wound healing and repair

Question 1

healing

Answer 1

repair process made of 2 distinct processes, regeneration and organisation in variable proportions

Question 2

resolution

Answer 2

complete disappearance of inflammatory exudate

Question 3

regeneration

Answer 3

growth of cells and tissues to replace lost structures, with a return to normal function

Question 4

organisation

Answer 4

formation of fibrous scar, with a loss of normal function

Question 5

fibrosis

Answer 5

accumulation of excessive amounts of fibrous tissue

Question 6

2 ongoing processes in healing

Answer 6

cell tissue regeneration
- endpoint: restoration of original tissue
- no loss of function

fibrous tissue repair
- endpoint: fibrous scar
- some loss of function since fibrous tissue not native tissue but body can compensate

Question 7

extracellular matrix

Answer 7

• stromal substance forming connective tissue that support cell
• made of collagen
• adhesion molecules (eg integrins, selectins) key in cell interactions with ECM

Question 8

5 steps of healing and repair

Answer 8

1. haemostasis (platelet plug, coagulation cascade)
2. granualtion tissue, angiogenesis
3. ECM deposition
4. re-epithelialisation
5. scar formation and remodelling

Question 9

growth factors

Answer 9

function: act on other cells to synthesis ECM

eg
macrophage-derived growth factor
fibroblast GF
vascular endothelial GF
placental GF
platelet driven GF

Question 10

which tissues can undergo regeneration

Answer 10

liver, skin, bone marrow

• tissue must contain pluripotent stem cell
• underlying ECM must remain intact

Question 11

which tissues cannot undergo regeneration

Answer 11

kidney, heart, brain

• more specialised, less likely to be replaced

Question 12

re-epithelialisation

Answer 12

forming an epithelium again after it is lost in wound

Question 13

name 4 labile tissues

Answer 13

mucosae (GIT, respiratory mucosa), hair follicles, skin, bone marrow

contain constantly dividing cells so most affected by cytotoxic metabolites and cancer drugs

Question 14

name stable tissues

Answer 14

pancreas, liver

• usually not dividing but can be stimulated to enter cell cycle
• tend to undergo hyper/atrophy rather than hyper/hypoplasia

Question 15

2 most impt permanent tissues

Answer 15

neurons, cardiac muscle
- unable to divide so cannot be regenerated

Question 16

use of stem cells in healing and repair

Answer 16

replace specialised cells to preserve function

Question 17

fibrous repair- processes involved

Answer 17

• granulation tissue formation
  (angiogenesis, fibroblast proliferation)
• wound contraction (myofibroblasts)
• collagen synthesis and maturation
• scar (collagen) remodelling

Question 18

granulation tissue begins forming / collagen synthesis begins ______ after injury.

This is well formed _____ after injury.

Answer 18

granulation tissue begins forming / collagen synthesis begins mere hours, nearly immediately after injury.

This is well formed 1 week after injury.

Question 19

Angiogenesis begins ____ hours after hemostasis.

Answer 19

Angiogenesis begins 48-72 hours after hemostasis

Question 20

granulation tissue formation is a combination of 3 steps occuring simultaneously

Answer 20

• angiogenesis of capillaries
• proliferation of fibroblastic and myofibroblastic cells to produce collagen
• ECM deposition

Question 21

What are the 3 cell types involved in granulation tissue formation & what are their roles?

Answer 21

immune cells (macrophages) -> debridement

vascular connective tissue cells (endothelial cells, RBC) -> for angiogenesis

fibroblasts, myofibroblasts -> ECM deposition

Question 22

What structure does granulation tissue grow from?

Answer 22

basement membrane

Question 23

mechanism of angiogenesis

Answer 23

1. start 48-72 hrs after hemostasis
2. endothelial cells divide to form solid sprouts
3. sprouts develop lumen through fusion of intracytoplasmic vacuoles containing RBC
4. formation of capillaries
5. capillaries join to form vascular network (network is temp and is resorbed and replaced by fibrous tissue)
   - just to bring nutrients, O2 and inflammatory cells to wound

capillaries surrounded by inflammatory cells and fibroblasts

Question 24

principal function of myofibroblasts

Answer 24

-Myo (muscle cells) -> wound contraction where secrete actin and myosin to build new smooth muscles to close wound

• Fibro: ECM, collagen secretion

Question 25

HOW DOES FRESH GRANULATION TISSUE BECOME A SCAR? 4 step process.

Answer 25

1. collagen III provisional matrix 2. replacement with collagen I (stiffer protein that gives tensile strength) 3. rearrangement of collagen along new lines of stress and development of cross linkages 4. vascular resorption (angiogenesis stops and replaced by fibrous scar)

Question 26

local factors affecting wound healing

Answer 26

1. wound factors (type, size, location, depth) 2. movement (excessive movement tear collagen fibres before enough tensile strength develops) 3. nearby infection or infection of wound itself -> immune response prolonged so wound healing delayed 4. perfusion (local vascular supply) -> venous congestion, diabetic will have poor healing because receive less nutrients, oxygen and inflammatory cells 5. others: radiation, medication

Question 27

systemic factors affecting wound healing

Answer 27

- metabolic status (diabetes) - endocrinopathies (hypothyroid, Cushing’s) some hormones improve healing and some worsen healing - systemic circulation status -> compromised cardiovascular sustem would mean reduced blood supply to site of wound - nutritional status (impt elements like zinc and vit C for linkage of collagen fibres) - age (OLD dont heal well)

Question 28

complications of wound healing

Answer 28

- defective scar formation (eg incisional hernia, dehiscence -> wound that is closed reopens) - excessive scar tissue formation (eg keloid or hypertrophic scar) - excessive contraction (eg burns, chemical injury)

Question 29

skin injuries

Answer 29

pure epidermal lesions -> repaired by epithelial proliferation (no scarring) ulcer -> injury to both epidermis and dermis (+subcutaneous tissue) and will have fibrous scaring once dermis and deeper involved

Question 30

healing by 1st intention vs healing by 2nd intention

Answer 30

wound factors 1: small wound with apposed skin (skin matches) 2: large wounds with skin edges not apposed myofibroblast involvement 1: no wound contraction 2: myofib involvement and contraction present intensity of angiogenesis and inflammation 1: low 2: high scar size 1: small or none 2: large, deforming, thick time taken to heal 1: 12 wks 2: much much longer

Question 31

why suture wounds

Answer 31

wound edges more opposed so more likely to heal by primary intention, lesser scarring and faster healing

Question 32

healing of mycocardial infarct

Answer 32

healing by fibrous repair (permanent cells) result: hypertrophy of surviving cardiomycocytes to compensate but limited large infarct cause heart failure

Question 33

complications of peptic ulcer disease

Answer 33

slow bleeding over a long time -> haemorrhage ->anemia contraction of stomach when wound healing -> obstruction of food because cannot enter small intestine rupture with perforation -> stomach acid leak out

Question 34

complications of myocardial infarction healing

Answer 34

Aneurysm of ventricle Arrythmia Thromboemboli -> blood clot in heart rupture with hemopericardium

Question 35

lung healing

Answer 35

if basement membrane intact, complete resolution possible if basement membrane damaged, fibrous tissue formation which decreases lunch capacity as alveolar replaced by fibrous tissue

Question 36

liver healing

Answer 36

acute injury: complete regeneration possible (if bile ducts affected, cannot regenerate because stem cells which are located near bile ducts are lost) chronci, persistent liver injury: fibrosis + regeneration but after a certain point, ability to regenerate decreases and hepatocytes replaced with fibrous tissues instead of being regenerated

Question 37

fracture healing

Answer 37

1. fracture bridged by hematoma (blood clot) and later granulation tissue and collagenous fibrous tissue 2. proliferation of osteoblasts to form new immature woven bone (callus) to bridge the gap but callus has no strength 3. bone remodelling (osteoclasts) -> formation of mature lamellar bone with good tensile strength (have residual fibrosis so functional status not 100% and more prone to fracture)

Question 38

complications of fracture healing

Answer 38

- bone does not join when heals (have gap)-> very unstable - fibrous union (bone heals with scar tissue and not bone -> unstable) - malunion (not align properly) -> mildly unstable - osteomyelitis (esp for open fracture where bone is exposed)