Page 129 Complete Your CE Test Online - Click Here system work together to stop the inflammatory process when the threat to the host is no longer present (Markiewski, DeAngelis, & Lambris, 2008). There is a definitive endpoint in the normal immune system response when the invader is phagocytosed and neutralized and debris is cleared. In sepsis, this endpoint is not realized, and the response spreads. Acquired immunity Acquired immunity (also known as adaptive immunity) relies on previous exposure to an invader. Acquired immunity includes white blood cells, such as lymphocytes, T cells and B cells. They make up between 20% and 40% of the white blood count and are important in fighting off infection (Foxx, 2016). The acquired immune system is activated if the innate response has not entirely rid the body of infection—both types of immunity work simultaneously to rid the body of infection. The acquired immune system has a specific plan to fight off the invading organism through experience of previous exposure. If the infection remains localized and the invading organism has been entirely neutralized through innate and acquired immune function, tissue is repaired, healing is complete, homeostasis resumes, and the body is rid of infection. Complement system The complement system is an important defense mechanism in fighting off infections and is activated during the innate immune response. Proteins are released that help with the destruction of microorganisms and help control the inflammatory reaction. These proteins act as a bridge between the innate and adaptive immune response (Markiewski et al., 2008). Regulatory complement proteins work to halt the inflammatory process after the successful removal of the invading organism or resolution of injured tissue (Markiewski et al., 2008). Coagulation cascade During the normal immune system response, inflammatory cytokines (specifically IL-1 and TNFa), in response to injury or invasion, trigger the release of tissue factors. This begins the coagulation cascade. This leads to the production of thrombin and fibrin and eventually to the formation of clots that help keep invading organisms localized. Bradykinin, a peptide, is a key component of the coagulation cascade that also causes increased vascular permeability and vasodilation. It is responsible for the inflammatory-mediated pain response that occurs during the process of acute inflammation and contributes to hypotension secondary to vasodilation. The following key points further describe the process. Key points ● ● Two types of immunity respond to an invader, innate immunity that we are born with and acquired or adaptive immunity that develops after exposure to an invader. ● ● Upon invasion from an organism, blood vessels dilate, and the site of invasion is flooded with coagulation factors, cytokines, chemokines, platelets, and inflammatory cells (white blood cells, such as neutrophils, macrophages, monocytes, eosinophils, and basophils). ● ● White blood cells—such as neutrophils, macrophages, and monocytes—recognize the invader and bind to it, causing the release of inflammatory cytokines. Elevated white blood counts indicate the presence of organisms that may lead to sepsis. ● ● Inflammatory cytokines recruit more inflammatory cells to the site, known as leukocytes. ● ● The innate and acquired immune systems work to neutralize the invader; the complement system is considered to be the bridge between the innate and acquired immune response. ● ● Proinflammatory cytokines, known as IL-1 and TNFa, also trigger the coagulation cascade to help form clots and keep the infection localized. ● ● Antiinflammatory cytokines, along with the regulatory proteins of the complement system, normally keep the inflammatory process in check. ● ● Homeostasis resumes when the invader is neutralized, debris is removed, and tissue repair and healing are complete. Self-evaluation: Question 1 Betty is a 66-year-old woman with a history of degenerative joint disease and diabetes. She has had several years of increasing hip pain and difficulty ambulating. Recently, she underwent surgery to replace the right hip joint. If Betty’s blood were drawn in the first few hours following surgery, what would be the most likely laboratory findings if she is showing an early response that may progress to sepsis? a. Leukocytosis (elevated WBC). b. Elevated hematocrit. c. Leukopenia (low WBC). d. Elevated hemoglobin. PATHOPHYSIOLOGY OF SEPSIS The pathophysiology behind sepsis is complicated and still widely researched. It is a complex manifestation of an abnormal response by the body’s inflammatory response to an infection. The development of sepsis is thought to depend on a variety of factors, including comorbidities (coexisting or preexisting conditions), the pathogen causing the disease, the virulence or harmfulness of the pathogen, and possibly a genetic predisposition (Neviere, 2017). Sepsis often begins from an infection acquired before hospitalization. Typically, when a person gets an infection, the body responds by initiating an inflammatory response to the infectious agent. There is a balancing of localized proinflammatory and antiinflammatory mediators, known as cytokines, that results in the destruction of the infectious agent and subsequent tissue healing and repair when the immune response remains localized (Neviere, 2017). If, however, the immune response does not stay localized to the site of infection and the response becomes generalized, sepsis can result (Neviere, 2017). In sepsis, the initial immune response becomes exaggerated and causes an imbalance between what is known as a proinflammatory response and an antiinflammatory response (Schulte et al., 2013). It is still not known why the immune system response remains localized in some instances and becomes generalized in other instances. It may be because of many factors, including what type of organism is invading and the toxic products it releases, the release of a large amount of proinflammatory cytokines, or genetic predisposition (Neviere, 2017). It is believed that the development of sepsis is mostly related to the dysregulation of the innate immune response rather than dysregulation of the acquired immune response. However, evidence of immune suppression in postmortem ICU patients with sepsis has been shown in the depletion of CD4 and CD8 lymphocytes (specific T cells of the adaptive immune response), suggesting there may be a role in the adaptive immune response in sepsis as well (de Pablo, Monserrat, Prieto, & Alvarez-Mon, 2014).