Water and solute exchanges. How far have we come in 100 years? What's next?

Two approaches have been used in descriptions of transvascular exchanges and net transfers of water and small solutes. The classical approach is based on Starling's four factors, vascular and interstitial hydrostatic and osmotic pressures, and on the concept of filtration in bulk without separation of solvent water from small solutes. In a physicochemical approach based on nonequilibrium thermodynamics and on multiple indicator-dilution experiments, diffusion is considered the dominant mechanism in transvascular exchanges of water with net transfers related primarily to the permeability and net passage of small solutes such as sodium and chloride ions (osmotic buffering).

Pulmonary distribution of iodoantipyrine: temperature and lipid solubility effects.

In multiple indicator-dilution studies in rat and dog lungs, we have found that the distribution of iodoantipyrine (IAP) is not limited by the endothelium at a temperature > 7 degrees C but is barrier limited at the epithelium at a temperature < 15 degrees C (permeability coefficient of 6.3 x 10(-5) cm/s at 8 degrees C). IAP extraction from the vascular surface to the tissues is greater than those of antipyrine (AP) and tritiated water (THO).

Pulmonary vascular extraction and distribution of antipyrine with alveolar flooding.

Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO) were assessed in dog lungs by multiple indicator-dilution experiments in vivo with anesthesia and in isolated perfused preparations before and after alveolar flooding. In controls, outflow patterns of AP and THO were nearly identical. In flooding, AP and THO patterns separated.

The diffusional transport of water and small solutes in isolated endothelial cells and erythrocytes.

The diffusional permeability coefficients, PD, for tritiated water (3HHO) 14C-antipyrine (AP) and 14C-iodoantipyrine (IAP) in isolated calf pulmonary artery endothelial cells and dog erythrocytes are measured with the linear diffusion technique at 11.5, 15, 20 and 37 degrees C. The PD values for both cell populations follow the sequence 3HHO > IAP > AP at each of the temperatures.

Quantitative assessment of epithelial lining fluid in the lung.

Current techniques for the measurement lung epithelial fluid (ELF) volume depend on the dilution by a known volume of wash fluid (bronchoalveolar lavage) of a resident solute, such as urea, in the ELF or of a foreign solute introduced at known concentration in the lavage fluid. Knowledge of the ELF volume allows calculation of solute ELF concentrations. Urea concentration in ELF is assumed to be the same as in plasma.

Endothelial and epithelial permeabilities to antipyrine in rat and dog lungs.

Temperature effects on the permeabilities of the structured endothelium and epithelium to antipyrine (AP) have been determined with the indicator dilution technique in isolated rat and dog lungs perfused between 38 and 8 degrees C. Permeability coefficients of the endothelium to AP [Pendo(AP)] from the Crone equation are smaller than values for isolated endothelial cells but close to the permeability coefficient of the interstitial epithelial plasmalemma [Pepi(AP)] obtained from physical and mathematical models. In these, tracer water is flow limited at the endothelium and the epithelium at all temperatures; AP is flow limited at the endothelium at T greater than 20 degrees C but barrier limited at the endothelium for T less than 20 degrees C and at the epithelium at all temperatures.

Water permeability of isolated endothelial cells at different temperatures.

The endothelial cells provide a potential pathway for water movement across the endothelium. The endothelial cell permeability to water can, therefore, be a factor in regulation of the rate of water movement out of the vasculature. Endothelial cells are isolated from calf pulmonary artery and cultured.

The influence of circulatory overload on extraalveolar microvessel endothelium of dog lung in vivo.

In an earlier study from this laboratory, morphometric evaluations of the alveolar capillary endothelium of the lungs of intact dogs were recorded after periods of sustained increases of pulmonary microvascular pressures (D. O. DeFouw, W.

The osmotic permeability of isolated calf pulmonary artery endothelial cells.

Osmotic permeability coefficients, PF, for water in isolated calf pulmonary artery endothelial cells determined over the temperature range 41 to 20 degrees C are 311.10(-5) cm.s-1 at 37 degrees C and 159.

Endothelial extraction of tracer water varies with extravascular water in dog lungs.

In multiple indicator-dilution experiments, transvascular passage of a permeating indicator is conventionally derived from the up-slope separation of the curve of the permeating indicator from that of a vascular reference and is expressed as the extraction (Ec). Extraction may be limited by the barrier (barrier-limited distribution). It may be limited by the volume of distribution accessible to it; in the time domain of an indicator-dilution experiment, the passage to and distribution in the extravascular volume are rapid relative to the velocity of blood in the exchange vessels.

Endothelial cell permeability to water.

We have calculated diffusional permeability coefficients for tracer water and for [14C]antipyrine in endothelial cells. With these values and those from studies in whole lungs we set a range for diffusional water permeability coefficients of the intact endothelium.

Water permeability of alveolar macrophages.

The hydraulic conductivity coefficient (Lp) of alveolar macrophages, recovered by lavage from dog lungs, was determined by following volume changes induced by changes of nonpermeating solute concentrations of suspending fluid as a function of time at 20 degrees C. The volume changes were monitored as changes in absorbance of the suspended cells at 600 nm. Cell surface area was calculated from cell volume and diameter.

Endothelial extraction of tracer water is independent of temperature in dog lungs.

Diffusion and viscosity-dependent flow rates generally decrease with decrease of temperature in biological systems. We have examined the extraction (Ec) of tracer water in isolated dog lungs perfused near 37 degrees C and near 15 degrees C with multiple-indicator dilution experiments. If Ec were barrier limited, Ec should be less at lower temperatures.

Terminology for mass transport and exchange.

Virtually all fields of physiological research now encompass various aspects of solute transport by convection, diffusion, and permeation across membranes. Accordingly, this set of terms, symbols, definitions, and units is proposed as a means of clear communication among workers in the physiological, engineering, and physical sciences. The goal is to provide a setting for quantitative descriptions of physiological transport phenomena.

Alveolar microvessels in isolated perfused dog lungs: structural and functional studies after production of moderate and severe hydrodynamic edema.

We have reported earlier that increased endothelial vesiculation follows the development of septal edema and alveolar flooding in isolated dog lung preparations. In this report, established ultrastructural morphometric analyses are coupled with data from physiologic and indicator-dilution studies to evaluate the stage of edema development at which de novo formation of alveolar microvessel plasmalemmal vesicles occurs. The interpretation that alveolar microvessel plasmalemmal vesicles increase prior to alveolar flooding, the final stage of edema formation, is consistent with the results reported here.

Solute-excluded volumes near the Novikoff cell surface.

A differential centrifugation technique, in which all extracellular water except that intimately associated with the cell (pericellular domain) is removed, has been applied to isolated Novikoff hepatoma cells. The pericellular volumes accessible to albumin, inulin, raffinose, and sucrose were inversely related to the molecular weights of the test solutes. This phenomenon was not detectable in erythrocytes or in fat cells.

Effects of sulfhydryl and other reagents on the diffusional permeability of dog erythrocytes to small solutes.

The effects of p-chloromercuriphenylsulfonic acid (PCMBS), 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB), phloretin and thiourea on the diffusional permeability of dog erythrocytes to tritiated water and to small 14C-labeled lipophilic and hydrophilic solutes were measured at 37 degrees C by means of the linear diffusion technique. Permeability to 3HHO was significantly decreased by PCMBS but was not affected by the other reagents. The permeability to the small hydrophilic solutes acetamide and urea was decreased by phloretin and thiourea but only the permeability to acetamide was reduced to a statistically significant extent by PCMBS.

Variations in cellular attenuation and vesicle numerical densities in capillary endothelium and type I epithelium of isolated, perfused dog lungs after acute severe edema formation.

Morphometric comparisons of nonedematous and edematous isolated, perfused dog lungs establish that there are significant differences between the degree of cellular attenuation and vesicle numerical densities in endothelial and type I epithelial cells of the alveolar septa after edema production. In nonedematous isolated lungs the extent of endothelial and epithelial attenuation was greater on the thin sides of the septa. In the edematous lungs, the differential of greater thin-side attenuation was maintained for the endothelium but not for the epithelium where the extent of attenuation in the septal thick segments was increased.

Pulmonary transport of water and solutes: functional and structural correlations.

Assessment of endothelial barrier parameters is based on formulations derived from the thermodynamics of irreversible processes. These formulations contain simplifying assumptions that, with uncertainties concerning the surface area involved in the transport, preclude definitive modeling with respect to the possible pathways. In the development of edema in isolated lung preparations perfused at 37 C, changes of structural features such as increases of vesicle volume density can be associated with changes of barrier parameters such as increased filtration coefficients and increased permeability coefficients to sodium ion.

Morphometric and physiological studies of alveolar microvessels in dog lungs in vivo after sustained increases in pulmonary microvascular pressures and after sustained decreases in plasma oncotic pressures.

Previous investigations from this laboratory of isolated-perfused dog lungs have shown that volume densities of vesicles in both capillary endothelial and type I epithelial cells are substantially increased after acute, severe edema produced by increasing microvascular pressures (D. O. DeFouw and P.