1. Ammonia, bicarbonate and pH were measured in samples of faecal dialysate from thirteen healthy subjects taking free diets. To observe the effect of marked changes in faecal pH, three subjects were also studied while taking 25 mmol/day of MgCO, or Na,S04 by mouth. Both salts increased stool weight without causing diarrhoea, but stool pH was significantly increased by MgCO, and decreased by Na2S0,.2. The total ammonia concentration and pH of faecal dialysate were very variable, but showed a highly significant negative correlation similar to that already established in man between urinary excretion of ammonia and urine pH. This relationship was more marked when individual subjects were studied while faecal pH was deliberately varied by administration of MgCO, and Na,SOa.3. Faecal bicarbonate concentrations were positively correlated with pH. Faecal Pco, was usually in the range 40-120 mmHg, the higher Pco, values being found in the more acid samples. Faecal total ammonia concentrations were negatively correlated with faecal bicarbonate. 4. These findings suggest that passive non-ionic diffusion is the main mechanism by which ammonia is absorbed by the colon, but do not exclude a minor contribution from diffusion of ionized ammonium. Colonic secretion of bicarbonate facilitates non-ionic diffusion of ammonia by providing an anion which is also absorbed by non-ionic diffusion, so maintaining an alkaline intraluminal reaction that continues to generate unionized ammonia.

SUMMARY The effect of lactulose on faecal pH and ammonia has been studied in three normal subjects with the aid of dialysis of faeces in vivo. Observations were also made with sodium sulphate and the two hexahydric alcohols, mannitol and sorbitol, given in doses sufficient to cause a similar increase in stool weight.All four cathartics rendered the stool more acid, but there was no increase in the concentration of faecal ammonia. Lactulose, despite increasing faecal volume, did not cause an increase in the absolute amount of ammonia lost in the faeces, but the other purgatives did show a modest rise.The results are inconsistent with the theory that lactulose benefits the clinical picture of portosystemic encephalopathy by trapping ammonia in an acid stool. An alternative suggestion is advanced, namely, that any cathartic (including lactulose) reduces ammonia absorption from the colon by decreasing colonic transit time, and so reducing the amount of ammonia generated by autolysis of colonic bacteria.Lactulose (1-4 ,B galactosido-fructose) was introduced in 1966 by Bircher, Muller, Guggenheim, and Haemmerli, in the treatment of portosystemic encephalopathy. This step had been suggested by Ingelfinger (1964-65) who recognized that the disaccharide is not hydrolysed in the ileum and when taken by mouth will reach the colon unchanged, where it promotes the growth of lactobacilli, organisms which lack urease, and other ammonia-generating enzymes (Phear and Ruebner, 1956;Macbeth, Kass, and McDermott, 1965). Ingelfinger (1964) suspected that a reduction in the number of proteolytic bacteria in the colon, in favour of lactobacilli, would reduce the formation of ammonia, leading to a decrease in portal venous ammonia.Clinical trials have since tended to confirm the value of lactulose in portosystemic encephalopathy (Bircher, Haemmerli, Scollo-Lavizzari, and Hoffmann, 1971a). Lactulose has also been shown to lower faecal pH (Mayerhofer and Petuely, 1959), a finding which has led to an alternative suggestion, that its effect on non-ionic diffusion of ammonia might explain its efficacy in portosystemic encephalopathy. It was argued (Elkington, Floch, and Conn,

1. A 25% faecal suspension in sodium chloride solution, incubated anaerobically at 37 degrees C for 48 h, showed excellent survival of all the main groups of faecal bacteria. 2. All faecal incubation systems studied generated large amounts of ammonia, particularly those in which bacterial counts fell during incubation. As normal faeces contain negligible amounts of urea this ammonia must have been generated from sources other than urea. 3. Ammonia was also generated by faeces delivered by sodium chloride enema, and by ileostomy fluid, indicating that the phenomenon is not confined to distal colonic contents. 4. Ammonia generation by incubated faeces was inhibited by prior autoclaving of the sample, but not by sterilization with gamma-irradiation. 5. Generation of ammonia by incubated stool was accompanied by release of large amounts of organic anion and a fall in pH. 6. These observations are interpreted as evidence that ammonia generated within the colon in situ is not derived exclusively from urea, but also from bacterial deamination of amino acids, peptides and proteins. Simultaneously bacterial activity generates large amounts of organacid. The presence of living bacteria is not essential for ammonia generation, provided that bacterial enzymes are present. 7. Bacterial generation of organic solute in faeces which have left the body is sufficiently rapid to cast serious doubts on the validity of faecal centrifugation, or other time-consuming techniques involving lengthy handling of faeces, as methods of obtaining extracellular faecal fluid for measurements of organic constituents or ammonia.

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