scholarly journals A modular and reusable model of epithelial transport in the proximal convoluted tubule

2021 ◽  
Author(s):  
David Phillip Nickerson ◽  
Leyla Noroozbabaee ◽  
Pablo Javier Blanco ◽  
Soroush Safaei
Keyword(s):  
Mathematical Model ◽  
Open Access ◽  
Proximal Tubule ◽  
Epithelial Transport ◽  
Proximal Convoluted Tubule ◽  
Sensitivity Analyses ◽  
Transport Models ◽  
Modular Model ◽  
Solute Fluxes

We review a collection of published renal epithelial transport models, from which we build a consistent and reusable mathematical model able to reproduce many observations and predictions from the literature. The flexible modular model we present here can be adapted to specific configurations of epithelial transport, and in this work we focus on transport in the proximal convoluted tubule of the renal nephron. Our mathematical model of the epithelial proximal convoluted tubule describes the cellular and subcellular mechanisms of the transporters, intracellular buffering, solute fluxes, and other processes. We provide free and open access to the Python implementation to ensure our multiscale proximal tubule model is accessible; enabling the reader to explore the model through setting their own simulations, reproducibility tests, and sensitivity analyses.

A model to account for the consequences of host nutrition on the outcome of gastrointestinal parasitism in sheep: model evaluation

Parasitology ◽  
2007 ◽  
Vol 134 (9) ◽  
pp. 1279-1289 ◽  
Author(s):  
D. VAGENAS ◽  
S. C. BISHOP ◽  
I. KYRIAZAKIS
Keyword(s):  
Mathematical Model ◽  
Worm Burden ◽  
Management Strategies ◽  
Sensitivity Analyses ◽  
Sheep Model ◽  
Host Nutrition ◽  
Gastrointestinal Parasitism ◽  
Different Characteristics ◽  
Nutritional Strategies ◽  
Different Levels

SUMMARYThis paper describes sensitivity analyses and expectations obtained from a mathematical model developed to account for the effects of host nutrition on the consequences of gastrointestinal parasitism in sheep. The scenarios explored included different levels of parasitic challenge at different planes of nutrition, for hosts differing only in their characteristics for growth. The model was able to predict the consequences of host nutrition on the outcome of parasitism, in terms of worm burden, number of eggs excreted per gram faeces and animal performance. The model outputs predict that conclusions on the ability of hosts of different characteristics for growth to cope with parasitism (i.e. resistance) depend on the plane of nutrition. Furthermore, differences in the growth rate of sheep, on their own, are not sufficient to account for differences in the observed resistance of animals. The model forms the basis for evaluating the consequences of differing management strategies and environments, such as breeding for certain traits associated with resistance and nutritional strategies, on the consequences of gastrointestinal parasitism on sheep.

Dependence of ion fluxes on fluid transport by rat proximal tubule

1986 ◽  
Vol 250 (4) ◽  
pp. F680-F689 ◽  
Author(s):  
K. Bomsztyk ◽  
F. S. Wright
Keyword(s):  
Proximal Tubule ◽  
Fluid Transport ◽  
Rat Kidney ◽  
Water Flux ◽  
Fluid Secretion ◽  
Proximal Convoluted Tubule ◽  
Ion Fluxes ◽  
Fluid Absorption ◽  
Fluid Flux ◽  
K Transport

The effects of changes in transepithelial water flux (Jv) on sodium, chloride, calcium, and potassium transport by the proximal convoluted tubule were examined by applying a microperfusion technique to surface segments in kidneys of anesthetized rats. Perfusion solutions were prepared with ion concentrations similar to those in fluid normally present in the later parts of the proximal tubule. Osmolality of the perfusate was adjusted with mannitol. With no mannitol in the perfusates, net fluid absorption was observed. Addition of increasing amounts of mannitol first reduced Jv to zero and then reversed net fluid flux. At the maximal rates of fluid absorption, net absorption of Na, Cl, Ca, and K was observed. When Jv was reduced to zero, Na, Cl, and Ca absorption were reduced and K entered the lumen. Na, Cl, and Ca secretion occurred in association with the highest rates of net fluid secretion. The lumen-positive transepithelial potential progressively increased as the net fluid flux was reduced to zero and then reversed. The results demonstrate that changes in net water flux can affect Na, Cl, Ca, and K transport by the proximal convoluted tubule of the rat kidney. These changes in net ion fluxes are not entirely accounted for by changes in bulk-phase transepithelial electrochemical gradients.

Response to parathyroid hormone in defined segments of proximal tubule

1976 ◽  
Vol 230 (2) ◽  
pp. 286-290 ◽  
Author(s):  
RJ Hamburger ◽  
NL Lawson ◽  
JH Schwartz
Keyword(s):  
Parathyroid Hormone ◽  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Base Line ◽  
Fluid Absorption ◽  
Functional Heterogeneity ◽  
Intrinsic Absorption ◽  
Pars Recta ◽  
Intrinsic Capacity ◽  
Control Fluid

Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule.

Water permeability and pathways in the proximal tubule

1983 ◽  
Vol 245 (3) ◽  
pp. F279-F294 ◽  
Author(s):  
C. A. Berry
Keyword(s):  
Proximal Tubule ◽  
Water Transport ◽  
Water Permeability ◽  
Intercellular Space ◽  
Proximal Convoluted Tubule ◽  
Pressure Gradients ◽  
Solvent Drag ◽  
Lateral Intercellular Space ◽  
Volume Absorption ◽  
Osmotic Water

The route of water transport in the proximal tubule could be either transjunctional or transcellular. A transjunctional route is supported by data showing high osmotic-to-diffusive water permeability ratios, the possible correlation of junctional leakiness to ions and nonelectrolytes with water permeability, and solvent drag of nonelectrolytes and ions. These data, however, are not convincing. A transcellular route of water transport is supported by data showing that the osmotic water permeability (Pf) for apical and/or basolateral cell membranes is sufficiently high to account for the transepithelial Pf, making a tentative conclusion for a transcellular route of water transport possible. In addition, measurements of Pf have yielded insights into the mechanism of solute-solvent coupling. Pf has been reported to be mostly between 0.1 and 0.3 cm/s. In the rabbit proximal straight and the Necturus proximal convoluted tubule, in which water transport rates are low, this range of Pf will account for volume absorption with only small osmotic gradients (less than 6 mosmol). Higher osmotic gradients are required in the rat and possibly the rabbit proximal convoluted tubule, where water transport rates are higher. Solute-solvent coupling in all species is probably due to both luminal hypotonicity and lateral intercellular space hypertonicity. These two processes are directly linked. Mass balance requires that generation of luminal hypotonicity also generates a hypertonic absorbate and, thus, some degree of lateral intercellular space hypertonicity. It is likely that, in the rabbit at least, effective osmotic pressure gradients due to differences in solute reflection coefficients play little role in solute-solvent coupling.

Axial heterogeneity in the rat proximal convoluted tubule. I. Bicarbonate, chloride, and water transport

1984 ◽  
Vol 247 (5) ◽  
pp. F816-F821 ◽  
Author(s):  
F. Y. Liu ◽  
M. G. Cogan
Keyword(s):  
Proximal Tubule ◽  
Water Transport ◽  
Wistar Rats ◽  
Proximal Convoluted Tubule ◽  
Free Flow ◽  
Concentration Profiles ◽  
Transport Capacity ◽  
Water Reabsorption ◽  
Substrate Concentrations

To measure simultaneously the concentration profiles of bicarbonate, chloride and inulin along the length of the superficial proximal convoluted tubule, free-flow micropuncture measurements were made sequentially from the end-proximal tubule to Bowman's space in 10 tubules of hydropenic Munich-Wistar rats. Bicarbonate and volume reabsorption were 354 +/- 21 pmol X mm-1 X min-1 and 5.9 +/- 0.4 nl X mm-1 X min-1 in the first millimeter and fell progressively in the remaining 3.8 mm of tubule, averaging 83 +/- 4 pmol X mm-1 X min-1 and 2.3 +/- 0.5 nl X mm-1 X min-1, respectively. The values in the initial millimeter represents a high transport capacity since they exceed rates that have been observed when comparable or even higher mean luminal substrate concentrations were presented to the late proximal tubule. In contrast, chloride reabsorption was only 206 +/- 55 peq X mm-1 X min-1 in the first millimeter compared with a mean of 306 +/- 22 peq X mm-1 X min-1 in the rest of the tubule. In conclusion, there is substantial axial transport heterogeneity, with bicarbonate and water reabsorption higher but chloride reabsorption lower in the early compared with the late superficial proximal convoluted tubule.

Oxalate secretion in the rat proximal tubule

1981 ◽  
Vol 240 (4) ◽  
pp. F295-F298 ◽  
Author(s):  
T. F. Knight ◽  
S. C. Sansom ◽  
H. O. Senekjian ◽  
E. J. Weinman
Keyword(s):  
Proximal Tubule ◽  
Sodium Cyanide ◽  
Proximal Convoluted Tubule ◽  
Oxalate Concentration ◽  
Oxalate Secretion ◽  
Secretory System ◽  
Rat Proximal Tubule

Simultaneous capillary and luminal microperfusion studies in the proximal convoluted tubule of the rat were performed to examine the transepithelial secretory flux of [14C]oxalate. Increases in the concentration of oxalate in the capillary solution from 0.096 to 4.3 mM resulted in progressively higher rates of oxalate secretion into the lumen. Further increases in the capillary concentration of oxalate indicated a tendency toward a plateau. The inclusion of para-chloromercuribenzoate, sodium cyanide, indanyloxyacetic acid, furosemide, or para-aminohippurate in the capillary solution significantly lowered the secretory flux of oxalate. the addition of probenecid in a concentration of 10(-4) M inhibited oxalate secretion when the oxalate concentration in the capillary solution ranged between 1.1 and 4.3 mM, but did not affect oxalate secretion at higher capillary concentrations of oxalate. These results indicate that oxalate secretion in the rat proximal tubule is an active carrier-mediated process. When considered in conjunction with prior studies, the present investigations suggest the possibility that more than one oxalate secretory system exists in the rat proximal tubule.

Effect of sustained flow perturbations on stability and compensation of tubuloglomerular feedback

2003 ◽  
Vol 285 (5) ◽  
pp. F972-F989 ◽  
Author(s):  
Darren R. Oldson ◽  
Leon C. Moore ◽  
Harold E. Layton
Keyword(s):  
Mathematical Model ◽  
Proximal Tubule ◽  
Limit Cycle ◽  
Critical Value ◽  
Tubuloglomerular Feedback ◽  
Feedback Gain ◽  
Acta Physiol ◽  
Pressure Oscillations ◽  
Intratubular Pressure ◽  
Abrupt Changes

A mathematical model previously formulated by us predicts that limit-cycle oscillations (LCO) in nephron flow are mediated by tubuloglomerular feedback (TGF) and that the LCO arise from a bifurcation that depends heavily on the feedback gain magnitude, γ, and on its relationship to a theoretically determined critical value of gain, γc. In this study, we used that model to show how sustained perturbations in proximal tubule flow, a common experimental maneuver, can initiate or terminate LCO by changing the values of γ and γc, thus changing the sign of γ - γc. This result may help explain experiments in which intratubular pressure oscillations were initiated by the sustained introduction or removal of fluid from the proximal tubule (Leyssac PP and Baumbach L. Acta Physiol Scand 117: 415–419, 1983). In addition, our model predicts that, for a range of TGF sensitivities, sustained perturbations that initiate or terminate LCO can yield substantial and abrupt changes in both distal NaCl delivery and NaCl delivery compensation, changes that may play an important role in the response to physiological challenge.

Osmolality, bicarbonate concentration, and water reabsorption in proximal tubule of the dog nephron

1963 ◽  
Vol 205 (2) ◽  
pp. 273-280 ◽  
Author(s):  
James R. Clapp ◽  
John F. Watson ◽  
Robert W. Berliner
Keyword(s):  
Plasma Concentration ◽  
Proximal Tubule ◽  
Proximal Convoluted Tubule ◽  
Water Reabsorption ◽  
Bicarbonate Concentration ◽  
Water Diuresis ◽  
Vasopressin Infusion ◽  
Proximal Tubular

Micropuncture and microanalytical techniques were used to study the effect of antidiuresis and water diuresis on osmolality, bicarbonate concentration, and water reabsorption in the proximal tubule of the dog nephron. Samples collected during antidiuresis and water diuresis remained isotonic to plasma throughout the first 50% of the proximal convoluted tubule. Mean bicarbonate concentrations of 16 mEq/liter and 17 mEq/liter were found in the middle third of the tubule during antidiuresis and water diuresis, respectively. These values were slightly less than the plasma concentration of 22 mEq/liter. Proximal tubular fluid samples for inulin concentration were collected during antidiuresis, water diuresis, and during vasopressin infusion in water-loaded dogs. A mean tubular fluid to plasma (TF/P) inulin ratio of 2.3 was found in the middle third of the proximal tubule during antidiuresis. This value is significantly different ( P < 0.01) from a mean of 1.6 in the same portion of the tubule during water diuresis. Vasopressin administration to hydrated dogs returned the TF/P inulin ratio in the middle third of the proximal tubule to 2.0. These results suggest that vasopressin stimulated Na reabsorption in the proximal tubule of the dog nephron.

A mathematical model of proximal tubule absorption

1979 ◽  
Vol 47 (4) ◽  
pp. 377-399 ◽  
Author(s):  
Ronald E. Huss ◽  
John L. Stephenson
Keyword(s):  
Mathematical Model ◽  
Proximal Tubule
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