Endotoxemia Flashcards
What is endotoxemia?
The presence of endotoxin in the ciruculation
What is endotoxin?
Heat-stable LPS component of the gram negative bacterial cell wall
What portion of the outer layer of the outer cell membrane is LPS?
75%
Why does LPS tend to form micelles in circulation?
Because it has both hydrophobic and hydrophillic regions
What is the polysaccharide O-region of LPS?
Polar antigenic region, responsible for smooth bacterial colonies in culture
What is the lipid A region of LPS?
Hydrophobic portion that is well preserved between all gram negative species
When is endotoxin produced in the highest quantities?
During death and rapid multiplication phases
Which structure of LPS is most responsible for the deleterious effects of endotoxins?
Lipid A
What does SIRS stand for?
Systemic inflammatory response syndrome
What is sepsis?
SIRS induced by infection manifested by two of more of: hyperthermia, HR>90bpm, RR >20bpm, arterial CO2
What is septic shock?
Sepsis induced by hypotension or need for vasopressors to maintain BP despite adequate fluids as well as lactic acidosis, oligura, and altered mental status
What does CARS stand for?
Compensatory anti-inflammatory response syndrome
T/F: CARS is a syndrome of immune suppresion
True
What does MODS stand for?
Multiple organ dysfunction
What does MOFS stand for?
Multiple organ failure syndrome
What is stage one endotoxemia?
Physical barriers breached and endotoxin enters the body
Where does stage one endotoxemia usually occur?
Skin and GIT (especially cecum and large intestine)
What can inhibit endotoxin from being absorbed in the GIT?
Binding of endotoxin to bile salts
What is stage two endotoxemia?
Endotoxin gains circulation and stimulates macrophages
What is LBP?
LPS binding protein that is involved in the acute phase response
What does LBP do?
Acts as a shuttle protein bringing LPS from aggregates to responding cells
What can happen after LPS binds to LBP?
- Elimination at liver
- Brought to macrophages and inactivated
- Brought to other cell types
- Transfers to high-density lipoproteins and decreases inflammatory cell interaction
- Transfers to macrophages and triggers inflammatory response
Can small amounts of endotoxin be eliminated without clinical signs?
Yes- if too large an amount it will overwhelm elimination pathways and activate inflammatory response
What receptor does the LPS-LBP complex interact with to initiate inflammatory response?
CD14
What pathway is primarily activated in equines leading to the increased pathogenesis when compared to other animals?
MyD88
What two pathways are activated when TLR-4 is activated?
MyD88 and TRIF
Is MyD88 pro- or anti-inflammatory?
Pro-inflammatory
Is TRIF pro- or anti-inflammatory?
Anti-inflammatory
What determines severity of clinical response to endotoxin?
Macrophage responsiveness
What is stage 3 endotoxemia?
Neutrophils bind to endothelial cells and become activated
What kind of cells do TNF and IL-1 act on?
Neutrophils and endothelial cells
What is the importance of cytokine induced receptor driven margination of neutrophils?
Accounts for leukopenia found in most horses with endotoxemia
What accounds to the procoagulant effects of endotoxemima
Stimulation of endothelial cells to produce procoagulant products and platelet aggregation
T/F: Once activation of neutrophils and endothelial cells occurs, the process becomes self-sustaining and malignant
True
What is stage 4 endotoxemia?
Compromised organ perfusion
What is normal organ perfusion maintained by?
- Vasodilators/constrictors
- Pro/anti-coagulants
- Proteases/ antiproteases
- Oxidants/ antioxidants