METABOLIC ALTERATIONS IN HEPATIC FAILURE A multitude of changes in metabolic processes occurs with hepatic failure. It is therefore particularly important to distinguish between correlations and causes when considering the pathogenesis of hepatic coma. The etiology appears to be multifactorial. First, to be considered a causative factor, an abnormality must be consistently present when hepatic encephalopathy is present. Second, creation of the abnormality in experimental animals should cause coma, and correction of the abnormality in animals and humans should reverse the process of encephalopathy and coma. Unfortunately hypotheses have been promoted in the absence of data which fulfill the latter criteria. Of the many abnormalities that occur with hepatic failure, the only ones that have been shown unequivocally to cause coma in experimental animals or patients are an ,xcess of ammonia, methanethiol (or its derivative dimethylsulfide), fatty acids, phenols, and the development of hypoxia, hypoglycemia, hypovolemia, hypotension, or electrolyte depletion. A summary of the metabolic abnormalities that may be present during hepatic encephalopathy (HE) is given in Table I and the following. (1) Acid-base and electrolyte abnormalities are usually present before HE develops. They probably play an auxiliary role in the progression and outcome of the HE. The patient may have respiratory alkalosis, metabolic alkalosis, a mixed respiratory and metabolic alkalosis, or metabolic acidosis, depending upon the extent and duration of respiratory or electrolyte abnormalities (Zieve, 1962). The most common variant is the mixed respiratory and metabolic alkalosis. The root causes are central respiratory center stimulation and coexistent hypokalemia. It is unlikely that enhanced movement of NH[ into cells during alkalosis has any practical significance in the progression of HE (Zieve, 1982).