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PLoS One. 2015 Aug 17;10(8):e0134477. doi: 10.1371/journal.pone.0134477. eCollection 2015.

Mathematical Model of Ammonia Handling in the Rat Renal Medulla.

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CoMPLEX, University College London (UCL), London, United Kingdom.
CoMPLEX, University College London (UCL), London, United Kingdom; Mathematics, UCL, London, United Kingdom.
Institute of Hepatology, UCL Medical School, London, United Kingdom.
IR4M (UMR8081), Université Paris-Sud, Centre National de la Recherche Scientifique, Orsay, France.


The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and [Formula: see text], and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts.

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