Hyperammonemia and severe
amino acid imbalances play central role in
hepatic encephalopathy (HE). In the article is demonstrated that the main source of
ammonia in cirrhotic subjects is activated breakdown of
glutamine (GLN) in enterocytes and the kidneys and the main source of GLN is
ammonia detoxification to GLN in the brain and skeletal muscle.
Branched-chain amino acids (BCAA;
valine,
leucine, and
isoleucine) decrease due to activated GLN synthesis in muscle.
Aromatic amino acids (AAA;
phenylalanine,
tyrosine, and
tryptophan) and
methionine increase due to
portosystemic shunts and reduced ability of diseased liver. The effects on aminoacidemia of the following variables that may affect the course of
liver disease are discussed: nutritional status,
starvation,
protein intake,
inflammation, acute hepatocellular damage,
bleeding from
varices,
portosystemic shunts,
hepatic cancer, and
renal failure. It is concluded that (1) neither
ammonia nor
amino acid concentrations correlate closely with the severity of
liver disease; (2) BCAA/AAA ratio could be used as a good index of liver impairment and for early detection of derangements in
amino acid metabolism; (3) variables potentially leading to overt
encephalopathy exert substantial but uneven effects; and (4) careful monitoring of
ammonia and aminoacidemia may discover important break points in the course of
liver disease and indicate appropriate therapeutic approach. Of special importance might be
isoleucine deficiency in
bleeding from
varices,
arginine deficiency in
sepsis, and a marked rise of GLN and
ammonia levels that may appear in all events leading to HE.