Ammonia is produced primarily from breakdown of amino acids in various cells of the body (“endogenous” ammonia or NH3). The ammonia is taken up by hepatocytes and converted, in the urea cycle, to urea, which is then exported into blood. Urea is primarily excreted in the kidneys (75%, and is a marker of glomerula filtration rate) and the intestine (around 25%). Once in the intestinal system, urea is broken down by bacteria (rumen in ruminants, colon in other species) forming ammonia, which is then absorbed into the portal circulation. The liver efficiently extracts (85%) of the ammonia from portal blood, leaving only 15% to enter the systemic circulation. Bacterial metabolism of other proteins (e.g. soybean meal in cattle), also produces ammonia from “exogenous” sources. Defects in hepatic function, portal blood flow and urea cycle enzymes or intermediates can result in hyperammonemia, as can excess production of ammonia in the gastrointestinal tract.
