Page 478 - Clinical Small Animal Internal Medicine

446 Section 5 Critical Care Medicine

Acute Phase Response spinal cord injury is composed of hemorrhage, edema,
VetBooks.ir The release of pro-inflammatory cytokines tumor necrosis vasospasm or enzymatically induced neurotoxicity. As
an organ, the brain is particularly sensitive to injury by
factor (TNF)‐alpha, interleukin (IL)‐1‐beta, and IL‐6 fol-
lowing trauma induces the acute phase response in the ROS due to high levels of unsaturated fatty acids and
low antioxidant capacity. Periods of hypoxia and hypo-
liver which results in up-regulation of positive acute tension lead to the accumulation of the excitatory neu-
phase proteins, including fibrinogen and prothrombin. rotransmitter glutamate in the interstitial compartment.
At the same time positive acute phase proteins are being High extracellular levels of glutamate in addition to
up-regulated, the production of negative acute phase intracellular depletion of ATP lead to accumulation of
proteins albumin, protein‐C, protein‐S, and antithrom- calcium and sodium ions within the neuronal cell and
bin (AT) is reduced. The net effect of the acute phase culminate in cellular dysfunction and death. Because of
response is generally in the direction of enhanced coagu- this, several autoregulatory countermeasures have been
lation through the increased production of prothrombin, developed, including the brain’s ability to regulate blood
fibrinogen and the decreased production of endogenous flow across a wide range of blood pressures. However, if
anticoagulants protein‐C, protein‐S, and AT. The result- hypoxia or shock is severe enough in magnitude or dura-
ant hypercoagulable state can contribute to the develop- tion, these defense mechanisms are overcome and sec-
ment of DIC in patients following severe trauma or ondary neuronal injury occurs.
burns.
It is important to remember that primary brain injury
can impair the autoregulatory functions of the brain,
Ischemia and Reperfusion making it susceptible to secondary injury that would
otherwise not occur. For this reason, initial resuscitative
Systemic ischemia can occur following trauma and is measures should be focused on improving oxygen delivery
attributed to hypoxemia and hypotension immediately to the vital organs, especially the brain.
following trauma and during the early resuscitative
period (<24 hrs). Local ischemia can occur due to blunt
trauma, disruption of local blood supply or compartment Burns
syndrome. During periods of ischemia, several impor- Local burns covering less than 30% of total body surface
tant intracellular changes occur. As energy stores are area (TBSA) rarely cause severe systemic effects while
depleted, adenosine triphosphate (ATP) levels decrease severe burns (those covering more than 30% of TBSA)
and ATP is degraded to adenosine diphosphate (ADP) are capable of inducing a syndrome called “burn shock”
and hypoxanthine. As ischemia continues, intracellular that is characterized by decreased intravascular volume,
pH decreases and lactate, hypoxanthine and sodium and reduced cardiac output (CO), and increased systemic
calcium ion concentrations increase, leading to cellular vascular resistance.
swelling. Upon reperfusion, oxygen interacts with The physiologic response to burns is generally divided
hypoxanthine, resulting in the formation of reactive oxy- into two distinct phases. The resuscitation phase begins
gen species (ROS). This occurs within seconds of rein- immediately following burn injury and is characterized
troduction of oxygen to ischemic tissues. Reactive by depleted circulating volume with increased vascular
oxygen species are capable of causing lipid peroxidation permeability and protein‐rich fluid loss into the intersti-
and cell death. The release of ROS into the systemic cir- tial space, resulting in edema formation of both burned
culation and their subsequent delivery to the lungs fol- and unburned tissue. This phase coincides with a sys-
lowing reperfusion may form the basis for the temic response similar to that observed in severe
development of acute lung injury associated with trauma. trauma patients as described above. Hypoproteinemia in
The liver and gut may be particularly sensitive to ischemia/
reperfusion injury. In fact, ischemia and reperfusion of burn patients occurs secondary to protein loss in the
form of edema fluid and fluid loss from the affected skin
the gut following shock and subsequent resuscitation surface and can develop during the resuscitative phase of
result in the gut becoming a source of proinflammatory burn management.
mediators capable of inducing SIRS.
Following the resuscitation phase of burn injury
(3–5 days), a hyperdynamic/hypermetabolic phase, pri-
marily mediated by counter-regulatory hormones
Traumatic Brain Injury/Spinal Cord Injury
including cortisol, glucagon, and catecholamines, begins.
The response of the brain and spinal cord to trauma is During the hyperdynamic phase, cardiac output is
unique. Similar to general trauma, brain injury consists increased and vascular permeability begins to return to
of primary (direct result of trauma) and secondary injury normal. In addition to the circulatory changes, an
(subsequent to primary injury). Secondary brain and increase in metabolic rate occurs that results in negative