Organ dysfunction during sepsis

Peroxisome proliferator-activated receptor γ (PPARγ) and sepsis

“…This immune response is boosted by a panel of secondary pro-inflammatory mediators, such as reactive oxygen or nitrogen species and degradation products from fatty acids. Additionally, the coagulation cascade is triggered, decreasing fibrinolysis, which causes the formation of micro-thrombi in capillaries and finally evokes multi-organ dysfunction syndrome (MODS) [39]. Following this hyper-inflammatory phase, or sometimes occurring simultaneously, soluble TNF-α receptors, IL-1-receptor antagonists, IL-4, or IL-10 are produced as anti-inflammatory molecules switching the cellular phenotype from pro-to anti-inflammatory (Fig.…”

Which Organs Become Dysfunctional in Sepsis? How Does This Occur? How Is It Diagnosed and Managed?

“…This results in anergy (a state of nonresponsiveness to antigen), immune suppression, an inability to clear infection, and a predisposition for nosocomial infection. 5,11 Neutrophil apoptosis is also delayed, resulting in sustained inflammation and increased tissue and organ damage through cytotoxic enzymes and oxygen free radicals. This is particularly marked in the lung.…”

“…Extracardiac factors such as pericardial disease and intrathoracic pressure also affect ventricular stiffness and, hence, filling. 5 Early theories of myocardial dysfunction suggested that global myocardial ischemia was a potential cause of impaired function. However, in contrast to patients with shock attributable to other causes, those with sepsis have high coronary blood flow, low vascular resistance, and diminished coronary artery-coronary sinus oxygen difference-decreased oxygen extraction, analogous to that seen in peripheral circulation.…”

“…11 Moreover, despite changes in the microvasculature, elevated tissue oxygen levels have been demonstrated in experimental sepsis, suggesting inefficiency of cellular oxygen utilization may be more significant than a failure of oxygen delivery or microvascular shunting. 5 This results in an inability of cells to perform normal processes such as protein synthesis, DNA repair, and membrane pump activity. When this failure is severe and widespread, organ function is compromised.…”

“…It appears that following a noninfective (systemic inflammatory response syndrome, or SIRS) or infective (sepsis) insult, a complex and intricate cascade of inflammatory mediators is activated. 5 Briefly, pathogens have a range of exogenous molecules on their surfaces that are recognized by toll-like receptors (TLRs) embedded in the cell membrane and by cytoplasmic pattern recognition receptors present on monocytes, tissue macrophages, and endothelial cells. Activation of these triggers the host immune response, 6 resulting in cleavage of proinflammatory cytokines (e.g., interleukin-1 [IL-1], IL-6, IL-8, and tumor necrosis factor [TNF]).…”