Chronic Inflammation 2

Question 1

What is the basic overview of wound healing?

Answer 1

Trauma
Cell/matrix damage
Inflammation
Repair: healing, fibrosis

Question 2

What is the definition of regeneration?

Answer 2

Replacement of lost or damaged tissue by that of similar type derived from the proliferation of the surrounding undamaged cells.

Question 3

What is the definition of repair?

Answer 3

The replacement of lost or frames tissue by granulation tissue which later matures into fibrous scar tissue.

Question 4

What are the two things that repair can lead to?

Answer 4

• Healing

- Fibrous tissue formation

Question 5

Is wound healing similar or not in many tissues?

What do we use as a reference when describing healing?

Answer 5

Yes

Small skin wound

Question 6

Give the basic structure of the skin

Answer 6

Epithelial layer ontop and connective tissue below.

Skin has a heterogeneous morphology.
Stratifies squamous epithelium at top and connective tissue with blood supply, nerve supply and lymphatics underneath.
The underneath will provide nutrients to the epithelial cells

Get same in mouth but with the salivary glands instead.

Have to consider healing process taking place in epithelium and connective tissue.

Question 7

What is healing by primary and secondary intention?

Answer 7

Healing by primary intention - the wound edges are in close apposition

Healing by secondary intention - the wound is more extreme and the wound edges are widely separated

Question 8

Give some features of primary and secondary intention?

Answer 8

Primary:

• Wound edges in close apposition
• Re-epithelialisation dominates healing

Secondary:

• Wound more extensive
• Granulation tissue covers wound
• Wound area reduced by contraction
• Re-epithelialisation from wound edges and residual appendages

(If in close apposition - key process is re-epithelialisation. Get a new epithelial surface and reestablished continuity in the connective tissue.
Stitches try to use primary intention by reducing wound size.

Secondary intention - contraction is where the epithelium on wither side of the wound contracts down to decrease the wound size. Get the re-epithelialisation occurring in both the would edges but also in any residual appendages.)

Question 9

What is the first thing that happens an hour after a wound has occurred?

Answer 9

Connective and epithelium undergo haemostatis.

Get a platelet plug and a fibrin clot forming.

Factors that can affect the platelet plus and fibrin clot include aspirin and warfarin. These thin the blood.

Question 10

What happens 48 hours after a wound?

Answer 10

In connective tissue and epithelium:

Get inflammation, macrophage infiltration and debridement.

Question 11

What happens 2-5 days after a wound?

Answer 11

Connective tissue:

Granulation tissue formation.

• Endothelial cell and fibroblast proliferation
• New blood vessels migrate from the wound edges
• Small blood vessels are accompanied by fibroblasts and inflammatory cells
• Collagen extra-cellular matrix

(Endothelial cells and fibroblasts - give rise to new blood vessels to migrate out from wound edges into the centre of wound.

Small blood vessels become accompanied by fibroblasts and inflammatory cells which lay down collagen extra-cellular matrix.

Granulation tissue is a repair tissue)

Question 12

Give the definition of granulation tissue

Answer 12

A loose cellular connective tissue with many plump, synthetic fibroblasts; dilated, irregular blood vessels and inflammatory cells.

Question 13

What happens after 5 days to a wound?

Answer 13

Connective tissue:

Maturation:

• decreased cellularity
• decreased vascularity
• remodelling of collagen matrix involving matrix metalloprotineases
• collagen cross linking

Question 14

What happens to the epithelium along side the connective tissue process from 1-3 days after a wound?

Answer 14

Re-epithelialisation

• proliferation of basal epithelial cells adjacent to the wound
• migration of bass epithelial cells across wound bed under fibrin scan to restore epithelial continuity
• epithelial cells differentiate and stratified squamous structures re-form

Question 15

What can we see in the histology of a small skin wound while it heals?

Answer 15

Can see granulation tissue.
There are cells and irregular spaces. These spaces have blood vessels in them and cells in between are the fibroblast cells.

Can see the epithelium proliferating under the scab, over the connective tissue, to meet with the epithelium on other side.

Question 16

What factors are important In wound healing?

Answer 16

Cell-cell interactions
Cell-matrix interactions
Autocrine/paracrine interactions

(wound healing involves many complex interactions)

Question 17

What is the role of the macrophage?

Answer 17

Phacocytosis
Protease synthesis
Regulation of immune cell function

Producing growth factors to initiate other reactions:
FGF alpha and beta
TGF beta 
PDGF
VEGF

Endothelial cell recruitment and activity

Fibroblast recruitment and activity

• cell proliferation
• ECM synthesis
• protease (MMP) synthesis

Question 18

What are the systemic factors involved in wound healing?

Answer 18

Age

Nutritional status e.g. proton deficiency, vitamin C deficiency

Iatrogenic e.g. glucocorticoids (steroids)

Pre-existing medical conditions e.g. diabetes

Question 19

What are the local factors in wound healing?

Answer 19

Blood supply
Infection 
Persistent irritation
Poor wound stability 
Poor apposition of wound edges
Skin wounds : direction of incision - langer lines (incision in the line of tension which increases chance of healing)
Ionising radiation

Question 20

What are some complications involved in wound healing?

Answer 20

Wound dehiscence (breakdown of wound)

Contractures (patten of wound contraction causes scar tissue formation)

Keloid / hypertrophic scar formation due to wound tissue being around for a while becomes pigmented

Weak scars (incisional hernia)

Neoplastic changes (marjolins ulcer) not in oral cavity

Keloid: a sharply elevated, progressively enlarging scar characterised by the formation of excessive amounts of collagen in the dermis during connective tissue repair. May be spread along margins of original wound.

Hypertrophic scarring: Similar to keloid but does not spread beyond wound margins.

Question 21

How ie embryonic wound healing and oral mucosal wound healing relevant to us as dentists?

Answer 21

Embryonic wound healing - heal without scarring. Immaturity of immune system compounded by a different enlivenment of cytosine growth factors and inflammatory mediators to that in adults.
If surgery could be carrels out on foetus, it could be carrie out without scarring e.g. repairing cleft lip and palate.

Oral mucosal wound healing - we find wound healing here.
Scarring is less of an issue than the skin. Reasons for this are unclear. Evidence to suggest the inflammatory repose and connective tissue remodelling may be different in oral mucosa.