Healing: Regeneration And Repair

Question 1

What processes are involved in wound healing?

Answer 1

1. Haemostasis -vessels are open
2. Inflammation - due to tissue injury
3. Regeneration (resolution, restitution) and/or repair (organisation)

Question 2

What is regeneration? (After wounds)

Answer 2

Restitution with no or minimal evidence that there was a previous injury
Eg
-healing by primary intention
-superficial abrasion

Question 3

What is the difference between an abrasion and an ulcer?

Answer 3

Abrasions: Epidermis and dermis effected- easily healed by regeneration

Ulcer: injury into submucosa below the level of mucosa

Question 4

Which cells replicate in regeneration?

Answer 4

Mainly derived from stem cells (many terminally differentiated cells cant divide)

Question 5

What type of replication do stem cells show?

Answer 5

Asymmetric replication

One stays as stem cell, other daughter cell differentiates into mature cell

Question 6

Whereabouts in the tissues are the stem cells:

1. Epidermis
2. intestinal mucosa
3. Liver

Answer 6

1. Basal layer (adj to basement membrane)
2. Bottom of crypts
3. Between hepatocytes and bile ducts

Question 7

What are the 3 types of stem cells?

Answer 7

1. Unipotent - most adult stem cells, only produce one type of cell
2. Multipotent - produce several types of differentiated cell eg haematopoietic stem cells
3. Totipotent - embryonic stem cells, can produce any type of cell and therefore any tissue of the body

Question 8

Not all tissues can regenerate, what are the two types that can and the one type that cant? Describe the types and give examples

Answer 8

Can:
1. Labile: short lived cells that are replaced from cells derived from stem cells. Eg surface epithelia, haemotopoietic tissues

2. Stable: normally low level or replication but are capable of rapid proliferation, both stem cells and mature cells proliferate. Eg bone, fibrous tissue, endothelium

Cant:
1. Permanent: mature cells cant undergo mitosis and no or only few stem cells present. Eg neural tissues, skeletal muscle, cardiac muscle

• in permanent tissue there isn’t enough or any stem cells to repair the wound so there is scaring instead of regeneration

Question 9

What stage of the cell cycle are the 3 types of tissue in?
Stable
Labile
Permanent

Answer 9

Stable- G0 - can enter cell cycle if needed

Labile- continually going round cell cycle

Permanent- not even in G0, they’re not part of the cycle

Question 10

In order for regeneration to occur in labile or stable tissue what must be intact?

Answer 10

A connective tissue scaffold

Question 11

What is fibrous repair?

Answer 11

Healing with formation of fibrous connective tissue = scar

• specialise tissue is lost
• healing by secondary intention

Question 12

When does fibrous repair occur?

Answer 12

When there is Significant tissue loss

And/or if permanent or complex tissue is injured

Question 13

What is the time line for scar formation?

Answer 13

Sec-min: haemostasis 
Min-hr: acute inflammation 
1-2 days: chronic inflammation 
3 days: granulation tissue forms 
7-10 days: early scar (when stitched are taken out)
Weeks-2 years: scar maturation

Question 14

What is granulation tissue and when does it occur in the formation of a scar?

Answer 14

Collection of developing capillaries, fibroblasts myofibroblasts and chronic inflammatory cells. Has a granular appearance and texture

3 days

Question 15

What is the function of granulation tissue in the process of fibrous repair? (3)

Answer 15

Fills the gap
Capillaries supply oxygen, nutrients and cells
Contracts and closes the hole

Question 16

Describe the process of fibrous repair (6)

Answer 16

1. blood clots
2. Neutrophils infiltrate and digest clot
3. Macrophages and lymphocytes are recruited
4. Vessels sprout, myofibroblasts and fibroblasts make glycoproteins
5. Vascular network, collagen synthesised, macrophages reduced
6. Maturity, cells much reduced, collagen mature, contracts and remodels

Question 17

What cells are involved in fibrous repair?

Answer 17

Inflammatory cells
Endothelial cells
Fibroblasts and myofibroblasts

Question 18

What is the role of inflammatory cells in fibrous repair?

Answer 18

• phagocytosis of debris- neutrophils and macrophages

- production of chemical mediators-lymphocytes and macrophages

Question 19

What is the role of endothelial cells in fibrous repair?

Answer 19

Proliferation leading to angiogenesis

Question 20

What is the role of fibroblasts and myofibroblasts in fibrous repair?

Answer 20

• produce extracellular matrix proteins eg collagen

- responsible for wound contraction (contraction of fibrils within myofibroblasts)

Question 21

Why are old scars white?

Answer 21

Because there is no regeneration of melanocytes

Question 22

Why do scars stretch as they age?

Answer 22

Because fibroblasts cant lay down elastin

Question 23

What is intracrine signalling?

Answer 23

When a cell produces signalling molecules that work within the cell on receptors.

Similar to autocrine accepted the signalling molecule never leaves the cell

Question 24

How are skin grafts taken so not to destroy the donor site?

Answer 24

You can spilt the skin at a very superficial level leaving the sweat glands and hair follicles intact, meaning the cells will grow up and healing of the donor site will be good.

Question 25

How does bone heal?

Answer 25

1. Haematoma: fills gaps and surrounds injury
2. Granulation tissue forms: cytokines activate osteoprogenitor cells
3. Soft callus: 1 week, fibrous tissue and cartilage within which woven bone forms (poorly organised)
4. Hard callus: several weeks, woven bone
5. Lamellar bone: relaxes woven bone, remodelling to direction of mechanical stress. Bone not stressed is reabsorbed and outline is re-established

Question 26

What local things can influence wound healing?

Answer 26

Local factors

1. Type, size, location of wound
2. Mechanical stress
3. Blood supply
4. Local infection
5. Foreign bodies (surgeons use very smooth thread so that foreign bodies cannot grow on it)

Question 27

What general factors can influence wound healing?

Answer 27

1. Age
2. Anaemia, hypoxia and hypovolaemia
3. Obesity
4. Diabetes
5. Genetic disorders
6. Drugs
7. Vitamin deficiency
8. Malnutrition

(7/8 do you have the proteins and minerals needed)

Question 28

What are the complications of fibrous repair?

Answer 28

• insufficient fibrosis
• formation of adhesions
• loss of function
• disruption of complex tissue relationships within an organ
• overproduction of fibrous scar tissue
• excessive scar contraction

Question 29

How is insufficient fibrosis an issue of fibrous repair?

Answer 29

Can lead to: Wound dehiscence/ hernia/ ulceration

Can happen in someone with obesity/elderly/malnutrition/steroids

There is not enough scaring and the wound opens

Question 30

How is formation of adhesions a complication of fibrous repair?

Answer 30

An adhesion is an area of fibrotic tissue that is formed between structures and organs, it can block tubes, wrap around tubes and compromise organs

Eg intestinal obstruction following abdominal surgery

Question 31

How is loss of function a complication of fibrous repair?

Answer 31

Lots of fibrosis can replace the tissues of an organ and that impacts on the function of the organ

Eg healed myocardial infarction with non-contracting area of myocardium

Question 32

How is ‘disruption of complex tissue relationships within an organ’ a complication of fibrous repair?

Answer 32

If there is distortion of architecture interfering with normal function of organs

Eg liver cirrhosis

Question 33

How is overproduction of fibrous scar tissue a complication of fibrous repair?

Answer 33

You can get keloid scars (big purple/pink scars bulging) as a result of collagen in Dermis

Question 34

How is excessive scar contraction a complication of wound repair?

Answer 34

Can cause obstruction of tubes, disfiguring scars can occur following burns or joint contracture-the skin doesn’t grow with the limb (fixed flexures)

Question 35

When might you get oesophageal strictures?

Answer 35

When acid reflux causes injury there is contraction during repair=stricture