Sepsis/SIRS/MODS Flashcards
Risk factors for nosocomial VAP?
age, obesity, chronic lung disease, previous pneumonia, sepsis, head trauma, stress ulcer prophylaxis, paralytics, enteral nutrition, multiple transfusions, immunosuppression, tracheostomy, reintubation, frequent vent circuit changes, multi central lines, u cath, post op infection
Guidelines for initiating empirical abs for suspected CRBSI
indwelling cath >48h, evidence of cath site infection, fever, hypotension, tachycardia, leukocytosis
In gram negative sepsis, LPS binds?
TLR-4
In gram positive sepsis, lipoteichoic acid binds?
TLR-2
Examples of PAMPs?
LPS, lipopeptides, lipoteichoic acid, flagellin, micobial DNA, microbial RNA
What are the downstream effects of activating PAR-1
synthesis of platelet activating factor, IL-6, IL-8, P-selectin, and adhesion molecule expression
Each hour delay in effective antimicrobial administration AFTER 6 HOURS of spetic shock decreases survival by what %?
7.6%
PRR stands for?
pattern recognition receptor
Major findings of CORTICUS NEJM 2008 study of hydrocortisone therapy in septic shock?
Hydrocortisone did NOT improve survival or reversal of shock in patients with septic shock, overall of in patients who did not have a response to corticotropin.
BUT, reversed shock faster in whom shock was reversed.
Increased incidence of superinfection, including new episodes of sepsis or septic shock, in the hydrocortisone group. Higher glucose in steroid group
What are caspases? Why they important?
- Cysteine proteases: degrade cellular proteins at aspartic acid sites along protein sequences
- Mediate programmed cell death
- Part of inflammasome signaling pathway
- Contribute to synthesis of mature IL-1
- Caspase dependent apoptosis of B and T cells
- Central to pathogenesis of sepsis-induced immunosuppression
List the criteria used to define SIRS in clinical patients
dogs- must have at least 2/4 criteria cats- must have at least 3/4 criteria temp: dogs 102.6, cats 104 HR: dogs >120, cats 225 RR: dogs >20, cats >40 WBC: dogs 16 or >3% bands, cats >19
what is the specificity and sensitivity of using the proposed SIRS criteria (temp, wbc, rr, hr) in dogs
sensitivity 97%
specificity 64%
list some factors from gram - & gram + bacteria and fungi that are known to induce inflammation via stimulation of monocytes and macrophages
LPS (gram -), lipoteichoic acid (gram +), peptidoglycan (gram +), flagellin (gram -), mannan (fungi)
list some pro-inflammatory mediators responsible for SIRS
TNFa, IL-6, prekallikreins, bradykinin, platelet activating factor
Name some anti-inflammatory mediators that are released in response to pro inflammatory mediators such as TNFa with SIRS
IL10, TGFb, IL13, reduction of B and T lymphocyte production, production of TNFa receptor antagonists
what type of disruptions of homeotasis occur with SIRS
loss of vascular tone, disruption of endothelial permeability barrier, stimulation of coagulation
what is the mechanism of loss of vascular tone in SIRS
excessive inducible nitric oxide synthase production, possible deficiency of vasopressin, possible cortisol deficiency
what is the mechanism of disruption of endothelial permeability barrier in SIRS?
cytokine production
list some reasons why hypercoagulability occurs with SIRS
- induced by cytokine-mediated tissue factor expression on leukocyte surface
- leads to fibrin deposition on microvascular surface
- anticoagulation factors such as protein C, TFPI, and AT are consumed and may be impaired as well
- TNFa downregulates protein C, which is an anti-inflammatory & anticoagulant protein
What 2 biomarkers are listed in hopperstein “SIRS” chapter that are extensively studied in human medicine to differentiate sepsis vs sirs?
C reactive protein
procalcitonin
what does the acronym PIRO stand for in regards to sepsis?
predisposition, insult/infection, response, organ dysfunction
describe CRP and its potential use for ID of sepsis
- acute phase protein, produced by hepatocytes in response to TNFa, IL-1b
- peaks 36-50 hrs after secretion; half life 19 hours
- increase in CRP in sepsis but also trauma, surgery, pancreatitis, myocardial infarction
- non-specific, not ideal marker
describe procalcitonin and its potential use for ID of sepsis
- precursor to calcitonin
- normally produced by thyroid gland; in sepsis may originate from mononuclear leukocytes after endotoxin/cytokine stimulation
- released hours after stimulation; peak up to 24 hrs
- increases nitric oxide release
- superior to CRP for biomarker of sepsis
- appears to be related to severity of inflammation and may have prognostic value in septic shock and sepsis
T/F: antagonist of TNFa, IL1, PAF have failed to show a survival benefit in people with sepsis
true; some studies show detrimental effects
which of the following have shown potential survival benefit with sepsis?
a-ibuprofen b-steroids c-IVIG d-statins e- recombinant human activated protein C
C & E
Statins have not been extensively studied yet
E- Protein C has had mixed results; some show no benefit, no longer available on market
in one study, dogs with and without SIRS (when compared to healthy controls) showed which coagulation abnormalities?
prolonged PT; PTT
reduced AT
reduced protein C
Name the diseases in small animals in which CRP has been shown to be elevated
IMHA, MMVD, neoplasias, pyometra
what are some biochemical abnormalities assoc with sirs?
hyper or hypoglycemia, hypoalbuminemia, elevated ALT and AST, +/- hyperbilirubinemia, evidence of tubular and glomerular dysfxn
what are the proposed mechanisms for increased t bili in SIRS?
cholestasis, immune mediated hemolysis
proposed mechanisms for hypoalbuminemia in SIRS?
negative acute phase protein, losses thru changes in endothelial permeability
