Tissue Healing/Repair

Question 1

Healing

Answer 1

Outcome of inflammation - regeneration or scarring

Question 2

Cell growth in scarring vs. regneration

Answer 2

Regen - tissue’s own cells divide

Scar- fibroblasts and vascular endothelial cells divide

Question 3

Liable cells

Answer 3

Continuously dividing
Short G0
Epithelial cells and hematopoietic cells

Question 4

Stable cells

Answer 4

Low rate of cell division
Long G0
Re-enter cell cycle only under certain circumstances (healing)
Vascular endothelial cells, parenchymal cells of organs, mesenchymal cells

Question 5

Permanent cells

Answer 5

Left cell cycle forever…will never undergo mitosis again

Neurons of CNS, cardiac muscle, skeletal muscle

Question 6

3 conditions for healing by regeneration

Answer 6

Tissue composed of labile or stable cells
Area of injury has surviving cells capable of undergoing cell division
Connective tissue framework intact

Question 7

Healing by scarring conditions

Answer 7

Tissue consists of permanent cells and/or no surviving cells remain and/or connective tissue framework is destroyed/disrupted

Question 8

Growth factors

Answer 8

May promote cell proliferation by recruiting G0 cells into cell cycle…may inhibit cell proliferation…may influence other cell function

Question 9

Epidermal growht factor family

Answer 9

EGF and TNF-alpha

Question 10

EGF

Answer 10

Produced by several cells, including macrophages
Mitogenic for epithelial cells, hepatocytes and fibroblasts
Binds to ERB B1

Question 11

TGF-alpha

Answer 11

Almost same to EGF, also binds to ERB B1

Question 12

PDGF

Answer 12

Stored in alpha granules of platelets
Released when platelets activated
Also produced by macrophages, edothelial cells, smooth muscle, and some tumor cells
Mitogenic and chemitactic for fibroblasts, smooth muscle cells, and monocytes

Question 13

FGF

Answer 13

Acidic and basic types
Produced by activated macrophages
Chemotactic and mitogenic for fibroblasts and endothelial cells
Induce angiogenesis

Question 14

TGF-B

Answer 14

Produced by platelets, endothelial cells, lymphocytes, and activated macrophages
Generally mitogenic for fibroblasts but can inhibit grwoth of epithelial cells
Stimulates fibroblast chemotaxis, and stimulates production of collagen and fibronection (important for scars)

Question 15

Fibrogenic cytokines

Answer 15

IL-1 and TNF

Mitogenic and chemotactic for fibroblasts
Stimulate collagen production by fibroblasts
Important in scar formation

Question 16

Direct binding of what is critical for regeneration and scar formation?

Answer 16

Cell to the ECM

Question 17

4 components of repair by fibrosis

Answer 17

Angiogenesis/neovascularization
Migration and proliferation of fibroblasts
Deposition of ECM components, including collagen
Organization of the fibrous tissue into a mature scar (remodeling)

Question 18

In fibrosis, 24 hours after tissue injury

Answer 18

Fibroblasts and vascular endothelial cells proliferate

Question 19

Granulation tissue

Answer 19

Formed by proliferation of fibroblasts and vascular endothelial cells

Question 20

2 important features of granulation tissue

Answer 20

Angiogenesis and fibroblast proliferation

Question 21

Angiogenesis - granulation tissue

Answer 21

New vessels originate from other blood vessels in the area
New vessels have leaky interendothelial junctions allowing exudate to form (tissue is edematous)
Need FGF and VEGF in order to grow

Question 22

Fibroblast proliferation - granulation tissue

Answer 22

Triggered by EGF, TGF-B, PDGF, and others

TGF-B stimulates newly created fibroblasts to secrete collagen

Question 23

Weeks to months after, how is granulation tissue turned into a scar?

Answer 23

Amount of collagen and other ECM proteins increases
Number of fibroblasts and other other vascularity decreases
Fully mature scare is practically avascular and has dense collagen

Question 24

Healing of a surgical incision

Answer 24

Scalpel blade injures a number of epidermal cells and underlying connective tissue
Space fills with clotted blood
Neutrophils appear (24 hours)
By day 3, replaced with macrophages
At day 3, granulation tissue begins to form because of growht factors from platelets, macrophages, and endothelial cells…TGF-B stimulates production of collagen and other ECM proteins
Growth factors induce basal cells of the epidermis to regenerate
By day 5, granulation tissue has filled incisional space
During second week, collagen accumulates while leukocytes, edema, and increased vascularity begin to disappear
By then end of the first month, scar is formed and epidermis fully regenerated

It is then complete