Infection 5) Pathogenesis of sepsis

Question 1

How many people worldwide does sepsis affect each year?

Answer 1

> 30 million people

Question 2

What is the definition of systemic inflammatory response syndrome (SIRS)?

Answer 2

2 or more of:

• fever
• tachycardia
• tachypnoea
• leucocytosis

Question 3

What is the consequence of pro-inflammatory cytokines being released in sepsis?

Answer 3

Increased vascular permeability
Decreased vascular resistance
Decreased cardiac contractility
Increased coagulation
Increased neutrophil migration, adhesion
Metabolic changes
 - insulin resistance
 - protein catabolism

Question 4

Describe the cardiovascular changes occurring in sepsis

Answer 4

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

Question 5

Describe the coagulation response in sepsis

Answer 5

Platelet activation
Activation of coagulation cascades
Down-regulation of anticoagulant mediators
Consumption of coagulation factors

Question 6

What metabolic changes occur in sepsis?

Answer 6

Protein catabolism
Insulin resistance
Decreased tissue oxygen uptake

Question 7

Give examples of PAMPs

Answer 7

Lipopeptides
Peptidoglycans
Flagellin
Microbial DNA / RNA

Question 8

Give examples of PRRs

Answer 8

TLRs 1 to 11
CD14
NOD1 and 2
Beta integrins
Mannose binding lectin

Question 9

Give examples of bacteria that can release superantigen exotoxins that can cause toxic shock syndrome

Answer 9

Staphylococcus aureus

Streptococcus pyogenes

Question 10

How did women present with toxic shock syndrome?

Answer 10

Fever
Confusion
Diarrhoea
Generalised erythema
Fulminant hypotension
Renal failure
Desquamation of palms and soles

Question 11

Where is S.aureus toxic shock commonly seen now?

Answer 11

Burns patients
ICU - especially neonatal
Nasal and surgical packs

Question 12

When can streptococcal toxic shock syndrome occur?

Answer 12

Following deep seated S.pyogenes infections
Necrotising fascitis
Myositis, septic arthritis

Question 13

Describe the immunopathogenesis of toxic shock syndrome

Answer 13

Protein exotoxins of certain bacteria function immunologically as superantigens
Superantigens trigger T cell responses in ≤20% of resting T cells

Question 14

What is the difference between superantigen and endotoxin mediated sepsis?

Answer 14

Fundamental mechanisms are different

• superantigens initiate by T cell
• endotoxins initiate by APC activation

Question 15

What is the SOFA score?

Answer 15

Sequential organ failure assessment score
Assesses function of 6 organ systems
Designed for ICU prognostication

Question 16

In primary care, what patients should be screened for sepsis?

Answer 16

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

Question 17

What is CRP synthesised by?

Answer 17

Hepatocytes

Question 18

What is CRP regulated by?

Answer 18

IL-6

Question 19

Give examples of new acute phase reaction biomarkers

Answer 19

PCT

CRP

Question 20

Give examples of coagulation biomarkers

Answer 20

Protein C receptor

Thrombomodulin

Question 21

Give examples of cytokine and chemokine biomarkers

Answer 21

IL-6
MCP-1
PCT

Question 22

Give examples of receptor markers as biomarkers

Answer 22

sTREM-1
LPS binding protein
TLRs

Question 23

Give examples of endothelial damage biomarkers

Answer 23

Heparin binding protein
Angiopoietin 1 and 2
ICAM-1

Question 24

Give an example of a cell damage biomarker

Answer 24

miRNA

Question 25

What potential uses do new biomarkers have?

Answer 25

Exclude sepsis
Monitoring responses to treatment
Identifying focus
Identifying likely pathogen
Predicting onset of sepsis / shock
Predicting outcome
Targeting interventions