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. http://accesspharmacy.com/content.aspx?aid=8005066.
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 |Favorite Table|Download (.pdf)
Table 1. Definitions Related
|Bacteremia (fungemia)||Presence of viable bacteria (fungi) in the bloodstream|
|Infection||Inflammatory response to invasion of normally sterile host
tissue by the microorganisms|
|Systemic inflammatory response syndrome||Systemic inflammatory response to variety of clinical insults
that can be infection but also of noninfectious etiology. Response
manifested ≥2 of following conditions: temperature >38°C
(100.4°F) or <36°c (96.8°f);="" heart="" rate="">90 beats/min; respiratory rate >20 breaths/min
or Paco2 <32 torr;="" wbc="">12,000
cells/mm3, <4000 cells/mm3,
or >10% immature (band) forms.|
|Sepsis||Systemic inflammatory response syndrome secondary to infection|
|Severe sepsis||Sepsis associated with organ dysfunction, hypoperfusion,
or hypotension. Hypoperfusion and perfusion abnormalities may include,
but are not limited to, lactic acidosis, oliguria, or acute alteration
in mental status.|
|Septic shock||Sepsis with hypotension, despite fluid resuscitation, along
with presence of perfusion abnormalities. Patients on inotropic
or vasopressor agents may not be hypotensive when perfusion abnormalities
|Multiple-organ dysfunction syndrome||Presence of altered organ function requiring intervention
to maintain homeostasis|
|Compensatory anti-inflammatory response syndrome||Compensatory physiologic response to systemic inflammatory
response syndrome considered secondary to actions of anti-inflammatory
- 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
- 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)
- 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,
- 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
- The pathophysiologic focus of gram-negative sepsis has been
on lipopolysaccharide (endotoxin) component of gram-negative cell
- 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