Sepsis and Septic Shock Flashcards
What is sepsis?
Life-threatening organ dysfunction caused by dysregulated host response to infection
What is septic shock?
Clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MAP >65mmHg and having serum lactate of >2mmol/L despite adequate volume resuscitation
How is organ dysfunction identified in sepsis?
Organ dysfunction identified as acute change in total SOFA score >2
What is sepsis caused by?
Is a systemic illness caused by microbial invasion of normally sterile parts of the body
Describe the traditional model of sepsis?
What is qSOFA used for?
To identify if a patient is likely to require ICU or die in hospital
Score of 2 or more indicates greater risk of poor outcome
What does qSOFA look at?
- Hypotension systolic BP <100mmHg
- Altered mental state
- Tachypnea RR >22/min
What is survival in septic shock based on?
Survival in septic shock is based on antimicrobial delay:
- Each hour delay increases mortality by 7.6%
Remember “time is life”
What are some of the bodies defences against sepsis?
- Physical barrier
- Skin, mucosa, epithelial lining
- Innate immune system
- IgA in gastrointestinal tract, dendritic cells, macrophages
- Adaptive immune system
- Lymphocytes, immunoglobulins
Describe the pathophysiology of sepsis?
- uncontrolled inflammatory response
- features consistent with immunosuppression
- Loss of delayed hypersensitivity
- Inability to clear infection
- Predisposition to nosocomial infection
- probable change of the sepsis syndrome over time
- Initially, increase in inflammatory markers
- Later, shift towards an anti-inflammatory immunosuppressive phase
What are the 3 phases of pathogenesis of sepsis?
-
Release of bacterial toxins
- Bacterial invasion into body tissues source of dangerous toxins
- May or may not be neutralised by existing immune system
- Commonly released toxins
- Gram negative
- Lipopolysaccharide (LPS)
- Gram positive
- Microbial-associated molecular pattern (MAMP)
- Lipoteichoic acid
- Murmyl dipeptides
- Superantigens
- Staphylococcal toxic shock syndrome toxin (TSST)
- Streptococcal exotoxins
- Microbial-associated molecular pattern (MAMP)
- Gram negative
-
Release of mediators
- Effects due to endotoxin release
- LPS needs an LPS-binding protein to bind to macrophages
- LTA do not need such proteins
- Effects due to exotoxin release
- Pro-inflammatory response
- Small amounts of superantigens cause a large amount of mediators to be secreted causing cascade effect
- Mediator role on sepsis
- Two types of mediators can be released
- Pro-inflammatory mediators – cause inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction – can cause immunoparalysis
- Effects due to endotoxin release
-
Effects of specific excessive mediators
- Pro-inflammatory mediators
- Promote endothelial cell – leukocyte adhesion
- Release of arachidonic acid metabolites
- Complement activation
- Vasodilation of blood vessels by NO
- Increase coagulation by release of tissue factors and membrane coagulants
- Cause hyperthermia
- Anti-inflammatory mediators
- Inhibit TNF alpha
- Augment acute phase reaction
- Inhibit activation of coagulation system
- Provide negative feedback mechanism to pro-inflammatory mediators
- Balance between pro and anti-inflammatory mediators determines outcome
- Pro-inflammatory stronger causes septic shock with multiorgan failure and death
- Pro-inflammatory mediators
Anti-inflammatory stronger causes immunoparalysis with uncontrolled infection and multiorgan failure
What are commonly released toxins that cause sepsis?
gram negative
- lipopolysaccharide (LPS)
gram positive
- microbial-associated molecular pattern (MAMP)
- lipoteichoic acid
- murmyl dipeptides
- superantigens
- staphylococcal toxic shock syndrome toxin (TSST)
- streptococcal exotoxins
What are examples of superantigens that can cause sepsis?
- Staphylococcal toxic shock syndrome toxin (TSST)
- Streptococcal exotoxins
What are the 2 types of mediators that can be released in the pathogenesis of sepsis?
- Pro-inflammatory mediators – cause inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction – can cause immunoparalysis
What do pro-inflammatory mediators cause in relation to sepsis?
Cause inflammatory response that characterises sepsis