Page 454 - Clinical Small Animal Internal Medicine

422 Section 5 Critical Care Medicine

Table 43.1 SIRS criteria for dogs and cats same time and in different combinations, a piece of
VetBooks.ir Criterion Cats Dogs music emerges. The appropriateness or lack thereof of
this process is the central driver in the pathology associ-

Temperature >103.5 °F >102.6 °F ated with sepsis and septic shock.
<100 °F <100.6 °F
Dysregulated Immunity
Heart rate bpm >225 >120 Once a pathogen has been recognized and the immune
<140 response initiated, there are numerous opportunities for
Respiratory rate >40 breaths per >20 breaths per minute dysregulation to occur, adding to morbidity and possibly
minute mortality of the patient. This dysregulated immunity was
White blood >19 500 or <5000 >16 000 or <6000 considered to be exclusively an overexuberant inflamma-
cells/μL >3% bands >3% bands tory response and in fact, the “inflammation only” the-
Source: Adapted from Brady et al. (2000) and Hauptman et al. (1997). ory explains most of the clinical signs observed in septic
patients. It does not, however, explain all the clinical
As a consequence, most of the clinical manifestations signs and it has subsequently become clear that hyperin-
associated with sepsis and SIRS, with few exceptions, are flammation alone does not fully account for the morbid-
associated with the response of the innate immune sys- ity and mortality experienced by septic patients.
tem. It is important to note that the body makes no dis- A compensatory anti-inflammatory response syndrome
tinction between these two systems and they function (CARS) was proposed as an alternative that may occur in
synergistically. For instance, proinflammatory cytokines some patients as a result of systemic inflammation. The
elicited as a result of an innate immune response help to CARS theory states that in some patients, overcompensa-
augment the subsequent or concurrent adaptive response. tion by the anti‐inflammatory arm of the immune system
Innate immunity relies on recognition by the host of results from a combination of excessive anti-inflammatory
some very specific, evolutionarily conserved molecular cytokine production and, possibly more importantly, from
patterns that are found in association with infection, the death and dysfunction of immune cells. This theory
inflammation, cell death or all of the above. Pattern recog- helps to explain some of the clinical manifestations of
nition receptors (PRRs) are a relatively small set of recep- sepsis/SIRS. It is convenient to consider these conditions
tors that are able to recognize a wide range of pathogens, in the extreme as distinct identities but clinically most
including viruses, bacteria, and fungi. Many cell types that patients will lie somewhere in the middle.
participate in immune function, including macrophages,
monocytes, dendritic cells, neutrophils, and epithelial Physiologic Consequences
cells, express PRRs that allow the rapid recognition of Patients with sepsis can develop shock that often shares
pathogens at the site of infection. Numerous PRRs have characteristics of hypovolemic, vasodilatory, and cardio-
been identified (Nod‐like receptors, C‐type lectin recep- genic etiology due to the actions of inflammatory media-
tors, RIG receptors, and RAGE receptors) with remarka- tors and their cumulative effect on the circulatory
ble homology across species in all parts of the phylogenetic system. In addition to tissue perfusion derangements,
tree. The fact that these PRRs are found in such diverse patients with sepsis or septic shock can suffer from cyto-
species highlights their importance for survival. pathic hypoxia or an inability to utilize oxygen at the
The most studied and best‐known PRRs are the toll‐ mitochondrial level. This further complicates under-
like receptors (TLRs), which are expressed by many cell standing the pathophysiology of sepsis and septic shock.
types including macrophages, dendritic, endothelial, and Hypovolemia often develops from vomiting, diarrhea or
epithelial cells. TLR activation is generally considered to bleeding but can also occur due to accumulation of cavitary
be proinflammatory and results in the production of effusion or peripheral edema reducing effective circulating
antimicrobial peptides, inflammatory cytokines and volume. Changes in vascular permeability, vascular hydro-
chemokines, and adhesion molecules, all of which work static pressure, decreased colloid osmotic pressure or lym-
together to coordinate the innate response. phatic occlusion all occur in septic patients and result in a
As a result of PRR activation, there is a coordinated tendency for fluid to move out of the vascular space. As a
response by the immune system to recruit other cells result, significant “third spacing” of fluid can occur in the
into the fight against infection. This recruitment, the thoracic or abdominal cavities or interstitium of patients
actions of the recruited cells, their associated killing with sepsis or SIRS. The net effect of this fluid movement is
mechanisms, and soluble factors have led some authors decreased intravascular volume that contributes to lower
to compare the TLRs and other PRRs to keys on a piano. cardiac output and impaired oxygen delivery.
When one key is struck alone, the resultant note does Besides loss of effective circulating volume, sepsis can
not make a song, but when several keys are played at the induce significant alterations in vascular tone. Because