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Typically, a bacterial pathogen enters a sterile site in which resident cells can detect the invader and initiate the host response. The host response is initiated when innate immune cells, particularly macrophages, recognize and bind to microbial components. Binding immune cell surface receptors to microbial components initiates a series of steps that result in the phagocytosis of invading bacteria, bacterial killing, and phagocytosis of debris from injured tissue. These processes are associated with the production and release of a range of proinflammatory cytokines by macrophages, leading to the recruitment of additional inflammatory cells, such as leukocytes. This response is highly regulated by a mixture of proinflammatory and antiinflammatory mediators. When a limited number of bacteria invade, the local host responses are generally sufficient to clear the pathogens. The end result is normally tissue repair and healing.
●Sepsis occurs when the release of proinflammatory mediators in response to an infection exceeds the boundaries of the local environment, leading to a more generalized response. It is uncertain why immune responses that usually remain localized sometimes spread beyond the local environment causing sepsis. The cause is likely multifactorial and may include the direct effects of invading microorganisms or their toxic products, release of large quantities of proinflammatory mediators, and complement activation. In this context, an anti-inflammatory response may reduce the toxic effects of the excessive inflammatory response, but may also compromise effective host protection from the infection. Some individuals may be genetically susceptible to developing sepsis.
●Despite a clear understanding of the inflammatory and coagulation mechanisms triggered during the early stage of severe sepsis, not much is known about the cellular aspects underlying the mechanisms that ultimately lead to organ dysfunction and death. Widespread cellular injury may occur when the immune response spreads beyond the site of infection causing sepsis. Cellular injury is the precursor to organ dysfunction. The precise mechanism of cellular injury is not understood, but proposed mechanisms include tissue ischemia (insufficient oxygen relative to oxygen need), cytopathic injury (direct cell injury by proinflammatory mediators and/or other products of inflammation), and an altered rate of apoptosis (programmed cell death). The mechanism of organ failure in sepsis may relate to decreased oxygen utilization associated with mitochondrial dysfunction rather than or in addition to poor oxygen delivery to tissues.
●The cellular injury, accompanied by the release of proinflammatory and antiinflammatory mediators, often progresses to organ dysfunction. No organ system is protected from the consequences of sepsis. Those that are most commonly involved include the circulation, lung, gastrointestinal tract, kidney, and nervous system.