Pathophysiology of the Adult Respiratory Distress Syndrome and Multi System Organ Failure.

Tighe, Derek (1992). Pathophysiology of the Adult Respiratory Distress Syndrome and Multi System Organ Failure. BPhil thesis The Open University.



Pulmonary dysfunction in patients with the adult respiratory distress syndrome (ARDS) is nearly always associated with damage to other organs, although such damage may not be clinically apparent. When non-pulmonary in origin ARDS should be considered as an element of multi system organ failure (MSOF). Most patients with MSOF do not die from hypoxemia. Major trauma is nearly always associated with some pulmonary dysfunction, although often subclinical. Medical conditions such as septicaemia, trauma, pancreatitis or burns cause severe inflammatory cascade activation (SICA), which is the most likely cause of MSOF.

Oxygen metabolism is central to the development of SICA. Once established SICA causes redistribution of blood flow to and within vital organs. Organs needing a high oxygen delivery (e.g. heart or brain) are deprived of blood by the relatively high flow in less dependant organs (e.g. skin, kidney, or splanchnic bed). In this condition, blood flow is redistributed, producing a relative ischemia and reduction in the production of ATP. This ischemia promotes the formation of super oxides by xanthine oxidase, causing further tissue damage.

Ultrastructure studies show that leucocytes aggregate in the lungs, liver and spleen and tissue damage is greatest in these organs. But, even when there is little leucocyte aggregation in the lungs, considerable tissue damage is observed. Leucocytes can be induced to aggregate in the lungs without causing tissue damage. Leucocytes do not aggregate in significant numbers in the heart, kidneys or muscle. Leucocytes are therefore important in the inflammatory cascade of MSOF but not essential.

Although there are many biochemical mediators of MSOF, the choke point enzyme phospholipase is the most important and its inhibition may be important in treating the condition.

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