Exam 3 - Endotoxemia Flashcards

1
Q

what is endotoxemia?

A

clinical manifestation of a systemic inflammatory response to a circulating endotoxin

subset of sepsis

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2
Q

what makes the endotoxin in gram negative bacteria?

A

LPS

o specific chain

core region

lipid A - most antigenic part

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3
Q

T/F: 30% of horses with endotoxemia will not have detectable levels of endotoxins

A

true

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4
Q

what is the difference between an endotoxin & an exotoxin?

A

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

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5
Q

what are the 3 steps of the cellular cascade of endotoxemia?

A
  1. LBP-LPS binding to TLR
  2. NF-kB activation
  3. gene expression & products release
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6
Q

when there is activation of NF-kB, what cytokines are involved in causing clinical signs including: fever, tachypnea, leukocytosis, leukopenia, & obtundation?

A

TNF-a, IL-1, & IL-6

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7
Q

why can you see thrombosis, hemorrhage, & DIC in horses with endotoxemia?

A

activation of TF & factor VIII - these both activate intrinsic & extrinsic pathways & impair fibrinolysis which activates coagulation leading to the clinical signs

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8
Q

NF-kB activation activates ICAM-1, VCAM-1, B2 integrins, e-selectin, & chemokines leading to what cascade?

A

endothelial damage!!!! neutrophils become activated & cause release of ROS, RNS, & proteolytic enzymes which cause endothelial activation/injury leading to increased endothelial permeability (tissue injury)

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9
Q

what is the major player in vasodilation as a part of the endotoxemia cascade in NF-kB activation?

A

nitric oxide - causes hypotension, cardiovascular hyporeactivity, tissue hypoperfusion, & hypoxia

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10
Q

what do reactive oxygen species cause in endotoxemia?

A

endothelial damage & potentiation of inflammation

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11
Q

what is the major vasoactive mediator?

A

nitric oxide

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12
Q

what are the major inflammatory cytokine mediators of endotoxemia?

A

IL-1, IL-6, & TNF-a

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13
Q

what are the major procoagulant mediators in endotoxemia?

A

tissue factor & factor VIII

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14
Q

which is not produced as a result of NF-kB activation:
a. IL-10
b. TNF-a
c. IL-6
d. iNOS

A

a. IL-10

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15
Q

what 3 components make up virchow’s triad?

A
  1. hypercoagulable state
  2. endothelial damage
  3. abnormal blood flow
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16
Q

on a cellular level, what’s going wrong in endotoxemia?

A
  1. endothelial adhesion by neutrophils & reduced chemotaxis - low WBC because they are sequestered
  2. increased metabolic demands by the cell
  3. impaired oxygen use by the cell - mitochondria is not acting like the normal powerhouse
17
Q

what cardiovascular effects are seen in early endotoxemia?

A
  1. decreased preload
  2. left ventricular dysfunction
  3. arterial vasodilation
18
Q

what is the major cause of death in endotoxemia?

A

myocardial depression!!!!!!

19
Q

what 3 components of hemodynamic stability are affected in endotoxemia?

A
  1. hypovolemia
  2. abnormal perfusion distribution
  3. myocardial depression
20
Q

when comparing infection, SIRS, sepsis, severe sepsis, & septic shock, how do they differ?

A
  1. infection - microbial invasion
  2. SIRS - exaggerated inflammation, doesn’t have to have bacteria present, can be sterile
  3. endotoxemia/sepsis - exaggerated inflammation with infection
  4. severe sepsis - exaggerated inflammation with infection with organ failure
  5. septic shock - exaggerated inflammation with infection with organ failure & hemodynamic compromise
21
Q

what are the criteria for SIRS in the adult? how many must be met to be classified as SIRS?

A
  1. hypo/hyperthermia
    - <98
    - >101.5
  2. leukopenia or leukocytosis
    - <5,000/uL
    - > 14,500/uL
  3. tachycardia
    - >50 bpm
  4. tachypnea
    - > 25 bpm

just need to meet 2!!!

22
Q

what is the major other organ manifestation of endotoxemia seen in horses?

A

laminitis!!!!

23
Q

what are some examples of abnormalities seen on physical exam in a horse with endotoxemia?

A

mental dullness, congested or toxic mucus membranes, prolonged CRT, cool extremities, prolonged jugular refill, & fever

24
Q

what are some examples of clinicopathologic abnormalities seen in a horse with endotoxemia?

A
  1. early & profound leukopenia - neutropenia, left shift, toxic change, & lymphopenia
  2. glucose derangements
  3. prolonged clotting times
  4. hyperlactatemia
  5. hypocalcemia
25
what is the prognosis for endotoxemia?
guarded at best
26
what are the 5 steps of treatment for endotoxemia?
1. cardiovascular resuscitation 2. laminitis prevention 3. eliminate cause 4. neutralize circulating endotoxin 5. inhibit inflammation
27
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
28
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
29
what therapy can be used for laminitis prevention in a horse with endotoxemia?
prompt fluid resuscitation, NSAIDS, & cryotherapy (ice on the feet)
30
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)
31
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!!!
32
what is the dose for flunixin for inhibiting inflammation in a horse with endotoxemia?
0.25 mg/kg IV every 6-8 hours
33
T/F: if a foal shows up at the hospital, and you're suspicious of endotoxemia, you should immediately provide oxygen supplementation
true