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. Tissue hypoxia-microvascular hypothesis
As a result of macro- and microvascular changes insufficient supply of oxygen occurs. Hypoxemia causes cell death and organ dysfunction. Mitochondrial DNA hypothesis
According to findings of Professor Zsolt Balogh and his team at the 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 bloodstream due to cell death of patients who survived major trauma.Mitochondrial DNA resembles bacterial DNA. If bacteria triggers leukocytes, mitochondrial DNA may do the same. When confronted with bacteria, white blood cells, or neutrophil granulocytes, behave like predatory spiders. They spit out a web, or net, to trap the invaders, then hit them with a deadly oxidative blast, forming neutrophil extracellular traps (NETs).This results in catastrophic immune response leading to multiple organ dysfunction syndrome. Integrated hypothesis
Since in most cases no primary cause is found, the condition could be part of a compromised homeostasis involving the previous mechanisms. Diagnosis
The European Society of Intensive Care organized a consensus meeting in 1994 to create the "Sepsis-Related Organ Failure Assessment (SOFA)" score to describe and quantitate the degree of organ dysfunction in six organ systems.
Using similar physiologic variables the Multiple Organ Dysfunction Score was developed.Four clinical phases have been suggested:
Stage 1: the patient has increased volume requirements and mild respiratory alkalosis which is accompanied by oliguria, hyperglycemia and increased insulin requirements. Stage 2: the patient is tachypneic, hypocapnic and hypoxemic; develops moderate liver dysfunction and possible hematologic abnormalities. Stage 3: the patient develops shock with azotemia and acid-base disturbances; has significant coagulation abnormalities. Stage 4: the patient is vasopressor dependent and oliguric or anuric; subsequently develops ischemic colitis and lactic acidosis. Definition
Multiple dysfunction syndrome is the presence of altered organ function in acutely ill patients such that homeostasis cannot be maintained without intervention. It usually involves two or more organ systems. It calls for an immediate intervention. Management
At present, there is no drug or device that can reverse organ failure that has been judged by the health care team to be medically and/or surgically irreversible (organ function can recover, at least to a degree, in patients whose organs are very dysfunctional, where the patient has not died; and some organs, like the liver or the skin, can regenerate better than others),- with the possible exception of single or multiple organ transplants or the use of artificial organs or organ parts, in certain candidates in specific situations. Therapy, therefore, is usually mostly limited to supportive care, i.e. safeguarding hemodynamics, and respiration. Maintaining adequate tissue oxygenation is a principal target. Starting enteral nutrition within 36 hours of admission to an intensive care unit has reduced infectious complications.