302 Bacterial pathogenesis and sepsis Flashcards
What in the membrane makes gram negative bacteria negative?
Lipopolysaccharide and proteins and pores on the outside
What are the different classifications of streptococci?
alpha: haemolytic (partial)
Beta: haemolytic (complete)
Gamma: non-haemolytic
Samples of what, from the body, are usually sterile?
urine and blood
Where is staph aureus a normal commensal of?
The nose (60%)
Which bacteria mainly causes cellulitis
Streptococcus pyogenes
What is necrotising fasciiatis?
A deeper strep pyogenes infection with signs of sepsis
It gets deeper and behaves differently and releases extensive tissue damage
How do you recognise necrotising fasciatis?
-Out of proportion pain
-Bruising and blistering
-Generalised toxaemia
-Renal impairment
-Very high CRP
-Raised creatine kinase sometimes
What are the superficial infections causes by strep pyogenes?
Pharyngitis
Cellulitis
What are the deeper infections caused by strep pyogenes?
Severe soft tissue infection
myositis
Necrotising fasciitis
What are some autoimmune sequalae of s.pyogenes infection?
Rheumatic fever
Glomerulonephritis
Why is lipopolysaccharide considered an endotoxin?
It stimulates a powerful immune response
Which bacteria is a common contaminant of urine and blood?
Staph epidermidis
What host responses in sepsis causes further disease
Dissemination
Cellular damage
Organ damage
What is SIRS?
Systemic inflammatory response syndrome
What are some cardiovascular changes in sepsis?
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)
What are some effects of pro-inflammatory cytokines in sepsis?
↑Vascular permeability
↓Vascular resistance
↓Cardiac contractility
Fever and Diarrhoea
Metabolic changes: Insulin resistance and Protein catabolism
↑Neutrophil migration, adhesion
↑Coagulation
What is the coagulation response in sepsis?
-Coagulation homeostasis disrupted early and profoundly in sepsis
Coagulation and inflammation closely linked:
-Coagulation factors – pro-inflammatory activity
-Anticoagulation factors – anti-inflammatory activity
During sepsis this causes:
-Platelet activation
-Activation of coagulation cascades
-Down-regulation of anticoagulant mediators
-Consumption of coagulation factors
-The term “consumption coagulopathy” is used. The extreme form of which is “Disseminated Intravascular Coagulation”
What does TLR4 detect?
Lipopolysaccharide (LPS)
What is PAMP?
Pathogen Associated Molecular Pattern
Eg. Lipopeptides
Peptidoglycans
Flagellin
Microbial DNA / RNA
What is PRR?
Pattern Recognition Receptor
Eg. LRs1-11
CD14
NOD1 and 2
Beta integrins
What is toxic shock syndrome?
Caused by Staphylococcus aureus or Streptococcus pyogenes
Because they release Superantigen exotoxins
What is the difference between antigens and superantigens?
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
What is the SOFA score?
Sequential Organ Failure Assessment
It assesses if the patient actually has sepsis:
Patients need to have infection and organ damage
What is CRP?
Synthesised by hepatocytes
Regulated by IL6
Following stimulus
Peak 48hrs
t½ 19 hours
Clearance constant in renal disease
Minimal genetic variation
Production impaired in severe liver disease
