Abstract
Ammonia produced in the kidney can be absorbed into the renal vein or excreted in urine. We developed a mathematical model of the rat renal medulla in order to identify some of the components controlling the fate of renal ammonia. The model simulates the movements of water, sodium, urea, NH3, NH4+ and a non‐reabsorbable solute along nephrons and vasa recta of various lengths and includes pH, potassium concentrations, and electrical potential as imposed boundary conditions at each medullary depth. A sensitivity analysis was performed to identify the transport parameters and micro‐environmental conditions that have the greatest effect on the simulated rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly controlled by the parameters that affect ammonia delivery to the descending segment of short nephron. In particular, interstitial pH in the outer medulla seems to be critical. The model provides the first coordinated picture of renal ammonia handling.Grant Funding Source: Supported by the EPSRC through the UCL CoMPLEX doctoral training centre (UK).
Highlights
The kidney is one of the organs that release ammonia into the circulation
Differences of electrical potential, pH, and potassium concentration gradients are imposed at each depth; this allows us to evaluate the role of these three factors in ammonia handling while keeping the size and complexity of the model manageable
To identify the parameters associated with a change in urinary ammonia excretion, a partial sensitivity analysis was performed; starting from our baseline scenario, each parameter value (e.g., NH3 permeability in the outer stripe collecting duct) was perturbed and the changes in renal ammonia transport were analyzed
Summary
The kidney is one of the organs that release ammonia into the circulation (unless otherwise specified, ‘ammonia’ refers to both NH3 and NHþ4 ). Renal ammonia metabolism contributes to acidbase homeostasis [1,2,3,4,5] and is one of the main determinants of plasma ammonia levels (along with the liver); yet the mechanisms controlling renal ammonia handling are not fully understood. Renal ammonia handling can be decomposed into two main steps: the renal production of ammonia, and the distribution of its subsequent exit between urine and the general circulation. This paper focuses on the mechanisms affecting this distribution between excretion and recovery. Between 30 and 50% of the ammonia produced in the kidney is PLOS ONE | DOI:10.1371/journal.pone.0134477. Between 30 and 50% of the ammonia produced in the kidney is PLOS ONE | DOI:10.1371/journal.pone.0134477 August 17, 2015
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