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:The relationship between inflammation and systemic organ injury during sepsis.

In most cases, focal infections are eradicated by anintense, localized inflammatory response. Collateral damage to regional tissues does occur and is repaired after the infection and associatedinflammation subside. By contrast, severe sepsis is characterized by dissemination of inflammatory mediators (e.g. circulating cytokines)

resulting in widespread activation of the immune system distal to the original site of infection, the clinical manifestations of which are commonly referred to as the systemic inflammatory response syndrome (SIRS). SIRS is often complicated by systemic hypotension and tissue hypoperfusion (shock), and direct (e.g. TNFa-mediated) cell injury, which ultimately leads to multiple organ dysfunction syndrome (MODS), and in many cases death.

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Sepsis is a disorder of the microcirculation.

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Sepsis is a disorder of the microcirculationMuch of the pathophysiology of sepsis can be explained within the microcirculatory unit the terminal arteriole, the capillary bed, and the postcapillary venule. The arteriole is where the characteristic vasodilation and vasopressor hyporesponsiveness of sepsis occurs. The capillarybed is where the effects of endothelial cell activation/dysfunction are most pronounced and microvascular thromboses are formed.

The postcapillary venule is where leukocyte trafficking is most disorderedleukocytes adhere to the vessel wall, aggregate, and further impair flow through the microcirculation. (From Trzeciak S, Cinel I, Phillip Dellinger R, et al. Resuscitating the microcirculation in sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challenges for clinical trials. Acad Emerg Med 2008;15:399413; with permission.)

2 OPS Orthogonal polarization spectral imagingOPS Side-stream dark-field imagingSDF

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Examples of high and low capillary density. The capillary density was calculated similar to the technique of De Backer et al.1 A grid of equidistant vertical and horizontal lines was superimposed on the image. The vessel density was calculated as the number of small vessels (20 m) intersecting the lines of the grid divided by the total length of the lines yielding the number of small vessels per millimeter. The image in A represents a high capillary density, and the image in B represents a low capillary density. Real-time video sequences of orthogonal polarization spectral imaging in severe sepsis and septic shock are available from the authors through a file download.

- -- DO2 DO2 VO2AO2 ARDS SHOCK MMDS

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*In most cases, focal infections are eradicated by anintense, localized inflammatory response. Collateral damage to regional tissues does occur and is repaired after the infection and associatedinflammation subside. By contrast, severe sepsis is characterized by dissemination of inflammatory mediators (e.g. circulating cytokines)resulting in widespread activation of the immune system distal to the original site of infection, the clinical manifestations of which arecommonly referred to as the systemic inflammatory response syndrome (SIRS). SIRS is often complicated by systemic hypotension and tissuehypoperfusion (shock), and direct (e.g. TNFa-mediated) cell injury, which ultimately leads to multiple organ dysfunction syndrome (MODS),and in many cases death.*Sepsis is a disorder of the microcirculation. Much of the pathophysiology of sepsis canbe explained within the microcirculatory unitthe terminal arteriole, the capillary bed, andthe postcapillary venule. The arteriole is where the characteristic vasodilation and vasopressorhyporesponsiveness of sepsis occurs. The capillary bed is where the effects of endothelialcell activation/dysfunction are most pronounced and microvascular thromboses areformed. The postcapillary venule is where leukocyte trafficking is most disorderedleukocytesadhere to the vessel wall, aggregate, and further impair flow through the microcirculation.(From Trzeciak S, Cinel I, Phillip Dellinger R, et al. Resuscitating the microcirculationin sepsis: the central role of nitric oxide, emerging concepts for novel therapies, and challengesfor clinical trials. Acad Emerg Med 2008;15:399413; with permission.)*