The interorgan exchange of amino acids and ammonia and the effect of plasmapheresis in acute liver failure

Abstract

Fulminant hepatic failure (FHF), defined as the appearance of hepatic encephalopathy (HE) in a patient with acute liver failure (ALF) within 14 days of first sign of liver disease, is a dramatic, life threatening condition with high mortality. Even though the condition is often associated with multiple organ dysfunction, the most common cause of death is cerebral oedema leading to brain herniation. The hypothesis that ammonia is involved in the pathogenesis of cerebral oedema in ALF is supported by increased arterial ammonia levels in this condition, the progression of other conditions associated with hyperammonemia, such as inborn errors in urea cycle enzymes, to cerebral herniation, and the progression of an animal model of liver disease, in which ammonia is infused, to cerebral herniation. Increased arterial ammonia levels in patients with ALF are strongly associated with the later development of cerebral herniation (Figure 1).1 These findings suggest that better understanding of ammonia and amino nitrogen metabolism in ALF should facilitate future therapeutic interventions. In the present series of studies we examined interorgan exchange of ammonia and amino acids with special emphasis on splanchnic and lower extremity regions. High volume plasmapheresis (HVP) has been proposed as a therapeutic option in ALF. Because the exchange of 8–10 L plasma should affect the plasma composition of amino acids, we also studied the effects of this treatment modality.