Introduction

• SIRS: systemic inflammatory response syndrome is a condition associated with an exaggerated defense response of the body to noxious stimuli, whereby there is activation of multiple inflammatory pathways. SIRS can be initiated by several conditions, including (but not limited to) gram-positive and negative bacterial products including endotoxin from gram-negative organisms, infection, trauma, surgery, reperfusion, malignancy and burns. The exact terminology used may reflect the presence or absence of underlying infection; whereby SIRS is a clinical manifestation of systemic inflammation resulting from either an infectious insult (septic SIRS) or a non-infectious insult (non-septic SIRS).
• Sepsis: The distinction between the terms “SIRS” and “sepsis” has been subject to changing terminology over the recent decades but at the time of writing the author understands that “sepsis” is simply SIRS with an underlying infectious insult and therefore the terms “Sepsis” and Septic SIRS may be used interchangeably.
• Septic shock: a subset of septic SIRS in which underlying circulatory and cellular/metabolic abnormalities are profound enough to substantially increase mortality. Patients have sepsis persistent hypotension that is unresponsive to fluid resuscitation (or inotrope and pressor administration).
• Multiple Organ Dysfunction (MODS): the sequelae of systemic inflammation (SIRS) can lead to a syndrome of MODS, characterized by abnormalities in organs that were not affected by the original insult.
• Endotoxemia: endotoxin is a structural component of the outer cell membrane of gram-negative bacteria. Endotoxin is a potent inflammatory stimulant capable of direct and indirect induction of multiple host inflammatory and immunological processes when released into the circulation. The term “endotoxemia” is now outdated, unless discussing experimental studies and has been replaced by the term SIRS. This is due to the fact that it is the inflammatory response to endotoxin and not the endotoxin per se that causes the clinical signs seen.
• Bacteremia: presence of bacteria in the blood stream. Bacteria are visible on stained blood smears viewed with a microscope.
• Pyemia: a type of septic SIRS/sepsis that leads to widespread metastatic abscesses. See Pyemia for further details.

Pathogenesis

Etiology

• SIRS can be initiated by a number of conditions, including (but not limited to) endotoxins, infection, trauma, surgery, reperfusion, malignancy and burns.
• Some causes are listed below:
  • Traumatic reticuloperitonitis Traumatic reticulitis.
  • Mastitis Mastitis: approach to the cow with acute mastitis.
  • Ruminal acidosis Subacute ruminal acidosis.
  • Pneumonia Aspiration pneumonia Contagious bovine pleuropneumonia (CBPP).
  • Peritonitis Peritonitis.
  • Metritis Uterine infection: overview.
  • Burns Burns.
  • Salmonellosis Salmonellosis.
  • Enteritis/colitis.
  • Lower limb necrosis Distal limb necrosis.
  • Cesarean section Cesarean section.
  • Flank laparotomy Flank laparotomy.
  • Intussusception .
  • Strangulated intestine Intestinal torsion.
  • Intestinal obstruction.
  • Rumenotomy Rumenotomy and ruminal fistulation.
  • Vaginal surgery Vaginal injury: repair.
  • Rectal tears Rectal tear: surgery.
  • Castration complications Castration: surgical options.
  • Urachal infections Urachal resection.
  • Urolithiasis Urolithiasis.
  • Clostridial disease Clostridial myositis.
  • Toxic ingestion Investigation and treatment of suspected poisoning of unknown etiology.
  • Drug reactions or overdose.

Other risks

• High concentrate diets can increase the risk of ruminal acidosis Subacute ruminal acidosis which will increase the risk of SIRS as a complicating factor following infection/surgery, etc.
• BVD Bovine viral diarrhea and other conditions leading to immunocompromise may increase the risk of SIRS developing in an individual exposed to infection/trauma, etc.
• Stressful experiences, such as shipping Handling cattle: transportation, dehorning Disbudding and dehorning, castration Castration: surgical options, calving Calving: normal, etc may result in immunocompromise, resulting in an individual being more susceptible to SIRS following an infectious/traumatic insult.
• Access to other cattle with infectious agents (E. coli  Escherichia coli, Salmonella Salmonella spp, Clostridium Clostridium tetani, etc).

Pathophysiology

• Systemic circulation of products from both the surface proteins of gram-positive and also gram-negative organisms in the form of lipopolysaccharide (LPS) are a common cause for triggering SIRS.

• In the case of gram-negative organisms, LPS binds to either lipopolysaccharide binding protein (LBP), which in turn binds to CD14 (macrophage membrane bound endotoxin receptor) or directly to CD14 (skipping the step with LBP).
• CD14 interacts with another membrane bound protein (MD2) to transfer a signal to Toll like receptor 4 (TLR-4).
• TLR-4 is a transmembrane spanning receptor that transduces the signal to an intracellular signaling cascade which is comprised of a number of enzymatic steps of various kinases, culminating in the intra-nuclear activation of NF-KB.
• Once the nucleus is activated transcription of proinflammation genes ensues. Representatives of these genes include TNF-α, IL-1, IL-6, IL-8, Platelet Activating Factor (PAF).
• The genetic transcription of these proinflammatory cytokines/mediators leads to activation of:
  • The coagulation cascade leading to endotoxin-induced coagulopathies.
  • Systemic inflammation (SIRS) prostaglandin and leukotriene mediated.
  • The complement pathway and macrophage lysis.
• The cumulative effects of these pathways (most particularly systemic inflammation) are responsible for cardiovascular depression, pulmonary hypertension, and arterial hypoxemia Hypoxemia.
• These effects can then lead to endotoxin induced decreased tissue perfusion and peripheral hypoxia.
• Eventually perfusion to major organ systems can be compromised and lead to multiple organ dysfunction syndrome (MODS) and death.
• Gram-positive bacteria can also activate a similar cascade via their surface proteins, as can viral or parasitic infections.
• Bacterial components such as peptidoglycan and lipoteichoic acid activate the host defense by engaging pattern recognition receptors (such as NOD-1 and NOD-2) and toll-like receptors (particularly TLR-2) of the innate immune system.
• TLR-2 is a transmembrane receptor similar to TLR-4 which initiates an intracellular enzymatic cascade that ends with NFkB translocation and subsequent gene expression of proinflammatory cytokines and mediators (TNF-α, IL-1, IL-6, IL-8).
• Similar to the response seen with gram-negative bacteria, these mediators can lead to cardiovascular depression, pulmonary hypertension, arterial hypoxemia, decreased tissue perfusion, peripheral hypoxia, and ultimately, multiple organ dysfunction syndrome (MODS) and death.
• In cattle, it is postulated that fatty liver disease Ketosis and fatty liver predisposes to sepsis, as bacteria enters the systemic circulation, rather than the portal circulation and thus bypass the phagocytic action of Kuppfer cells in the liver.

Diagnosis

Treatment

Outcomes