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Multiple organ dysfunction syndrome

Multiple organ dysfunction syndrome

Classification and external resources

ICD-10 R65.2

ICD-9-CM 995.92

eMedicine med/3372

MeSH D009102

[edit on Wikidata]

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,[1] 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.

Definition

Multiple organ 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.[1]
Cause

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 in operative and non-operative patients. Sepsis 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.[1] 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.[2] 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).[3] 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
myeloperoxidase and malonialdehyde activity; these last two are endogenous oxidizing
compounds produced during tissue inflammation. The authors assessed the level
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.
Pathophysiology

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 after the original insult.
Subsequently, one might see liver failure (5–7 days), gastrointestinal bleeding (10–15 days)
and kidney failure (11–17 days).[1]

Gut hypothesis

The most popular hypothesis by Deitch to explain MODS in critically ill patients is the gut
hypothesis.[4] 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.[1]

Endotoxin macrophage hypothesis

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.[1]

Tissue hypoxia-microvascular hypothesis

As a result of macro- and microvascular changes insufficient supply of oxygen occurs.

Hypoxemia causes cell death and organ dysfunction .[1]

Mitochondrial DNA hypothesis

According to findings of Professor Zsolt Balohh and his team at University of Newcastle
(Australia), Mitochondrial DNA is the leading cause of severe inflammation due to massive
amount of Mitochondrial DNA that leaks into the blood stream due to cell death into the
blood stream of patients that survived Major trauma.

Mitochondrial DNA is very similar-looking like bacterial DNA. And if bacteria is triggering
leukocytes, maybe the mitochondrial DNA does the same. When confronted with bacteria,
white blood cells, or Neutrophil granulocyte, behave like predatory spiders. They spit out a
web, or net, to trap the invaders, then hit them with a deadly oxidative blast. Neutrophil
extracellular traps (NETs)

This result in catastrophic immune response leading to multiple organ dysfunction

syndrome.[5][6]

Integrated hypothesis

Since in most cases no primary cause is found, the condition could be part of a
compromised homeostasis involving the previous mechanisms.[1]

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.[1]

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.

Management

At present there is no agent that can reverse the established organ failure. Therapy
therefore is 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.[1]

Prognosis

Mortality varies from 30% to 100% where the chance of survival is diminished as the
number of organs involved increases. Since the 1980s the mortality rate has not changed.[1]
In patients with sepsis, septic shock, or multiple organ dysfunction syndrome that is due to
major trauma, the rs1800625 polymorphism is a functional single nucleotide polymorphism,
a part of the receptor for advanced glycation end products (RAGE) transmembrane receptor
gene (of the immunoglobulin superfamily) and confers host susceptibility to sepsis and
MODS in these patients.[7]

History

The historical origin of the concept of MODS is as follows. For many years, some patients
were loosely classified as having sepsis or the sepsis syndrome. In more recent years, these
concepts have been refined – so that there are specific definitions of sepsis – and two new
concepts have been developed: the SIRS and MODS.[1]

References

^ a b c d e f g h i j k l Intensive Care Medicine by Irwin and Rippe Archived November 7,

2005, at the Wayback Machine.