ehlers-Danlos syndromes - defective conversion of procollagen to tropocollagen so very strecthy skin and hypermobility in joints.
Osteogenesis imperfecta - aka brittle bone disease.
Alport syndrome.

Question 26

What are some key components of the extracellular matrix?

Answer 26

Matrix glycoproteins - organise and orientates cells and support cell migration.
Proteoglycans - matrix organisation, cell support, regulate availability of growth factors.
Elastin - provides tissue elasticity.

Question 27

What is the process of fibrous repair?

Answer 27

Inflammatory cells infiltrate: blood clot forms, acute inflammation around the edges and chronic inflammation causes macrophages and lymphocytes to migrate into clot.
Clot replaced by granulation tissue: angiogenesis, myo/fibroblasts migrate and differentiate, they produce extracellular matrix.
Maturation: fairly long lasting, cell population falls. Collagen increases, matures and remodels, myofibroblasts contract to reduce the volume of the defect. Vessels differentiate and reduce and there is a fibrous scar left.

Question 28

How is fibrous repair controlled?

Answer 28

Inflammatory cells by chemotaxis.
Angiogenesis by platelets, ECM and angiogenic cytokines.
Fibrosis by macrophages producing cytokines and fibroblast proliferation and ECM production.

Question 29

How does a skin wound heal by primary intention?

Answer 29

Incised wound has apposed edges. There is minimal clot and granulation tissue. The epidermis regenerates and the dermis has fibrous repair. After 10 days of sutures, the wound has 10% of the normal strength. Scar matures for 2 years, there is minimal contraction so small scar and good strength.

Question 30

What is healing by primary intention at risk of?

Answer 30

Abscess.

Question 31

How does a skin wound heal by secondary intention?

Answer 31

Infarct, ulcer, abscess, or any large wound with unapposed wound edges. Large clot forms a scar, or eschar. The epidermis regenerates from base up. There is more granulation tissue so extensive scarring.

Question 32

How does healing by secondary intention differ from by primary intention?

Answer 32

More contraction in secondary to reduce volume of defect. but still a larger scar. Takes longer by secondary intention.

Question 33

How do bone fractures heal?

Answer 33

Haematoma forms from ruptured vessels within marrow cavity and periosteum. Necrotic tissue is removed and capillaries develop. There is a soft callous - specialised mixture of cells. Bone is laid down in an irregular woven pattern, with some islands of cartilage. Woven callous gradually replaced by more organised lamellar bone. Bone remodelled in direction of mechanical stress.

Question 34

What local factors affect wound healing?

Answer 34

Type size and location of wound. Apposition and lack of movement. Blood supply. Infection. Foreign material. Radiation damage.

Question 35

What general factors affect wound healing?

Answer 35

Age, drugs, general dietary deficiency, general state of health, general cardiovascular status.

Question 36

What can insufficient fibrosis lead to?

Answer 36

Wound dehiscence, hernia or ulceration. Common in obesity, elderly, malnourished etc.

Question 37

What can excessive fibrosis lead to?

Answer 37

Cosmetic scarring like keloids. Or cirrhosis and lung fibrosis.

Question 38

What is the difference between a hypertrophic and keloid scar?

Answer 38

Hypertrophic scars are just raised from the surface but still within the wound space. Keloid scars are hypertrophic but also they extend outside the realms of the original wound.

Question 39

What can excessive contraction in fibrous repair lead to?

Answer 39

Obstruction of tubes and channels. Limitation of joint movement.