Lecture 32 4/10/25 Flashcards
What is endotoxemia?
presence of endotoxin in a horse’s blood that can lead to shock, laminitis, and death
What are the risks of grain overload?
-excessive fermentation
-bacterial overgrowth
-hindgut acidosis
What is the treatment for grain overload?
-passage of NG tube and lavage
-substances that absorb toxins
-NSAIDs
How do gram+ and gram- bacteria differ in terms of cell wall type?
-gram+ bacteria have teichoic acid in their walls
-gram- bacteria have lipoprotein lipopolysaccharide in their walls, which acts as an endotoxin
What are the components of the gram- bacterial endotoxin?
-lipid A: most toxic; highly conserved inner aspect
-core polysaccharide
-O-specific antigen; outer aspect
When is endotoxin released?
bacteriolysis and/or rapid growth
Which conditions is endotoxin exposure associated with?
-GI dz
-metritis
-neonatal sepsis
-pneumonia
What are the characteristics of endotoxin exposure associated with GI dz?
-large amounts of endotoxin present in GI tract
-any compromise to the GI tract can lead to endotoxemia
-gram- infections such as Salmonella in the GI tract can increase risk
What are the defense mechanisms involved in combating endotoxemia?
-skin and mucosal barriers
-hepatic Kupffer cells
-specific immune system responses
What is the pathophysiology of endotoxemia?
-physical barrier breach
-LPS-macrophage interaction
-neutrophil activation
-compromised perfusion
-recovery (+/-)
What can lead to a physical barrier breach and set an animal up for potential endotoxemia?
-gram- infections
-any damage to the gut wall
-administration of contaminated solutions
What are the characteristics of endotoxin-macrophage interaction?
-endotoxin binds via LPS binding protein
-processing of macrophage plasma membrane arachidonic acid occurs
-many inflammatory mediators are released
What are the characteristics of neutrophil involvement in endotoxemia?
-cytokines induce expression of adhesion molecules on the endothelium, leading to neutrophil “margination”
-neutropenia and toxic change are common
-cytokines also induce the activation of neutrophils
What are the steps of organ perfusion compromise that occur in endotoxemia?
-initial vasoconstriction that eventually transitions into vasodilation
-vascular leakage
-systemic arterial hypotension
-inadequate tissue perfusion
How do horses recover from endotoxemia?
negative feedback pathway that is designed to terminate the inflammatory response
What are the clinical signs of endotoxemia?
*early:
-vasoconstriction
-blanching
*late:
-vasodilation
-toxic line
-congested, dark MM
-prolonged CRT
-tachycardia
-tachypnea
-decreased GI motility
-diarrhea
-lethargy
-hypotension
What are the clinical signs of circulatory failure and disordered hemostasis secondary to severe endotoxemia?
-rapid, weak pulses
-cool extremities
-sweating
-muscle fasciculations
-hypercoagulation
-hemorrhage
-edema
-laminitis
What are the clin path findings in endotoxemia cases?
-neutropenia/left shift
-increased PCV
-hyperglycemia initially; then hypoglycemia
-altered hemostasis
-altered tissue perfusion; azotemia, inc. liver enzymes, inc. cardiac troponin
How is endotoxemia diagnosed?
-typically presumptive based on clinical signs and clin path
-detection of endotoxin using limulus amebocyte lysate assay, rFactor C, or monocyte activation testing
What are the general principles of therapy for endotoxemia?
-treat underlying disease
-supportive therapy (fluids)
-inhibition of inflammation
-neutralization of toxin
Which NSAIDs can be used to inhibit inflammation in endotoxemia cases?
-flunixin meglumine (most common, good results)
-ketoprofen
-firocoxib
-meloxicam
-phenylbutazone
Which other medications besides NSAIDs can be used to inhibit inflammation in endotoxemia cases?
-lidocaine
-DMSO
-pentoxifylline
-low molecular-weight heparin
-ethyl pyruvate
-levothyroxine
Which medications can be used to neutralize endotoxin?
-polymixin B
-di-tri-octahedral smectite
-antibody
What are the characteristics of polymixin B?
-directly binds endotoxin
-can be toxic; most importantly nephrotoxicity
-toxicity can limit the amount of endotoxin bound
