Lecture 13: Healing-Repair and Regeneration 2

Question 1

What determines whether a tissue will regenerate or repair

Answer 1

• Cellular factors
• Chemical mediators: Growth factors
• Stromal factors: ECM
• Additional factors

Question 2

What are the features of tissue regeneration and repair?

Answer 2

1. Healing by primary intention
2. Healing by secondary intention
3. Complications in skin wound healing
4. Healing in liver, bone and nervous tissue

Question 3

1. Healing of Primary Intention.

There are 4 stages, what are they?

Answer 3

=regeneration and repair-typical of surgical incisions in skin: i.e epidermis regenerates, dermis and hypodermis repairs

4 stages:
1. Inflammation
2.Granulation tissue formation 3. Wound contraction 4.Remodelling
slide 6

Question 4

Healing by secondary Intention

Occurs in wounds with separate edges- the same stages occur as in hewing by primary

Answer 4

Occurs in wounds with separated edges.
The same stages occur as in healing by primary intention, however:
The inflammatory reaction is more intense
There are much greater amounts of granulation tissue formation
Wound contraction is much greater
There is substantial scar formation and thinning of the epidermis

Question 5

Healing by Primary Intention

Answer 5

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Surgical incision = minimal cell death and tissue and injury.
Nonetheless, cell injury and death and vascular damage do occur :1. the activation of hemostasis,
2. the formation of a fibrin clot, and the
3. activation of an inflammatory response.
Within 24 hours:
- neutrophils appear at incision margins
- surface epithelium at the margins begin to proliferate.
-Within 36 hours most of the neutrophils are replaced by macrophages

Question 6

Granulation Tissue Formation

Answer 6

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Day 3, granulation tissue begins to invade the incision space. FGF2 and VEGF from macrophages, keratinocytes and endothelial cells promote angiogenesis. Endothelial cells express new integrins so they can sprout from pre-existing capillaries.
1. BM broken down & capillary sprouts form

2. Endothelial cells migrate towards the angiogenic stimulus
3. Endothelial cells proliferate behind the tip of the sprout
4. The newly formed sprouts become canalized
5. Perivascular connective tissues surround & support the new vessels

Day 5
the incisional space is filled with granulation tissue
Collagen fibres become more abundant and begin to bridge the incision (Type III)
Neovascularisation is maximal
The basal layer of the epidermis will have bridged the defect and differentiation will have started
At 7 days wound strength is 10% of unwounded skin

Question 7

Wound Contraction

Answer 7

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Wound contraction is achieved by the formation of myofibroblasts within the granulation tissue (TGF-b, increasing tissue tension)
By the end of the first month, a scar replaces the incision.
The scar is composed of cellular connective tissue, covered by an intact epidermis
Tensile strength progressively increases

Question 8

Remodelling

Answer 8

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During the first 2 months of healing, collagen synthesis exceeds collagen degradation, resulting in tensile strength of the healed skin approaching 70-80% of non-wounded skin (Type III replaced by Type I).

Tensile strength will never achieve that of unwounded skin, however a gradual increase in tensile strength is achieved by cross linking of collagen fibres & increased fibre size after collagen synthesis ceases.

Question 9

What are the complications in skin wound healing?

Answer 9

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3 General categories:
Deficient scar tissue formation:
1)Wound dehiscence: mechanical stresses
2)Ulceration: deficient blood supply
Excessive formation of the repair components:
1)Proud flesh: Excessive granulation tissue
2) Hypertrophic scar/ Keloid: XS collagen/ XS scar tissue
3) Desmoids: exuberant fibroblast proliferation
Formation of contractures

And Deformities of the wound +/- surrounding tissue

Question 10

Bone:
Healing of bone
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Answer 10

Healing of bone:

• same basic process as skin,
• growth factors released in the developing granulation tissue
• + osteoprogenitor cells in the bone and soft tissue surrounding the fracture + future bone remodelling and matrix production

Week 1: Soft tissue callus= granulation tissue
Week 3:Granulation tissue, osteoid & cartilage
Week 6: Mineralisation of osteoid, bony callus
Unstable # –>fibrous union/ non-union
Poor oxygenation –> cartilage>bone at # site

Question 11

Liver
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Stable populations (Go), capable of regeneration provide supporting stroma is not disrupted.
If stroma is extensively and repeatedly disrupted, fibrosis can:?

Answer 11

a) Compress hepatocytes
b) isolate hepatocytes from blood supply
c) isolate hepatocytes from biliary tract

A vicious cycle of fibrosis, hepatic regeneration and degeneration can develop –> liver failure (cirrhosis)

Question 12

Nervous tissue

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Answer 12

-Central nervous tissue
-limited capacity to regenerate, can’t form fibrous tissue.
-neuroglia (=connective tissue of the CNS) is a stable cell population,
-non-lethal injury to the CNS inflammatory cells, macrophages and astrocytes clean up the area, with minimal peripheral fibrosis and a central fluid-filled cavity.
-Peripheral nerves
can regenerate but if axonal ends are not apposing, any proliferation is usually nonfunctional.

Question 13

Brain
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Nectrotic tissue is removed by ____ and the cavity is lined by ____

Answer 13

Necrotic tissue is removed by Gitter cells and the cavity is lined by astrocytes.