Pathophysiology of Sepsis Flashcards
Who is most at risk of sepsis?
- Very young (<1 year) and older adults (>75 years) or the very frail.
- Those with impaired immune system due to illnes or medication.
- Those who have had surgery / invasive procedure in last 6 weeks.
- Anyone with breach of skin integrity (cuts, burns, blisters, skin infection).
- IVD users.
- People with indwelling lines or catheters.
- Women who are pregnant, have given birth or had a termination of pregnancy or miscarriage in the last 6 weeks.
- Neonates.
Define sepsis.
Life-threatening organ dysfunction caused by a dysregulated host response to infection.
Define septic shock.
A subset of sepsis in which particularly profound circulatory, cellular and metabolic abnormalities are associated with greater risk of mortality than sepsis alone.
Give 3 examples of common causative pathogens of sepsis.
- Any 3 from:
- Neisseria meningitidis
- Streptococcus pneumoniae
- Streptococcus pyogenes
- Staphylococcus aureus
- Salmonella typhimurium
- Klebsiella pneumoniae
- Gram negative bacilli
- Candida species
- Asplenics are at risk of infection by encapsulated organisms
What are the main factors affecting infection?
- Virulence of pathogen
- Bioburden
- Portal of entry
- Host susceptibility
- Temporal evolution
Describe the difference between the virulence of a pathogen with endotoxin and without endotoxin.
Use streptococcus pyogenes as an example.
- Without endotoxin, streptococcus pyogenes causes:
- Cellulitis
- Local pain
- With endotoxin, streptococcus pyogenes causes:
- Cellulitis
- Toxic shock
- Hypotension
- Altered mental state
Describe the bioburden of a pathogen based on the number of colony-forming units.
Use salmonella typhimurium as an example.
- 103 CFUs
- Gurgling tummy
- Loose stools
- 105 CFU
- Haemorrhagic colitis
- Fever
- Abdominal pain
Describe the differences in the effect of a pathogen based on host susceptibility.
Use streptococcus pneumoniae as an example.
- In the fit adult, streptococcus pneumoniae will cause:
- Fever
- Pneumoniae
- In the elderly, streptococcus pneumoniae will cause:
- Fever
- Pneumonia
- Physical unsteadiness
- Confusion
- Altered mental state
Describe the principal of temporal evolution using neisseria meningitidis as an example.
- Neisseria meningitidis in its early stage will cause:
- Fever
- Malaise
- Headache
- Myalgia
- Arthralgia
- Neisseria meningitidis in its late stage will cause:
- Septic shock
- Altered mental state
- Hypotension
Give an overview of host innate immunty.
- First line of defence against pathogenic insult.
- Comprises many immune molecules / cells / receptors:
- Complement
- Mannose-binding-lectin (MBL)
- Phagocytes
- Toll-like receptors (TLRs)
- Nucleotide-binding oligomerisation domain receptors (NLRs)
- These may initiate the production of inflammatory markers:
- Interleukins (ILs)
- Tumour necrosis factor alpha (TNFα)
- Reactive oxygen species (ROS)
Describe the acute phase response of TNFα and IL-1.
- Fever
- Hypotension
- Increased HR
- Corticosteroid and ACTH release
- Release of neutrophils
What are the effects of TNFα and IL-1 on the CVS?
- Generalised vasodilation (NO)
- Increased vascular permeability (activated leukocytes)
- Intravascular fluid loss
- Myocardial depression (tissue hypoxia)
- Circulatory shock
What is the SOFA score?
- Screening tool for sepsis.
- Consider screening patient for sepsis if they:
- Present with unexplained illness
- Clearly look unwell and have a likely infective cause OR presents with (or subsequently deteriorate to) and individual parameter score o 3 or aggregate score of 4 or higher on NEWS / locally derived equivalent.
- Screening is a binary decision: this patient COULD have sepsis OR this patient DOES NOT have sepsis.
When should a patient be commenced on the sepsis 6 care pathway?
- Any patient with presumed sepsis with ONE or more red flag should be assumed to have sepsis or septic shock and immediately commenced on SEPSIS SIX care pathway.
What are the red flags when screening for sepsis?
-
Red flags:
- Responds only to voice / unresponsive
- Systolic BP <90mmHg
- HR >130 bpm
- RR ≥ 25
- Needs oxygen to keep SpO2 ≥ 92%
- Non-blanching rash, mottled / ashen / cyanotic
- Not passed urine in the last 18 hours
- Urine output < 0.5ml/kg/hour
- Lactate ≥ 2mmol/L
- Recent chemotherapy
Describe the SEPSIS SIX care pathway.
Which antimicrobials are prescribed (Fife guidelines) for sepsis of unknown origin?
