91: Sepsis and Septic Shock COPY Flashcards
What is the incidence and mortality rate of sepsis in veterinary medicine?
- the incidence rate is not established
- mortality ranges from 20-68%
What is the definition of Bacteremia?
presence of live bacterial organisms in the bloodstream
What is the definition of sepsis?
clinical syndrome caused by infection and the host’s systemic inflammatory response to it
can be bacterial, viral, protozoal, or fungal in origin
What is the definition of septic shock?
Acute circulatory failure and persistent arterial hypotension despite volume resuscitation, associated with sepsis
what is the arterial blood pressure cutoff for the definition of septic shock in veterinary and human patients?
the critical BP cutoff is not established in veterinary patients, but extrapolated from the human consensus:
- In people, hypotension is defined by a systolic arterial pressure less than 90 mm Hg, a mean arterial pressure less than 60,
- or a reduction in systolic pressure of greater than 40 mm Hg from baseline despite adequate volume resuscitation, in the absence of other causes of hypotension.
what is the definition of Systemic inflammatory response syndrome (SIRS)?
The clinical signs of systemic inflammation in response to infectious or noninfectious insults (e.g., trauma, pancreatitis, burns, snakebites, neoplasia, and heat stroke).
what is the definition of multiple organ dysfunction syndrome (MODS)?
Physiologic derangements of the endothelial, cardiopulmonary, renal, nervous, endocrine, and gastrointestinal (GI) systems associated with the progression of uncontrolled systemic inflammation and disseminated intravascular coagulation (DIC).
- two or more organs affected
What are the 4 hallmarks of sepsis
- Dysregulation of vasomotor tone
- Increased vascular permeability
- Dysfunctional microcirculation
- Coagulation abnormalities
What is PIRO?
a concept to stage sepsis, adopted after the 2001 international sepsis definition conference
to describe clinical manifestation of the infection and the host response to it
Predisposition, Insult or Infection, Response, Organ dysfunction
not yet adapted in vet med due to lack of advanced diagnostic techniques
What is the most common orignin of gram negative sepsis in cats and dogs?
gastrointestinal and genitourinary systems
What is the most common origin of gram positive sepsis in dogs and cats?
skins, injured soft tissue, IV catheters
What is the most important pathogen-associated molecular pattern of gram negative bacteria?
Explain how it leads to inflammation and what receptors/cytokines/cells are involved in this pathway
Lipopolysaccharide (LPS) > part of the gram-negative bacterial cell wall
- binds to lipololysacchardie binding protein (LBP) > forms LPS-LBP complex
- LPS-LBP complex binds to macrophage membrane-bound CD14
- macrophage activation > Toll-like receptors > signaling transfuction to the nucleus > starts transcription of inflammatory cytokines
inflammatory cytokines:
- tumor necrosis factor-alpha (TNF-alpha)
- IL-1, IL-6, IL-8
- interferon gamma
What does CARS stand for? List 3 of its cytokines.
compensatory anti-inflammatory response syndrome > counter-inflammatory mediators to reduce inflammatory response
IL-4, IL-10, IL-13
What are the most important pathogen-associated molecular patterns (PAMPs) of gram positive bacteria?
cell wall components:
- lipoteichoic acid
- peptidoglycan
- peptidoglycan stem peptides
bacterial DNA
exotoxins
why are exotoxins of gram positive bacteria “superantigens”?
soluble bacterial exotoxins induce widespread T cell activation > inflammatory cytokines released:
- interferon gamma
- TNF-alpha
How can neutrophils lead to extensive host tissue damage?
release of:
- ROS
- proteases
- lysozymes
- lactoferrin
- cathepsins
- defensins
explain the main mechanism of sepsis leading to hypotension
bacterial endotoxins, cytokines like TNF-alpha and IL-1, and mediators like PAF (platelet activating factor) >
> lead to accumulation of iNOS (inducible nitric oxide synthase) >
> high levels of NO produced >
> potent smooth muscle relaxant >
> loss of vasomotor tone >
> septic shock
what are ways to quantify/measure the extent of NO production in dogs?
plasma nitrate and nitrite measurements
= breadown products of NO
have shown to be elevated in septic dogs with SIRS compared to healthy controls
Briefly summarize how inflammation leads to a hypercoagulable state
inflammatory cytokines > upregulate TF (tissue factor) levels > TF combines with VIIa > initate coagulation cascade
TF-VIIa complex and subsequent products trigger release of even more inflammatory cytokines and cause platelet activation
downregulation of anticoagulants
- downregulation of antithrombin, tissue factor pathway inhibitor, tissue plasminogen activator (tPA)
- inhibition of protein C/S pathway > less active protein C
- increased plasminogen activator inhibitor (PAI-1)
Explain how sepsis can lead to cryptic shock
endothelial damage, increased vascular permeability, microcirculatory derangements from:
- endothelial dysfunction
- alteration and damage to the endothelial glycocalyx layer
- rheologic changes to red blood cells
- leukocyte activation
- microthrombosis
- loss of vascular smooth muscle autoregulation
⇒ decreased tissue oxygen extration ⇒ tissue hypoxia
What is cryptic shock?
microcirculatory disturbances despite normal macrohemodynamic variables
What is VEGF?
Vascular endothelial growth factor
- hypoxia-responsive angiogenic factor associated with increasing vascular permeability
- higher levels in septic dogs have been associated with increased mortality
How does increased vascular permeability lead to tissue hypoxia?
increased vascular permeability ⇒ efflux of water, proteins, and solutes into the interstitial space ⇒ increased distance from RBC in capillaries to target cells and mitochondira
what is cytopathic hypoxia?
primary mitochondiral dysfunction, e.g., from sepsis itself
