The Disappearance of Macromolecules from the Peritoneal Cavity during Continuous Ambulatory Peritoneal Dialysis (CAPD) is Not Dependent on Molecular Size

The transport of macromolecules from the circulation to the peritoneal cavity is a size-selective restricted process, while the transport of these solutes from the peritoneal cavity is probably mainly by lymphatic absorption. If so, it should be independent of molecular size. Therefore, we studied with a clearance technique the disappearance of intra peritoneally administered inulin and polydisperse dextran 70 in nine continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results with the simultaneously measured appearance clearance of serum proteins. Using gel permeation chromatography 18 dextran fractions with different molecular radii could be analyzed. Inulin clearance (2.94 mL/min) was higher than total dextran clearance (1.30 mL/min). The maximal dextran concentration in all dialysate samples was found in the 50.4 Å fraction. The clearances of the dextran fractions were the same for different molecular sizes. All disappearance clearances were higher than the appearance clearances: the protein/dextran clearance ratio ranged from 0.15 for albumin/36 Å to 0.04 for alpha2-macroglobulin/91 Å. This confirms that the appearance of a macromolecule, but not its disappearance is dependent on molecular size. It is concluded that the disappearance of macromolecules from the peritoneal cavity is mainly a size independent convective process, possibly by lymphatic uptake. This implies that total dextran 70 clearance can be used for measurement of lymphatic absorption in CAPD patients.

Permeability of blood-brain barrier to various sized molecules

We studied disruption of the blood-brain barrier (BBB) by acute hypertension and a hyperosmolar solution. The goals were to determine whether 1) disruption of the BBB occurs primarily in arteries, capillaries, or veins, and 2) transport of different-sized molecules is homogeneous or size dependent. Sprague-Dawley rats were studied using intravital fluorescent microscopy of pial vessels and fluorescein-labeled dextrans (FITC-dextran, mol wt = 70,000, 20,000, and 4,000 daltons). The site of disruption was determined by the appearance of microvascular leaky sites. Transport of different-sized molecules was calculated from clearance of FITC-dextran. During gradual hypertension and osmotic disruption, all leaky sites were venular. Rapid hypertension produced venular leaky sites and, in some experiments, diffuse arteriolar extravasation of FITC-dextran. Clearance of different-sized molecules was homogeneous during acute hypertension. In contrast, clearance of molecules during osmotic disruption was size dependent. The findings suggest that 1) venules and veins are the primary sites of disruption following acute hypertension and a hyperosmolar solution; 2) transport of different-sized molecules is homogeneous following acute hypertension, which suggests a vesicular mechanism; and 3) transport following hyperosmolar disruption is size dependent, which suggests that hyperosmolar disruption may involve formation of pores as well as vesicular transport.

Transtubular leakage of glomerular filtrate in human acute renal failure

Ten postcardiac surgical patients with acute renal failure (ARF) were infused with inulin and dextran 40. Plasma and urine were then submitted to gel-permeation chromatography to ascertain the apparent fractional clearance profile for the dextrans. Compared to normal volunteer controls, the fractional clearance profile was substantially elevated for dextran molecules in the Einstein-Stokes radius (r) range 20-40 A. For the smaller molecules (r = 20-28 A), fractional dextran clearance in ARF was frequently in excess of unity. A simple mass conservation model which assumes that the "true" fractional dextran clearance profile for the glomerulus (in Bowman's space) in ARF is the same as that for normal controls, when applied to the experimental observations, revealed that in ARF, on the average, 50% of filtered inulin is lost by tubular backleakage. Furthermore, the model permitted an estimate of the permeability properties of the damaged tubular wall. This indicated tubular permeability not unlike that of the normal glomerulus to dextran molecules with r less than 30 A, but relative impermeability to larger dextran molecules.

Human Glomerular Membrane Porosity and Filtration Pressure: Dextran Clearance Data Analysed by Theoretical Models

1. The renal clearance of dextran of different molecular sizes has been measured in normal humans from 6 days to 61 years of age. Gel chromatography of dextran has been used for determination of molecular weight distribution. 2. Information about the functional ultrastructure of the glomerular membrane has been deduced from the experimental clearance data in the light of theoretical models. The glomerular membrane was here visualized as a gel filter, localized in the basement membrane. The physical analogue of this membrane was interpreted as a somewhat heteroporous structure of quite well defined pore sizes: one system of smaller pores in the range of 20–28 Å radius and an additional system of larger pores of radii up to 80 Å. These larger pores are quite few in number with an approximate ratio of one large pore per 10 000 small pores. 3. The values obtained for the transglomerular pressure difference were low, about 1 cm of water or less. This supports the concept that tubular reabsorption may be the rate limiting factor in the process of urine formation and may also control the glomerular filtration rate. 4. The changes of the dextran clearance with ageing found in this investigation may be explained by an increase of the pore radii of the glomerular membrane and a concomitant decrease of the transglomerular pressure difference.