SIRS and sepsis Flashcards
What are PRRs, DAMPs and PAMPs?
PRRs
- Pattern recognition receptors (also know as TLRs/Toll like receptors)
- interact with PAMPs and DAMPs => immune response
DAMPs
- Damage Associated Molecular Patterns
- antigens associated with damaged or dead host cells
PAMPs
Pathogen Associated Molecular Patterns
What is systemic inflammatory response syndrome (SIRS)?
A self-amplifying, dysregulated systemic inflammatory response
Non-infectious causes:
- burns
- neoplasia
- pancreatitis
Can lead to coagulopathies and other clinical effects
What is sepsis?
SIRS (systemic inflammatory response syndrome) + infection within patient (caused by bacteria, fungi, viruses or protozoa
Inflammatory response in sepsis involves leukocyte activation in response to PAMPs and DAMPs
Exacerbated production of pro- and anti-inflammatory cytokines - dysregulated response to infection
A hyperactive response to infection which could induce immune paralysis
Describe severe sepsis
- sepsis with severe organ hypo-perfusion or organ dysfunction
- no predictive biomarkers or therapeutic markers
What factors affect the clinical manifestation of sepsis?
site of infection
Source of infection
Health status of patient
Time of diagnosis and treatment
Why is spontaneous sepsis common in horses?
horses have a susceptibility to developing bacterial endotoxins and their predisposition to GI diseases e.g., colic and diarrhoea
Give examples of pro-inflammatory enzymes
iNOS
COX-2
Give examples of pro-inflammatory cytokines
TNFa
IL-6
IL-4
Give examples of anti-inflammatory cytokines
IL-10
Soluble TNF receptors
IL-4
IL-11
What is septic shock
Severe sepsis + systemic hypotension
Common in foals and small animals
Increased HR, plasma adrenaline and noradrenaline
Decreased BP
Leukocytosis
Form of distributive shock - vasodilation, hypovolaemia
What is MODs?
Multi-organ dysfunction syndrome = Altered organ function in an acutely ill animal such that hemostasis cannot be maintained without intervention
What is primary MODs?
Well-defined insult
Organ dysfunction occurs early
A direct consequence of the insult itself – burns and neoplasia
What is secondary MODs?
Organ failure not in direct response to the insult
A consequence of a host response (SIRS)
Dynamic process that is reversible if detected early enough
What is DIC?
Disseminated intravascular coagulation
‘consumptive coagulopathy’
increased risk of bleeding due to pro-coagulatory agents and platelets being used up
What is the effect of DIC?
Pathological activation of coagulation =>
- Microvascular clotting
- haemorrhagic diathesis (impaired synthesis of clotting factors)
- Consumption of procoagulants
- excessive thrombin and fibrin in circulating blood causing increased platelet coagulation (a result of endothelial glycocalyx disruption)
- en
What other pathologies are commonly associated with DIC?
SIRS
Sepsis
Septic shock
MODS
systemic neoplasia
enteritis and colitis
What are the clinical signs of DIC in large animals?
Thrombosis=>
- petechial haemorrhages
- bleeding following trauma e.g., surgical sites
How can DIC be diagnosed?
Thrombocytopenia (low platelet count)
Prolonged PT or aPTT
Increased fibrin degradation products
Decreased antithrombin 3
D-dimers - biomarker of ongoing fibrin lysis
Why is low fibrinogen not used as a sign of DIC?
Reference range is <4g/L - in cases of low fibrinogen you cannot tell how low it actually is
