Sepsis: the inflammatory foundation of pathophysiology and therapy

Sepsis, defined as an infection accompanied by inflammation, is a complex disease process wherein the body's response to a pathogen is amplified far beyond the initial site of infection. The process begins when pathogen-associated molecular patterns on the bacteria or other pathogens induce an inflammatory cascade in the host. In the United States, it is estimated that every minute a patient with severe sepsis or septic shock presents to an emergency department and that > 751 000 cases of severe sepsis occur annually, resulting in an estimated 215 000 deaths. A rapid progression of illness severity from sepsis to severe sepsis to septic shock frequently occurs, driven by the body's inflammatory and anti-inflammatory responses to a pathogen, making sepsis a condition requiring timely intervention. The clinical management of severe sepsis and septic shock has evolved dramatically over the past decade and these new therapeutic approaches have been built on a deeper understanding of the natural evolution of sepsis. This article examines the underlying pathophysiological mechanisms of sepsis to help explain the clinical signs and symptoms manifested by severe sepsis patients. It also examines the significance of current proposed treatment strategies, including early goal-directed therapy, from a pathophysiological and inflammatory perspective.