Endotoxemia Flashcards by Corinne Perra

What is the progression of endotoxemia?

Disease -> sepsis -> endotoxemia -> systemic inflammatory response syndrome -> compensated anti-inflammatory response syndrome -> multiple organ dysfunction syndrome —> multiple organ failure

How well did you know this?

Not at all

Perfectly

What are the primary causes multiple organ dysfunction syndrome?

Acute respiratory distress syndrome (ARDS)

Disseminated intravascular coagulation (DIC)

How well did you know this?

Not at all

Perfectly

What are the criteria for diagnosis of systemic inflammatory response syndrome?

At least 2 of the following..

Leukopenia, leukocytosis, or >10% bands

Hyperthermia or hypothermia
Tachycardia
Tachypnea
Evidence of sepsis in foals

How well did you know this?

Not at all

Perfectly

What is endotoxemia?

Presence of endotoxin in circulation
-LPS from the cell wall of gram negative bacteria

—> recognition of pathogen leads to inflammatory response that cannot be sufficiently controlled

How well did you know this?

Not at all

Perfectly

What are the 3 structural domains of LPS?

Polysacchardie O region (polar) -> accounts for the serologic differentiation among bacterial species

Core acidic polysaccharide

Lipid A (hydrophobic) 
-> unique and well conserved

How well did you know this?

Not at all

Perfectly

What part of LPS is most responsible for the toxic effect of endotoxemia?

Lipid A

How well did you know this?

Not at all

Perfectly

What preventative mechanisms does the body have against endotoxemia?

Mucosal epithelial cells/ physical barrier

restrict bacterial transmural movement across the bowel wall
secrete lysozyme, enzymes, and antibodies

Circulation

liver removes endotoxin from portal blood (monocytes AKA kupffer cells)
intravascular macrophages
anti-endotoxin antibodies bind and remove

How well did you know this?

Not at all

Perfectly

Where can bacteria breach physical barriers leading to endotoxemia?

Digestive 
Respiratory 
Reproductive 
Integumentary 
Urinary

How well did you know this?

Not at all

Perfectly

You do an abdominocentesis on a colic horse, what cbc and biochem results would indicate significant compromise of the GI system ?

High protein and high WBC

How well did you know this?

Not at all

Perfectly

T/F: the larger the section of compromised bowel, the larger the chance of developing endotoxic shock

True

—> reperfusion injury due to ischemia and necrosis

How well did you know this?

Not at all

Perfectly

How does an enteritis or colitis lead to endotoxemia?

Damage to the GI walls allowing bacterial translocation

How well did you know this?

Not at all

Perfectly

What organism causes Potomac horse fever?

Neorickettsial

AKA equine monocytic ehrlichiosis

How well did you know this?

Not at all

Perfectly

What pathology is associated with Potomac horse fever?

Acute entercolitis —> colic, fever, and diarrhea

Laminitis often appears due to systemic inflammation

How well did you know this?

Not at all

Perfectly

What is a sand colic? What are methods of diagnosis?

Horse consumes sand, large amounts settle in large intestine

Auscultation of cranial abdominal cavity-> hear waves washing onto the shore

Passage of mineral oil and check for sand

How well did you know this?

Not at all

Perfectly

How does carbohydrate overload lead to endotoxemia?

Carbohydrate overload-
> lowers pH -> bacterial overgrowth -> high amount of fermentation injury mucosa —> bacteria gains access to portal circulation

How well did you know this?

Not at all

Perfectly

What drugs can induce a colitis?

Antibiotics

NSAIDS: Banamine (flunixin meglumine) or phenylbutazone

How well did you know this?

Not at all

Perfectly

T/F: pleuropneumonia is most commonly viral

False

Bacterial

How well did you know this?

Not at all

Perfectly

What is the usually the treatment for a pleuopneumonia?

Thoracotomy - provide drainage

How well did you know this?

Not at all

Perfectly

Horse has watery green tinged nasal discharge

Dysphagia
Gagging

What is your dx?

Choke - esophageal obstruction with feed

Often leads to aspiration pneumonia -> Ecoli and Klebsiella

How well did you know this?

Not at all

Perfectly

What gram positive organism of the skin can pass into the blood causing endotoxemia?

Clostridium myositis

What reproductive disease most commonly leads to endotoxemia?

Retained placenta

Other causes

uterine rupture
severe metritis

What disease of the urinary tract can lead to an endotoxemia?

Infection

Obstruction

What is the pathophysiology of equine metabolic syndrome ?

Lipotoxicity (excessive conversion of glucose to fat)

disruption of insulin receptors progress until insulin resistance
associated with oxidative stress and inflammation
> increased IL6, IL8, IL10, and TNFa
> prolonged cytokine expression in circulatory leukocytes - increased inflammatory response (also lead to laminitis )

Hyper-cortisolemic state is caused by what endocrine disease in horses?

Pituitary par intermedia dysfunction (PPID)

-> ACTH overstimulates adrenal glands —> cortisol synthesis

What is the pathophysiology of endotoxemia?

Physical barrier breach Endotoxin stimulate macrophages Macrophages stimulates TXA2 and vasoconstriction Macrophages synthesize cytokines TNF and IL1 act on neutrophils and endothelial cells —> margination of neutrophils and emptying of granular content Endothelial damage -> hypercoagulable state Vasodilator substances from endothelium —> shock Compromised organ perfusion

What receptors on macrophages are responsible for binding LPS? And what pathway is activated in the macrophages?

Pathogen associated molecular pattern (PAMP; LBP which binds to CD14 cell surface and activation of pathogen recognition receptors (PRR) on toll like receptors Toll like receptor 4 -> MyD88 pathway -> TNF and IL1 production (pro inflammatory)

In the early stage of macrophage activation, it stimulates TXA2 causing ??

Vasoconstriction | —> pulmonary vasoconstriction results in increase in pulmonary arterial pressure

In the later stages of macrophage activation, they synthesize cytokines (TNF and IL1) which results in??

Amplification of endotoxin signal Endogenous pyrogens, cortisol, epi, procoagulant activity NO -> vasodilation

TNF and IL1 act on what cells and what response do they produce??

Neutrophils and endothelial cells -> cytokine induced margination of neutrophils (leukopenia)

___________ cells contribute to the procoagulant activity while ______ contribute to the procoagulant effect

Endothelial; platelets

What substances produced by the endothelium are vasodilator?

Prostacyclin | NO

Endotoxemia causes abnormal vascular tone. In the initial stage there is _________ shock, in later stages there s _________ shock

Hyperdynmaic (vasoconstriction); hypodynamic (vasodilation)

What contributes to the compromised organ perfusion seen with endotoxemia?

``` Vasodilation Vascular leakage and injury Intravascular cellular plugging Coagulation Systemic arterial hypotension ```

Damaged endothelium caused by extravasation of neutrophils causes leakage of??

Proteins

In recovery from endotoxemia, LPS induces _____ which results in deactivation of mononuclear phagocytes and inhibits pro-inflammatory cytokines

IL10

What clinical signs are associated with EARLY endotoxemia?

``` Tachypnea and tachycardia (Associated with vasoconstriction) - depression, restlessness, inappetence, fever Pale MM colour and prolonged CRT Fever ``` Toxic line

At 4-6hours what clinical signs do you see associated with endotoxemia?

Tachycardia and tachypnea Fever Circulatory failure and coagulopathy Dehydration - dry MM - skin tenting - sunken eye

At later stages of endotoxemia what are associated clinical signs?

``` Decrease rectal temp Oliguria or anuria Rapid weak pulses Muscle tremors Hemostatic dysfunction -petechia, ecchymosis -hypercoagulable ```

At 24hrs what clinical signs are associated with endotoxemia?

Ventral edema and laminitis

T/F: horses have a higher sensitively to LPS compared to other species

True

What is the equine-specific cellular response to flagellin?

Flagellin induces pro-inflammatory responses by neutrophils (TLR5)

``` Physical exam shows Increased HR (>48bpm) Toxic mucus membranes Cold extremities Poor pulse Fever ``` You suspect endotoxemia.. what diagnostics can you do to confirm?

CBC -> leukopenia, neutropenia and left shift Arterial blood gas: hypoxemia and metabolic acidosis Platelet and fibrinogen low due to DIC Limulous ameobcyte lysate assay —> direct measurement fo circulating endotoxins

When treating a horse for endotoxemia, you see on the biochem it has hyperglycemia. What is the prognosis for this animal

Poor

How can endotoxemia be prevented?

Vaccination with S. Typhimurium mutant -> partial protection and little support LPS repeated exposure -> diminish pro inflammatory response (short duration of tolerance)

What are the goals in treatment of endotoxemia?

``` Circulatory support Remove causes Neutralize endotoxin Inhibit inflammation Prevent laminitis ```

What can you do to improve cardiovascular function in endotoxemia?

Balance polyionic solution - LRS or Normosol - volume and rate depend on the degree of hypovolemia Hypertonic saline (7.5%) - always follow with balanced IV fluids Plasma proteins

What therapies can be used to neutralize circulating endotoxin?

Hyperimmune plasma -> antiLPS IgM and IgG antibodies (very $$$$) Polymixin B - cationic polypenptide antibiotic -> interact with lipid A forms stable molecules and decrease TNFa Endoserum from hyper-immune horses

What therapies inhibit inflammation induced by endotoxins?

NSAIDS - flunixin meglumine prevents increase in TXA2 and PGI2 Glucocorticoids is controversial (immunosuppressive and laminitis) Pentoxifylline: phosphodiesterase inhibition -> inhibit TNFa and IL6 DMSO -> decrease expression of TNFa, IL6, and macrophage inflammatory protein 1-a Ketamine -> cytokine modulating activity (last choice) Lidocaine CRI -> anti TNFa Ethyl pyruvate -> down regulates TNFa, IL6, and COx2

T/F: flunixin meglumine is more efffective in treating hemodynamic effects off LPS when combined with pentoxifylline

True