Sepsis Flashcards
CONCEPT OF SEPSIS
i) what is it a syndrome of? what response mostly causes it?
ii) what causes an end point of sepsis? what is the hallmark of sepsis?
iii) what does the sepsis 3 criteria define sepsis as?
i) syndrome irrespective or organism or focus
- caused by host response to high burden of infection
ii) end point of a range of infections
- hallmark is organ damage
iii) life threatening organ dysfunction caused by a dysregulated host response to infection
PATHOGENESIS OF SEPSIS
i) what does sepsis begin with? which process is changed and produces the physiological response seen in sepsis?
ii) which two things change in the vasculature? does this happen early or late? how does this manifest?
iii) how is neutrophil migration and adhesion affected?
iv) what happens to cardiac contractility?
v) what happens to coagulation
i) begins with wide spread recognition of generic microbial elements eg LPS/TLRs
- change in regulation of cytokine gene transcription
ii) changes in vascular permeability (increases) and decrease in vascular resistance (vasodilation) > happens early on and can manifest as shock
iii) increased migrat and adhesion > some pts can become neutropenic
iv) decreased cardiac contractility
v) increased coag which gives a mixed picture of clotting in some small blood vessels but overall increased bleeding
CV CHANGES IN SEPSIS
i) which type of shock is seen early? how will the peripheries feel? why is this?
ii) what shock happens next? how do the peripheries feel? what causes this (3)
iii) what shock happens late? how do peripheries feel? name two things that cause this
i) early distributive shock > warm peripheries
- periph vasodilation
ii) then hypovolaemic shock > cold peripheries
- capillary leak, periph and pulm oedema, low filling pressure
iii) late cardiogenic shock > cold peripheries
- cardiac myocyte supression and high filling pressure (not fluid responsive)
COAGULATION RESPONSE IN SEPSIS
i) when does coagulation disruption occur?
ii) what happens to platelets? (2) what does this ultimately lead to?
iii) what is activated? what does this lead to?
iv) what is downregulated? what is consumed?
v) what is a consumption coagulopathy? what is the extreme form of this?
i) occurs early and profoundly in sepsis
ii) plats are activated and aggregate > depletion of plat counts
iii) activation of coag cascades > leads to coag in small BVs
iv) downreg of anti coag mediators
- consumption of coag factors > bleeding
v) consumption coag = mixed picture of clotting in small blood vessels as well as bleeding elsewhere
- extreme form is DIC
METABOLIC CHANGES IN SEPSIS
i) what happens to protein consumption?
ii) what blood sugar levels are seen? what needs to be done to improve outcomes? what insulin levels are seen
iii) do tissues take up more or less oxygen? what does this leave the body prone to?
iv) name three things that result in tissue hypoxia? what ultimately happens due to this?
i) protein catabolism > consume muscle mass
ii) high blood sugar may be seen > need tight control to improve outcomes
- may see insulin resistance
iii) tissues take up less oxygen > prone to anaerobic resp even if enough oxygen is present
iv) circulatory change, coagulation and metab change result in tissue hypoxia > lactic acidosis (poor prognostic sign)
IMMUNOPATHOLOGY OF SEPSIS
i) which toxin in principally implicated and binds receptors such as complement receptor, MP scavenger receptor and CD14/TLR4?
ii) why does blocking endotoxin or TLR4 not solve the problem of sepsis?
iii) name three gram negative bacteria that can be implicated in sepsis? when did the emergency of gram positives in sepsis happen
i) LPS (endotoxin)
ii) there are many PAMPs (endotox) and PRRs (TLR4) implicated and lots of redundancy within these systems
iii) e coli, klebsiella, pseudomonas
- gram pos emerged in 1990-2000s
GRAM POSITIVE SEPSIS
i) what does gram positive bacteria not contain?
ii) name two things in gram pos that can activate innate immune procesess? what do these act like?
iii) name two superantigen exotoxins that are gram positive?
iv) what specific form of sepsis can these cause?
i) doesnt contain LPS
ii) peptidoglycans and lipotechoic acid > act like LPS in vivo
iii) staph aureus and strep pyogenes > superantigen exotox that excrete into their environment
iv) can cause toxic shock syndrome
TOXIC SHOCK SYNDROME
i) name five things women were presenting with when it was first described?
ii) what can happen during recovery?
iii) what was the most common organism responsible for TSS?
i) fever, confusion, diarrhoea, generalised erythema, fulminant hypotension, renal fail
ii) desquamation of palms and soles (lose skin)
iii) staph aureus
STAPH AUREUS, STREP PYOGENES AND TSS
i) what type of TSS is caused by s aureus? what other type of shock can it cause?
ii) in which patients are there high rates of s aureus TS? which area of the hospital does it occur in most?
iii) which group is strep TS commonly seen in? what can it lead to?
iv) what is the approx mortality for strep TS? what is it associated with?
v) name three things seen in strep TS
i) TSST-1
- can also cause tampon shock - but rare
ii) high rates of staph TS seen in burns patients and on neonate ICU
iii) strep pyogenes - commonly presents in children with severe strep infections eg nec fasc
- can lead to deep seated strep pyogenes infections eg nec fasc, myositis, septic arthritis
iv) high mortality - 20-50%
- associated with superantigen producing strains of s pyogenes
v) erythema, desquamation of palms and soles, nec fasc
IMMUNOPATHOGENESIS OF TOXIC SHOCK
i) what is it caused by? which molecules are the main drivers?
ii) what do these molecules do in relation to T cells?
i) caused by production of exotoxins that function immunologically as super antigens
ii) superantigens strongly activate T cells > up to 20% of all resting T cells
- SA responses not restricted to antigen specificty of cells and are usually large
SUPERANTIGEN VS ENDOTOXIN MEDIATED SEPSIS
i) how do the fundamental mechanisms differ?
ii) how may they work in clinical sepsis?
iii) name three end points that are similar between them
i) superantigen responses are initiated by T cells and endotoxin med sepsis is initiated by APC activation
ii) may act synergistically
iii) final end points - cytokine mediation, cell/organ damage, death
SOFA SCORE
i) what is it? in which setting is it used?
ii) what does a SOFA score of 2 or more from baseline indicate?
iii) what is the qSOFA score? what three things does it look at?
iv) what type of antibiotic should be given when sepsis is suspected? within what time frame
i) assess func of six organ systems - resp, coag, liver, CV, CNS, renal
- used in ITU to assess level of organ dysfunction
ii) >2 from baseline indicates life threatening organ dysfunction
iii) qSOFA = used outside ITU
- looks at tachypnoea, GCS and SBP
- tachypnoea >22, GCS <15, SBP <100 - need more than one of these for organ dysfunc
iv) empric broad spec abx to cover all likely pathogens within an hour
KEY LEARNING POINTS
i) what two things does a person have to be labelled as having sepsis?
ii) which two things are urgent
iii) what should be sent for when systemic abx are started?
i) need infection and organ dysfunction
ii) antibiotics commencing and a senior review
iii) send cultures
BIOMARKERS
i) which cells is CRP snth by? what IL regulates it? after how many hours to levels peak post stimulus?
ii) in which case is production of CRP impaired?
iii) which biomarker was discovered as a BM for small cell lung cancer but later seen to be used as a BM for sepsis?
i) CRP is synth by hepatocytes and regulated by IL-6
- peaks 48hrs post stimulus
ii) production of CRP impaired in severe liver disease
iii) Procalcitonin
