The inflammatory process represents one of the most important responses of the body. Many insults can produce an inflammatory response. Traumatic injuries, biological insults, thermal burns, immune and chemical injuries are capable of developing the inflammatory response, which plays a primary role in protecting the living being, nevertheless an exaggerated response can be harmful and can lead to death.

Failure of systemic host defense homeostasis in SIRS is related to inappropriate regulation of acute immune and inflammatory response, causing most of the clinical signs and leading patients to mortality.

The classical signs of inflammatory response that you can observe are: pain, heat, lack of function and tumor. These have been changed in the light of the actual scientific knowledge for more complex physiological events.

In the first minutes after an insult occurs, the initial changes are:

 Increase blood flow in the affected area.

 Increase capillary permeability

 Attraction of phagocytical cells to the area.

Immediate trauma causes an increase in blood flow of the affected area; besides there is vasoconstriction of those vessels, therefore the capillary area is full of blood and that is the origin of heat and erythema.

The increases in capillary permeability lead to loss of fluids from the vascular into the tissue and the intersticium. This fluid has a large quantity of protein, which in turn attracts more liquids, thus forming the tumor of the affected area. This increase in permeability facilitates the migration of phagocytical cells that in turn will release their lysosomal enzymes in the damaged tissue.

If the injury is bigger than the ability to respond of the neutrophils, in 5 or 6 hours the area will be full of lymphocytes and macrophages that will attract other inflammatory cells to the injured area in order to control the tissular damage and start healing. In this phase, and product of new cell signals, the four main enzymatic systems of plasma activates: Coagulation, fibrinolytic, kinins and complement.

The main mediators and controllers in this response are cytokines, enzymatic products and vasoactive mediators.

MEDIATORS BIOLOGICAL ACTIONS

 Histamine: increase vascular permeability and smooth muscle contraction.

 Serotonin: causes the same action as histamine

 PAF: causes the release of platelet mediators, increase in vascular permeability, smooth muscle contraction and activation of neutrophils, there is some evidence that show it play a main role in bowel necrosis

 Thromboxanes: causes platelet and PMN aggregation, vasoconstriction

 IL-8: causes monocytes attraction.

 C3a: causes smooth muscle contraction and mastocytes degranulation.

 C5a: provokes smooth muscle contraction, increase in capillary permeability, attraction and activation of neutrophils and macrophages.

 Kinins: vasodilatation, smooth muscle contraction, increases in capillar permeability.

 Fibrinolytic system: increase in vascular permeability, attraction to macrophages and neutrophils.

 PgE2: vasodilatation increases histamine action.

 LtB4: neutrophil attraction, synergism with PgE2, enhance capillary leakage

 LtD4: smooth muscle contraction, increase in vascular permeability

 LtC4: depression os cardiac contractility

TRAUMA AND SIRS

The multiple trauma patients as an example of SIRS, represent one of the most important challenges in veterinary practice. All the environmental aspects of these events make it imperative to have an accurate clinic semiologic system to assess these cases.

It is important to remember that the clinical effects observed in these patients are only the expression of local inflammatory phenomena. Due to the extent of the injury and the organic response, it turns to be general involving other systems and organs, being so severe as to result in death.

It has to be clear that SIRS does not occur without a pre-existing injury or insult. Any kind of organic damage will prompt the release of the previous mediators in order to produce a proinflammatory state. All together assemble a response that is designed to limit new damage and to ameliorate any damage that has already been done. To ensure that the effect of these proinflammatory mediators does not become harmful, the body launches a compensatory anti-inflammatory response. This state is only the local reaction in the site of injury or infection.

If the original insult is too severe, the regulation of the inflammatory response is lost a massive reaction occurs. This reaction is usually proinflammatory producing the clinical findings of SIRS: hypotension, tachypnea, tachycardia, increased microvascular permeability, ischemia, reperfusion injury, and vasodilatation. Often, the result is the developing of a profound shock that further compromises blood flow to vital organs. Organ dysfunction and systemic failure can result if nothing is dome to prevent it.

Sometimes the compensatory anti-inflammatory mechanisms are overwhelmed and the patient can develop immune suppression, that has been describes as "immune paralysis" or as a "window of immunodeficiency". It can be considered as compensatory anti-inflammatory response syndrome (CARS), these syndrome explains the increased susceptibility to infection of trauma patients. Therefore MARS or mixed antagonistic response syndrome includes SIRS and CARS components.

The final stage of MODS (multiple organ dysfunction syndrome) is reached when the patient develops immunologic dissonance. In these patients organ dysfunction results from an ongoing inflammation, and it will end in death unless the inflammation can be down regulated. Organ failure occurs sequentially: first the lungs and then the liver, gastrointestinal tract and then the kidneys. The underlying proinflammatory response affects all the organs simultaneously.