Page 455 - Clinical Small Animal Internal Medicine

43 Septic Shock 423

these patients may have low intravascular volume, com- and increased vascular permeability that impairs gas
VetBooks.ir pensatory mechanisms are activated in an effort to exchange. This disease has been termed acute lung injury
(ALI) or acute respiratory distress syndrome (ARDS),
maintain blood pressure. To minimize the effect of
hypovolemia on organ systems in nonseptic patients,
manifestation than ARDS. Both are characterized by
systemic vascular resistance generally increases to com- depending on severity, with ALI describing a less severe
pensate for the lower cardiac output and maintain acute‐onset bilateral pulmonary infiltrates with no evi-
organ perfusion. In sepsis, however, numerous factors dence of left‐sided heart failure. Classification is further
counteract these compensatory mechanisms to the det- determined by the degree of hypoxemia. For more infor-
riment of the patient. This can result in decreased effec- mation on ALI/ARDS the reader is referred to Chapter 38.
tiveness of vasoconstriction or, worse, to pathologic Significant alterations in normal gastrointestinal func-
dilation of the vessels. tion, motility, and vascular permeability result from
The most well‐understood vasodilatory agent in sepsis inflammatory mediators, altered blood flow, and oxida-
is nitric oxide (NO). In sepsis and septic shock, inducible tive stress. This may allow exposure of the bloodstream
nitric oxide synthase (iNOS) produces supraphysiologic to the luminal contents of the gastrointestinal (GI) tract
levels of nitric oxide that interfere with myocyte calcium and allow bacteria access to the bloodstream or lymph,
metabolism and impair the ability of vascular smooth although the clinical significance and actual incidence of
muscle cells to contract. The end‐result is vasodilation bacterial translocation are unknown.
with a characteristically poor response to vasoconstric- Hepatic dysfunction in sepsis is manifested as hypoal-
tive stimuli, including reduced vascular response to cat- buminemia, icterus, hypoglycemia, and coagulation
echolamines. Additionally, the surplus of nitric oxide abnormalities and decreased detoxifying ability. The
leads to production of reactive oxygen species, including underlying cause of hepatic dysfunction is unknown but
peroxynitrite, which are directly toxic in the local envi- may result from hypoperfusion of the liver, or may be
ronment and act to cause further damage to endothe- directly due to the systemic inflammatory process (i.e.,
lium and smooth muscle myocytes. Nitric oxide is also inflammatory mediators) as many of the constitutive
responsible to some degree for the cardiac depression functions of the liver are downregulated as part of the
found in patients with sepsis or septic shock. acute phase response.
Endocrine abnormalities occur in sepsis and can also Coagulation abnormalities can be significant and can
adversely affect the ability of the vascular tree to respond lead directly to the death of the patient. Sepsis‐induced
to stimuli. With the additional demand for vasoconstric- coagulopathy is a manifestation of the procoagulant
tion, the neurohypophysis (posterior pituitary) depletes nature of almost all proinflammatory mediators. In gen-
its stores of vasopressin and is unable to meet the eral terms, the procoagulant state in sepsis causes gen-
demand, leading to a well‐documented deficiency in eration of microthrombi that result in inflammation
some septic patients. within the vascular beds in which they lodge. This sys-
A distinct cardiac failure component is present in temic activation of the coagulation system finally results
some human patients with septic shock but is of unknown in the consumption of coagulation factors and in the
clinical relevance in veterinary medicine. It was believed later stages ultimately induces a hypocoagulable state.
that a circulating myocardial depressant factor was This scenario has been termed disseminated intravascu-
present in the blood of septic patients that decreased lar coagulation (DIC) and continues to be a significant
cardiac function. This myocardial depressant factor was clinical complication in the management of sepsis.
subsequently identified as tumor necrosis factor (TNF)‐ Unfortunately, due to clinical limitations in identifying
alpha which, together with interleukin (IL)‐1, has been patients in the procoagulant phase of DIC, this compli-
associated with cardiac myocyte dysfunction. TNF‐alpha cation is often found in the last stages when profound
and IL‐1, both potent inducers of iNOS, are now known bleeding tendencies predominate and it is extremely dif-
to be the offending molecules that lead to sepsis‐induced ficult to manage or reverse.
cardiac dysfunction. If decreased systolic function is The discovery of renal dysfunction or acute kidney
coupled with decreased systemic vascular resistance, as injury is an easily identified marker of multiple organ
seen in septic shock, the cardiac output often stays the dysfunction syndrome. Acute kidney injury results from
same or even increases although tissue perfusion is decreased renal blood flow secondary to systemic hypo-
severely compromised. However, if vasoconstriction tension; alterations in renal blood flow from vasoactive
persists, as seen in uncomplicated or severe sepsis, substances, microthromboembolism, and poorly under-
decreased systolic function can lead to a significant stood renal cellular apoptosis are also believed to con-
reduction in cardiac output. tribute. Patients may exhibit a progressive increase in
Sepsis‐induced endothelial injury affects the lungs by creatinine and decreased urine production despite nor-
allowing neutrophil migration into the lung parenchyma mal intravascular fluid volume. Even small changes in