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Biomedical subjects

C R Robertson

Publications and source records attributed to C R Robertson.

At least 55 records · Page 3Linked to original sources

Dynamics of glomerular ultrafiltration following open-heart surgery.

To elucidate how individual determinants might lower the rate of glomerular ultrafiltration (GFR) in some patients following cardiac surgery, we performed hemodynamic measurements and clearance of inulin (as a measure of GFR), PAH (as a measure of effective renal plasma flow [ERPF]), and dextran-40. Two groups of 17 patients each were distinguished by the presence or absence of prerenal azotemia. Glomerular hypofiltration (GFR = 21 +/- 2 vs. 76 +/- 6 ml/min/1.73 m2, P less than 0.001) in the former was accompanied by depressed left ventricular function, arterial pressure, and ERPF (152 +/- 26 vs. 317 +/- 32 ml/min/1.73 m2, P less than 0.001). To determine if factors beside ERPF play a role in lowering GFR, we calculated the efferent oncotic pressure (pie). Failure of GFR to change over a 24-hour period despite increases in ERPF suggested that both patient groups were at filtration pressure disequilibrium (FPD). This condition permits calculation of a unique glomerular ultrafiltration coefficient (Kf). Over a range of pressures for transcapillary hydraulic pressure (deltaP), such that 3 less than or equal to (deltaP - pie) less than or equal to 10 mm Hg (to simulate FPD), Kf was less than 0.08 ml . sec-1 . mm Hg-1 . 1.73 m-2 in azotemic, but exceeded this value in nonazotemic patients. Although a selective reduction of Kf is predicted to lower the fractional clearance of dextrans, these were significant elevated in azotemic relative to nonazotemic patients (molecular radii 30 - 40 A). A theoretical analysis of the latter data suggests that over the foregoing range of FPD, a 15 to 30% decline in deltaP combined with a 30 to 0% reduction in Kf from values in nonazotemic patients best explains the experimental findings in azotemic patients.

Cardiac Surgical Procedures↗

Serum gastrin and the family environment in duodenal ulcer disease.

The study investigated the relationships between specific demographic, psychosocial, and physiological variables and the severity of duodenal ulcer disease in a population of patients with proved duodenal ulcer. Intercorrelations between psychosocial and physiological variables were also studied. The study design was cross sectional and retrospectively assessed life change units and DUD severity during the previous 6 months in 39 male ulcer clinic outpatients. Anxiety, depression, life change units, the family environment, ABO blood type, secretor status, serum pepsinogen, and serum fasting gastrin were evaluated. A DUD severity score was calculated from self-reported ulcer pain symptoms and ulcer complications. Gastrin levels correlated significantly with three Family Environment Scale (FES) subscales, including: (a) independence, (b) achievement orientation, and (c) expressiveness. Duodenal ulcer disease severity scores correlated with Zung SDS scores, but not with state or trait anxiety, life change units, or the FES.

Achievement↗

Editorial review. Recent formulations of the urinary concentrating mechanism: a status report.

The status of the purely passive mode of solute concentration as of 1979 appears to be similar to that of the original countercurrent hypothesis 10 years ago. The passive mode concept has advanced our understanding of the concentrating process by qualitatively incorporating the permeability characteristics of tubule segments and the lack of an active transport process in the thin loop of Henle into a mechanism which has attractive economy and explanatory value. But in the final analysis some assumptions are not borne out by experimental findings (for example, the high urea concentration of fluid in the rat and hamster end-descending limb; the likelihood of net transepithelial addition of sodium chloride to the Psammomys descending limb; the removal of sodium chloride from the hamster ascending limb against an apparent electrochemical gradient under certain circumstances; and the osmotic lag between vasa recta blood and interstitium in the rat). Furthermore, when the known permeability and transport characteristics of the renal tubule are incorporated into a mathematic model of the passive operating mode, numerical simulations fail to establish a progressively hyperosmotic inner medulla. This does not rule out the applicability of the more general model (Eq. 1), particularly if evidence for some form of active transport in the inner medulla, heretofore lacking, is forthcoming.

Animals↗

Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall.

The influence of molecular configuration on the filtration of macromolecules across glomerular capillary walls was examined by comparing fractional clearances of two uncharged polysaccharides of distinctly different molecular configuration in the Munich-Wistar rat. The macromolecules employed were dextran, a slightly branched polymer of glucopyranose, and ficoll, a highly cross-linked copolymer of sucrose and epichlorohydrin. Differences in effective shape between these two polymers were determined from measurements of several physical properties of aqueous solutions containing either dextran or ficoll. It was found that dextran is best represented as a prolate ellipsoid with axial ratios of 4, 9, and 16 for molecules with Stokes-Einstein radii of 22, 32, and 40 A, respectively. On the other hand, ficoll is more closely approximated as spherical since the axial ratio was found to be between 1 and 2 for all molecular sizes. Fractional clearances of dextran and ficoll ranging in effective radius from 18 to 44 A were determined in each of seven Munich-Wistar rats. Fractional clearances of dextran were found to be greater than those of ficoll, the difference being significant for molecular radii ranging from 24 to 44 A. In addition, as shown previously for dextran, ficoll was found to be neither secreted nor reabsorbed by the renal tubules. These results, therefore, suggest that in addition to molecular size and charge, molecular configuration is also a determinant of the filtration of macromolecules across the glomerular capillary wall.

Animals↗

Permselectivity of the glomerular capillary wall. Facilitated filtration of circulating polycations.

To examine the electrostatic effects of fixed negative charges on the glomerular capillary wall, polydisperse [(3)H]DEAE dextran, a polycationic form of dextran, was infused into 10 Munich-Wistar rats. Fractional clearances of DEAE ranging in radius from 18 to 44A were determined in these rats, together with direct measurements of the forces and flows governing the glomerular filtration rate of water. These results were compared with data previously obtained in Munich-Wistar rats receiving tritiated neutral dextran (D) and polyanionic dextran sulfate (DS). Measured values for the determinants of the glomerular filtration rate of water in rats given DEAE were found to be essentially identical to those in rats given either D or DS. In addition, DEAE was shown to be neither secreted nor reabsorbed. Fractional clearances of polycationic DEAE were increased relative to both D and DS, the increase relative to D being significant for effective molecular radii ranging from 24 to 44A. Fractional DEAE clearances were also measured in a separate group of six Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Fractional DEAE clearances in NSN rats were reduced significantly, relative to values measured in normal rats, for effective DEAE radii ranging from 18 to 42A. Moreover, in NSN rats, fixed negative charges on the glomerular capillary wall were greatly reduced, relative to non-NSN rats, as evidenced by a reduction in intensity of colloidal iron staining. Thus, in NSN rats, DEAE clearances were essentially indistinguishable from values obtained with both neutral D and polyanionic DS.

Animals↗

A total internal-reflection technique for the examination of protein adsorption.

A total internal-reflection fluorescence (TIRF) technique for examining protein adsorption at solid-liquid interfaces is described. For the representative case of adsorption of bovine gamma-globulin onto silicone rubber, the applicability of the technique to serveral important aspects of protein adsorption phenomena is demonstrated. Specifically, in addition to the tightly adsorbed protein layer observed herein and previously by maany others, the presence of a loosely adsorbed protein layer was also noted under conditions of either static or flowing protein solutions. Taking advantage of the continuous real-time measurements possible with TIRF, a rate constant for the protein adsorption step during laminar flow was estimated at both 25 and 37 degrees C. These results serve to demonstrate that the TIRF technique represents a significant and versatile new tool for the study of protein adsorption phenomena.

Adsorption↗

Mechanism of angiotensin II-induced proteinuria in the rat.

To investigate the mechanism(s) of angiotensin II-induced proteinuria, polydisperse [3H]dextran (D) (radius = 18-42 A) was infused into seven Munich-Wistar rats before and during intravenous infusion of angiotensin II (AII), 0.35 microgram/kg per min. During AII infusion, UprotV rose approximately twofold, and the fractional clearances of D [(U/P)D/(U/P)In] increased significantly for dextrans with radii greater than 22 A. Single nephron filtration fraction increased, due to a measured rise in the glomerular transcapillary hydraulic pressure difference from 34 to 43 mmHg. Near constancy of single nephron glomerular filtration rate resulted, however, from the offsetting effect of a decrease in glomerular plasma flow rate from 83 to 60 nl/min. These measured hemodynamic changes were found, by the use of pore theory, to account to a large extent for the measured increases in (U/P)D/(U/P)In. In seven other rats, fractional clearances of polyanionic dex-ran sulfate (a more reliable marker of albumin filtration than D) were also found to increase significantly with AII, suggesting that the proteinuria induced by AII can be explained, in large part, by hemodynamic factors.

Angiotensin II↗

Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules.

To investigate the mechanism(s) of increased filtration of serum proteins after glomerular injury, polydisperse samples of uncharged [(3)H]dextran (D) or anionic [(3)H]dextran sulfate (DS) were infused into 14 control and 16 puromycin aminonucleoside- (PAN) treated Munich-Wistar rats. Fractional clearances of D or DS ranging in radius from 18 to 42A were determined in these rats, together with direct measurements of the forces governing the glomerular filtration rate of water. Whole kidney and single nephron glomerular filtration rates were approximately 40% lower in PAN-treated rats, relative to controls, due mainly to a marked reduction in the glomerular capillary ultrafiltration coefficient and, to a lesser extent, to a small reduction in glomerular plasma flow rate as well. In PAN-treated rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and both D and DS were shown to be neither secreted nor reabsorbed. Fractional clearances of uncharged D were reduced after PAN administration, falling significantly for effective D radii from 22 to 38A. Utilizing a theory based on macromolecular transport through pores, these results indicate that in PAN-treated rats, effective pore radius is the same as in controls, approximately 44A. In PAN nephrosis, however, the ratio of total pore surface area/pore length, a measure of pore density, is reduced to approximately one-third that of control, due very likely to a reduction in filtration surface area. In contrast to the results with uncharged D, fractional clearances of DS were found to increase after PAN administration for all DS radii studied. These results with D and DS suggest that proteinuria in PAN nephrosis is due, not to an increase in effective pore radius or number of pores, but rather to a diminution of the electrostatic barrier function of the glomerular capillary wall, thereby allowing increased passage of polyanions such as DS and albumin.

Animals↗

Determinants of the transglomerular passage of macromolecules.

In addition to molecular size, at least two other factors influence the transglomerular passage of macromolecules. The hemodynamic determinants of glomerular filtration rate affect macromolecule transport by altering the volume flux through the glomerular capillary wall and the profile of macromolecule concentrations along a glomerular capillary. The electrostatic properties of the glomerular capillary wall markedly restrict the passage of circulating polyanions, relative to neutral macromolecules of similar size. In the normal animal, the combined effects of these various mechanisms ensure that only very small quantities of plasma proteins are filtered. In experimental proteinuric conditions such as nephrotoxic serum nephritis and puromycin-induced nephrosis, reduction in the fixed negative charges on the glomerular capillary wall appears to be largely responsible for the increased transglomerular passage of anionic macromolecules such as albumin. Other evidence suggests that hemodynamic factors may contribute to proteinuria under certain circumstance. The possibility of an increase in number and/or radius of glomerular "pores" being responsible for proteinuria, perhaps the most intuitively obvious and widely held view, has yet to receive direct experimental support.

Animals↗

Water extraction from the inner medullary collecting tubule system: a role for urea.

Recent examinations of the inner medullary collecting tubule membrane in vitro have demonstrated that its reflection coefficient to urea (sigma urea) is significantly less than unity and less than sigma NaClhe presence of antidiuretic hormone. Fluid entering the inner medullary collecting tubule has a higher urea concentration and lower NaCl concentration than does the medullary interstitium, although total osmolarity is nearly equal on either side of the membrane. The transtubular difference in solute composition, together with the difference between sigma urea and sigma NaCl, should result in a driving force for extraction of water from the tubule. This hypothesis was examined in a differential analysis of water and solute fluxes across the collecting tubule epitheliu. The results indicate that this driving force contributes significantly to water extraction from the inner medullary collecting tubule.

Animals↗

An examination of transcapillary water flux in renal inner medulla.

We recently demonstrated that net fluid uptake occurs in the capillary system of the inner medulla. To define the site of fluid uptake, the concentration of protein was determined in plasma from descending vasa recta at the base and tip of the exposed papilla in Munich-Wister rats. The vasa recta plasma-to-arterial plasma protein concentration ratio (VR/P) was 1.43 +/- 0.09 at the base and 1.66 +/- 0.09 at the tip. These results, which indicate fluid loss from the descending vasa recta, are difficult to explain on the basic of hydraulic and oncotic forces alone. The osmolality of the contents of descending vasa recta increased between base and tip (delta = 72 +/- 30 mosmol/kg H2O). If the increase in osmolality of plasma in descending vasa recta lags behind that of the adjacent medullary interstitium, a transcapillary osmotic driving force exists favoring water loss from descending vessels. It is concluded that fluid uptake by the inner medullary circulation occurs beyond descending vasa recta in interconnecting capillaries or ascending vasa recta. In our view the most likely interpretation of these results is that fluid movement across vasa recta in the inner medulla is influenced by three forces: those owing to transcapillary differences in osmotic, oncotic, and hydraulic pressures.

Animals↗