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1. Healthy subjects, given a long-acting preparation of vasopressin intramuscularly, excreted a significantly less concentrated urine than when subjected to fluid deprivation for 28 h. 2. When fludrocortisone, a potent mineralocorticoid, was given in addition to vasopressin the urine was not significantly less concentrated than after fluid deprivation. 3. Oral urea-loading also enhanced the urine-concentrating power of vasopressin but its effect was less marked than that of fludrocortisone. Oral urea did not increase further the urine concentration achieved by combined fludrocortisone and vasopressin. 4. Renal concentrating power was assessed in fourteen patients with renal disease and impaired concentrating ability. Fludrocortisone significantly enhanced the urine concentration achieved by vasopressin alone and the resultant urine was not significantly less concentrated than that achieved by fluid deprivation. 5. The action of fludrocortisone in enhancing the urine-concentrating effect of vasopressin is similar to that of aldosterone and is probably due to the increased sequestration of solute in the renal medulla, caused by increased reabsorption of sodium chloride in the ascending limb of the loop of Henle. 6. In the clinical assessment of renal concentrating power, the combined use of fludrocortisone and vasopressin has potential advantages over established methods.

1. To establish the role of endogenous urea as a source of faecal ammonia, the plasma urea of two healthy men was labelled with 15N at a constant level for several days and its 15N enrichment was compared with that of faecal ammonia and total nitrogen. 2. Faeces collected after one complete gastrointestinal transit from the onset of plasma labelling had ammonia 15N enrichments which were only 8.5 ± 1.2% and total nitrogen enrichments which were 6.8 ± 0.7% of the plasma urea 15N enrichment. 3. These results show that endogenous urea is not the main precursor of faecal ammonia, which is probably derived by bacterial deamination from the protein of dietary residues, intestinal secretions and shed epithelial cells. The minor contribution of endogenous urea to faecal ammonia suggests that the lumen of the large bowel is not the main site of endogenous urea hydrolysis. The similar labelling of faecal total nitrogen and ammonia nitrogen supports other evidence that these faecal nitrogen fractions are in a constant state of exchange.

1. Saliva obtained from the parotid duct of normal and uraemic subjects had an average urea concentration of 86% of the plasma concentration whereas in mixed saliva obtained from the mouth the urea concentration was only 31% of the plasma concentration. Ammonia concentrations were low or unmeasurable in parotid saliva but varied between 0·6 and 26 mmol/kg in oral saliva, showing a positive correlation with the plasma urea concentration. 2. The urea in samples of mixed oral saliva incubated at 37°C disappeared by 290 min. Ammonia steadily increased during incubation; within the first 100 min, the increase could be largely accounted for by bacterial hydrolysis of urea, but later non-urea sources became relatively more important. 3. These findings suggest that the ammonia in mixed oral saliva is derived by bacterial hydrolysis of urea within the mouth. However, the concentration of ammonia plus urea nitrogen in oral saliva was only 76% of the urea nitrogen concentration of parotid saliva, which suggests that some ammonia is lost from the mouth by buccal absorption or by volatilization. 4. To assess the role of non-ionic diffusion of ammonia through the buccal mucosa, we studied the effect of pH on the disappearance of ammonia from buffered solutions retained in the mouth. Ammonia concentrations fell more rapidly at pH 9 than at pH 7, as also did those of hydrazine, a non-volatile analogue of ammonia which is known to be absorbed through other mucosae by non-ionic diffusion. These findings suggest that salivary ammonia is reabsorbed passively through the oral mucosa in the un-ionized phase.

1. A 25% faecal suspension in sodium chloride solution, incubated anaerobically at 37°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 organic acid. 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.

1. Sodium tartrate labelled with 14C was given orally and parenterally to man and rats, and by direct injection into the caecum in rats. From the differences in urinary excretion after oral and parenteral administration intestinal absorption of tartrate was calculated as 18% of the dose in man and 81% in rats. Urinary tartrate was equivalent to 14% of the dose in man and 70% in rats, the difference between absorption and urinary excretion representing metabolism in body tissues. 2. Both man and the rat excreted part of the 14C as respiratory carbon dioxide. This occurred to a small extent after parenteral injection, suggesting metabolism of tartrate by body tissues, but was greater after oral or intracaecal administration, indicating that the main site of tartrate metabolism is the intestine. 3. Several genera of intestinal bacteria were shown to liberate [14C]carbon dioxide from labelled tartrate, and in a faecal incubation system l-tartrate, the natural isomer, was metabolized five times as rapidly as d-tartrate. 4. Oral sodium l-tartrate, 1·5 mmol day—1 kg—1, was given to two subjects and was shown to alkalinize the urine like sodium salts of other organic acids which are metabolized in the body. The reduction in renal hydrogen ion excretion showed that an average of 84% of the dose was metabolized. 5. Only 5% of labelled tartrate given by mouth appeared in faeces, and pharmacological doses of unlabelled l-tartrate had little or no aperient effect. 6. No evidence of toxicity of l-tartrate was encountered.

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 MgCO3 or Na2SO4 by mouth. Both salts increased stool weight without causing diarrhoea, but stool pH was significantly increased by MgCO3 and decreased by Na2SO4. 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 MgCO3 and Na2SO4. 3. Faecal bicarbonate concentrations were positively correlated with pH. Faecal Pco2 was usually in the range 40–120 mmHg, the higher Pco2 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.

1. Ammonia absorption has been studied in closed loops of rat jejunum, ileum and colon. 2. Ammonia absorption was significantly greater from solutions buffered at higher pH. Absorption was also greater in the presence of the bicarbonate ion, and this effect was not due solely to the influence of bicarbonate upon the initial pH of the solutions studied. In the presence of ammonia net bicarbonate absorption was increased and net bicarbonate secretion was decreased. 3. The above effects are compatible with the hypothesis that non-ionic diffusion plays an important role in the absorption of ammonia. 4. Ammonia absorption was significantly less from hypertonic solutions than from hypotonic or isotonic solutions. This effect persisted even after the hypertonic solution had been removed, and therefore appears to have been due to a change in ileal wall permeability rather than an effect of these solutions on water movement. The absorption of hydrazine was similar to that of ammonia in these circumstances; as there is evidence that hydrazine is absorbed by a process of non-ionic diffusion in the lipid phase, this finding is a further indication that hypertonicity exerts its effect through a change in membrane permeability.

Accelerated hypertension sometimes presents as acute oliguric renal failure, which may be difficult to distinguish from other causes of acute renal failure. Papilloedema need not be present in such patients even though the kidneys show typical vascular lesions of accelerated hypertension. Recovery of renal function may occur after a period of dialysis and vigorous treatment of the hypertension.