Exam 3 - Endotoxemia Flashcards
what is endotoxemia?
clinical manifestation of a systemic inflammatory response to a circulating endotoxin
subset of sepsis
what makes the endotoxin in gram negative bacteria?
LPS
o specific chain
core region
lipid A - most antigenic part
T/F: 30% of horses with endotoxemia will not have detectable levels of endotoxins
true
what is the difference between an endotoxin & an exotoxin?
endotoxin - LPS attached to the outer membrane of bacterium which is liberated when the cell wall is broken
exotoxin - proteins are produced inside the bacterium & are secreted or liberated upon cell death
what are the 3 steps of the cellular cascade of endotoxemia?
- LBP-LPS binding to TLR
- NF-kB activation
- gene expression & products release
when there is activation of NF-kB, what cytokines are involved in causing clinical signs including: fever, tachypnea, leukocytosis, leukopenia, & obtundation?
TNF-a, IL-1, & IL-6
why can you see thrombosis, hemorrhage, & DIC in horses with endotoxemia?
activation of TF & factor VIII - these both activate intrinsic & extrinsic pathways & impair fibrinolysis which activates coagulation leading to the clinical signs
NF-kB activation activates ICAM-1, VCAM-1, B2 integrins, e-selectin, & chemokines leading to what cascade?
endothelial damage!!!! neutrophils become activated & cause release of ROS, RNS, & proteolytic enzymes which cause endothelial activation/injury leading to increased endothelial permeability (tissue injury)
what is the major player in vasodilation as a part of the endotoxemia cascade in NF-kB activation?
nitric oxide - causes hypotension, cardiovascular hyporeactivity, tissue hypoperfusion, & hypoxia
what do reactive oxygen species cause in endotoxemia?
endothelial damage & potentiation of inflammation
what is the major vasoactive mediator?
nitric oxide
what are the major inflammatory cytokine mediators of endotoxemia?
IL-1, IL-6, & TNF-a
what are the major procoagulant mediators in endotoxemia?
tissue factor & factor VIII
which is not produced as a result of NF-kB activation:
a. IL-10
b. TNF-a
c. IL-6
d. iNOS
a. IL-10
what 3 components make up virchow’s triad?
- hypercoagulable state
- endothelial damage
- abnormal blood flow
on a cellular level, what’s going wrong in endotoxemia?
- endothelial adhesion by neutrophils & reduced chemotaxis - low WBC because they are sequestered
- increased metabolic demands by the cell
- impaired oxygen use by the cell - mitochondria is not acting like the normal powerhouse
what cardiovascular effects are seen in early endotoxemia?
- decreased preload
- left ventricular dysfunction
- arterial vasodilation
what is the major cause of death in endotoxemia?
myocardial depression!!!!!!
what 3 components of hemodynamic stability are affected in endotoxemia?
- hypovolemia
- abnormal perfusion distribution
- myocardial depression
when comparing infection, SIRS, sepsis, severe sepsis, & septic shock, how do they differ?
- infection - microbial invasion
- SIRS - exaggerated inflammation, doesn’t have to have bacteria present, can be sterile
- endotoxemia/sepsis - exaggerated inflammation with infection
- severe sepsis - exaggerated inflammation with infection with organ failure
- septic shock - exaggerated inflammation with infection with organ failure & hemodynamic compromise
what are the criteria for SIRS in the adult? how many must be met to be classified as SIRS?
- hypo/hyperthermia
- <98
- >101.5 - leukopenia or leukocytosis
- <5,000/uL
- > 14,500/uL - tachycardia
- >50 bpm - tachypnea
- > 25 bpm
just need to meet 2!!!
what is the major other organ manifestation of endotoxemia seen in horses?
laminitis!!!!
what are some examples of abnormalities seen on physical exam in a horse with endotoxemia?
mental dullness, congested or toxic mucus membranes, prolonged CRT, cool extremities, prolonged jugular refill, & fever
what are some examples of clinicopathologic abnormalities seen in a horse with endotoxemia?
- early & profound leukopenia - neutropenia, left shift, toxic change, & lymphopenia
- glucose derangements
- prolonged clotting times
- hyperlactatemia
- hypocalcemia
what is the prognosis for endotoxemia?
guarded at best
what are the 5 steps of treatment for endotoxemia?
- cardiovascular resuscitation
- laminitis prevention
- eliminate cause
- neutralize circulating endotoxin
- inhibit inflammation
what treatment components make up cardiovascular resuscitation in horses with endotoxemia?
early goal directed therapy!!!
expansion of blood volume - balanced polyionic crystalloid
with little improvement - retention of iv fluids, colloids
improved blood pressure - inotrope/vasopressin
what are some risk factors of a horse with endotoxemia developing laminitis?
pony, BCS >5/9, > 24 hours of endotoxemia, & temp higher than 101.5
what therapy can be used for laminitis prevention in a horse with endotoxemia?
prompt fluid resuscitation, NSAIDS, & cryotherapy (ice on the feet)
what therapy can be used for eliminating the cause in a horse with endotoxemia?
drainage/lavage, surgical removal, antimicrobials (broad spectrum, bactericidal, but controversial with developing colitis)
what therapy can be used for neutralizing the circulating endotoxin in a horse with endotoxemia?
smectite - if gut level
polymixin b - bloodstream, will only work if the toxin isn’t bound!!!
what is the dose for flunixin for inhibiting inflammation in a horse with endotoxemia?
0.25 mg/kg IV every 6-8 hours
T/F: if a foal shows up at the hospital, and you’re suspicious of endotoxemia, you should immediately provide oxygen supplementation
true
