Clinical aspects of sepsis

Question 1

What is purpura fulminans?

Answer 1

Bleeding into skin and it’s commonly caused by meningococcal septicaemia

Question 2

What are Koch’s postulates?

Answer 2

Characteristics of things that cause disease, to establish that an organism causes disease, it must:
Be found in all cases of disease examined
Prepared and maintained in a pure culture
Capable of producing original infection even after several generations in culture
Be retrievable from an inoculated animal and cultured again

Question 3

What is sepsis?

Answer 3

Series of pathological processes that make people very ill and can be caused by a number of different routes
SIRS with a presumed or confirmed infectious process

Question 4

What is SIRS?

Answer 4

Systemic inflammatory response syndrome- body expressing its displeasure about whats going on within the body

Question 5

Sepsis is a non-specific clinical response and includes 2 or more of what?

Answer 5

Temperature >38 degrees or <36 degrees
Heart rate >90 beats/min
Resp rate >20/min
White blood cell count >12000/mm3 or <4000/mm3

Question 6

What is severe sepsis?

Answer 6

Sepsis with signs of at least one acute organ dysfunction:
Renal
Resp
Hepatic
Haematological
CNS
Unexplained metabolic acidosis
Cardiovascular

Question 7

What is septic shock?

Answer 7

Severe sepsis with hypotension despite giving fluid to restore adequate volume

Question 8

What is the SOFA?

Answer 8

Sepsis- related Tr organ failure assessment- rate how deranged organ functions are

Question 9

What is the most important organ affected in sepsis?

Answer 9

Vascular endothelium

Question 10

Where are the bacteria involved in Gram-negative sepsis found?

Answer 10

In the gut

Question 11

What is a key factor associated with Gram-negative toxicity?

Answer 11

LPS

Question 12

What does LPS consist of?

Answer 12

Lipid A- toxic
Core region
O-antigen polysaccharide

Question 13

What happens when you just administer isolated endotoxin?

Answer 13

Effects that are similar to Gram negative infection

Question 14

What are the direct effects of LPS?

Answer 14

Triggers complement

Coagulation, fibrinolytic and kinin pathways

Question 15

What are the indirect effects of LPS?

Answer 15

Initiator of cytokine cascade in inflammatory response

Question 16

What are the main nosocomial infections?

Answer 16

ESCAPE pathogens

Most important is pneumonia

Question 17

What happens to endotoxin in circulation?

Answer 17

It gets bound to by lipopolysaccharide binding protein (LBP). This endotoxin-LBP complex then binds to a receptor (CD14) on macrophages/monocytes- this sends a message to the genome of the cell so that it reacts in a particular way

Question 18

Why can’t CD14 directly talk to the inside of the cell?

Answer 18

It doesn’t have a transmembrane domain

Question 19

How does CD14 talk to the inside of the cell?

Answer 19

TLR4 binds to CD14 and then talks to the genome leading to transcriptional changes within the cell (production of inflammatory cytokines, recruitment of neutrophils)

Question 20

Why does endotoxin cause alveolar damage?

Answer 20

Neutrophils are recruited and they are actually quite big-
around the same size as pulmonary capillaries so they start to get stuck and end up in alveoli where they release various cytokines that damage the alveoli

Question 21

How does endotoxin cause oedema?

Answer 21

The endothelium begins to come apart to allow neutrophils into tissues and this means that the vascular endothelium is leaky leading to oedema

Question 22

What else does the response to endotoxin lead to?

Answer 22

Unregulated release of nitric oxide which causes vasodilation and a drop in blood pressure

Question 23

What is the role of the endothelium?

Answer 23

Interacts with leukocytes
Release of cytokines and inflammatory mediators
Release of mediators of vasodilation and vasoconstriction
Functional effects on coagulation system

Question 24

What are the different types of cardiovascular failure?

Answer 24

Hypovolaemia- Disease, leak, reduced vascular tone
Hypotension- Hypovolaemia, reduced vascular tone, myocardial depression
Shock- Failure in oxygen supply and utilisation

Question 25

What types of cardiovascular support are there?

Answer 25

Maintenance of circulating volume- give fluid | Restoration of blood pressure using vasoactive drugs- e.g. adrenaline/noradrenaline, dobutamine and vasopressin

Question 26

What are the variety of causes for renal failure?

Answer 26

Hypovolaemia Hypotension Intrinsic vasoconstriction Acute tubular necrosis

Question 27

What types of renal support are there?

Answer 27

Volume resuscitation Blood pressure restoration Diuretics Renal replacement therapy- dialysis

Question 28

How is sepsis managed?

Answer 28

``` Recognise patients at risk of sepsis or that have sepsis Resuscitation Call for help Provisional diagnosis Investigation and sampling Early antibiotics Source control ```

Question 29

What do you measure within 3 hours of identifying a potential case of sepsis?

Answer 29

Lactate because it is produced when the body is breaking down glucose but not using it properly because of a lack of available oxygen so it's a marker of not being very well

Question 30

What is the sepsis six?

Answer 30

``` Model for managing sepsis: Administer high flow oxygen Take blood cultures and consider infective source Administer IV antibiotics Give IV fluid resuscitation Check haemoglobin and serial lactates Commence hourly urine output measurement ```