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J L Stephenson

Publications and source records attributed to J L Stephenson.

50 records · Page 3Linked to original sources

Electrolyte transport across a simple epithelium. Steady-state and transient analysis.

A simple transporting epithelium is represented as a cellular compartment, compliant in all dimensions, and a paracellular channel, of arbitrary shape, between well-stirred mucosal ans serosal baths. The equations for mass balance, Poiseuille flow, and the Nernst-Planck equation are used to describe the continuous behavior of the system along cell and channel, whereas passive transport across membranes is given by the relations of Kedem and Katchalsky. Time-dependent terms are retained to permit study of transient phenomena. Boundary conditions at the baths demand only mass conservation and specify no a priori estimates of the system variables. A numerical model containing Na+,K+,Cl-, and impermeant cellular anions is formulated with membrane parameters taken from the literature on Necturus gallbladder. The differential equations are represented as a finite difference scheme and solved using Newton's method. It appears that apical cellular NaCl cotransport is necessary to obtain a reasonable cell chloride concentration. Investigation of the osmolality of the transepithelial flow shows that at steady state a leaky epithelium cannot separate baths of substantially different tonicity, although this does not guarantee isotonic transport between equiosmolar media. Changes in bath pressure, application of transepithelial electrical potential, and simulation of ion-substitution experiments are performed to understand the role of membrane permeabilities in determining the dynamic behavior of the epithelium.

Animals↗

Concentrating engines and the kidney. III. Canonical mass balance equation for multinephron models of the renal medulla.

The canonical mass balance relation derived for the central core model of the renal medulla is extended to medullary models in which an arbitrary assemblage of renal tubules and vascular capillaries exchange with each other both directly and via the medullary interstitium and in which not all of the vascular loops or loops of Henle extend to the papilla. It is shown that if descending limbs of Henle and descending vasa recta enter the medulla at approximately plasma osmolality, the concentration ratio is given by: r = 1/[1 - ft(1 - fu)(1 - fw)], where ft is fractional solute transport out of ascending Henle's limb, fu is fractional urine flow, and fw is fractional dissipation; fw is a measure of the solute returned to the systemic circulation without its isotonic complement of water. A modified equation that applies to the diluting as well as the concentrating kidney is also derived. By allowing concentrations in interstitium and vascular capillaries to become identical at a given medullary level, conservation relations are derived for a multinephron central core model of the renal medulla.

Kidney↗

Model of solute and water movement in the kidney.

Finite difference equations describing salt and water movement in a model of the mammalian kidney have been solved numerically by an extension of the Newton-Raphson method used for the medullary counterflow system. The method permits both steady-state and transient solutions. It has been possible to simulate behavior of the whole kidney as a function of hydrostatic pressures in renal artery, vein, and pelvis; protein and other solute concentrations in arterial blood; and phenomenological equations describing transport of solute and water across nephron and capillary walls. With the model it has been possible to compute concentrations, flows, and hydrostatic pressures in the various nephron segments and in cortical and medullary capillaries and interstitium. In a general way, calculations on the model have met intuitive expectations. In addition, they have reemphasized the critical dependence of renal function on the hydraulic and solute permeabilities of glomerular, postglomerular, and medullary capillaries. These studies provide additional support for our thesis that the functional unit of the kidney is not the single nephron, but a nephrovascular unit consisting of a group of nephrons and their tightly coupled vasculature.

Blood Pressure↗

Quantitative analysis of mass and energy balance in non-ideal models of the renal counterflow system.

A modified Newton-Raphson method for solving finite difference equations for the renal counterflow system is described. The method has proved generally stable and efficient, and has given significant computational results for a variety of models: calculations on single solute models of the coupled vasa recta nephron counterflow system have shown that for large water and solute permeabilities of the exchanging membranes, behavior of the non-ideal system approaches that of the previously described ideal central core model. Concentration by salt and urea mixing in two solute models has been analyzed and previous conclusions from central core models have been found to remain valid in non-ideal systems. The numerical solutions have set some order of magnitude bounds on permeability requirements for concentration in different types of non-ideal systems. Finally, from the detailed concentration profiles it has been possible to relate the rate of free energy creation and dissipation from transmembrane transport of solutes and water to the net rate of free energy efflux from the counterflow system, and so to compute in a given model the fraction of power used for solute concentration.

Biological Transport, Active↗

Concentrating engines and the kidney. I. Central core model of the renal medulla.

Mass balance relations, valid for any counterflow system, are derived and applied to a central core model of the renal medulla, in which descending Henle's limbs (DHL), ascending Henle's limbs (AHL), and collecting ducts (CD) exchange with a central vascular core (VC) formed by vasa recta loops, assumed so highly permeable that the core functions as a single tube open at the cortical end, closed at the papillary. Solute supplied to the VC primarily by the water impermeable AHL may either enter the DHL to be recycled or remain in the core to extract water by osmosis from DHL and CD. If concentrations in core and descending flows are nearly equal, then for all degrees of recycling the ratio of entering DHL concentration to loop concentration is given by r = 1/[1 - f(T)(1 - f(U))], where f(T) is the fractional net solute transport out of AHL and f(U) is the ratio of CD flow to the sum of CD and AHL flows. Differential equations for a single solute are derived for core and AHL concentrations. Explicit analytic solutions are given for solute transport out of the AHL governed by Michaelis-Menten kinetics. Finally the energy requirements for concentration are analyzed.

Biological Transport↗

Concentrating engines and the kidney. II. Multisolute central core systems.

The analysis of the central core model of the renal medulla is extended to multisolute systems. It is shown that total solute concentration obeys the same differential equations for core and ascending limb as in a single solute system. Equations are derived for the concentration of individual solutes. Application of these equations to a two solute system shows that a central core system can concentrate with all transport being down a concentration gradient. This analysis applied to the renal medulla shows that mixing of urea from the collecting duct (CD) and salt from the loop of Henle in the central core of the inner medulla contributes to the concentration of urine during antidiuresis. It also sets criteria for completely passive function of the loop in the inner medulla, but whether these are satisfied cannot be determined from present experimental data.

Biological Transport↗

Concentration in renal counterflow systems.

In this paper earlier work on two-loop counterflow systems is extended to n-loop systems. It is shown that a large class of such systems in which exchange between the flow tubes is passive is unable to concentrate or dilute.

Biological Transport, Active↗

Ion/ion chemistry of high-mass multiply charged ions.

Electrospray ionization has enabled the establishment of a new area of ion chemistry research based on the study of the reactions of high-mass multiply charged ions with ions of opposite polarity. The multiple-charging phenomenon associated with electrospray makes possible the generation of multiply charged reactant ions that yield charged products as a result of partial neutralization due to ion/ion chemistry. The charged products can be readily studied with mass spectrometric methods, providing useful insights into reaction mechanisms. This review presents the research done in this area, all of which has been performed within the past decade. Ion/ion chemistry has been studied at near-atmospheric pressure in a reaction region that leads to the atmospheric/vacuum interface of a mass spectrometer, and within a quadrupole ion trap operated with a bath gas at a pressure of 1 mtorr. Proton transfer has been the most common reaction type for high-mass ions, but other forms of "charge transfer," such as electron transfer and fluoride transfer, have also been observed. For some ion/ion reactions, attachment of the two reactants has been observed. Multiply charged ion/ion reactions are fast, due to the long-range Coulombic attraction, and they are universal in that any pair of oppositely charged ions is expected to react due to the high exothermicity associated with mutual neutralization. The kinetics of reaction for multiply charged ions, derived from the same molecule with a given singly charged reactant ion, follow a charge-squared dependence, at least under normal quadrupole ion trap conditions. This dependence suggests that reaction rates are determined by the long-range Coulomb attraction, and that the ions react with constant efficiency as a function of charge state. In the case of proton transfer reactions from polypeptides to even-electron perfluorocarbon anions, no fragmentation of the polypeptide product ions has, as yet, been observed. Electron transfer from small oligonucleotide anions to rare gas cations, on the other hand, results in extensive fragmentation of the nucleic acid product ions. The extent of fragmentation decreases as the size of the oligonucleotide anions increases, reflecting a decrease in fragmentation rates associated with an increase in the number of internal degrees of freedom of the oligonucleotide. When ion-cooling rates become competitive with dissociation rates, the initially formed product ions are stabilized and fragmentation is avoided. Collisional cooling, therefore, likely plays an important role in the relative lack of dissociation observed thus far as a result of ion/ion reactions for most high-mass ions. The observed dependence of ion/ion reaction rates on the square of the ion charge, the universal nature of mutual neutralization, and the relative lack of fragmentation that arises from ion/ion reactions, makes ion/ion chemistry a particularly useful means for manipulating charge states. This review emphasizes applications that take advantage of the unique characteristics of ion/ion proton transfer chemistry for manipulating charge states. These applications include mixture analysis by electrospray, precursor ion charge state manipulation for tandem mass spectrometry studies, and simplified interpretation of product ion spectra.

Anions↗