Renal medullary microcirculation.
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Biomedical subjects
Publications and source records attributed to T L Pallone.
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We have developed a mathematical model that predicts the performance of continuous arteriovenous hemodialysis. Given patient (plasma protein concentration, hematocrit, mean arterial pressure, central venous pressure) and circuit (flow resistance, membrane hydraulic permeability, dialyzer mass transfer coefficient, ultrafiltrate column height, dialysate flow rate) characteristics as inputs, predictions of hydraulic and oncotic pressure distribution, filtration rate, blood flow, total, diffusive, and convective urea clearances are provided. The model was tested by perfusing a circuit with bovine blood under conditions of pure ultrafiltration, zero net ultrafiltration and dialysis, or combined ultrafiltration and dialysis (countercurrent dialysate flow at rates of 10, 20, and 30 ml/min). In order to permit computation, membrane hydraulic permeability and flow resistances were measured. Dialyzer mass transfer coefficient for urea could not be measured directly and so was determined by fitting model predictions to measured urea clearances. For all conditions of operation, a urea mass transfer coefficient of 0.014 cm/min successfully simulated the data. Predictions of blood flow, filtrate generation rate, and circuit pressure distribution were accurate. At lower dialysate flow rates, urea clearance approximated the sum of dialysate flow and filtration rate. At higher dialysate flows, however, departure from this ideal blood-dialysate equilibrium was observed. Model predictions regarding the relative contributions of diffusion and convection to urea clearance were explored. Under conditions of nearly perfect equilibration of urea between blood and dialysate at the blood inlet, the model predicts that the diffusive clearance of urea will increase with increasing rate of filtration and may exceed the rate of dialysate inflow.
Volume efflux from descending vasa recta (DVR) of hydropenic rats occurs despite a higher oncotic pressure than hydraulic pressure. To explain this, we previously proposed that transcapillary small-solute gradients exert an additional driving force for volume efflux. This hypothesis was tested by micropuncture of DVR at the base and tip of the exposed renal papilla of control hydropenic and furosemide-treated rats. The DVR plasma osmolality at the base, 573 +/- 40, rose to 1,011 +/- 118 mosmol/kg H2O at the tip in control animals but was 356 +/- 8 and 377 +/- 6, respectively in furosemide animals, demonstrating that the axial osmotic gradient was nearly eliminated. The DVR plasma protein concentration in control hydropenic rats was higher at the tip, 6.8 +/- 0.4 g/dl, than at the base, 5.2 g/dl (P less than 0.01), because of volume efflux from DVR between base and tip, but was 5.4 +/- 0.3 and 5.5 +/- 0.2 g/dl at the base and tip, respectively, in furosemide animals, indicating virtual abolition of volume efflux. In DVR at the tip in control animals, plasma protein concentration positively correlated with plasma osmolality (R = 0.72, P less than 0.02). These results support the hypothesis that transcapillary small-solute gradients influence transcapillary fluid movement in DVR.
In vitro and mathematical models of continuous arteriovenous hemofiltration (CAVH) have been developed. Human erythrocytes resuspended in normal saline containing 5% bovine albumin were used to perfuse the circuit from a gravity driven pressure source. Membrane hydraulic permeability was observed to decline from 31.2 x 10(-5) +/- 11.9 x 10(-5) cm/(min.mm Hg) before use to 12.3 x 10(-5) +/- 3.3 x 10(-5) (mean +/- SD) after use. This fall occurred during the first one to two hours whether perfused with blood or 5% albumin alone. Pressure-flow relationships of each circuit component, measured with 40% sucrose as a calibration medium, conformed to Poiseuille's equation. Use of high resistance blood access on the venous end of the circuit resulted in a low blood flow rate and high filtration fraction. The same access, when placed on the arterial end, produced both low blood flow rate and low filtration fraction. These results were a consequence of pressure distribution within the circuit as demonstrated by measurements of perfusion, prefilter, and postfilter pressures. The importance of negative pressure applied to the filter chamber in order to maintain favorable Starling forces, when the system was operated with a small bore arterial access, was demonstrated by similar methods. Enhancement of urea clearance by predilution was verified. Model simulations suggest that predilution will be of less benefit or even detrimental for other solutes which fail to distribute across the erythrocyte membrane. Comparison of results with predictions of a mathematical model demonstrated good agreement, but with some tendency to overestimate filtrate production. The latter was attributed to neglect of concentration polarization of plasma proteins in model development.
To elucidate the role of the ureter in urinary concentration we studied the effect of partial and complete ureteral excision on urinary osmolality and papillary interstitial osmolality and on sodium, potassium, and urea concentrations in the antidiuretic rat. Urine and descending vasa recta (DVR) plasma samples were obtained by micropuncture of the left renal papilla before (period 1) and 45 min after (period 2) complete (group 1, n = 10 rats) or partial (group 2, n = 10 rats) ureteral excision. Urine osmolality fell from 2,063 +/- 156 (mean +/- SE) to 736 +/- 116 mosmol/kgH2O after complete ureteral excision (P less than 0.01). After partial ureteral excision, the fall was less than half as great, from 2,038 +/- 167 to 1,551 +/- 162 mosmol/kgH2O (P less than 0.01). Vasa recta plasma osmolality decreased from 1,742 +/- 133 to 860 +/- 119 mosmol/kgH2O after complete excision (P less than 0.01) but only from 1,830 +/- 146 to 1,504 +/- 154 mosmol/kgH2O after partial excision (P less than 0.05). Mean DVR plasma sodium concentration declined from 339 +/- 25 to 211 +/- 25 meq/l (P less than 0.01) in group 1 but did not change in group 2 (348 +/- 21 to 347 +/- 28 meq/l). The fraction of DVR plasma osmolality accounted for by urea decreased significantly from 0.59 +/- 0.01 to 0.46 +/- 0.02 mM/(mosmol/kgH2O) in group 1 and from 0.59 +/- 0.02 to 0.49 +/- 0.03 mM/(mosmol/kgH2O) for group 2 (P less than 0.01, both groups). We interpret these findings to show that the remnant ureter moderates the fall in interstitial osmolality at least in part through preservation of the corticomedullary sodium chloride gradient.
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A theoretical model has been developed to simulate solute and water transport in the medullary microcirculation of the normal hydropenic rat. The model is formulated in terms of a countercurrent vascular unit consisting of one descending (DVR) and several ascending vasa recta (AVR) extending from the corticomedullary junction to the tip of the papilla. Steady-state mass balances relate gradients in NaCl, urea, and plasma protein concentrations and variations in the flow rates of plasma and red blood cells to permeability properties of the vasa recta and erythrocytes. In contrast to previous models, transmural volume fluxes are assumed to be present in both DVR and AVR. Available micropuncture measurements suggesting net volume removal from DVR within the inner medulla are found to be consistent with NaCl reflection coefficients in DVR between 0.10 and 0.80. The hydraulic permeability in the DVR is estimated to be greater than 0.18 X 10(-6) cm X s-1 X mmHg-1. Based on currently available data, reliable bounds cannot yet be placed on the hydraulic permeability of the AVR. The vascular unit is predicted to accomplish substantial net removal of NaCl and water from the inner medullary interstitium but relatively little removal of urea. Red cells leaving the inner medulla in the AVR are found to be slightly dehydrated. It is calculated that at a given blood flow rate, the lower the initial medullary hematocrit, the more effective the vascular unit is at removing water. Several unresolved issues are discussed, including the role of the capillary plexus that joins DVR with AVR. To the extent that the volume uptake observed in the exposed papilla in structures beyond the DVR occurs in the capillary plexus and not in the AVR, estimated values of AVR hydraulic permeability are reduced, as is predicted overall volume uptake by the vascular unit in the inner medulla.
In order to determine the degree to which blood and dialysate achieve equilibration of urea concentration during continuous arteriovenous hemodialysis (CAVHD), CAVHD circuits employing the Hospal AN69S dialyzer were perfused with bovine blood (85 to 90 ml/min, hematocrit 28%) containing 50 mg/dl of urea in the presence of countercurrent dialysate flowing at 10, 20, or 30 ml/min. The circuits were constructed and perfusion pressure (66 mmHg) set to yield a near zero net ultrafiltration rate. Urea clearances were measured and found to approximate the dialysate inflow rate, Qd, up to about 15 ml/min. At higher dialysate flow rates, equilibration was incomplete so that urea clearance was 24.7 +/- 0.5 (mean +/- SE) ml/min when Qd was 30 ml/min. A simplified model of urea transport in the dialyzer successfully simulated the data.
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