Sepsis and Septic Shock Flashcards
What is the definition of sepsis?
Life threatening organ dysfunction caused by dysregulation host response to infection
Organ dysfunction can be identified by SOFA score more than 2 (mortality risk)
What is the definition of septic shock?
Can be identified with a clinical construct of sepsis with persisting hypotension requiring vasopressors to maintain MBP > 65mmHg and having serum lactate over 2 mmol/l
What is sepsis?
Systemic illness caused by microbial invasion of normally sterile parts of the body
What is included in SIRS - systemic inflammatory resp. sydnrome?
Temp. above 38C or under 36C, HR>90, RR>20 or PaCO2 <32
WBC >12000 or <4000 or >10% bands
What is qSOFA?
3 categories which score 1 point each
Hypotension - systolic BP <100mmHg
Altered mental state
Tachypnoea - RR > 22
Score of above 2 suggests greater risk of poor outcome
Why is sepsis important?
Common condition, increased mortality and increased morbidity
How much does mortality increase when hour delay in administering antibiotics in septic shock?
Mortality increases by 7.6%
What is the body’s defence against sepsis?
Physical barrier - skin, mucosa and epithelial lining
innate immune system - IgA in GIT, dendritic cells/ macrophages
Adaptive immune system - lymphocytes and immunoglobulins
Describe the origin of sepsis
Originates from breach of integrity of host barrier, whether physical or immunological
Organism enters the bloodstream creating a septic state
Describe the pathophysiology of sepsis
Uncontrolled inflammatory response
Probable change of the sepsis syndrome over time - initially increase in inflammatory mediators, then later shift towards anti-inflammatory immunosuppressive phase
What features are consistent with patients with sepsis having immunosuppression?
Loss of delayed hypersensitivity
Inability to clear infection
Predisposition to nosocomial infection
What are the 3 phases of pathogenesis of sepsis?
Release of bacterial toxins
Release of mediators
Effects of specific excessive mediators
Describe phase 1 - release of bacterial toxins
Bacterial invasion into body tissues
May or may not be neutralised and cleared by existing immune system
Commonly released toxins - gram negative is LPS and gram positive - MAMP and super antigens
Describe phase 2 - release of mediators in response to infection
Effects of infection due to endotoxin release
Effects of infections due to exotoxin release
Mediator role of sepsis
What is involved in endotoxin release?
LPS needs an LPS binding protein to bind to macrophages
LTA do not need these proteins
What is involved in exotoxin release?
Pro-inflammatory response
Small amounts of super antigens will cause a large amount of mediators to be secreted - cascade effect
Describe the mediator role in sepsis
Two types of mediators can be released - Th1 and Th2
Th1 - pro-inflammatory mediators which cause inflammatory response which characterises sepsis
Th 2 - compensatory anti-inflammatory reaction which causes immunoparalysis
What are some main pro-inflammatory and anti-inflammatory mediators?
Pro - TNF-alpha and IL1b,-2,-8 and -15
Anti- IL-1RA,- 4, -10, and -13
What are the effects of pro-inflammatory mediators?
Promotes endothelial cells - leukocyte adhesion
Release if arachidonic acid metabolites
Complete activation
Vasodilatation of blood vessels by NO
Increase coagulation
Causes hypothermia
What are the effects of anti-inflammatory mediators?
Inhibits TNF alpha
Augment acute phase reaction
Inhibits activation of coagulation system
Provides negative feedback mechanisms to pro-inflammatory mediators
What happens if there is more pro-inflammatory response?
Septic shock with multiorgan failure and death
What happens if there is more compensatory anti-inflammatory response?
Immuno-paralysis with uncontrolled infection and multi-organ infection
What can show signs of organ dysfunction in sepsis?
Altered conscious state
Tachypnoea - PaO2< 70mmHg and sats <90%
jaundice as increased liver enzymes, PT and decreased albumin
Oliguria, anuria and increased creatinine
Tachycardia and hypotension
Decreased platelets and protein C
Increased D-dimer
What are the general features of sepsis?
Fever more than 38C - chills, rigors, flushes, cold and night sweats
Hypothermia - elderly and young children
Tachycardia and tachypnoea
Altered mental status
Hyperglycaemia > 8mmol/l
