Chapter 9 Wound Healing Flashcards
Name the 3 phases of wound healing
- Inflammatory phase
- Proliferative phase
- Maturation phase
What are the 3 subphases of the inflammatory phase?
- Hemostasis
- Early inflammation
- Late inflammation
Inflammation phase - hemostasis
What is the earliest signal of injury to the surrounding cells?
What occurs during hemostasis
IL-1 is the earliest signal that alerts surrounding cells of injury
Platelet aggregation and coagulation cascade
Whats the predominant cell type in early inflammation
Neutrophils
What are the neutrophils roles in early inflammation and what environmental factors are important
Neutrophils kill bacteria but are dependent on a PaO2 > 40mmHg in the wound bed
Release ROS
Breakdown extracellular matrix through the release of proteolytic enzymes
Phagocytize degraded bacteria and matrix debris
Release more cytokines to prolong inflammation
What is the primary leukocyte in the wound during the late inflammatory stage of the inflammatory phase
Macrophages
What are the roles of macrophages during the late inflammatory stage
Continue to phagocytize bacteria and debris
Release MMPs
MMPs are essential for next phase
Presence of ____ is an indication of the proliferative phase
Granulation tissue
What is granulation tissue made up of and what phase is it present in?
Macrophages, fibroblasts, collagen, and HA
Proliferative phase
What occurs during proliferative phase
- Angiogenesis
- Fibroblast migration
- Collagen synthesis
- Contraction
- Epithelialization
What do fibroblasts synthesize?
Procollagen - Type III and Type I
HA, proteoglycans, GAGs, elastin, and fibronectin
What occurs during fibroblast migration?
Differentiation from dormant mesenchymal cells.
Fibroblasts synthesize type I and type III pro collagen, HA, proteoglycans, GAGs, elastin, and fibronectin
What type of collagen is present in unwounded dermis and what percentage?
80% type I collagen
20% type III collagen
After injury and during collagen synthesis what type of collagen predominates?
Type III
What is collagen synthesized by during collagen synthesis in the proliferative phase
Fibroblasts
TGF-B increases synthesis of type I and decreases MMPs
What occurs during contraction?
Fibroblasts differentiate into myofibroblast in response to TGF-B
Myofibroblasts cause wound contraction
How do myofibroblasts work
They increase expression of alpha-smooth muscle actin isotope and appearance of stress fibers.
They orient linearly along the line of tension and form attachments causing wound contraction
What type of collagen and what percentage is in a final scar?
10% type III collagen remainder is type I
What is the strength of the final scar in relation to unwounded tissue?
70-80%
What is the sequela of abnormal mechanical tension during the maturation phase
Fibroblasts and myofibroblasts will persist and produce collagen then contract leading to contracture
What is the timeline for granulation tissue formation in dogs vs cats
Dogs - 4.5 days
Cats - 6.3 days
How long does it take dogs to have a complete granulation tissue bed compared to cats
Dogs - 7.5 days
Cats - 19 days
True or false - Contracture occurs quicker in cats
False - faster in dogs
What was the breaking strength of the wound in cats vs dogs 7 days post op
0.4kg in cats
0.8kg in dogs
Healing of wound edges cats vs dogs
Cats - contraction along wound edges
Dogs - central pull of fibroblasts and epithelialization
What percentage of epithelialization occurred in dogs vs cats 21 days post experimental wounding with and without their subcutis? what was the total healing percentage of each?
Cats with subcutis 34% healed, without subcutis 20% healed, and total healing 84%
Dogs with subcutis 89%, without subcutis 61%, and total healing of 98%
Wound strength chart - Skin, colon, stomach, bladder
120 days - Bladder 85%
Stomach 70%
Colon 60%
Skin 50%
Compare factors involved in healing of GI and skin (flora, collagen type, production of collagen, collagenase activity, vascular perfusion, shear stress)
Skin -
aerobic not polymicrobial
Type I, III collagen
Fibroblasts produce collagen
No significant collagenase activity
Relatively constant perfusion
Variable shear stress - ex coap can help
GI -
aerobic and anaerobic polymicrobial
Type I, III, V collagen
Smooth muscle cells and fibroblasts produce collagen
Collagenase activity increased days 0-3
Vascular perfusion can be down regulated due to shock
Wound shear stress is increased due to intestinal motility and peristalsis
Collagen types and percentages in submucosa, skin, bone, and articular cartilage
Submucosa: Type I 68%, Type III 20%, Type V 12%
Skin: Type I 80% and type III 20%
Bone: Mostly type I with small amounts of III and V
Articular cartilage: Type II 85-90%
What PaO2 is necessary for neutrophil function in the wound bed and why?
> 40mmHg
Wound hypoxia impairs resistance to infection and is associated with an inability of neutrophils to kill bacteria
Wounds over the distal extremity heal more by ________ and over the thorax heal more by _____
Distal extremity - epithelialization
Thorax - contraction
What are myofibroblasts role in wound healing? Where do they come from?
They are associated with increase expression of what?
Cause wound contraction during the proliferative phase by orienting along the line of tension and forming attachments to ECM and itself.
They’re differentiated from fibroblasts
They are associated with increase expression of alpha-smooth muscle actin and stress fibers
How do neutrophils work in the wound bed
Neutrophils kill bacteria in the wound through release of ROS, breakdown of extracellular matrix through the release of proteolytic enzymes, phagocytize bacteria and debris, and release additional cytokines
Conversion of ___ to ___ is sensitive to PaO2 in the wound
oxygen to superoxide
What cells form granulation tissue
Fibroblasts, inflammatory cells, collagen, and macrophages
Origin of collagen
Collagen polypeptide molecules are synthesized on the membrane-bound ribosomes of fibroblasts
Fascial healing in relation to skin
Strength is dependent on sutures for first 7 days
Fascia regains tensile strength faster than skin with increased fibroplasia and collagen production
Higher strength than skin at 7 days post but similar by day 21
What factors cause poor healing of the GI compared to skin
Peristalsis causes increased intraluminal pressure and high shear forces
Aerobic and anaerobic bacteria
Vascular perfusion decreases during shock
Bladder mucosa re-epithelializes in how long
2-4 days
How long for the bladder to regain 100% of its strength
within 21 days
When does collagen synthesis peak during bladder healing
Day 5 after injury
Suture in proteus-infected urine
PDS lost all strength after 1 day in proteus infected urine
PDS, monocryl, and others disintegrated after 7 days in proteus infected urine
Infected urine had little to no effect on catgut
How does loose skin heal (trunk, neck, thorax) vs tighter skin (extremities)
The loose skin that covers the trunk and neck heals primarily by contraction, whereas tighter skin (extremities) by epithelialization.
