Ch 9. Wound Healing Flashcards
What is autocrine signaling
production of signaling molecules by one cell type that only acts on cells of the same type
What is paracrine signalling
production of signaling molecules by one cell type that acts on different but local cell types
What is juxtacrine signaling
this is contact dependent signalling and will occur between cells in cotact which each other
What are the layers of the mucosa of the GI tract
epithelial (mostly enterocytes) lamina propria (connective tissue, blood vessels, lymphatics, mesenchymal cells, inflammatory cells) muscularis mucosa (thin layer of smooth muscle)
What collagen types make up the submucosa of the GI?
type 1 - 68%
type 3 - 20%
type 5 - 12%
How quickly does an intestinal mucosal defect heal
within 3 days if direct mucosal apposition is accomplished because of enterocyte migration
What cell type is the key source of growth factors in the GI
macrophages
In the skin, collagen is mostly formed by fibroblasts. In the GI, which cells make the collagen?
fibroblasts AND smooth muscle cells make collagen and elastin and the smooth muscle cells have a greater contribution
What collagen types predominate in the healing of the GI tract?
I, III, and V
Where do the collagen synthesizing smooth muscle cless of the GI live?
muscularis mucosa layer and the muscularis propria
Why does the strength of a GI anastomosis decrease 48 hours after surgery
collage breakdown secondary to collagenase activity occurs in 1-2 days
At what PaO2 does mature collagen formation fail?
below 40 mmHg
and below 10 mmHg, other components of wound healing like angiogenesis also fail
How anemic does a patient need to be to impair GI wound healing if the cardiac output is normal
less than 15%
How soon does colon reach 50% of its wound strength after wounding?
21-28 days
How soon does bladder reach 50% of its wound strength after wounding?
about 7 days
How soon does stomach reach 50% of its wound strength after wounding?
14 -21 days
What is the predominant collagen in fascia
parallel bundles of type I
True or false
Fascia derived fibroblasts show a more robust response to acute wounding compared to dermally derived fibroblasts
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
How do fascial fibroblasts differ from dermally derived fibroblasts
longer cell doubling times
large cell volume
higher glucose requirements
What are three undeniable facts of fascial healing
- failure of fascial incision is often due to early, high mechanical forces
- fascial healing can be optimized by using continuous, non absorbable or slowly absorbable inert sutures
- sutures should be placed a minimum of 3 mm from the wound edge, outside of the zone of inflammation
true or false
urothelial cells have a high rate of turnover
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
What growth factors may play a significant role in urinary bladder wound healing
epidermal growth factor, keratinocyte growth factor, TGF alpha
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
response to injury upregulates growth factors throughout the bladder
How fast does bladder regain 100% of its unwounded strength?
21 days but collagen synthesis does not return to normal until 70 days post injury
What type of bone ossification is involved in bone healing? Which is typically the predominant form?
intramembranous and endochondral ossification
endochondral ossification is the predominant
What factors mediate endochondral ossification?
TNF alpha PDGF TGF Beta VEGF fibroblast growth factors bone morphogenic proteins (BMPs) which are of the TGF beta family
What cells does bone require for wound healing that differs from other tissues
chondroblasts
osteoblasts
osteoclasts
**type III collagen also likely plays a role in osteoblast differentiation
Local factors impairing wound healing
wound perfusion tissue viability hematoma/seroma infection mechanical factors
systemic factors impairing wound healing
related to immunology, oncology, systemic conditions like diabetes mellitus, obesity or malnutrition
thermal injuries
external agents
excessive scarring
Why is preventing hematoma/seroma formation so important for wound healing
- 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
How does infection influence the inflammatory phase
- 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
How does infection influence the proliferative phase?
- 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
What amount of bacterial contamination at closure will result in an incidence of 50-100% infection
10^5 bacteria per gram
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
8.2 times as likely
interestingly, none of those animals were diabetics
How does excess glucocorticoids (exogenous or Cushings) impair wound healing
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
What is a hypothesis for why blood transfusion may be linked to adverse effect on wound healing
blood transfusion may have an immunosuppressive effect associated with inhibition of IL-2 and/or with donor blood leukocyte interactions
