Editing Sepsis (section)

=== Host factors ===
Upon detection of microbial [[antigen]]s, the host systemic immune system is activated. Immune cells not only recognise pathogen-associated molecular patterns but also [[damage-associated molecular pattern]]s from damaged tissues. An uncontrolled immune response is then activated because leukocytes are not recruited to the specific site of infection, but instead, they are recruited all over the body. Then, an immunosuppression state ensues when the proinflammatory [[T helper cell]] 1 (TH1) is shifted to TH2,<ref name="Yuki"/> mediated by [[interleukin 10]], which is known as "compensatory anti-inflammatory response syndrome".<ref name="Polat"/> The [[apoptosis]] (cell death) of lymphocytes further worsens the immunosuppression. [[Neutrophil]]s, [[monocytes]], [[macrophages]], [[dendritic cell]]s, [[CD4|CD4+ T cells]], and [[B cell]]s all undergo apoptosis, whereas [[regulatory T cell]]s are more apoptosis-resistant.<ref name="pmid31611560" /> Subsequently, [[multiple organ dysfunction syndrome|multiple organ failure]] ensues because tissues are unable to use oxygen efficiently due to inhibition of [[cytochrome c oxidase]], possibly as part of a "cell hibernation" mechanism, in order to conserve oxygen.<ref name="Yuki"/>

Inflammatory responses cause [[multiple organ dysfunction syndrome]] through various mechanisms as described below. Increased permeability of the lung vessels causes leaking of fluids into alveoli, which results in [[pulmonary edema]] and [[acute respiratory distress syndrome]] (ARDS). Impaired utilization of oxygen in the liver impairs [[bile salt]] transport, causing [[jaundice]] (yellowish discoloration of the skin). In kidneys, inadequate oxygenation results in tubular epithelial cell injury (of the cells lining the kidney tubules), and thus causes [[acute kidney injury]] (AKI). Meanwhile, in the heart, impaired calcium transport, and low production of [[adenosine triphosphate]] (ATP), can cause myocardial depression, reducing cardiac contractility and causing [[heart failure]]. In the [[gastrointestinal tract]], increased permeability of the mucosa alters the microflora, causing mucosal bleeding and [[paralytic ileus]]. In the [[central nervous system]], direct damage of the brain cells and disturbances of neurotransmissions causes altered mental status.<ref name=Fujishima2016/> Cytokines such as [[TNF-alpha|tumor necrosis factor]], [[Interleukin 1 family|interleukin 1]], and [[interleukin 6]] may activate [[coagulation|procoagulation]] factors in the [[endothelium|cells lining blood vessels]], leading to endothelial damage. The damaged endothelial surface inhibits anticoagulant properties as well as increases [[antifibrinolytic|antifibrinolysis]], which may lead to intravascular clotting, the formation of [[thrombus|blood clots]] in small blood vessels, and multiple organ failure.<ref name= Nimah2003/>

The low blood pressure seen in those with sepsis is the result of various processes, including excessive production of chemicals that [[Vasodilation|dilate blood vessels]] such as [[nitric oxide]], a deficiency of chemicals that [[vasoconstriction|constrict blood vessels]] such as [[vasopressin]], and activation of [[ATP-sensitive potassium channel]]s.<ref name="Marik2014"/> In those with severe sepsis and septic shock, this sequence of events leads to a type of [[circulatory shock]] known as [[distributive shock]].<ref name="Marik2014Chest"/>