Sepsis and Septic Shock Flashcards
(50 cards)
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
What is the effect of excessive anti-inflammatory mediators?
- Inhibit TNF alpha
- Augment acute phase reaction
- Inhibit activation of coagulation system
- Provide negative feedback mechanisms to pro-inflammatory mediators
What happens when there is loss of balance between immune responses in favour of pro-inflammatory mediators?
Septic shock with multi-organ failure and death
What happens when there is loss of balance between immune responses in favour of compensatory anti-inflammatory mediators?
Immunparalysis with uncontrolled infection and multi-organ failure
What does the clinical manifestation of sepsis depend on?
- Host
- Organism
- Environment
