Page 575 - Fluid, Electrolyte, and Acid-Base Disorders in Small Animal Practice

Shock Syndromes 563

Inflammatory Mediators Gastrointestinal tract hypoperfusion has been shown to
The immune response following an insult such as be an important contributor to posttrauma multiple
hypoxic tissue injury maybe biphasic in nature with an organ dysfunction syndrome in experimental animals
99,143
and people. Ischemia and reperfusion of the gastro­
initial proinflammatory response (systemic inflammatory
response syndrome [SIRS]) mediated primarily by the intestinal tract can lead to production of inflammatory
innate immune system and proinflammatory cytokines. mediators and activation of neutrophils. This can amplify
the inflammatory response occurring following cellular
This can be followed by a compensatory antiinflammatory
ischemia subsequent to shock and lead to severe SIRS
response syndrome (CARS), which is associated
and MODS. Bacterial translocation and subsequent bac­
with immune suppression and the production of
teremia can also occur following a severe circulatory
antiinflammatory cytokines. These immune responses
shock insult and further drives the development of severe
have local and systemic effects that if excessive can result 27
SIRS. In summary the immune response to injury or
in MODS and death.
illness is complex and yet to be fully understood. The
Cellular ischemia alters gene transcription including
cellular changes that occur following an insult have a
activation of NF-kB, which leads to cellular production
protective role but in some circumstances they can
of inflammatory mediators including tumor necrosis fac­
become a source of harm to the patient. As clinicians
tor-a (TNF-a), interleukin-1b (IL-1b), IL-2, IL-6, inter­
the corner stones of therapy of systemic inflammatory
feron-g, nitric oxide synthase, and cellular adhesion
molecules. 10,28,94 If this inflammatory response is sub­ responses are maximizing oxygen delivery to the cells
stantial enough it will spill over into the systemic circula­ and minimizing further systemic insults. Currently there
are no recommended specific therapeutic agents to
tion (SIRS). When regulated, these responses are
modulate the immune response.
important to the maintenance of an effective immune
response and tissue repair. An imbalanced or overzealous
SEQUELAE OF CIRCULATORY SHOCK
inflammatory response may result in global increases in
capillary permeability, vasodilatation, leukocyte activation Circulatory shock may be rapidly fatal if it leads to signifi­
and adhesion, procoagulant changes, and mitochondrial cant hypoperfusion of the heart and brain that cannot be
dysfunction. 47,79,82,88 Clinically this can result in the adequately compensated for by cardiovascular responses
development of both hypovolemic and distributive shock. and treatment is unavailable or inadequate. This can
These mechanisms are potential contributors to acquired occur if the insult is severe or in association with less
organ dysfunction following illness or injury. 88 severe insults in patients whose ability to compensate is
In addition to an exuberant proinflammatory compromised, as may occur in anesthetized patients or
responses, an antiinflammatory response (CARS) can in animals with comorbidities.
also occur, which has been associated with Circulatory shock can be fatal in the hours following
immunocompromise and in some studies it correlates to insult or injury, despite aggressive resuscitative efforts,
a higher mortality. 151 The development of CARS is if the degree of shock was severe or prolonged enough
associated with increased production of antiinflammatory to lead to myocardial injury and/or sympathoinhibition.
cytokines, such as IL-10, IL-1 receptor antagonist, This is referred to as decompensated or irreversible shock.
and transforming growth factor-b. Leukocyte inhibition Animals that survive the acute episode of circulatory
and down regulation of NF-kB have also been shock may still be at risk of developing SIRS, which, if
demonstrated. 1,2 There is some discussion in the current severe, may result in MODS and possibly death in the
literature that CARS occurs concomitantly with SIRS as days following the original insult or injury. The likelihood
a normal response that limits the systemic inflammatory of SIRS and MODS following circulatory shock will
2
process. Although there is evidence that CARS maybe increase with increasing severity and duration of the
associated with an enhanced susceptibility to infection, shock episode. 28 In human medicine, other independent
this relationship is complicated and in many respects predictors of MODS following trauma include male
CARS may be a protective response. Following trauma, gender, elderly patients, amount of red blood cell
the immune system is activated and a second immune stim­ transfusions, and the persistence of an elevated blood
ulus during this period may augment the initial response lactate concentration 12 to 24 hours postinjury. 123
(second hit phenomenon) and potentially worsen the out­ There is evidence in human medicine that certain
come. 102,150 For this reason there may be a benefit in functional genetic polymorphisms can influence patient
delaying major surgery, such as fracture repair, for at least mortality. 96,103 For example variants of the tumor necro­
4 days following injury. sis factor gene are associated with the occurrence of sepsis
Inadequate perfusion of the gastrointestinal tract is and death following trauma. 96 Further the cellular
common in circulatory shock because sympathetic responses to injury show sexual dimorphism. For exam­
responses tend to shunt blood flow toward vital organs ple, in animal experimental models and human clinical
and cause disproportionate splanchnic hypoperfusion. 11 patients estrogen plays a protective role following