Immunopathology of sepsis Flashcards
ILO 1.14a: have knowledge of the causes of infection, mechanisms and routes of spread of infection and principles of treatment
what is sepsis?
- life-treatening organ dysfunction to a dysregulated host response to infection
- can be due to infection spread throughout the body via the blood but is not an infection itself
- cannot occur in the absence of infection
what is sepsis shock?
sepsis in which the underlying circulatory and celular and/or metabolic abnormalities are marked enough to substantially increase mortality
what is qSOFA? how does it work?
quick -Sequential Organ Failure Assessment
* tool to clinically characterise patients at risk of sepsis
* baseline qSOFA baseline is 0 unless the patient has pre-existing organ dysfunction BEFORE onset of infection (score of 1 per organ)
* altered respiratory rate greater than 22bpm - increased and shallow
* altered mentation (Glasgow coma scale <15)
* systolic blood pressure <= 100mmHg - low bp
* higher score = more at risk
who is more likely to get sepsis?
5
- very young/old people
- pregnant females
- immunocompromised (transplant, HIV/AIDS)
- pre-existing organ dysfunction (CKD, CVD, diabete, cirrhosis)
- hospital patients
what are the common organ systems that are affected by sepsis?
- neurological (altered mental status)
- pulmonary (hypoxemia)
- cardiovascular (shock)
- renal (oligouria - low urine output)
what is the immunopathogenesis of sepsis associated with the activation of?
5
- innate immunity
- complement system
- vascular endothelium
- coagulation system
- adaptive immunity
describe the pathophysiology of sepsis
- PRRs on immune cells recognise DAMPs and PAMPs but there is excessive immune activation causing widespread inflammation and tissue damage
- pro-inflammatory cytokines are released from activated macrophages and neutrophils which results in increased vascular permeability - hypotension and tissue oedema
- tissue oedema leads to **reduced oxygen delivery ** and ischaemia and so organ dysfunction
- multi-organ failure leads to septic shock and death
what are PAMPs? give examples
pattern associated molecular patterns which are conserved exogenous (non-self) factors expressed by pathogens which activate inflammatory signalling pathways
* e.g. LPS, peptidoglycan, nucleic acids
what are DAMPs? give examples
damage associated molecular patterns which are endogenous (host) factors released following cell damage which activate inflammatory signalling pathways
* e.g. heat-shock proteins, nucleic acids
what is the role of TNFa in sepsis?
- a pro-infammatory cytokine that co-ordinates local containment of infection but drives sepsis when released systemically
- produced by macrophages, monocytes, dendritic cells and neutrophils when PRRs recognise PAMPs
- initiate inflammation but can be harmful in excess
causes:
* systemic vasodilation
* increased vascular permeability
* loss of blood pressure
* systemic blood clotting of microvasculature
what is the role of TNFa?
- produced by macrophages, monocytes, dendritic cells and neutrophils when PRRs recognise PAMPs
- important for controlling local infections
- increases immune cell activation and recruitment to infection sites
- promotes phagocytosis of pathogens
- stimulates the release of other inflammatory mediators (IL-6, IL-1)
- stimulates expression of adhesion molecules on endothelial cells and proteins that trigger blood clotting
- prevents pathogen spreading via blood
how is compliment involved in sepsis?
- it is a hallmark of sepsis
- it is activated immediately upon recognition of ‘pathogenic surfaces’
- all three pathways (classical, mannose-binding lectin and alternative pathways) lead to the formation of C3 convertase which cleaves C3 into C3a and C3b
- generates anaphylatoxins C3a and C5a which cause excessive immune activation - neutrophil overaction, cytokine release, vascular permeability, vasodilation and hypotension, organ failure, septic shock
- activates leukocytes/endothelial cells/platelets and the coagulation system (C3b)
how does sepsis result in hypercoagulation? what is it characterised by?
- complement activates platelets and the coagulation system
- TNFa and other inflammatory mediators stimulates expression of adhesion molecules on endothelial cells and proteins that trigger blood clotting
characterised by:
* microvascular thrombi (blocking of small vessels to prevent bacteria reaching systemic circulation via capillaries)
* haemorrhage (excessive bleeding due to consumption of clotting factors and platelets)
how do you treat sepsis?
- antibiotics (most important)
how does dentistry relate to sepsis?
- sepsis can be a serious complication of acute dental infections
- abcesses and periodontitis can be potential sources
what are the red flag signs and symptoms of spreading dental infection?
6
- temperature <36 or >38
- elevated breathing rate (>20 breaths/min)
- elevated or reduced heart rate
- varying degrees of facial swelling
- trismus
- dehydration
