Wound healing

Question 1

What is parenchyma?

Answer 1

Organ-specific cells related to the function (e.g. parenchyma of the kidneys = epithelial tissue)

Question 2

What is stroma?

Answer 2

‘Background’ tissue providing structure, mechanical and nutritional support to the organ

Question 3

Define healing

Answer 3

Process of returning to health

Restoration of structure and function of injured or diseased tissue

Question 4

Define tissue repair

Answer 4

The restoration of structure and function of damaged tissue (through regeneration or scar formation)

Question 5

What are the stages of wound healing?

Answer 5

1. Haemostasis process (first 24 hours): wound closed by coagulation process, adherence of platelets and fibrin to site, formation of thrombus

Question 6

Define regeneration

Answer 6

Healing in which new growth completely restores portions of damaged tissue to their normal state

Question 7

What are the stages of wound healing?

Answer 7

1. Haemostasis process (first 24 hours)
2. Inflammatory process (0-4 days)
3. Proliferative process (1-14 days)
4. Remodelling process (Day 21 - years)

Question 8

What does the haemostasis phase of wound healing involve?

Answer 8

Wound closed by coagulation process
Platelets and fibrin adhere to site
Thrombus formed

Question 9

What does the inflammatory phase of wound healing involve?

Answer 9

Platelets control bleeding; macrophages prevent infection; neutrophils involved in inflammation

Question 10

What does the proliferative phase of wound healing involve?

Answer 10

Angiogenesis (formation of new blood vessels)
Epithelialisation (formation of granulation tissue)
Contraction
Fibrous tissue formation

Question 11

What does the remodelling phase of wound healing involve?

Answer 11

Maturation phase

Collagen is remodelled and becomes realigned

Question 12

What aids regeneration?

Answer 12

Growth factors (e.g. PDGF, VEGF, TGF-Beta, ECM)

Question 13

What are labile tissues?

Answer 13

Tissue that is continuously proliferating in order to replace dead or sloughed-off cells

Question 14

What are some examples of labile tissues?

Answer 14

Skin, GI, Salivary gland

Question 15

What is stable tissue?

Answer 15

Cells that normally exist in a non-dividing state but may enter the cell cycle in response to certain stimuli (e.g. cell injury)

Question 16

What are some examples of stable tissue?

Answer 16

Parenchymal cells of the liver, kidneys and pancreas

Question 17

What is permanent tissue?

Answer 17

Non-dividing cells leading to scar formation

Question 18

What are some examples of permanent tissue?

Answer 18

Cardiac and skeletal tissue

Question 19

What are growth factors?

Answer 19

Proteins that stimulate survival and proliferation of particular cells
Can also promote migration and differentiation

Question 20

Where are growth factors produced?

Answer 20

By macrophages and lymphocytes at the site of injury as part of the inflammatory process
Can also be produced by parenchymal cells or stromal cells in response to cell injury

Question 21

What is the role of growth factors?

Answer 21

Stimulate entry of a cell into the cell cycle

Question 22

How do growth factors work?

Answer 22

Produced in response to an external stimulus and act by binding to cellular receptors

Question 23

What is the role of the extracellular matrix in regeneration?

Answer 23

Stores and presents growth factors

Acts as a scaffold to which migrating cells can adhere

Question 24

What is scar formation?

Answer 24

Replacement of damaged parenchymal cells with connective tissue leading to incomplete restoration of architecture and function

Question 25

When does scar formation occur?

Answer 25

In severe or chronic injuries that result in damage of parenchymal cells AND connective tissue Also occurs in permanent non-dividing tissues

Question 26

What is angiogenesis?

Answer 26

New blood vessel development (sprouting from existing vessel) via endothelial cell proliferation and migration

Question 27

When does angiogenesis occur?

Answer 27

Healing at injury sites | Development of collateral circulations at sites of ischaemia

Question 28

How does the formation of granulation tissue occur?

Answer 28

1. Migration and proliferation of fibroblasts into the site of injury 2. Deposition of ECM proteins produced by these cells [Derived by growth factors]

Question 29

What is granulation tissue?

Answer 29

New connective tissue with new blood vessels | [Have pink, granular appearance]

Question 30

How does skin wound healing occur?

Answer 30

[Involves epithelial regeneration and the formation of a connective tissue scar] Can occur by: 1. First intention (primary union) 2. Second intention (secondary union)

Question 31

What are examples of when first intention skin wound healing should occur?

Answer 31

Healing of a clean, uninfected surgical incision (approximated by sutures)

Question 32

What is the main mechanism of repair in first intention healing?

Answer 32

Epithelial regeneration | Causes small scar with minimal wound contraction

Question 33

How does first intention healing occur?

Answer 33

1. Incisional space fills with fibrin-clotted blood (a scab) 2. Within 24 hours, neutrophils seen at incision margin, migrating towards fibrin clot (acute inflammation) 3. Within 24-48 hours, epithelial cells from both edges begin to migrate and proliferate along dermis 4. By days 3-7, neutrophils largely replaced by macrophages and angiogenesis peaks - granulation tissue invades incisional space 5. By week 2, there is continued collagen accumulation and fibroblast proliferation (scar maturation) 6. Remodelling of scar continues for months to increase wound tensile strength

Question 34

What is an example of second intention healing?

Answer 34

Large wounds at sites of abscess formation, ulceration and infarction

Question 35

How do first intention and second intention healing differ?

Answer 35

Secondary healing has: Larger clot/ scab More intense inflammation Greater volume of granulation tissue (and therefore greater mass of scar tissue) Wound contraction (reducing original size of defect within approx. 6 weeks)

Question 36

How does fracture healing differ between cortical and trabecular bone?

Answer 36

Trabecular bone tends to have a better blood supply and therefore less necrosis than cortical bone

Question 37

What are the stages of fracture healing?

Answer 37

1. Haematoma (bleeding from ruptured vessels, inflammatory reaction) 2. Granulation tissue replaces haematoma (cell proliferation in response to GF/ cytokines) 3. Callus formation (irregular swelling that bridges gap between bone ends - made up of fibrocellular material and cartilage initially) 4. Woven bone (osteoprogenitor cells proliferate and move into area forming woven bone strengthening callus) 5. Lamellar bone (replaces woven bone gradually) 6. Remodelling (by osteoclasts and osteoblasts into appropriate form, excess callus resorbed and medullary cavity re-established)

Question 38

What is fibrosis?

Answer 38

Excessive deposition of collagen and other ECM components in tissue (Scar and fibrosis often used interchangeably, fibrosis usually refers to deposition of collagen in chronic diseases)

Question 39

What local factors affect tissue repair?

Answer 39

Infection (prolongs inflammation) Mechanical factors (e.g. increased local pressure or torsion can cause wounds to pull apart/ dehisce) Foreign bodies Size/ location of wound Type of wound (injury to tissue composed of permanent cells, rather than stable/ labile cells, results in scarring)

Question 40

What systemic factors affect tissue repair?

Answer 40

Nutritional status (e.g. protein deficiency, vitamin C deficiency - inhibit collagen synthesis) Metabolic status Circulatory status (poor perfusion impairs healing) Hormones Age Collagen disorders

Question 41

What are the possible complications of tissue repair?

Answer 41

Inadequate formation Excessive formation Formation of contracture

Question 42

What is the consequence of inadequate tissue formation?

Answer 42

Dehiscence/ rupture Evisceration Ulceration

Question 43

What is dehiscence?

Answer 43

Separation of layers of surgical wound

Question 44

What is evisceration?

Answer 44

Extrusion of viscera outside the body through a surgical incision

Question 45

What is ulceration?

Answer 45

Lesion through the skin or a mucous membrane resulting from loss of tissue, usually with inflammation

Question 46

What is the consequence of excessive tissue formation?

Answer 46

``` Keloid formation (formation of excess collagen giving rise to raise, prominent scarring - common in Africans) Generation of excess granulation tissue (protruding above level of surrounding skin and hindering re-epithelialisation) ```

Question 47

What are contractures?

Answer 47

Fibrosis of connective tissue in skin, fascia, muscles or a joint capsule that prevents normal mobility of the related tissue or joint (e.g. in severe burns)