Review article: hyperammonaemic and catabolic consequences of upper gastrointestinal bleeding in cirrhosis

Abstract

Summary Background Upper gastrointestinal (UGI) bleeding in patients with cirrhosis of the liver induces hyperammonaemia and leads to a catabolic cascade that precipitates life‐threatening complications. The haemoglobin molecule is unique because it lacks the essential amino acid isoleucine and contains high amounts of leucine and valine. UGI bleed therefore presents the gut with protein of very low biologic value, which may be the stimulus to induce net catabolism. Aim To describe the hyperammonaemic and catabolic consequences of UGI bleeding in cirrhosis. Methods A semi‐structured literature search was performed using PubMed and article references. Results It has recently been proven that (‘simulation of ’) a UGI bleed in patients with cirrhosis leads to impaired protein synthesis that can be restored by intravenous infusion of isoleucine. This may have therapeutic implications for the function of rapidly dividing cells and short half‐life proteins such as clotting factors. Renal and small bowel ammoniagenesis were shown to be the most prominent causes for the hyperammonaemia that resulted from a UGI bleed. This provides an explanation for the therapeutic failure of the current clinical therapies that are aimed at large bowel‐derived ammonia production. Isoleucine infusion did not diminish renal ammoniagenesis. Conclusions New pharmacological therapies to diminish postbleeding hyperammonaemia should target the altered inter‐organ ammonia metabolism and promote ammonia excretion and/or increase the excretion of precursors of ammoniagenesis, e.g. l‐ornithine–phenylacetate.

Ornithine phenylacetate prevents disturbances of motor-evoked potentials induced by intestinal blood in rats with portacaval anastomosis

“…In addition, it is possible that OP affects ammonia metabolism at other sites. We observed marked differences in the course of the aminoacidemia that follows GIB [35] between OP-treated and control rats for which we do not have an explanation. OP may have attenuated the negative protein balance that follows GIB and that has been attributed to the lack of isoleucine in the molecule of hemoglobin [36].…”

“…3A) in the total concentration of plasma amino acids (n = 24). All amino acids contributed to this increase, except for isoleucine (Table 1), which is well known to drop following gastrointestinal bleeding in patients and experimental models [21]. Rats treated with OP exhibited a lower rise in the concentration of amino acids (Fig.…”

Role of Nutrition in the Management of Hepatic Encephalopathy in End-Stage Liver Failure

“…In addition, hyperammonemia may be more prominent after gastrointestinal bleeding due to the absence of isoleucine [31]. Since haemoglobin molecule lacks the essential amino acid isoleucine, gastrointestinal bleed may stimulate the induction of net catabolism [32]. …”

Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU

“…Malnutrition can lead to urea cycling in the gut[13] and refeeding syndrome[21]. High protein diets[14], somatic protein catabolism (burns, trauma, strenuous exercise, steroids), IV amino acid containing solutions including TPN[22, 23] and N-Acetylcysteine, GI bleeding[24], porto-systemic shunts unrelated to liver disease, blind loop intestinal bypass and bariatric surgery[3, 6, 25] have also been shown to be associated with hyperammonemia.…”