sepsis Flashcards
(33 cards)
what is sepsis?
life-threatening organ dysfunction due to dysregulated host response to infection
what is sepsis triggered by?
infection
what differentiates sepsis from infection?
organ dysfunction
what causes the organ dysfunction?
overwhelming immune response
how is organ dysfunction identified?
acute change in total SOFA score of >_ 2 points
what is SOFA?
a tool to clinically characterise px at risk of sepsis (prolonged ICU or death)
what is the SOFA criteria?
resp >_ 22 breaths/min
altered mentation (ggow coma scale <15)
systolic bp
what is baseline SOFA?
0, unless px has pre-existing organ dysfunction before onset of infection
what are the common sites of infection causing sepsis?
lungs
abdomen
bloodstream
urinary system
what are the common sources of infection causing sepsis?
gram + bacteria -staph aureus gram - bacteria fungal -candida -associated with higher mortality
who is more likely to get sepsis?
older people medically/immune compromised px cancer cirrhosis autoimmunity HIV/AIDS organ transplantation diabetes
what inflammatory pathways are activated?
innate immunity complement system vascular endothelium coagulation system adaptive immunity
what is the pathophysiology of sepsis?
body-wide blood clotting and leaky vessels
one or more organs begin to fail
persistent hypotension
describe PRRs
pattern recognition receptors
-can be specific to one or more molecules
activated by PAMPs/DAMPs
leads to activation of inflammatory signalling pathways
what are PAMPs?
pattern-associated molecular patterns conserved exogenous (non-self) factors expressed by pathogens eg LPS, peptidoglycan, nucleic acids
what are DAMPs?
damage-associated molecular patterns
endogenous (host) factors released following cell damage
eg heat-shock proteins, nucleus acid
what does TNF-alpha coordinate?
local containment of infection, but drives sepsis when released systemically
what does TNF-a do?
stimulates expression of: -adhesion molecules on endothelial cells -proteins that trigger blood clotting recruits immune cells to site of infection prevents pathogen spreading via blood
how does systemic release of TNF-a contribute to onset of sepsis and septic shock?
systemic vasodilation
increased vascular permeability
loss of blood pressures
systemic blood clotting of microvasculature
what is the hallmark of sepsis?
complement
how does complement contribute to sepsis?
activated immediately upon recognition of PAMPs and DAMPs
generation of peptides C3a and C5a
C5a drives immunopathogenesis
potent chemoattractant
further amplifies inflammation
contributes to vasodilation, tissue damage and organ failure
why do changes in vascular endothelium occur during sepsis?
response to inflammatory stimuli
-endothelial barrier dysfunction
what are the characteristics of a hypercoagulative state?
microvascular thrombi fibrin deposition neutrophil extracellular trap formation endothelial injury
what effect does sepsis have on the coagulation system?
results in a hypercoagulative state
