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Source: Lang-Birken SL, Killgore-Smith, K. Severe Sepsis and Septic Shock. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. Accessed July 15, 2012.

  • Systemic inflammatory response syndrome secondary to infection
  • Definitions of terms related to sepsis in Table 1.

Table 1. Definitions Related to Sepsis

  • Sites of infection that most frequently lead to sepsis:
    • Respiratory tract (21–68%)
    • Urinary tract (14–18%)
    • Intra-abdominal space (14–22%)
  • Caused by:
    • Gram-negative bacteria (38% of cases)
      • Most common isolates: Escherichia coli and Pseudomonas aeruginosa
        • P. aeruginosa most frequent cause of sepsis fatality.
      • Other common gram-negative pathogens:
        • Klebsiella spp.
        • Serratia spp.
        • Enterobacter spp.
        • Proteus spp.
  • Gram-positive bacteria (40% of cases)
    • Common gram-positive pathogens:
      • Staphylococcus aureus
      • Streptococcus pneumonia
      • Coagulase-negative staphylococci
      • Enterococcus species
  • Fungi (17% of cases)
    • Candida species (particularly Candida albicans) common cause of sepsis in hospitalized patients.

  • Result of complex interactions among invading pathogen, host immune system, and inflammatory responses
  • Invading microorganisms trigger proinflammatory mediators (e.g., tumor necrosis factor-α [TNF-α]; interleukin [IL]-1, IL-6)
    • TNF-α considered primary mediator of sepsis.
      • Concentration correlates with severity of sepsis.
    • IL-6 more consistent predictor of sepsis, as it remains elevated for longer periods of time than does TNF-α.
  • Inflammatory response leads to damage of host tissue.
    • Anti-inflammatory response (e.g., IL-1 receptor antagonist, IL-4, and IL-10) activates leukocytes.
  • Loss of local inflammatory process results in systemic inflammatory response converting infection to sepsis, severe sepsis, or septic shock.
  • The pathophysiologic focus of gram-negative sepsis has been on lipopolysaccharide (endotoxin) component of gram-negative cell wall.
    • Endotoxin activates complement.
    • Complement stimulates:
      • Leukocyte chemotaxis, phagocytosis ,and lysosomal enzyme release
      • Increased platelet adhesion and aggregation
      • Production of toxic superoxide radicals
  • Proinflammatory mechanisms in sepsis are also procoagulant and antifibrinolytic.


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