What is sepsis
Life threatening organ dysfunction due to a dysregulated host response to infection
What is sepsis triggered by
infection (in susceptible patients)
what differentiates sepsis from infection
presence of organ dysfunction
What are the major changes to the definition of sepsis between 1990s and 2016
1990s - focus on inflammation
2016 - focus on organ dysfunction and qSOFA score
What qSOFA score do you need to be at risk of developing sepsis
score of 2 or more
what is qSOFA
a tool to clinically characterise patients at risk of sepsis (at risk of prolonged ICU or death)
what is a person’s baseline qSOFA score
0 unless patient has pre-existing organ dysfunction before onset of infection
what does a qSOFA score of ≥2 mean
overall 10% mortality risk, requires prompt medical intervention
what are SIRS criteria used for
to aid diagnosis of infection
What are the SIRS criteria
‘Systemic inflammatory response syndrome’ (used in 1990s to define sepsis)
Patients experiencing at least 2 of the following symptoms:
- body temp <36,>38
- heart rate >90bpm
- resp rate >20 breaths/pm
- white cell count >12 x10-6l-1
What is the glasgow coma scale (GCS) used for
a way to communicate about the level of consciousness of patients in a coma
- 3 = deep unconciousness
- 15 = concious
What is assessed in the glasgow coma scale
- eyes
- verbal
- motor response
What causes sepsis
any infection can trigger sepsis
what are the most common sites of infection for sepsis
why do the % not add up to 100
- lungs (64%)
- abdomen (20%)
- bloodstream (15%)
- urinary system (14%)
cause of multiple infections
What are the most common sources of infection that trigger sepsis
- gram negative bacteria (62%)
- gram positive bacteria (47%) e.g. staph aureus 20%
- fungal (19%) e.g. candida (17%)
- viral
Which is associated with higher ICU mortality? Candida or bacterial bloodstream infections
candida
What factors cause some infections to progress to sepsis
Microbial
- virulence factors e.g. LPS, Lipoteichoic acid, peptidoglycan, pili, finbriae, capsule etc
- antigens
- competitive adantage
Host factors
- innate immunity
- adaptive immunity
- immuno-compromised e.g. HIV, cancer, organ transplantation
- pre-existing chronic conditions e.g. diabetes, cirrhosis
- age
- genetics
What is the outcome of infection (pathogenicity) determined by
interactions between microbes and host immune response
Why are microbes more pathogenic in immunocompromised hosts
gives them a competitive advantage
Who gets sepsis
- older people
- immunocompromised
Describe the pathophysiology of sepsis
- dysregulated, excessive systemic inflammation
- body-wide blood clotting and ‘leaky vessels’
- organs begin to fail
- persistent hypotension
what is the difference between sepsis and septic shock
Sepsis: Bacteremia or another infection triggers a serious bodywide response (sepsis), which typically includes fever, weakness, a rapid heart rate, a rapid breathing rate, and an increased number of white blood cells
Septic shock: Sepsis that causes dangerously low blood pressure (shock) is called septic shock
Describe normal acute inflammation in response to localised infection
- protective immune reaction to invading microorganisms or endogenous signals from damaged cells
- PAMPS-PRRs
- cytokines, complement
- cardinal signs of inflammation, localised to site of infection
- clearance of the source of injury and necrotic tissues
- elimination of pathogen
- immune suppression via IL-10 and TGF-beta
- followed by tissue repair and return to homeostasis
Describe the immunopathogenesis of sepsis
- immune response fails to eliminate the pathogen
- localised acute inflammation progresses to acute systemic inflammation
- excessive inflammation AND immune suppression
Excessive inflammation
- tissue injury from sustained inflammation
- activation of innate immunity via PAMPS/DAMPS
- complement, coagulation and vascular endothelium activated
Immune supression
- both innate and adaptive
- apoptosis of T and B cells
- dysfunctional DCs
- delayed apoptosis of dysfunctional neutrophils
