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Background. Portal hypertensive gastropathy (PHG) is a common anomaly with potential for bleeding found in portal hypertension. Blood ammonia levels correlate well with liver disease severity and existence of portosystemic shunts. Increased ammonia results in vasodilation and hepatic stellate cell activation causing and exacerbating portal hypertension. Objective. To assess the relation of blood ammonia to the presence and severity of portal hypertensive gastropathy in cirrhosis. Methods. This cross-sectional study included 381 cirrhotics undergoing screening for esophageal varices (EV) divided into a portal hypertensive gastropathy group (203 patients with EV and PHG), esophageal varix group (41 patients with EV but no PHG), and control group (137 patients with no EV or PHG). A full clinical examination, routine laboratory tests, abdominal ultrasonography, child score calculation, and blood ammonia measurement were performed for all patients. Results. Blood ammonia, portal vein, splenic vein, and splenic longitudinal diameters were significantly higher and platelet counts lower in patients with EV and EV with PHG than controls. Patients having EV with PHG had significantly higher bilirubin and ammonia than those with EV but no PHG. Severe PHG was associated with significantly higher ammonia, EV grades, and superior location and a lower splenic longitudinal diameter than mild PHG. The PHG score showed a positive correlation with blood ammonia and a negative correlation with splenic longitudinal diameter. Conclusions. Blood ammonia levels correlate with the presence, severity, and score of portal hypertensive gastropathy in cirrhosis suggesting a causal relationship and encouraging trials of ammonia-lowering treatments for the management of severe PHG with a tendency to bleed. [ABSTRACT FROM AUTHOR]

Ammonia is diffused and transported across all plasma membranes. This entails that hyperammonemia leads to an increase in ammonia in all organs and tissues. It is known that the toxic ramifications of ammonia primarily touch the brain and cause neurological impairment. However, the deleterious effects of ammonia are not specific to the brain, as the direct effect of increased ammonia (change in pH, membrane potential, metabolism) can occur in any type of cell. Therefore, in the setting of chronic liver disease where multi-organ dysfunction is common, the role of ammonia, only as neurotoxin, is challenged. This review provides insights and evidence that increased ammonia can disturb many organ and cell types and hence lead to dysfunction. [ABSTRACT FROM AUTHOR]

It has been proposed that key enzymes of ureagenesis and the alanine aminotransferase activity predominate in periportal hepatocytes. However, ureagenesis from alanine, when measured in the perfused liver, did not show periportal predominance and even the release of the direct products of alanine transformation, lactate and pyruvate, was higher in perivenous cells. An alternative way of analyzing the functional distributions of alanine aminotransferase and the urea cycle along the hepatic acini would be to measure alanine and urea production from precursors such as lactate or pyruvate plus ammonia. In the present work these aspects were investigated in the bivascularly perfused rat liver. The results of the present study confirm that gluconeogenesis and the associated oxygen uptake tend to predominate in the periportal region. Alanine synthesis from lactate and pyruvate plus ammonia, however, predominated in the perivenous region. Furthermore, no predominance of ureagenesis in the periportal region was found, except for conditions of high ammonia concentrations plus oxidizing conditions induced by pyruvate. These observations corroborate the view that data on enzyme activity or expression alone cannot be extrapolated unconditionally to the living cell. The current view of the hepatic ammonia-detoxifying system proposes that the small perivenous fraction of glutamine synthesizing perivenous cells removes a minor fraction of ammonia that escapes from ureagenesis in periportal cells. However, since urea synthesis occurs at high rates in all hepatocytes with the possible exclusion of those cells not possessing carbamoyl-phosphate synthase, it is probable that ureagenesis is equally important as an ammonia-detoxifying mechanism in the perivenous region. [ABSTRACT FROM AUTHOR]

Botini FF, Suzuki-Kemmelmeier F, Nascimento ÉA, Ide LT, Bracht A. Zonation of alanine metabolism in the bivascularly perfused rat liver. Liver International 2005: 25: 861–871. © Blackwell Munksgaard 2005 Zonation of alanine metabolism was investigated in the bivascularly perfused rat liver, a technique in which a selective area of the periportal region can be reached via the hepatic artery. Bivascular liver perfusion was done in both the antegrade and retrograde modes. Predominance of a given metabolic parameter in the periportal or perivenous area was deduced from comparisons of the changes caused by alanine infusion into the hepatic artery in antegrade and retrograde perfusion. Confirming previous notions, glutamine synthesis predominated in the perivenous area, however, the contribution of the periportal area was significant. Gluconeogenesis and the associated extra oxygen consumption were more pronounced in the periportal region. The capacity of urea synthesis in the periportal region was relatively small as indicated by the ratios of urea to glucose production, which were lower in this region. Ammonia in the periportal region was considerably above the mean ammonia production of whole the liver parenchyma. The overflows of pyruvate and lactate were considerably smaller in the periportal region. The distribution of alanine metabolism seems to reflect mainly zonation of the fates of the carbon skeleton (mainly gluconeogenesis). The production of glutamine in the periportal area is in agreement with recent reports about the presence of glutamine synthetase in Kupffer and endothelial cells. [ABSTRACT FROM AUTHOR]