ISSN 2398-2993      



Vetstream Ltd

Paul Wood


  • Endotoxemia is the name commonly given to a state of systemic inflammation, particularly associated with gram-negative bacteria, but a systemic inflammatory response syndrome (SIRS) can occur secondary to a great number of bacterial, viral and parasitic conditions.
  • Cause: endotoxin - a structural part of the bacteria's outer cell membrane which is released upon lysis of the cell membrane or during rapid cell growth periods.
  • Gram-negative bacteria, or endotoxins, within the systemic circulation may result in endotoxemia alongside the initial pathologies that have allowed access to the bloodstream.
  • Signs: endotoxin is a potent inflammatory stimulant which initiates inflammatory cascades → major alterations in homeostatic mechanisms and severe clinical signs.
  • Diagnosis: clinical signs, hematology, biochemistry, bacteriology - if suspect bacteremia.
  • Treatment: difficult; aimed at eliminating the source of gram-negative sepsis, binding endotoxin after its release but before inflammatory response is initiated, supportive patient care, moderation of host's inflammatory response.
  • Prognosis: guarded.



  • Liposaccharide liberated from gram-negative bacteria upon rapid multiplication or bacteriolysis.


  • Endotoxin is a structural component of the outer cell membrane of gram-negative bacteria.
  • Essentially a lipopolysaccharide combined with cell wall capsular polysaccharide and proteins.
  • The outer part of the endotoxin 'O-antigen' or 'O-specific' repeating polysaccharide region is very variable between bacterial species and is the antigenic stimulus for antibody production and serospecificity.
  • The remaining two components of the endotoxin are very similar among bacterial species and have been used as antigens in vaccine development:
    • The central or core oligosaccharide region.
    • The innermost lipid A region which is responsible for most of the toxic effects.
  • The endotoxin is a potent inflammatory stimulant capable of direct and indirect induction of multiple host inflammatory and immunological processes.
  • The main source of endotoxin is the gut as there are a high number of resident gram-negative organisms.


  • Sources in adult bovines include:
    • Gastrointestinal disorders, particularly where there is compromise to the intestinal wall, eg strangulating lesions or inflammatory lesions (septic peritonitis , enteritis, colitis, ruminal acidosis Subacute ruminal acidosis). The majority of endotoxin is restricted to the gut lumen by an efficient mucosal barrier consisting of epithelial cells, specific secretions and resident commensal bacteria. Any endotoxin gaining entry is normally removed by the Kupffer cells in the liver. Damage to the mucosal barrier can occur secondary to a variety of gastrointestinal problems:
    • Changes in the normal commensal population of the GI tract can allow the overgrowth of pathological endotoxin organisms Rumen function and fermentation.
      • Rapid dietary changes, especially to high carbohydrate rations.
      • Enteral and parenteral antimicrobial agents.
    • Peritonitis, following rupture of the GI system or uterus or penetrations into the peritoneum, eg through the body wall or GI tract.
    • Pneumonia Adult respiratory disease: overview.
    • Toxic metritis Uterine infection: overview.
    • Toxic mastitis Mastitis: approach to the cow with acute mastitis .
    • Liver failure can result in endotoxemia due to failure of the liver to clear the normal amount of endotoxin absorbed by the gut Liver disease: diagnosis.


  • Neonates much more commonly suffer from septicemia (translocation of bacteria) rather than endotoxemia (translocation of endotoxin into the blood) per se Neonatal septicemia.
  • Certain bacterial infections (E. coli Escherichia coli, Salmonella spp Salmonella spp, Actinobacillus spp Actinobacillus lignieresii and other gram-negative organisms) are quite common due to failure of passive transfer Colostrum: overview and immature immune systems. Exposure of the gram-negative bacteria occurs in utero or peri-parturiently via the gut, respiratory tract or umbilicus.


  • Endotoxemia is caused by endotoxins - potent inflammatory stimulants which initiate inflammatory cascades → major alterations in homeostatic mechanisms and severe clinical signs.
  • If the epithelial barrier is breached the secondary host defense mechanisms come into play:
    • Phagocytic cells, ie Kupffer cells in the liver.
    • Lymphocytes.
    • Humoral factors, eg immunoglobulins, complement, acute phase reactants.
  • Endotoxin enters the circulation → binds with lipopolysaccharide-binding protein (LBP) which is rapidly synthesized by the liver (has a strong affinity to the Lipid A part of the endotoxin and a receptor on mononuclear phagocytes (CD14)) → all 3 bound together → the phagocyte becomes activated → production of pro-inflammatory mediators → overzealous inflammatory response.
  • A soluble form of CD14 when bound can activate similar cells which lack the cell-bound form.
  • The mediators include:
    • Cytokines.
    • Lipid-derived mediators.
    • Coagulation/fibrinolytic factors.
  • The main cytokines produced are tumor necrosis factor (TNF-alpha):
    • Associated with development of hypotension, hemoconcentration, acidosis, disseminated intravascular coagulation (DIC), death.
    • Induce synthesis of interleukins, prostaglandins, various tissue factors (thromboxane, leukotrienes).
    • Initiate acute phase response.
  • Interleukins, especially Interleukins 1 and 6 which regulate many of the animal's inflammatory and immunologic responses.
  • The lipid-derived mediators of inflammation:
    • Are based on arachidonic acid released from the phospholipid in the cell membrane and metabolized by cyclooxygenase/lipoxygenase.
    • Remnants of the phospholipid become the precursor for platelet activating factor (PAF).
  • Include:
    • Prostaglandins: many of the early hemodynamic, platelet and behavioral effects of endotoxemia are due to cyclooxygenase-derived metabolites, eg thromboxane A2 and prostaglandins F2-alpha, I2 and E2.
    • Thromboxanes.
    • Leukotrienes: the role of the leukotrienes are less well defined but include chemotaxis, vaso- and bronchoconstriction and increased vascular permeability.
  • PAF → thrombus formation, thrombocytopenia, microvascular permeability and hypotension.
  • Activation of nuclear factor kb (NFkB) is key in the proceeding cascade of inflammatory events.
  • Neutrophils move from the blood into the tissue in response to the inflammatory cascade.
  • Endotoxin directly activates the complement, coagulation and fibrinolytic cascades.
  • Clinical cases tend to develop a hypercoagulable state and consumptive coagulopathy.
  • Hypoxia, eicosanoid metabolism and leukocyte activity can → formation of oxygen-derived free radicals → induce oxidative damage to surrounding tissues.


  • SIRS can progress very rapidly and result in death within a short time if not detected early.


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Further Reading


Refereed Papers

  • Recent references from PubMed and VetMedResource.
  • Constable P D, Trefz F M, Sen I et al (2021) Intravenous and oral fluid therapy in neonatal calves with diarrhea or sepsis and in adult cattle. Front Vet Sci 7, 603358 PubMed.
  • Arai S (2019) Effect of endotoxemia on rumen motility, abomasal motility and liver function in cattle. Japanese Journal of Large Animal Clinics 10 (1), 1-16 CABI.
  • Nabi I, Singh D & Sood N K (2019) A comparative evaluation of different treatment regimens in endotoxemic buffalo calves - A physio-pathological perspective. J Biomed Sci Engineer 12 (4), 12 SciRes.
  • Smith G (2005) Supportive therapy of the toxic cow. Vet Clin North Am 21 (3), 595-614 PubMed.
  • Pankey and sabath (2004) Clinical relevance of bacteriostatic versus bactericidal mechanisms of action in the treatment of Gram-positive bacterial infections Clin Inf Dis 38 (6), 864-870 PubMed.
  • Andersen P H (2003) Bovine endotoxicosis – some aspects of relevance to production diseases. A review. Acta Vet Scand 98, 141-155 DNB.
  • Shuster R et al (1997) Survey of diplomates of the American college of Veterinary Internal Medicine and the American College of Veterinary surgeons regarding clinical aspects and treatment of endotoxemia in horses. JAVMA 210 (1), 87-92 PubMed.
  • Moore J N (1991) Rethinking endotoxemia in 1991. Equine Vet J 23 (1), 3-4 PubMed.
  • Lavoie J P et al (1990) Hemodynamic, pathologic, hematologic and behavioral changes during endotoxin infusion in equine neonates. Equine Vet J 22 (1), 23-29 PubMed.

Other sources of information

  • Corley K T T & Hallowell G D (In Press) Treatment of Endotoxemia. In: Equine Acute Abdomen. 2nd edn.

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