1.04 - Would Healing & Repair

Question 1

What are the two phases of tissue repair?

Answer 1

Regeneration

Replacement of tissue by connective tissue

Question 2

What similar mechanisms do regeneration and replacement share?

Answer 2

Cell migration
Cell proliferation
Cell differentiation
Cell-matrix interactions (scaffolding)

Question 3

What is the ECM?

Answer 3

Extracellular matrix molecules made up of, fibrous proteins (collagen, elastin), adhesive glycoproteins (fibronectins and laminins) and gel of preteoglycans and hyaluronan

Question 4

What is the function of the ECM?

Answer 4

Provide form and structure
Retain water giving tissue turgor in soft tissues
Retain minerals in “hard” tissues
Repository for growth factors

Question 5

How do cells interact and attach with the ECM

Answer 5

Integrins

Question 6

Describe Tissue Repair by Fibrosis

Answer 6

Tissue destruction affecting parenchymal cells and ECM

• Angiogenesis
• Migration & proliferation of fibroblasts
• Deposition of new ECM
• Maturation and organisation of fibrous tissue (remodelling)

Question 7

Describe Angiogenesis

Answer 7

The formation of new blood vessels
‘Buds’ develop from existing vasculature
Control is via factors such as VEGF (VEGF expression stimulated by cytokine and hypoxia)

Question 8

Describe the steps in normal wound healing

Answer 8

Induction of an inflammatory response
Regenerations of parenchymal and connective tissue
Synthesis of ECM
Remodelling
Same process for skin and all tissues and organs

Question 9

Under what circumstances does healing by primary intent occur?

Answer 9

A clean incised wound with opposed edges (surgical incision).
Relatively little tissue damage (a limited number of cells are killed and there is relatively little disruption of the surround supportive tissue)

Question 10

List the events that happen in days 1-3 of healing by primary intent

Answer 10

Would fills with thrombus
Dehydration of the clot forms a scab –> seals the wound
Neutrophils migrate (24 hours)
Basal cells of epidermis divide and grow –> deposit basement membrane
Fibroblasts are activated –> produce collagen and ECM
Angiogenesis
This new tissue is called granulation tissue

Question 11

List the events that happen in days 3-5 of healing by primary intent

Answer 11

Neutrophils replaced by macrophages

Epidermal regeneration and production of granulation tissue continue –> forms an immature scar

Question 12

List the events that happen from week 2 onwards in healing by primary intent

Answer 12

Continued fibroblast proliferation –> production of collagen
Inflammation, oedema & vascular proliferation subside –> scar becomes paler
Scar is remodelled with contraction of the tissues and increasing tensile strength

Question 13

Under what circumstances does healing by secondary intent occur

Answer 13

Extensive tissue damage
Edges of the wound are not approximated
Large tissue defect which must be filled
E.g. Infarction, ulceration, infection or large surface wound

Question 14

Compare Secondary to Primary Intent

Answer 14

More fibrin and necrotic debris
Inflammatory response proportionately more intense
More granulation tissue
Wound contraction much greater due to the action of myofibroblasts

Question 15

What factors influence wound healing?

Answer 15

Nutrition
Glucocorticoids
Infection or foreign bodies
Mechanical factors (increased abdominal pressure may open surface wounds)
Individual factors (defects in collagen synthesis, diabetes mellitus)
Drugs
Radiotherapy

Question 16

Q. Does an ulcer heal by primary or secondary intent?

Answer 16

Seconday. The edges cannot be opposed and covering skin must grow in across the bed of granulation tissue

Question 17

Q. If a segment of liver is donated to a child as a transplant, would the architecture of liver ultimately be normal?

Answer 17

Yes. The histological picture will have well defined portal triads etc with main bile duct etc. However, at a macroscopic level, there will not be the usual lobar construction and the gall bladder will be absent.

Question 18

Q. Is cirrhosis of the liver a picture of normal regeneration? (To answer, first what does “cirrhosis” mean and then consider what is happening).

Answer 18

No. There are significant amounts of fibrous (connective) tissue separating lobules of regenerated hepatocytes and biliary tubules. (By definition cirrhosis is liver disease characterised by loss of normal microscopic lobular architecture). Consider chronic inflammation.

Question 19

Q. In TB of the lung following treatment, is the lung parenchyma normal or abnormal? (consider when treated)

Answer 19

No, there has been destruction of tissue and where infection has been present, there will be significant scarring and fibrosis.

Question 20

Q. In TB of lung, as seen on X-ray, what tissue does a Ghon focus represent?

Answer 20

Site of the chronic inflammatory process (caseous necrosis) with subsequent scarring and calcification.

Question 21

Q. Following major surgery, might stiches be left in situ longer in a diabetic patient than another patient of the same age?

Answer 21

Yes. Poor tissue healing is common in diabetes mellitus. A combination of altered blood supply (↓ perfusion) and high blood glucose altering (immune) cell function.