Sepsis Flashcards
(36 cards)
what is sepsis?
life threatening organ dysfunction due to a dysregulated host response to infection
what is a SOFA score?
score which assesses the risk of organ failure in patients
what are the signs and symptoms of systemic inflammatory response syndrome? (SIRS)
patients experiencing two of the following symptoms:
- body temperature > 38°C or < 36°C
- rapid heart rate (>90 beats per minute)
- rapid respiratory rate (>20 breaths per minute or arterial CO2 <32mmHg)
- high white blood cell count ( >12x10^9l)
what are the signs and symptoms of sepsis?
systemic inflammatory response syndrome and proven or suspected infection
what would classify as severe sepsis?
sepsis and acute organ dysfunction
signs and symptoms of a patient suffering from septic shock?
sepsis and persistent hypotension after fluid resuscitation
what is a tool that helps to characterise patients at risk of sepsis/
qSOFA
what is the baseline qSOFA?
0 (unless patient has pre-existing organ dysfunction before onset of infection)
what is the most common cause of sepsis?
bacterial infection
examples of conditions that may make patients more at risk of developing sepsis?
- cancer
- cirrhosis
- autoimmunity
- HIV/AIDS
- organ transplantation
- diabetes
what is the immunopathogenesis of sepsis associated with?
activation of:
- 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 begins to fail
- persistent hypotension
what are pattern recognition receptors? (PRRs)
receptors expressed by the host (on host cells, innate immune cells, endothelial cells, fibroblasts) which recognise:
- PAMPs
- DAMPs
what are PAMPs?
conserved exogenous (non-self) factors expressed by pathogens - molecules expressed by pathogens
what are DAMPs?
endogenous (host) factors released following cell damage
- nucleic acid
- heat shock proteins
if PRRs are activated (by PAMPs or DAMPs) what occurs?
activation of inflammatory signalling pathways
what are Toll-like receptors?
they are pattern recognition receptors (PRRs) which play a crucial role in the activation of the innate immune response
what is TNFalpha?
a master regulator cytokine
what is the function of TNFalpha? how can this affect sepsis?
it co-ordinates local containment of infection but drives sepsis when released systemically
how does TNFalpha control local infections?
TNFa stimulates expression of:
- adhesion molecules on endothelial cells
- proteins that trigger blood clotting
TNFa also recruits immune cells to site of infection and prevents pathogen spreading via blood
what does the systemic release of TNFa contribute to?
onset of sepsis and septic shock by:
- systemic vasodilation
- increased vascular permeability
- loss of blood pressure
- systemic blood clotting of microvasculature
how does activation of the complement system drive sepsis?
- complement pathway is activated immediately upon recognition of PAMPs and DAMPs
- this causes generation of peptides C3a and C5a (extremely inflammatory)
- C5a drives immunopathogenesis of sepsis as it is a potent chemoattractant (for macrophages, neutrophils and monocytes)
- this further amplifies inflammation by contributing to vasodilation, tissue damage and organ failure
what changes occur in the vascular endothelium in response to inflammatory stimuli during sepsis?
- endothelium is converted to a pro-coagulant state
- the disrupted endothelium mediates loss of fluid & also facilitates the recruitment, attachment and extravasion of INFLAMMATORY CELLS through the endothelium
what effect does sepsis have on the coagulation system?
sepsis results in a hypercoagulative state, characterised by:
- microvascular thrombi
- fibrin deposition
- neutrophil extracellular trap formation
- endothelial injury
