Multiple organ dysfunction syndrome

Multiple organ dysfunction syndrome (MODS), also known as multiple organ failure (MOF), total organ failure (TOF) or multisystem organ failure (MSOF), is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis. Multiple organ dysfunction syndrome (MODS), also known as multiple organ failure (MOF), total organ failure (TOF) or multisystem organ failure (MSOF), is altered organ function in an acutely ill patient requiring medical intervention to achieve homeostasis. Although Irwin-Rippe cautions in 2005 that the use of 'multiple organ failure' or 'multisystem organ failure' should be avoided, both Harrison's (2015) and Cecil's (2012) medical textbooks still use the terms 'multi-organ failure' and 'multiple organ failure' in several chapters, and do not use 'multiple organ dysfunction syndrome' at all. The condition usually results from infection, injury (accident, surgery), hypoperfusion and hypermetabolism. The primary cause triggers an uncontrolled inflammatory response. Sepsis is the most common cause of Multiple Organ Dysfunction Syndrome and may result in septic shock. In the absence of infection, a sepsis-like disorder is termed systemic inflammatory response syndrome (SIRS). Both SIRS and sepsis could ultimately progress to multiple organ dysfunction syndrome. However, in one-third of the patients no primary focus can be found. Multiple organ dysfunction syndrome is well established as the final stage of a continuum: SIRS + infection sepsis severe sepsis Multiple organ dysfunction syndrome. Currently, investigators are looking into genetic targets for possible gene therapy to prevent the progression to Multiple Organ Dysfunction Syndrome. Some authors have conjectured that the inactivation of the transcription factors NF-κB and AP-1 would be appropriate targets in preventing sepsis and SIRS. These two genes are pro-inflammatory. However, they are essential components of a normal healthy immune response, so there is risk of increasing vulnerability to infection, which can also cause clinical deterioration. Some have developed a mouse model sepsis via cecal ligation and puncture (CLP). Male Balb/c mice subjected to CLP were given an IL-10-carrying vector or an empty control vector. Lung, Liver and kidney tissue destruction were measured by assessing malondialdehyde and myeloperoxidase activity; these last two are endogenous oxidizing compounds produced during tissue inflammation. The authors assessed the level of neutrophil infiltration in lung and liver tissue. IL-10 protein expression was measured using immunohistochemistry. The expression of Tumor necrosis factor-alpha (TNF-α) mRNA was measured at 3, 8 and 24 hours after CLP using reverse transcription polymerase chain reaction. Their results show significantly reduced organ damage by IL-10 gene transfer, as quantified by reduced myeloperoxidase activity in the lung, liver and kidney. The malonialdehyde level was not affected by the transfer into the liver. The livers of the mice infected with the adenoviral vector showed reduced neutrophil activity. The lung and kidney samples in mice carrying the gene showed lower expression of TNF-α mRNA. The investigators concluded that increased IL-10 expression significantly reduced sepsis-induced multiple organ injury. A definite explanation has not been found. Local and systemic responses are initiated by tissue damage. Respiratory failure is common in the first 72 hours. Subsequently, one might see liver failure (5–7 days), gastrointestinal bleeding (10–15 days) and kidney failure (11–17 days). The most popular hypothesis by Deitch to explain MODS in critically ill patients is the gut hypothesis. Due to splanchnic hypoperfusion and the subsequent mucosal ischaemia there are structural changes and alterations in cellular function. This results in increased gut permeability, changed immune function of the gut and increased translocation of bacteria. Liver dysfunction leads to toxins escaping into the systemic circulation and activating an immune response. This results in tissue injury and organ dysfunction. Gram-negative infections in MODS patients are relatively common, hence endotoxins have been advanced as principal mediator in this disorder. It is thought that following the initial event cytokines are produced and released. The pro-inflammatory mediators are: tumor necrosis factor-alpha (TNF-α), interleukin-1, interleukin-6, thromboxane A2, prostacyclin, platelet activating factor, and nitric oxide. As a result of macro- and microvascular changes insufficient supply of oxygen occurs. Hypoxemia causes cell death and organ dysfunction. According to findings of Professor Zsolt Balogh and his team at University of Newcastle (Australia), mitochondrial DNA is the leading cause of severe inflammation due to a massive amount of mitochondrial DNA that leaks into the blood stream due to cell death of patients that survived major trauma.