Clinical aspects of sepsis Flashcards
What is purpura fulminans?
Bleeding into skin and it’s commonly caused by meningococcal septicaemia
What are Koch’s postulates?
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
What is sepsis?
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
What is SIRS?
Systemic inflammatory response syndrome- body expressing its displeasure about whats going on within the body
Sepsis is a non-specific clinical response and includes 2 or more of what?
Temperature >38 degrees or <36 degrees
Heart rate >90 beats/min
Resp rate >20/min
White blood cell count >12000/mm3 or <4000/mm3
What is severe sepsis?
Sepsis with signs of at least one acute organ dysfunction: Renal Resp Hepatic Haematological CNS Unexplained metabolic acidosis Cardiovascular
What is septic shock?
Severe sepsis with hypotension despite giving fluid to restore adequate volume
What is the SOFA?
Sepsis- related Tr organ failure assessment- rate how deranged organ functions are
What is the most important organ affected in sepsis?
Vascular endothelium
Where are the bacteria involved in Gram-negative sepsis found?
In the gut
What is a key factor associated with Gram-negative toxicity?
LPS
What does LPS consist of?
Lipid A- toxic
Core region
O-antigen polysaccharide
What happens when you just administer isolated endotoxin?
Effects that are similar to Gram negative infection
What are the direct effects of LPS?
Triggers complement
Coagulation, fibrinolytic and kinin pathways
What are the indirect effects of LPS?
Initiator of cytokine cascade in inflammatory response
What are the main nosocomial infections?
ESCAPE pathogens
Most important is pneumonia
What happens to endotoxin in circulation?
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
Why can’t CD14 directly talk to the inside of the cell?
It doesn’t have a transmembrane domain
How does CD14 talk to the inside of the cell?
TLR4 binds to CD14 and then talks to the genome leading to transcriptional changes within the cell (production of inflammatory cytokines, recruitment of neutrophils)
Why does endotoxin cause alveolar damage?
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
How does endotoxin cause oedema?
The endothelium begins to come apart to allow neutrophils into tissues and this means that the vascular endothelium is leaky leading to oedema
What else does the response to endotoxin lead to?
Unregulated release of nitric oxide which causes vasodilation and a drop in blood pressure
What is the role of the endothelium?
Interacts with leukocytes
Release of cytokines and inflammatory mediators
Release of mediators of vasodilation and vasoconstriction
Functional effects on coagulation system
What are the different types of cardiovascular failure?
Hypovolaemia- Disease, leak, reduced vascular tone
Hypotension- Hypovolaemia, reduced vascular tone, myocardial depression
Shock- Failure in oxygen supply and utilisation
What types of cardiovascular support are there?
Maintenance of circulating volume- give fluid
Restoration of blood pressure using vasoactive drugs- e.g. adrenaline/noradrenaline, dobutamine and vasopressin
What are the variety of causes for renal failure?
Hypovolaemia
Hypotension
Intrinsic vasoconstriction
Acute tubular necrosis
What types of renal support are there?
Volume resuscitation
Blood pressure restoration
Diuretics
Renal replacement therapy- dialysis
How is sepsis managed?
Recognise patients at risk of sepsis or that have sepsis Resuscitation Call for help Provisional diagnosis Investigation and sampling Early antibiotics Source control
What do you measure within 3 hours of identifying a potential case of sepsis?
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
What is the sepsis six?
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
