Immunopathology of Sepsis Flashcards
what is sepsis
a life-threatening organ dysfunction due to a dysregulated host response to infection
what is sepsis triggered by?
infection in susceptible patients
what is a qSOFA
quick sequential organ failure assessment - tool used to clinically characterise patients at risk of sepsis
what is the baseline qSOFA
0 unless the patient has pre-existing organ dysfunction before the onset of infection
what is SIRS
systemic inflammatory response syndrome
what does the Glasgow Coma Scale assess?
level of consciousness of patients, checks ability to communicate properly, assign a score according to the highest responses
what score on the Glasgow Coma Scale signifies an altered mentation rate?
15
what is the source of sepsis infection?
gram+ bacteria (staph aureus), gram negative bacteria, or fungal (candida)
who gets sepsis?
aging population and medically and immunocompromised patients (cancer, cirrhosis, HIV/AIDS, diabetes)
what is immunopathogenesis associated with?
innate immunity, complement system, vascular endothelium, coagulation system, adaptive immunity
how is sepsis differentiated from infection?
due to the overwhelming immune response triggered by infection that leads to tissue damage and organ failure
what is the pathophysiology of sepsis?
body-wide blood clotting and leaky vessels due to excessive release of inflammatory mediators, one or more organs begin to fail due to lack of blood flow, persistent hypotension
what are pattern recognition receptors (PRRs)
receptors expressed on innate immune cells but also the epithelia, endothelia and fibroblasts. They include TLRs and each receptor has specificity for one or more molecules - PAMPS and DAMPS
what are PAMPS
pattern associated molecular patterns - conserved exogenous factors expressed by pathogens
give examples of PAMPS
LPS, peptidoglycan, nucleic acids
what are DAMPS?
damage associated molecular patterns, endogenous factors, released following cell damage
give examples of DAMPS
heat shock proteins, nucleic acid
what causes the activation of inflammatory signalling pathways?
PAMPS and DAMPS
describe the activation of inflammatory signalling pathways
1 - cell surface and intracellular receptors detect PAMPS and DAMPS
2 - TLR4 recognises some DAMP molecules
3 - both PAMPS and DAMPS activate multiple signalling pathways
4 - each transcription factor regulates transcription of genes
5 - once the cytokines are released by cells, they further activate immune responses and initiate a cascade of other cytokines and chemokines
what does TNF alpha do?
coordinate local containment of infection but drives sepsis when released systematically, recruits immune cells to site of infection, prevents pathogen spreading via blood
what does TNF alpha stimulate the expression of?
adhesion molecules on endothelial cells, proteins that trigger blood clotting
how does TNF alpha contribute to the onset of sepsis and septic shock?
due to the systemic release of TNFa as it causes systemic vasodilation, increased vascular permeability, loss of blood pressure, systemic blood clotting of microvasculature
describe how TNF alpha works?
1 - TNF released by macrophages
2 - TNF acts on blood vessels
3 - local release allows influx of fluid, cells, and proteins to allow host defence
4 - if this is not successful there can be macrophages in the liver and spleen activated and releasing TNF into circulation which leads to intravascular coagulation preventing blood flow to organs causing organ failure and death
when is complement activated?
immediately upon recognition of PAMPS and DAMPS
