Infection 5) Pathogenesis of sepsis Flashcards
How many people worldwide does sepsis affect each year?
> 30 million people
What is the definition of systemic inflammatory response syndrome (SIRS)?
2 or more of:
- fever
- tachycardia
- tachypnoea
- leucocytosis
What is the consequence of pro-inflammatory cytokines being released in sepsis?
Increased vascular permeability Decreased vascular resistance Decreased cardiac contractility Increased coagulation Increased neutrophil migration, adhesion Metabolic changes - insulin resistance - protein catabolism
Describe the cardiovascular changes occurring in sepsis
Early distributive shock - peripheral vasodilatation Hypovolaemic shock - cold peripheries - capillary leak, peripheral and pulmonary oedema - low filling pressure Late cardiogenic shock - cardiac myocyte suppression - high filling pressure
Describe the coagulation response in sepsis
Platelet activation
Activation of coagulation cascades
Down-regulation of anticoagulant mediators
Consumption of coagulation factors
What metabolic changes occur in sepsis?
Protein catabolism
Insulin resistance
Decreased tissue oxygen uptake
Give examples of PAMPs
Lipopeptides
Peptidoglycans
Flagellin
Microbial DNA / RNA
Give examples of PRRs
TLRs 1 to 11 CD14 NOD1 and 2 Beta integrins Mannose binding lectin
Give examples of bacteria that can release superantigen exotoxins that can cause toxic shock syndrome
Staphylococcus aureus
Streptococcus pyogenes
How did women present with toxic shock syndrome?
Fever Confusion Diarrhoea Generalised erythema Fulminant hypotension Renal failure Desquamation of palms and soles
Where is S.aureus toxic shock commonly seen now?
Burns patients
ICU - especially neonatal
Nasal and surgical packs
When can streptococcal toxic shock syndrome occur?
Following deep seated S.pyogenes infections
Necrotising fascitis
Myositis, septic arthritis
Describe the immunopathogenesis of toxic shock syndrome
Protein exotoxins of certain bacteria function immunologically as superantigens
Superantigens trigger T cell responses in ≤20% of resting T cells
What is the difference between superantigen and endotoxin mediated sepsis?
Fundamental mechanisms are different
- superantigens initiate by T cell
- endotoxins initiate by APC activation
What is the SOFA score?
Sequential organ failure assessment score
Assesses function of 6 organ systems
Designed for ICU prognostication
In primary care, what patients should be screened for sepsis?
Patients for whom you are considering antibiotics
Patients with ‘‘flu’’
Patients with possible gastroenteritis
Unwell patient without a clear cause
Risk factors: immunosuppression, >75 years, recent trauma or surgery, invasive devices
What is CRP synthesised by?
Hepatocytes
What is CRP regulated by?
IL-6
Give examples of new acute phase reaction biomarkers
PCT
CRP
Give examples of coagulation biomarkers
Protein C receptor
Thrombomodulin
Give examples of cytokine and chemokine biomarkers
IL-6
MCP-1
PCT
Give examples of receptor markers as biomarkers
sTREM-1
LPS binding protein
TLRs
Give examples of endothelial damage biomarkers
Heparin binding protein
Angiopoietin 1 and 2
ICAM-1
Give an example of a cell damage biomarker
miRNA
What potential uses do new biomarkers have?
Exclude sepsis Monitoring responses to treatment Identifying focus Identifying likely pathogen Predicting onset of sepsis / shock Predicting outcome Targeting interventions
