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Evidence for Altered Phenylalanine Metabolism and Comparison With Hepatic Encephalopathy

Barry A. Mizock, MD; Hector C. Sabelli, MD, PhD; Alvin Dubin, MS; Javaid I. Javaid, PhD; Ann Poulos; Eric C. Rackow, MD

Arch Intern Med. 1990;150(2):443-449.

Abstract
• We elected to test the hypothesis that the metabolic encephalopathy associated with systemic sepsis may have a pathogenesis that is similar to hepatic encepathology, ie, as the consequence of hepatic dysfunction that induces alterations in synthesis of catecholic and noncatecholic neurotransmitters. Eleven patients with septic encephalopathy were compared with nine patients with hepatic encephalopathy and nine normal controls with respect to blood and cerebrospinal fluid (CSF) amino acid profile, phenylethylamine and its metabolite phenylacetic acid, and blood ammonia. Blood and CSF levels of phenylacetic acid increased markedly in septic and hepatic encephalopathy while CSF phenylethylamine levels were not increased in either condition, presumably due to rapid turnover. The CSF concentrations of all the aromatic amino acids were increased in hepatic encephalopathy, whereas in the patients with sepsis, only phenylalanine levels were increased. Evidence of stimulated neutral amino acid transport into brain was demonstrated in hepatic not septic encephalopathy and appeared to correlate with the CSF glutamine concentration. Blood ammonia levels were increased in hepatic but not in septic encephalopathy. Our data support the hypothesis that metabolites of phenylethylamine contribute to encephalopathy in systemic sepsis and hepatic failure; however, the entitles differ in other respects.

(Arch Intern Med. 1990;150:443-449)

Author Affiliations
From the Department of Medicine and Division of Critical Care Medicine, Cook County Hospital (Dr Mizock), Hektoen Institute (Drs Mizock and Dubin and Ms Poulos), and The Chicago Medical School (Drs Rackow and Mizock), and the Department of Psychiatry (Drs Sabelli and Javaid) and Biochemistry (Dr Dubin), Rush-Presbyterian-St Luke's Hospital, Chicago, Ill.

Footnotes
Accepted for publication September 15,1989.

Read before the 73rd annual meeting of the Federation of American Societies for Experimental Biology, New Orleans, La, March 22,1989.

Reprint requests to Department of Medicine, Cook County Hospital, 1835 W Harrison St, Chicago, IL 60612 (Dr Mizock).

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