C h a p t e r 2 0
Heart Failure and Circulatory Shock
507
enhanced awareness of the diagnosis, increased number
of resistant organisms, growing number of immunocom-
promised and elderly persons, and greater use of inva-
sive procedures.
69
With early intervention and advances
in treatment methods, the mortality rate has decreased;
however, the number of deaths has increased because of
the increased prevalence.
The pathogenesis of sepsis involves a complex process
of cellular activation resulting in release of proinflam-
matory mediators such as cytokines; recruitment of neu-
trophils and monocytes; involvement of neuroendocrine
reflexes; and activation of complement, coagulation, and
fibrinolytic systems.
66
Initiation of the response begins
with activation of the innate immune system and release
of a number of proinflammatory and anti-inflammatory
mediators (Chapter 15). Two of these mediators, tumor
necrosis factor (TNF)-
α
and interleukin-1, are involved
in leukocyte adhesion, local inflammation, neutrophil
activation, generation of fever, tachycardia, lactic acido-
sis, ventilation–perfusion abnormalities, and other signs
of sepsis. Although activated neutrophils kill microor-
ganisms, they also injure the endothelium (endothelial
dysfunction) by releasing mediators that increase vas-
cular permeability. In addition, injured endothelial cells
release an excess of nitric oxide, a potent vasodilator
that acts as a key mediator of septic shock.
Another important aspect of sepsis that is also
related to endothelial dysfunction is an alteration of
the procoagulation–anticoagulation balance with an
increase in procoagulation factors and a decrease in
anticoagulation factors. Lipopolysaccharide on the sur-
face of microorganisms stimulates endothelial cells lin-
ing blood vessels to increase their production of tissue
factor, thus activating coagulation
67
(see Chapter 12).
Fibrinogen is then converted to fibrin, leading to the
formation of microvascular thrombi that further
amplify tissue injury. In addition, sepsis lowers levels of
protein C, protein S, antithrombin III, and tissue factor
pathway inhibitor, substances that modulate and inhibit
coagulation.
67
Sepsis and septic shock are typically manifested by
hypotension and warm, flushed skin. Whereas other
forms of shock (i.e., cardiogenic, hypovolemic, and
obstructive) are characterized by a compensatory
increase in systemic vascular resistance, septic shock
often presents with a decrease in systemic vascular
resistance. Hypovolemia is due to arterial and venous
dilatation, plus leakage of plasma into the interstitial
spaces. Abrupt changes in cognition or behavior are
due to reduced cerebral blood flow and may be early
indications of septic shock. Regardless of the underly-
ing cause, fever and increased leukocytes are present. An
elevated serum lactate or metabolic acidosis indicates
anaerobic metabolism due to tissue hypoxia or cellular
dysfunction and altered cellular metabolism.
70
Tissue
hypoxia produces continued production and activation
of inflammatory mediators, resulting in further increases
in vascular permeability, impaired vascular regulation,
and altered hemostasis. As sepsis continues, organ sys-
tem failure can occur. Multiple organ dysfunction is the
major cause of death in sepsis.
Early recognition of the signs and symptoms of con-
ditions that could lead to sepsis is key to optimizing
outcomes and decreasing sepsis-related mortality. The
treatment of sepsis and septic shock focuses on con-
trol of the causative agent, support of the circulation
and the failing organ systems.
68
The administration of
antibiotics that are specific for the infectious agent is
essential. However, antibiotics do not treat inflamma-
tion; thus, the cardiovascular status of the patient must
be supported to increase oxygen delivery to the cells
and prevent further cellular injury. Swift and aggressive
fluid administration is needed to compensate for third
spacing, though which type of fluid is optimal remains
controversial.
71
Equally aggressive use of vasopressor
agents, such as norepinephrine or epinephrine, is needed
to counteract the vasodilation caused by inflammatory
mediators.
67
Diffuse endothelium disruption and
impaired microvascular function
Suspected or confirmed infection
Systemic inflammatory response
Severe sepsis with organ
dysfunction
Septic shock
Microorganisms
Hypotension, hypoxemia, oliguria,
metabolic acidosis, thrombocytopenia
FIGURE 20-10.
Pathogenic mechanisms leading from
infection to septic shock.
