Lec4 Would Healing and Repair

Question 1

Regeneration vs Healing

Answer 1

Regeneration: restore lost tissues

• occurs with superficial wounds, some inflammatory process, intact tissue framework
• ex. liver regeneration, superficial skin wound, resorption exudate in pneumonia

Healing: restore original structure but collagen formation and scar formation

• occurs with damaged tissue framework, deep wounds
• ex. deep excisional wound, MI

Question 2

Fibrosis

Answer 2

Tissue scar formation when persistent tissue damage

- ex. chronic inflammatory disease - cirrhosis, chronic pancreatitis, pulmonary fibrosis

Question 3

Early state of healing

Answer 3

• 0-3 days
• thrombosis
• inflammation [neutrophils + macrophages]
• re-epithelialization [this new epidermis above scar]

in order:
0-4 hrs: fibrin clot forms
1-3 days: phagocytosis
1-4 days: chemoattraction and migration of inflammatory cells to wound

Question 4

fibronectin

Answer 4

in early wound healing:

• helps fibroblasts bind fibrin to form fibrin clot
• promotes phagocytosis

Question 5

Migration in wound healing

Answer 5

• occurs days 1-4
• monocytes [macrophages, neutrophils] are recruited and adhere to site of injury
• produce cytokines including: PDGF [platelet derived growth factor] and TGF-B
• — stimulate proliferation + migration + matrix production

Question 6

What is PDGF?

Answer 6

• Platelet derived growth factor
• mitogenic cytokine
• released by platelets and endothelial cells
• mitogen for formation of fibroblasts, smooth muscle, connective tissue
• part of early wound repair?

Question 7

What is FGF?

Answer 7

• Fibroblast growth factor
• mitogenic cytokine
• has many types and isoforms
• produced by macrophages and fibroblasts
• stimulates fibroblast proliferation and new vessel growth

Question 8

4 Markers of Organizing wound??

Answer 8

Organizing = wound undergoing repair

• secondary change in thrombus
• dissolution of clot
• formation new vessels
• deposition of stroma

Question 9

Mid State of Wound Healing

Answer 9

1-10 days

• early formation new collagen III matrix, dissolution of clot and phagocytosis [2-4 days]
• More collagen III and matrix molec [2-5 days]
• Granulation tissue

Question 10

Granulation tissue

Answer 10

• part of mid stage of wound healing
• components
• – macrophages, myofibroblasts, fibroblasts, capillaries
• angiongenesis via canalization and connection of capillaries

Question 11

2 mitogenic cytokines

Answer 11

PDGF - platelet derived growth factor

FGF - fibroblast growth factor

Question 12

2 Fibrogenic cytokines

Answer 12

TGF-B [transforming growth factor -B]

IL-4 [interleukin-4]

Question 13

What is TGF-B?

Answer 13

• fibrogenic cytokine
• secreted by lymphocytes, macrophages, platelets
• chemoattractant for inflammatory cells
• inhibits inflammatory response

Question 14

What is IL-4?

Answer 14

• fibrogenic cytokine
• effects many cell types [B and T]
• modulates inflammatory response [TH2]
• essential in fibrosis along with TGF-B

Question 15

What is VEGF?

Answer 15

• angiogenic cytokine
• vascular endothelial growth factor
• promotes growth of blood vessels
• binds receptors on endothelial cells

Question 16

What is EGF?

Answer 16

• epithelial proliferation cytokine
• produced by keratinocytes and macrophages
• promotes epidermal migration and proliferation

Question 17

Metalloproteinases

Answer 17

• aid in remodeling extracellular matrix activation and inhibition

Question 18

Late stage of wound healing

Answer 18

3-30 days and more

- formation of definitive collagen I matrix

Question 19

Content of extracellular matrix

Answer 19

• collagens I, III, IV
• glycosaminoglycans
• elastin
• microfibrils
• fibronectin
• integrins

Question 20

Myofibroblast

Answer 20

• expresses antigens of smooth muscle
• responds to agents that contract smooth muscle
• responsible for wound contraction

Question 21

Wound strength

Answer 21

Elastic fibers are not replaced in scar tissue

• after 1 wk: 10% strength
• after 2 months: 50% strength
• after 3 months: 70-80% strength

Question 22

Re-epithelialization

Answer 22

• source is stem cells from hair follicle
• must reform protective barrier
• close wounds by migration or purse string
• differentiate again
• role of basement membrane

Question 23

Mechanisms of re-epithelialization

Answer 23

1. leap-frog method
   - keratinocyte B leap frogs over keratinocyte A
2. train method
   - keratinocyte A puls keratinocyte B and C

Question 24

3 Types of proliferative cells

Answer 24

Labile: rapidly dividing
ex. epidermis, GI tract epithelium

Stable/quiescent: slowly dividing unless stimulus
- ex. liver

permanent: incapable of dividing
- ex. neurons, cardiac myocytes

Question 25

stem cells

Answer 25

• cell capable of self-renewal and production of another cell for differentiated phenotype-assymetric replication
• embryonic + adult

Question 26

Local factors influence wound healing

Answer 26

• type, size, location of wound
• adequacy blood supply
• presence infection
• exposure to ionizing radiation
• exposure to ultraviolet light

Question 27

Systemic factors influence wound healing

Answer 27

• circulatory status [age]
• metabolic status
• presence infection, diabetes, neaplasia
• adequate levels Vic C, AA [met]
• hormones: corticoids, ACTH, estrogens, growth hormone

Question 28

Complications of wound healing

Answer 28

• deficient scar formation: ulceration, dehiscence
• excessive scar formation: keloids, hypertrophic scar
• excessive contraction: contracture or cicatrisation
• excessive regeneration
• painful scar
• pigmentary change

Question 29

Healing by primary vs secondary intention

Answer 29

primary intention: wounds with apposed edges
– approximation surgical wounds, minimal wound contraction, good esthetic result

secondary intention: wounds with separated edges
–non-approximation wound edges, massive contraction, poor esthetic resutl

Question 30

would dehiscence

Answer 30

would ruptures along surgical suture