Pathogenesis of Hepatic Coma

Hepatic coma is a complex pathophysiologic state that is multifactorial in origin. Incomplete and uncontrolled but significant observations in patients have offered clues for experimental study. Unfortunately the body of solid experimental data is small, and the amount of uninhibited speculation excessive. To compound this problem there has been confusion between correlation and causation. Hepatic en­ cephalopathy has many associated alterations, some of which are noncausal corre­ lated changes and some consequences of the encephalopathy. Seen after the fact, these two types of alterations cannot be differentiated from causal factors. This has often been forgotten in this field where everyone is primarily interested in etiology, and claims have been made that do not withstand careful inspection. Several previous reviews offer broad perspectives on the whole subject (1-3). In 1966 we (4) reviewed the subject of pathogenesis in detail, and we will assume acquaintance with that material for purposes of the present review. In addition to the known metabolic abnormalities, which will again be summarized and brought up to date, that article provided a brief discussion of the clinical picture, the role of precipitating factors, and the contribution of electrolyte and acid-base abnormali­ ties. Since then Zimmon (5, 6) has shown that the well-known shift to the right in the in vivo oxyhemoglobin dissociation curve, when more than minimal, is asso­ ciated with the presence of hepatic encephalopathy and is due to an unidentified small molecular weight acidic plasma factor. When the hepatic encephalopathy disappears, the shift to the right is reversed. Such reversal has been observed following suppression of gut bacteria.