Abstract
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 , 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.
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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