Endotoxemia Flashcards
What are the 3 main components of a gram-negative bacterial endotoxin?
- Polysaccharide O-region
- Lipid A region
- Core (acidic polysaccharide region)
Which disease are usually associated with the development of endotoxemia in the horse?
Gram-negative bacterial infections
What are 2 times gram-negative endotoxins are released?
- During both cell death
- Small extent during rapid multiplication phase
What are 6 possible etiologies of endotoxemia?
- Any GIT disturbance
- Metritis, placentitis
- Pleuropneumonia
- Bacterial pleuritis and/or peritonitis
- Septicemia (neonates)
- Possibly with wound infections
What is the most common etiology of endotoxemia?
Any GIT disturbance
Why is endotoxemia seen with pleuropneumonia but not often with pneumonia?
Pleuropneumonia involves a larger surface area so more endotoxins get absorbed.
Where does the highest amount of endotoxin likely come from?
GI disturbance
Why, if produced constantly, are horses not endotoxic at all times?
Not enough endotoxin crossing the GIT mucosa going into circulation to cause endotoxemia.
Why is the integrity of the GIT mucosa important?
Prevents large amounts of endotoxin from gaining the circulation.
What can endotoxins be bound to within the GIT allowing it to be removed from the body?
Bile salts
What are 3 possible disposition locations of endotoxin from the GIT once it reaches circulation?
- Bind to circulating LPS antibodies present
- Removed by RES in the liver
- Bind to circulating LBP (LPS binding protein)
What is an acute phase LPS binding protein that acts as a shuttle?
LBP
What cells are targeted by endotoxins in the horse?
Pulmonary intravascular macrophages
What is the first parameter altered by endotoxemia?
Increase in pulmonary arterial pressure.
What are 3 responses triggered by endotoxemia?
- Vasoactive substances released
- Endothelial disruption
- Systemic inflammatory response syndrome (SIRS)
How does the release of vasoactive substances caused by endotoxemia affect the body?
Alteration of flow
What are 2 forms of endothelial disruption seen with endotoxemia?
- Increased vascular permeability
- Hypercoagulability
What are 3 events resulting from mediator production as a result of SIRS caused by endotoxemia?
- Neutrophil adhesion
- Monocyte/macrophage activation
- Platelet adhesion
What is considered to be the horse shock organ?
Lungs
In general, endotoxemia results in the activation of what 5 host responses?
- Inflammatory mediators
- Kinins (altered clotting balance)
- Oxygen radicals
- Complement cascade
- Coagulation cascade
Failure of the circulatory system to maintain adequate blood flow is known as what?
Shock
What are 2 main categories of shock?
- Pump failure
- Circuit failure
What is an example of a pump failure form of shock?
Is this common in horses?
- Cardiogenic shock
- Not as common in horses
What are 4 examples of circuit failure forms of shock?
- Hypovolemic shock
- Hemorrhagic shock
- Distributive (maldistributive) shock
- Obstructive shock
What are 4 variations of distributive (maldistributive) shock?
- Septic shock
- Anaphylactic shock
- Adrenal insufficiency
- Neurogenic shock
Septic shock is also known as what?
Endotoxemic shock
What does SIRS stand for?
Systemic inflammatory response syndrome
What is sepsis?
SIRS induced by infection
What is septic shock (endotoxemic shock)?
Sepsis associated with organ dysfunction, hypoperfusion or hypotension.
What does MODS stand for?
Multiple organ dysfunction syndrome
What does CARS stand for?
Compensatory anti-inflammatory response syndrome
What does MOFS stand for?
Multiple organ failure syndrome
What are the 2 clinical phases of shock?
- Hyperdynamic state
- Hypodynamic state
Typically early on with endotoxemia, there is what type of vascular state?
Vasoconstricted state
As the endotoxemia progresses, there is a tendency toward what type of vascular state?
What is an example of a mediator of this state?
- Progressive vasodilatory state
- Prostacyclin
How do the mucus membranes appear in a hyperdynamic state of shock?
In a hypodynamic state?
- Injected, brighter
- Congested, toxic line, darker color
How is the CRT during a hyperdynamic state of shock?
During a hypodynamic state?
- Likely normal
- Prolonged
How is the pulse during a hyperdynamic state of shock?
During a hypodynamic state?
- Strong
- Weak, thready
How do the extremities feel during a hyperdynamic state of shock?
During a hypodynamic state?
- Warm
- Normo to hypothermic
What is the temperature of the patient like in a hyperdynamic state of shock?
In a hypodynamic state?
- Likely elevated
- Typically subnormal
Is tachycardia seen during a hyperdynamic state, hypodynamic state or both?
Both
Is tachypnea seen during a hyperdynamic state, hypodynamic state or both?
Both
What is the gold standard test in research for detecting endotoxemia?
Limulus test
Are portable endotoxin tests available?
Yes for humans
What is seen with an endotoxemia CBC?
- Neutropenia
- Leukopenia
- Lymphocytes WNL
What is seen with a stress leukogram?
- Leukocytosis
- Neutrophilia
- Lymphopenia
What is seen on a CBC with both stress and endotoxemia?
- Total WBC WNL
- Neutrophils WNL
- Lymphopenia
Why might a CBC be done for endotoxemia?
To evaluate the presence and/or severity of cardiovascular compromise and organ dysfunction.
What does APACHE stand for?
What is is?
- Acute physiology and chronic health evaluation
- Scoring system developed for quantifying the severity of the illness for the intensive care patients.
What is the first thing to do with an endotoxemia case?
Remove the cause.
What are 2 things that might need to be removed surgically from the GIT when treating endotoxemia?
- Devitalized gut tissue
- Gut content
Do giving bacteriostatic antimicrobial drugs affect the endotoxin levels of in horses?
Yes in foals but no in adults.
What 2 antimicrobials can be given to foals to treat endotoxemia?
Are these given separate or together?
- Ceftiofur and Amikacin
- Given together
What is the next major step after the source of endotoxemia has been removed?
Provide CVS support
What is given in the fluid if TP levels are less than 4.2 g/dL?
Hetastarch
What might need to be added to fluid given to foals with endotoxemia?
Glucose
What are 3 fluids that may be given for CVS support of endotoxemia?
- High volume crystalloids
- Hypertonic saline
- Combination
What are 2 things that may be given to neutralize circulating endotoxins?
- Endoserum (anti-endotoxin ABs) as a preventative
Polymixin B infusions as a therapeutic to bind toxins
What is the DOC for the inhibition of endotoxin associated inflammation and mediators?
Flunixin meglumine in low doses.
What are 3 other NSAIDs that can be given for the inhibition of endotoxin associated inflammation and mediators?
- Phenylbutazone
- Ketoprofen
- Ibuprofen
What can be given with flunixin meglumine (banamine) that might limit the amount of mediators produced?
Pentoxyfylline
What is an anti-oxidant that can be given to reduce enema associated with endotoxemia?
DMSO
DMSO is an anti-inflammatory that inhibits what?
IL-8 and neutrophilic adhesion
What does DMSO reduce?
Platelet aggregation
When dealing with GI conditions, is a high or low dose generally used?
Low dose
What is a drug that can be used to reduce post-op ileus?
Lidocaine
What is an anti-oxidant that is an xanthine oxidase inhibitor that may reduce free radical production?
Allopurinol
What can be used in the face of altered coagulability that can be seen with endotoxemia?
Heparin
What are 6 possible clinical manifestations or complications associated with endotoxemia?
- GIT problems
- Laminitis
- Renal failure
- Coagulopathies
- Hepatopathies
- Respiratory distress
Is renal failure common in horses?
What is it often caused by?
- No
- Nephrotoxic drugs
What is a potential complication of endotoxemia that can cause facial edema?
Which form is more dangerous?
- Jugular thrombosis
- Bilateral
Why are horses more sensitive to DIC?
AT3 levels are already on the low end as a species.