Most of what is known concerning sepsis pathogenesis comes from study of lipopolysaccharide-LPS or endotoxin (Munford, 2015). The lipid A moiety is bound by mononuclear blood cells, becomes internalized, and stimulates release of mediators and a series of complex downstream perturbations. Clinical aspects of the sepsis syndrome are manifest when cytokines are released that have endocrine, paracrine, and autocrine actions (Angus, 2013; Singer, 2016).
Although the sepsis syndrome in obstetrics may be caused by several pathogens, most cases represent a small group. For example, pyelonephritis complicating pregnancy caused by Escherichia coli and Klebsiela species commonly is associated with bacteremia and sepsis syndrome (Cunningham, 1987; Snyder, 2013). And although pelvic infections are usually polymicrobial, bacteria that cause severe sepsis syndrome are frequently endotoxin-producing Enterobacteriaceae, most commonly E coli (Eschenbach, 2015). Other pelvic pathogens are aerobic and anaerobic streptococci, Bacteroides species, and Clostridium species. Some strains of group A 3-hemolytic ) SIRS-fever, tachycardia, tachypnea, leukocytosis, leukopenia t::,
Organ system dysfunctionacidosis, encephalopathy, oliguria, hypoxemia, coagulopathy
Spectrum of Severity
FIGURE 47-3 The sepsis syndrome begins with a systemic inflammatory response syndrome (SIRS) in response to infection that may progress to septic shock.
streptococci and Staphylococcus aureus-including communityacquired methicillin-resistant strains (CA-MRSA)-produce a superantigen that activates T cells to rapidly cause all features of the sepsis syndrome-toxic shock syndrome (Moellering, 2011; Soper, 2011). his is discussed further in Chapter 37 (p. 675).
drome. Examples include exotoxins from Clostridium pertingens or sordellii, toxic-shock-syndrome toxin-1 (TSST -1) from S au reus, and toxic shock-like exotoxin from group A 3-hemolytic streptococci (Daif, 2009; Soper, 2011). These last exotoxins cause rapid and extensive tissue necrosis and gangrene, especially of the postpartum uterus, and may cause profound cardiovascular collapse and maternal death (Nathan, 1993; Sugiyama, 2010). In a review discussed subsequently, the maternal mortality rate from these infections was 58 percent (Yamada, 2010).
Thus, the sepsis syndrome begins with an inflammatory response that is directed against microbial endotoxins and exotoxins (Angus, 2013). CD4 T cells and leukocytes are stimulated to produce proinflammatory compounds that include tumor necrosis factor-a (TNF-a), several interleukins, other cytokines, proteases, oxidants, and bradykinin that result in a "cytokine storm" (Russell, 2006). Many other cellular reactions then follow that include stimulation of pro-and antiinflammatory compounds, procoagulant activity, gene activation, receptor regulation, and immune suppression (Filbin, 2009; Moellering, 2011). It is also likely that interleukin-6 (IL-6) mediates myocardial suppression (Pathan, 2004).