Sepsis and Septic Shock Flashcards
What is sepsis?
Systemic illness caused by microbial invasion of normally sterile parts of the body
What is the traditional mode of sepsis?
SIRS
-Hypo/hyperthermic, tachycardia, tachypnoea, high/low WCC
Sepsis
-SIRS + infection
Severe sepsis
-Sepsis + end organ damage
Septic shock
-Severe sepsis + hypotension
Sepsis
A life-threatening organ dysfunction caused by dysregulated host response to infection
How is organ dysfunction identified?
- Organ dysfunction can be identified as an acute change in total SOFA score >2 points consequent to the infection
- SOFA score >2 reflects an overall mortality risk of approximately 10% in a general hospital population with suspected infection
Septic Shock
Clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg and having a serum lactate of >2mmol/l despite adequate volume resuscitation
What does qSOFA identify?
Patients with suspected infection who are likely to have a prolonged ICU stay or die in the hospital can be promptly identified with a qSOFA
What are the components of qSOFA?
Score of 2 or more suggest greater risk of poor outcome
- Hypotension systolic BP <100mmGg
- Altered mental status
- Tachypnoea (RR>22)
Why is sepsis so important?
- Common condition
- Becoming more common
- Increased morbidity
- Increased mortality
What defences does the body have against sepsis?
Physical barrier
-Skin, mucosa, epithelial lining
Innate immune system
-IgA in GIT, dendritic cells/macrophages
Adaptive immune system
-Lymphocytes, immunoglobulins
How does sepsis originate?
- Originates from a breach of integrity of host barrier, whether physical or immunological
- Organism enters the bloodstream creating a septic state
Essentially what is sepsis?
An uncontrolled inflammatory response
What features consistent with immunosuppression do patients with sepsis exhibit?
- Loss of delayed hypersensitivity
- Inability to clear infection
- Predisposition to nosocomial infection
What is the shift of the sepsis syndrome that occurs over time?
- Initially there is an increase in inflammatory mediators
- Later, there is a shift toward an anti-inflammatory immunosuppressive phase
- Depends on the health of the individual patient
What are the 3 phases of the pathogenesis of sepsis?
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
What commonly release toxins can be responsible for sepsis?
Gram negative
-Lipopolysaccharide
Gram positive
-Microbial associated molecular pattern (MAMP)
-Lipoteichoic acid
-Muramyl dipeptides
Superantigens
-Staphylococcal toxic shock syndrome toxin (TSST)
-Streptococcal exotoxins
What happens in phase 2 of sepsis (release of mediators)?
- Effects of infection due to endotoxin release
- Effects of infections due to exotoxin release
- Mediator role on sepsis
How are endotoxins released?
- LPS (gram negative) require a binding protein to bind to the toll like receptor
- LTA (gram positive) do not require a protein to bind to the toll like receptor
- Binding to toll like receptors on macrophages leads to release of mediators
How are exotoxins released?
Pro-inflammatory response caused by small amounts of super antigens causing a large amount of mediators to be secreted in a cascade effect
What are the 2 types of mediators which can be released in sepsis?
- Pro-inflammatory mediators which cause the inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction which can cause immunoparalysis
What is the effect of excessive pro-inflammatory mediators?
- Promote endothelial cell – leukocyte adhesion
- Release of arachidonic acid metabolites
- Complement activation
- Vasodilatation of blood vessels by NO
- Increase coagulation by release of tissue factors and membrane coagulants
- Cause hyperthermia
