Ch 9. Wound Healing

Question 1

What is autocrine signaling

Answer 1

production of signaling molecules by one cell type that only acts on cells of the same type

Question 2

What is paracrine signalling

Answer 2

production of signaling molecules by one cell type that acts on different but local cell types

Question 3

What is juxtacrine signaling

Answer 3

this is contact dependent signalling and will occur between cells in cotact which each other

Question 4

What are the layers of the mucosa of the GI tract

Answer 4

epithelial (mostly enterocytes)
lamina propria (connective tissue, blood vessels, lymphatics, mesenchymal cells, inflammatory cells)
muscularis mucosa (thin layer of smooth muscle)

Question 5

What collagen types make up the submucosa of the GI?

Answer 5

type 1 - 68%
type 3 - 20%
type 5 - 12%

Question 6

How quickly does an intestinal mucosal defect heal

Answer 6

within 3 days if direct mucosal apposition is accomplished because of enterocyte migration

Question 7

What cell type is the key source of growth factors in the GI

Answer 7

macrophages

Question 8

In the skin, collagen is mostly formed by fibroblasts. In the GI, which cells make the collagen?

Answer 8

fibroblasts AND smooth muscle cells make collagen and elastin and the smooth muscle cells have a greater contribution

Question 9

What collagen types predominate in the healing of the GI tract?

Answer 9

I, III, and V

Question 10

Where do the collagen synthesizing smooth muscle cless of the GI live?

Answer 10

muscularis mucosa layer and the muscularis propria

Question 11

Why does the strength of a GI anastomosis decrease 48 hours after surgery

Answer 11

collage breakdown secondary to collagenase activity occurs in 1-2 days

Question 12

At what PaO2 does mature collagen formation fail?

Answer 12

below 40 mmHg

and below 10 mmHg, other components of wound healing like angiogenesis also fail

Question 13

How anemic does a patient need to be to impair GI wound healing if the cardiac output is normal

Answer 13

less than 15%

Question 14

How soon does colon reach 50% of its wound strength after wounding?

Answer 14

21-28 days

Question 15

How soon does bladder reach 50% of its wound strength after wounding?

Answer 15

about 7 days

Question 16

How soon does stomach reach 50% of its wound strength after wounding?

Answer 16

14 -21 days

Question 17

What is the predominant collagen in fascia

Answer 17

parallel bundles of type I

Question 18

True or false

Fascia derived fibroblasts show a more robust response to acute wounding compared to dermally derived fibroblasts

Answer 18

true
fascial fibroblasts have been shown to have a higher rate of collagen synthesis on day 7 than dermal fibroblasts, leading to the conclusion that fascia derived fibroblasts show a more robust response to acute wounding compared to dermally derived fibroblasts

Question 19

How do fascial fibroblasts differ from dermally derived fibroblasts

Answer 19

longer cell doubling times
large cell volume
higher glucose requirements

Question 20

What are three undeniable facts of fascial healing

Answer 20

1. failure of fascial incision is often due to early, high mechanical forces
2. fascial healing can be optimized by using continuous, non absorbable or slowly absorbable inert sutures
3. sutures should be placed a minimum of 3 mm from the wound edge, outside of the zone of inflammation

Question 21

true or false

urothelial cells have a high rate of turnover

Answer 21

FALSE - urothelial cells actually have a very low basal mitotic activity but when injured, bladder mucosa reepithelializes in 2-4 days
How? increase in mitotic activity in the basal layer and terminally differentiated superficial cells undergo mitosis in response to injury as well

Question 22

What growth factors may play a significant role in urinary bladder wound healing

Answer 22

epidermal growth factor, keratinocyte growth factor, TGF alpha

Question 23

What does it mean that keratinocyte growth factor and TGF alpha are increased 4.5-8 times normal adjacent to the bladder wound and 3.5-6 times normal throughout the rest of the bladder

Answer 23

response to injury upregulates growth factors throughout the bladder

Question 24

How fast does bladder regain 100% of its unwounded strength?

Answer 24

21 days but collagen synthesis does not return to normal until 70 days post injury

Question 25

What type of bone ossification is involved in bone healing? Which is typically the predominant form?

Answer 25

intramembranous and endochondral ossification

endochondral ossification is the predominant

Question 26

What factors mediate endochondral ossification?

Answer 26

TNF alpha
PDGF
TGF Beta
VEGF
fibroblast growth factors
bone morphogenic proteins (BMPs) which are of the TGF beta family

Question 27

What cells does bone require for wound healing that differs from other tissues

Answer 27

chondroblasts
osteoblasts
osteoclasts
**type III collagen also likely plays a role in osteoblast differentiation

Question 28

Local factors impairing wound healing

Answer 28

wound perfusion
tissue viability 
hematoma/seroma
infection
mechanical factors

Question 29

systemic factors impairing wound healing

Answer 29

related to immunology, oncology, systemic conditions like diabetes mellitus, obesity or malnutrition
thermal injuries
external agents
excessive scarring

Question 30

Why is preventing hematoma/seroma formation so important for wound healing

Answer 30

• if the pressure exerted by the buildup of fluid exceeds capillary perfusion pressure, tissues will become ischemic
• dead space within the wound increases the distance that signalling molecules and migrating cells must travel
• the fluid is ideal for bacterial proliferation

Question 31

How does infection influence the inflammatory phase

Answer 31

• presence of infection will increase consumption of complement proteins resulting in decreased chemotaxis
• platelets are depleted and white cells function is impaired
• increased production of cytotoxic enzymes and free oxygen radicals increase tissue damage

Question 32

How does infection influence the proliferative phase?

Answer 32

• fibroblast proliferation is depressed
• disorganized collagen production
• increased breakdown of collagen and then decreased wound strength
• bacterial metabolites inhibit keratinocyte migration and digest dermal proteins
• proteases from neutrophils damage the neoepithelium
• bacterial endotoxins decrease deposition and cross linking of collagen fibers

Question 33

What amount of bacterial contamination at closure will result in an incidence of 50-100% infection

Answer 33

10^5 bacteria per gram

Question 34

In a study of postoperative wound infection in clean contaminated wounds of dogs an cats, animals with a concurrent endocrinopathy were —- times more likely to develop a post op wound infection

Answer 34

8.2 times as likely

interestingly, none of those animals were diabetics

Question 35

How does excess glucocorticoids (exogenous or Cushings) impair wound healing

Answer 35

impair macrophage activity
decrease fibroblast proliferation
decrease collagen synthesis
inhibit the synthesis of matrix metalloproteinases
*the negative impact of steroids on wound healing is both time and dose dependent

Question 36

What is a hypothesis for why blood transfusion may be linked to adverse effect on wound healing

Answer 36

blood transfusion may have an immunosuppressive effect associated with inhibition of IL-2 and/or with donor blood leukocyte interactions