Layton Anita T, Bankir Lise
Department of Mathematics, Duke University, Durham, NC 27708-0320, USA.
Physiol Rep. 2013 Sep 10;1(3). doi: 10.1002/phy2.34.
It has been observed experimentally that early distal tubular urea flow exceeds urea delivery by the proximal convoluted tubule to the pars recta and loop of Henle. Moreover, the fractional excretion of urea in the urine may exceed values compatible with the reabsorption known to occur in the proximal convoluted tubule in the cortex. A likely explanation for these observations is that urea may be actively secreted into the pars recta, as proposed in a few studies. However, this hypothesis has yet to be demonstrated experimentally. In this study, we used a mathematical model of the renal medulla of the rat kidney to investigate the impacts of active urea secretion in the intrarenal handling of urea and in the urine concentrating ability. The model represents only the outer and inner medullary zones, with the actions taking place in the cortex incorporated via boundary conditions. Blood flow in the model vasculature is divided into plasma and red blood cell compartments. We compared urea flow rates and other related model variables without and with the hypothetical active urea secretion in the pars recta. The simulation suggests that active urea secretion induces a "urea-selective" improvement in urine concentrating ability by enhancing the efficiency of urea excretion without requiring a higher urine flow rate, and with only modest changes in the excretion of other solutes. These results should encourage experimental studies in order to assess the existence of an active urea secretion in the rodent kidney.
实验观察发现,早期远曲小管的尿素流量超过了近端曲小管向直部和髓袢输送的尿素量。此外,尿中尿素的排泄分数可能超过与已知在皮质近端曲小管中发生的重吸收相符的值。对这些观察结果的一个可能解释是,如一些研究所提出的,尿素可能被主动分泌到直部。然而,这一假设尚未得到实验证实。在本研究中,我们使用大鼠肾脏髓质的数学模型来研究直部尿素主动分泌对肾内尿素处理及尿液浓缩能力的影响。该模型仅代表外髓和内髓区,通过边界条件纳入在皮质发生的作用。模型血管中的血流分为血浆和红细胞部分。我们比较了直部不存在和存在假设的尿素主动分泌情况下的尿素流速及其他相关模型变量。模拟结果表明,尿素主动分泌通过提高尿素排泄效率,在不要求更高尿流率且仅使其他溶质排泄有适度变化的情况下,诱导尿液浓缩能力出现“尿素选择性”改善。这些结果应促使开展实验研究,以评估啮齿动物肾脏中尿素主动分泌的存在情况。