Lecture 11: Wound Healing & Surgical Inflammation (Exam 1) Flashcards
1
Q
Surgery = what
A
Creation of a wound
2
Q
What is the product of disruption of tissue homeostasis
A
Inflammation
3
Q
What is considered norm surgical inflammation
A
- Acute
- Mild - moderate (dep on the procedure & body system)
- Local
- Short duration (Reduced w/ primary wound closure
4
Q
What is considered abnorm surgical inflammation
A
- Prolonged (Chronic)
- Severe
- Signs of infection
- Systemic signs (Underlying pathology)
5
Q
What are the phases of wound healing & how long do they last
A
- Hemostasis
- Inflammation (4 to 6 days)
- Proliferation (4 to 24 days)
- Remodeling (21 days to 2 years)
6
Q
What is the goal of hemostasis
A
To stop bleeding while maintaining perfusion
7
Q
For hemostasis there is a balance btw/ what two things
A
Vasoconstriction = vasodilation
8
Q
What occurs during hemostasis
A
- Immediate vasoconstriction
- Exposure of vWF -> platelet activation & aggregation
- Coagulation cascade
9
Q
What causes redness & heat
A
Endothelial cells release vasodilators -> vasodilation -> increased blood flow
10
Q
What is the release of vasodilators by endothelial cells mediated by
A
- Histamine
- NO
- LTs
- PGs
- Complement
11
Q
what happens due to post capillary venule leakiness
A
- Increase in inflammatory cell & inflammatory mediator infiltration
- Protein leakage
12
Q
What causes edema formation (swelling)
A
Protein leakage
13
Q
What happens b/c of protein leakage
A
- Decreased osmotic pressure
- Increased blood viscosity
- Increased interstitial pressure
14
Q
What does edema do
A
- Facilitates delivery of soluble factors & cells
- Causes pain
- Loss of fxn
15
Q
What is vascular congestion
A
- Fluid loss to edema
- Hemoconcentration
- Reduced velocity of blood flow
16
Q
Explain inflammation
A
- the “debridement phase”
- Two phases: neutrophil recruitment (early) & Monocyte transformation (late)
17
Q
What is the fxn of inflammation
A
- Prepares the body for next phases of wound healing
- Removes dead tissue & foreign material
18
Q
Severity of trauma –> intensity of inflammation –> ?
A
Extent of scar tissue formed
19
Q
Where are leukocytes are recruited from
A
Circulation by chemoattractants (from coagulation)
20
Q
What do leukocytes initiate
A
- Activation
- Tight adhesion
- Transmigration of cells through microvascular endothelium cells
21
Q
Define diapedesis
A
The passage of blood cells through intact capillary walls
22
Q
What is neutrophil diapedesis encouraged by
A
Increased capillary permeability
23
Q
When does neutrophil diapedesis occur & when does it peak
A
- W/in mins
- Peaks 1 - 2 days after injury
24
Q
Describe neutrophils
A
- First line of defense against contaminated would
- Destroy debris
- Phagocytose bacteria
25
When does neutrophil diapedesis end
* When the wound is cleaned up
* Ends early phase of inflammation
26
Where do monocytes migrate from
Vasculature
27
Monocytes ---> ?
Macrophages
28
Describe macrophages
* Pro-inflammatory fxns
* Stimulate proliferation of dermal, endodermal & epithelial tissues
* Help w/ remodeling phase
29
What helps to orchestrate all the phases of wound healing
Macrophages
30
How is each pathway halted or reversed
Apoptosis of cells
31
What happens if there is not resolution of inflammation
* Can lead to chronic suppurative inflammation & a non-healing wound
* Excessive granulation tissue (proud flesh in horses)
32
How is the inflammatory phase modulated by clinicians
* Proper surgical debridement
* Good hemostasis
* Adequate drainage
* Medications (NSAIDs & Steroids)
33
What occurs during proliferation
* Fibroplasia (necessary for other processes)
* Angiogenesis
* Epithelialization
34
What is fibroplasia
* Formation of granulation tissue by fibroblasts (Scaffold & temporary barrier of infection)
35
What are the steps of makes granulation tissue
1. Macrophages - debride, produce cytokines & growth factors that stimulate angiogenesis & fibroplasia
2. Fibroblasts - proliferate & make new extracellular matrix
3. Blood vessels - carry O2 & nutrients for cell metabolism & growth
36
When will there be noticeable granulation tissue
Around day 5
37
what are fibroblast directed by
Macrophages via cytokines & growth factors
38
What do fibroblasts do
* Produce ECM
* Initially more type III (immature)
* Later more type I collagen ( mature)
39
What is fibroplasia considered
* Time of increasing wound strength
* Rapid gain 7 to 14 days (corresponds to time of suture removal)
40
Describe angiogenesis
* Formation of new capillaries from pre-existing vessels
* Regulated by macrophages & endothelium (VEGF & Other misc. angiogenesis growth factors)
* Increase tissue hypoxia which leads to increase in vessel ingrowth
41
What is epithelialization
Epithelium covers the wound
42
What happens when epithelium covers wounds
* Reform barrier of infection
* Centripetal
* 0.1 to 0.2 mm/day
43
What happens during maturation
* Continued epithelialization
* Wound contraction
44
Describe continued epithelialization
Thickening of epidermis
45
Describe wound contraction
* Fibroblasts differentiate into myofibroblasts under the influence of GF & cytokines
* Myofibroblasts contain alpha-smooth muscle actin
46
Explain remodeling
* Conversion of granulation tissue into scar tissue
* Involves matrix metalloproteinases aka "MMPs" (Collagenases, gelatinases, & stromelysins = demolition team)
* May take up to 1-2 Y depending on the size of the wound
* Progressive increase in tensile strength of the wound
47
When does healing stop
* Wound edges meet (ideal)
* Tension surround skin > force of myofibroblasts (not ideal)
* Reduced #s of myofibroblasts (not ideal)
* Granulation tissue is proliferative (Epithelial cells can't climb
48
Explain shock
* Cascade of events that begins when cells/tissue are oxygen deprived from inadequate perfusion
* Can lead to SIRs & MOD
49
What is systemic inflammatory response response syndrome (SIRs)
* Normal?
* Many causes but on syndrome (infectious & noninfectious)
* Generally considered excessive response
* Must meet any 2 w/ underlying pathologic causes)
50
Why is SIRs considered excessive response
* "Cytokine storm"
* Leukocyte dysfunction
* Delayed resolution inflammation
51
What are clinical pathologic diseases that can cause
* Hyper or hypothermia
* Tachycardia
* Tachypnea
* Leukocytosis or leukopenia (neutrophils +/- to the left shift)
* Depression
52
Describe hyperthermia (fever)
IL-1, IL-6, TNF alpha, & PGE2 act on hypothalamus to increase the body's thermostat
53
Describe hypothermia
* Shock (hypoperfusion & central blood sequestration)
* BAD sign
54
Describe tachycardia
55
What causes Tachypnea
56
What primarily causes CBC alterations
Change in neutrophils
57
Describe the first CBC alterations (Leukopenia)
* < 48 H
* Initial - endothelial "stickiness"
* Increased us
58
Describe the second CBC alterations (Leukocytosis)
* > 48 H
* Release from sequestered areas (bone marrow spleen)
59
Describe the third CBC alterations (left shift [variable])
* Immature neutrophils
* Supply < demand
60
What causes depression during wound healing
* Cytokines
* Kicosanoids
61
Describe the stress response in wound healing
* IL-1 & TNF alpha increase adrenocorticotropic hormone which increases corticosteroids
62
What are the effects of corticosteroids on surgical healing
* REDUCES healing
* Anti-inflammatory
* Reduce activity/production of growth factors
63
Describe stress leukogram
* Variable by species
* Due to endogenous (or exogenous) Corticosteroids
* Neutrophilia (usually mature, no bands)
* Lymphopenia
* Monocytosis (more common in dogs)
* Eosinopenia
64
What leads up to multiple organ dysfunction syndrome (MODS)
65
Define MODs
Presence of altered organ fxn in an acutely ill patient such that homeostasis can't be maintained w/out intervention
