A confused child: Answer

Abstract

This boy had a urinary tract infection (UTI), dilated urinary system and associated hyperammonaemic encephalopathy. Differential diagnoses include infectious, metabolic, toxic or hypertensive encephalopathy. This boy responded over 24 h to rehydration, urinary tract drainage and antibiotics. His blood pressure settled to 100/60 without specific antihypertensive treatment and did not become a chronic problem. We did not culture an organism from this boy's urine on presentation; however, approximately 10 days later Corynebacterium urealyticum (mucoid colony) was cultured from a subsequent urine. As he remained apyrexial and had no other signs of sepsis with a rapid recovery after the measures above, it is likely he had a lower urinary tract infection. He had a grossly dilated urinary tract and, in the setting of urinary tract infection, urinary stasis and dehydration, an increased urea load. Urease-producing bacteria in the urine of the dilated urinary tract and bladder form ammonia from urea and this results in alkalinization of the urine. As the dissociation constant of the ammonia/ammonium ion pair is 9.8, an alkaline environment favours the formation of proportionately more ammonia than ammonium ions compared with that at a lower pH. Ammonia is lipid soluble and can readily diffuse across cell membranes of the dilated urinary tract and bladder. At a physiological pH of about 7.40 within the venous circulation the equilibrium is overwhelmingly in favour of ammonium formation which is significantly less lipid soluble [1,2]. This mechanism is known as diffusion trapping. Complete hydrolysis of the 30 g (0.5 mol) of urea usually excreted by an adult each day would lead to 17 g (1.0 mol) of ammonia potentially being absorbed. This is four times the amount produced each day by the gastrointestinal tract [3]. The venous drainage from the bladder bypasses the liver and thus is not detoxified. The serum ammonia concentration rises and encephalopathy may develop. Hyperammonaemia leads to glutamine-mediated toxicity with mitochondrial toxicity, astrocyte swelling and cerebral oedema. Urea-splitting bacteria include Ureaplasma urealyticum, Corynebacterium urealyticum, Proteus, Pseudomonas, Klebsiella and Staphylococcus.Increased absorption of ammonia at a renal parenchymal level is another potential mechanism. With infection of the parenchyma with Proteus for example, hydrolysis of urea occurs within the tubules leading to a high intraluminal ammonia concentration and favouring diffusion into the tubular cells and thus into the systemic circulation. Ammonia is also produced within the renal tubular cells. Generally 75% is excreted into the urine; however, with a high urinary pH the ammonia tends to be reabsorbed.