Week 5 - Fibrous Healing and Repair

Question 1

What are the 2 tissue processes initiated following injury?

Answer 1

Regeneration
Repair

Both these processes are responsible for the re-establishment of the structure + function of the injured tissue.

Question 2

What are the 3 types of cells that have the ability to regenerate tissues?

Answer 2

Labile cells
Stable cells
Permanent cells

Question 3

What do labile cells do and example?

Answer 3

These cells undergo continuous proliferation, have a short lifespan and a rapid turnover.

eg. epithelial cells in the skin and digestive system.

Question 4

What do stable cells do and example?

Answer 4

These usually divide infrequently, but can divide rapidly when stimulated by lost cells, for example after a fracture.

e.g. bone cells, liver cells

Question 5

What do permanent cells do and example?

Answer 5

Divide only in the foetus and cannot be replaced when lost.

e.g. neurones, cardiac muscle cells

Question 6

Key feature of permanent cells?

Answer 6

Some, e.g. RBC’s, cannot proliferate but can be replaced
(as bone marrow can create more)

Question 7

What is regeneration?

Answer 7

New growth completely restores portions of damaged tissue back to their normal state.

→ Occurs through proliferation of the cells in injured tissue.
→Minor types of damage where the cells damaged are labile cells.
→No scar tissue formed when regeneration is primary mode of healing.
→ No permanent damage remaining.

Question 8

What are the two types of repair?

Answer 8

Primary intention
Secondary intention

Question 9

What does healing by primary intention involve?

Answer 9

→ Occurs in wounds with dermal edges close together.

→ Usually faster then by secondary intention
→ End result is (in most cases) a complete return to function, with minimal scarring and loss of skin appendages.

e.g. surgical wound - c section

Question 10

What does healing by secondary intention involve?

Answer 10

→ Occurs when sides of wound are not opposed, so healing must occur from the bottom of the wound and upwards.
→ Extensive tissue loss or damage
→ Involves formation of fibrovascular connective tissue (fibrous scar tissue)

e.g. dog bite

Question 11

Similarity between primary and secondary intention?

Answer 11

In both primary and secondary intention, the same 4 stages of repair occur.

Question 12

What are the 4 stages of repair?

Answer 12

Haemostasis
Inflammation
Proliferation
Remodelling

Question 13

Haemostasis key points? (1)

Answer 13

→ Reduces blood loss if vessel wall is damaged
→ Collagen is exposed at site
→ 3 stages

Question 14

What are the 3 stages of haemostasis?

Answer 14

1. Vascular spasm → Constriction of blood vessel reduces blood loss
2. Platelet plug → Platelets stick to exposed collagen, chemical released to encourage more platelets to the area, temp. seal.
3. Blood clotting → Cascade of enzymes (clotting factors)

Question 15

Inflammation key points? (2)

Answer 15

1-6 days
Once bleeding stopped, blood vessels within wound dilate allowing fluid carrying cells necessary for healing to enter wound.

→ Leucocytes (WBC’s) enter wound (inc. neutrophils, lymphocytes and 𝗺𝗮𝗰𝗿𝗼𝗽𝗵𝗮𝗴𝗲𝘀)
→ Involves growth factors
→ Damaged and dead tissue removed - prepares way to rebuild.

Question 16

Signs of inflammation?

Answer 16

Pain
Redness
Swelling
Heat

(The result of prostaglandins and histamine at wound site.)

Question 17

How do macrophages impact inflammatory process?

Answer 17

→ Macrophages have lifespan of several months and 2 years
→ Number present at wounds starts to decrease at end of inflammatory process due to apoptosis.
→ No macrophages = tissue debridement incomplete and reduced influx of fibroblasts (key to healing)

Question 18

What is apoptosis?l

Answer 18

Programmed cell death

Question 19

What is tissue debridement?

Answer 19

Breakdown of dead and damaged tissue

Question 20

What are fibroblasts responsible for?

Answer 20

Most collagen and elastin synthesis

Question 21

What are the 5 roles of macrophages during the inflammatory process?

Answer 21

1→ Phagocytose damaged tissue + bacteria
2→ Produce chemotaxins for continuing white cell recruitment
3→ Release proteases that break down necrotic tissues
4→ Make cytokines to regulate new tissue formation
5→ Involved w/release of matric metalloproteinases that assist with the clearance of the damaged extracellular matrix.

Question 22

What are proteases?

Answer 22

Enzymes that break down protein

Question 23

What are growth factors in inflammation?

Answer 23

Proteins that activate the cells involved with the inflammatory process.

Question 24

What occurs during proliferation? (3)

Answer 24

Usually lasts 3-24 days
Rebuilding job

→ New tissue regenerated + constructed by fibroblasts, the cells responsible for dev. on new blood vessels, collagen and other connective tissue.
→ Tiny new capillaries join together in a scaffold within the wound; this develops into granulation tissue - fills wound cavity.

Question 25

Key note about granulation tissue?

Answer 25

pale pink but becomes bright red as more blood vessels develop

Question 26

What occurs during the remodelling phase? (4)

Answer 26

Last bet. 21 days and 2 years

→ Epithelial cells, located in intact hair follicles, sweat glands and around wound edges, move over newly formed granulation tissue and reduce size of the wound.
→ They do this by contracting, thereby pulling the edges together.
→ Macrophages re-organise the collagen within the newly healed wound to form a scar.

Question 27

What occurs to the scar tissue post remodelling?

Answer 27

The scar tissue will fade from red to white over time.

However, it will only regain around 80% of non-injured skin (unlike regeneration)

Question 28

What are the 3 phases of muscle repair?

Answer 28

1→ Destruction and inflammatory phase
2→ Repair phase
3→ Remodelling phase

Question 29

What occurs in the destruction and inflammatory phase? (1)

Answer 29

1-3 days

→ Myofibers rupture and necrotize (programmed death)
→ Haematoma is formed (bruise)
→ Inflammatory cells can freely invade site as blood vessels are torn (most abundant are polymorphonuclear leukocytes).
→ Replaced by monocytes a few hours after injury which transform into macrophages.

Question 30

What functions do macrophages have in the inflammatory phase?

Answer 30

→ Remove nectrotic myofibers by phagocytosis.
→ Produce (together with fibroblasts) chemotactic signals such as growth factors, eytokines and chemokines.

Some of these growth factors can active myogenic precursors called satellite cells.

Question 31

What are chemotactic signals?

Answer 31

Chemicals that attract

Question 32

Satellite cell key features?

Answer 32

• lying dormant when not needed
• found on muscle fibres
• when damage present, chemical. signals trigger satellite cells to wake up/go into action
• replicate + form one new dormant cell and proliferating cell
• the proliferating satellite cells can either form a new fibre or patch the original

Question 33

What occurs during the repair phase? (2)

Answer 33

𝟭. 𝗥𝗲𝗴𝗲𝗻𝗲𝗿𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗱𝗶𝘀𝗿𝘂𝗽𝘁𝗲𝗱 𝗺𝘆𝗼𝗳𝗶𝗯𝗲𝗿𝘀

𝟮. 𝗙𝗼𝗿𝗺𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗰𝗼𝗻𝗻𝗲𝗰𝘁𝗶𝘃𝗲 𝘁𝗶𝘀𝘀𝘂𝗲 𝘀𝗰𝗮𝗿 𝗯𝘆 𝗳𝗶𝗯𝗿𝗶𝗻 𝗮𝗻𝗱 𝗳𝗶𝗯𝗿𝗼𝗻𝗲𝗰𝘁𝗶𝗻

Question 34

What occurs during regeneration of disrupted myofibers?

Answer 34

→ satellite cells will proliferate and eventually differentiate into myoblasts
→ new myoblasts fuse with injured myofibers, the gap formed between the two ends of the injured myofibre refilled.

Question 35

What occurs during formation of connective tissue scar by fibrin + fibronectin?

Answer 35

Scar tissue gives muscle strength to withstand contractions, and gives the fibroblasts an anchoring site to invade granulation tissue.

Question 36

What may happen to fibroblasts in the repair phase of muscle repair?

Answer 36

Fibroblasts may excessively divide + proliferate.

Scar tissue may become too dense - interferes with repair process and contributes to incomplete functional recovery.

Question 37

What occurs during the remodelling phase? (3)

Answer 37

3-6 weeks
→ scar tissue re-organised and contracts
→ in process - collaged fibres realigned to position of maximum efficiency
→ fibres are parallel to lines of tension
→ gradually assumes normal appearance/function
→ usually after 3 weeks a firm, contracted non-vascular scar exists

total maturation phase may take years to be totally complete

Question 38

What is the process of a healing skeletal muscle in terms of a schematic diagram?

Answer 38

1. Torn myofibrill
2. Muscle contracts, demarkation membrane seals the torn fibre ends, satellite cells proliferating - inflammation reaction is beginning
3. Satellite cells differentiate into fibroblasts and myoblasts - produce collagen which forms scar tissue.
4. Myoblasts fuse into myotubes
5. Myotubes fuse with surviving parts of torn fibres
6. Fibre fully regenerates but some scar tissue may remain (collagen)