Sepsis and Septic shock Flashcards
What is the definition of sepsis?
- Sepsis derives from the Greek work “sepo” meaning decay or decomposition - Systemic illness caused by microbial invasion of normally sterile parts of the body
What is the traditional pathway of sepsis?
SIRS (systemic inflammatory response syndrome) - Sepsis (SIRS + infection) - Severe sepsis (Sepsis and end organ damage) - Septic shock (severe sepsis and hypotension)
What is the definition of septic shock?
Identified with a 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 Patients with septic shock have a hospital mortality of 40%
What do we use to score sepsis and what are the scores?
JAMA score
0 - 4
What is the criteria of qSOFA?
- Hypotension systolic <100mmHg
- Altered mental status
- Tachypnea RR >22/min
- Score of >= 2 suggestes greater risk of poor outcome
Why is sepsis important?
- Common condition
- Becoming more common
- Increased morbidity
- Increased mortality
For each hour delayed in giving antibs how much does mortality increase?
7.6%
Sepsis: time is ……?
Life
In what three main ways does the body defend against sepsis?
- Physical barrier: skin, mucosa, epithelial lining
- Innate immune system: IgA in GI tract, dendritic cells, macrophages
- Adaptive immune system - lymphocytes, immunoglobulins
What is the origin of sepsis?
- Originates from a breach of integrity of host barrier, whether physical or immunological
- Organism enters the bloodstream creating a septic state
What are the three stages of pathogenesis of sepsis?
- Release of bacterial toxins
- Release of mediators
- Effects of specific excessive mediators
Explain phase 1 in depth.
What are commonly released toxins in stage 1 of pathophysiology in sepsis?
- Bacterial invasion into body tissues is the source of dangerous toxins
- May/may not be cleared by innate immune system
Commonly released toxins
- Gram negative: lipopolysaccaride
- Gram positive: MAMP, staphylococcal toxic shock syndrome toxin
Elaborate on stage 2 of pathophysiology of sepsis.
Release of mediators in response to infection
- Effects of infections due to endotoxin release
- Effects of infections due to exotoxin release
- Mediator role on sepsis
What occurs in the pathway of endotoxin release?
- LPS needs an LPS-binding protein to bind to macrophages
- LTA do not need such proteins
What two types of mediators and what are their roles in sepsis?
- Two types of mediators can be released
- Pro-inflammatory mediators – causes inflammatory response that characterises sepsis
- Compensatory anti-inflammatory reaction – can cause immunoparalysis
What is stage 3 of sepsis?
The effects of specific excessive mediators:
- 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
- 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 the scales are tipped towards the pro-inflammatory side of sepsis?
What occurs when the scales are tipped towards the compensatory anti-inflammatory side of sepsis?
Immunoparalysis with uncontrolled infection and multiorgan failure
What does the clinical features of sepsis depend on?
- Dependent on a number of factors
- Host
- Organism
- Environment
How does organ dysfunction present in: brain, blood, liver, lungs, heart, kidney?
What are the general clinical features of sepsis? (6)
- Fever >38oC – presenting as chills, rigors, flushes, cold sweats, night sweats, etc
- Hypothermia <36oC – especially in the elderly and very young children (remember the immunosuppressed)
- Tachycardia >90 beats/min
- Tachypnoea >20 /min
- Altered mental status – especially in the elderly
- Hyperglycaemia >8mmol/l in the absence of diabetes
What are some of the host effects on the way sepsis presents?
- Age
- Co-morbidities (COPD, DM, CCF, CRF, disseminated malignancy)
- Immunosuppression
- Acquired – HIV/AIDS
- Drug-induced – steroids, chemotherapeutic agents, biologics
- Congenital – agammaglobulinaemia, phagocytic defects, defects in terminal complement component
- Previous surgery - splenectomy
What are some of the organism effects on the way sepsis presents?
- Gram positive versus Gram negative
- Virulence factors (example: MRSA, toxin secretion, ESBL, KPC, NDM-1)
- Bioburden
Effect of environment on sepsis presentation?
- occupation
- travel
- hospitalisation
