sepsis

Question 1

how are infectious disease entities usually defined as?

Answer 1

Organisms
Measles, HIV, Malaria, Meningococcal disease

Anatomical foci
Pneumonia, Meningitis, UTI

Sepsis – a syndrome irrespective of organism or focus

Question 2

what is the problem with the SIRS criteria?

Answer 2

Too sensitive– may represent a healthy response to infective process

Too non-specific – many SIRS patients have non-infective process

‘infection’ (proven or probable) – too hazy. Patients with sepsis easily missed.

Question 3

What is the endotoxin paradigm?

Answer 3

• Gram negative LPS (endotoxin)
• Recognised by TLR4
• Monocyte/macrophage lineage responses
• Proinflammatory state
• Triggers clinical features of sepsis

Question 4

what are examples of other PAMPS apart from LPS?

Answer 4

Lipopeptides
Peptidoglycans
Flagellin
Microbial DNA / RNA

Question 5

what are other PRRs apart from TLR4?

Answer 5

TLRs1-11
CD14
NOD1 and 2
Beta integrins
manose binding lectin

Question 6

what’s the split between gram positive and negative causes of sepsis?

Answer 6

• almost 50:50

Question 7

where are super antigen exotoxins found?

Answer 7

Staphylococcus aureus
Streptococcus pyogenes

• gram positive sepsis
• responsible in spite toxic shock syndrome

Question 8

what are symptoms of toxic shock syndrome?

Answer 8

Fever
Confusion, diarrhoea
Generalised erythema
Fulminant hypotension
Renal failure
~5% mortality
 Desquamation of palms and soles

Question 9

what types of pathogen is responsible for toxic shock in burns patients?

Answer 9

S. aureus

Question 10

what type of strep infection can cause toxic shock syndrome?

Answer 10

Following deep seated S. pyogenes infections
Necrotising fasciitis (flesh-eating disease)
Myositis, septic arthritis etc

Question 11

how do super antigens cause sepsis?

Answer 11

Antigens: trigger T cell responses in tiny proportions of resting T cells

Superantigens: trigger T cell responses in up to 20% of all resting T cells
Superantigen responses are:
Not restricted by antigen specificity of cells
Big

Question 12

compare super antigen and endotoxin mediated sepsis

Answer 12

Fundamental mechanisms different
Initiated by T cell vs APC activation

Superantigens and endotoxin may act synergistically in clinical sepsis
Up to 50,000x augmented responses

Final end-points very similar
Cytokine mediated
Cellular damage, Organ damage
Death

Question 13

what is the scoring system for sepsis in ITU?

Answer 13

SOFA

Assesses function of SIX organ systems

Really designed for ICU prognostication

Question 14

what is the definition of sepsis?

Answer 14

life-threatening organ dysfunction caused by a dysregulated host response to infection

Question 15

what is the scoring system for sepsis outside ITU?

Answer 15

qSOFA

>1 of Tachypnoea: >22, GCS: <15, SBP: <100

Question 16

what times should we give Abx for sepsis?

Answer 16

1 hour time to antibiotics has become embedded

Very little evidence that delays <3-6 hours matter

Question 17

what are the cardiovascular changes seen in sepsis?

Answer 17

Early distributive shock (warm peripheries)
Peripheral vasodilatation

Then hypovolaemic shock (cold peripheries)
Capillary leak, peripheral and pulmonary oedema
Low filling pressure (fluid responsive)

Late cardiogenic shock (cold peripheries)
Cardiac myocyte suppression
High filling pressure (not fluid responsive)

Question 18

what happens to coagulation in sepsis?

Answer 18

Activation of coagulation cascades

Down-regulation of anticoagulant mediators

Consumption of coagulation factors

DIC is a complication of sepsis

Question 19

what are some pathological features of sepsis?

Answer 19

• increase vascular permeability and reduced vascular resistant
• decreased cardiac contractility
• fever and diarrhoea
• insulin resistance and catabolism
• increased neutrophil migration and adhesion
• decreased coagulation