Definitions, Epidemiology and Pathophysiology

Despite significant progress in the understanding and treatment of sepsis, it continues to be a major health problem in United States and around the world. Sepsis accounted for nearly 4,500 deaths (mortality rate 10%) and approximately $2 billion per year in healthcare expenditures in the U.S. alone. In this review, we will revisit the definitions of pediatric sepsis and discuss the epidemiology of sepsis in the United States. During inflammatory states, the vascular endothelium plays a crucial role in modulating the host immune response and regulates the levels of coagulation, pro-inflammatory and anti-inflammatory factors in the blood. We review the role of endothelium in nitric oxide generation and activation of the coagulation cascade. Studies in critically ill patients and animal models have shown that increased apoptosis or “programmed cell death” of lymphoid organs contributes to immune suppression, anergy, and organ system dysfunction. In this chapter, we outline both intrinsic and extrinsic pathways that lead to apoptosis.