Fine Structural Basis for Hemoglobin Filtration by Glomerular Capillaries

Abstract

The presence of filtered hemoglobin in Bowman’s space of in vivo fixed glomeruli was ascertained by microspectrophotometry and special staining of sections for light microscopy. By electron microscopy, hemoglobin appeared as a finely granular material in the lumens of glomerular capillaries and in Bowman’s space. Filtration of hemoglobin was usually unassociated with morphologic alterations in endothelial or epithelial cells. During filtration, the hemoglobin molecules seemed to traverse the endothelium across the diaphragm closing the fenestrae. Following transport through the basement membrane, the molecules gained access to Bowman’s space by passing through the filtration slit membranes between the foot processes. Uptake of hemoglobin by glomerular epithelial cells was minimal or lacking. Fusion of foot processes was noted occasionally at late intervals after the induction of hemoglobinuria; it appeared to reflect focal damage of epithelial cells, rather than a general, immediate reaction of epithelial cells to filtration of the concentrated solution of hemoprotein molecules.

The Permeability of Glomerular Capillaries to Graded Dextrans

“…The stratified nature of the glomerular capillary wall has been known for over 15 years, but at the present time there is still controversy regarding which of its several layers serves as the main filtration barrier for plasma proteins. A number of attempts have been made to identify the filtration barrier by electron microscopy using various electron-opaque tracers (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15). Initially, only a few such tracers were available, and these were mostly of large size (ferritin, colloidal particles of mercuric sulfide, gold, and thorotrast).…”

Studies on the relationship between proteinuria and glomerular ultrastructural change in hyperalbuminaemic female wistar rats

“…Other results concerned with protein uptake by the glomerular epithelium suggest, however, that the process is more complex than originally thought and that it is relatively restricted, particularly in comparison with that in the tubular epithelium. Albumin is readily taken up by both glomerular and tubular epithelial cells when increased quantities are filtered at the glomerulus (Exaire et al, 1972;Lawrence and Brewer, 1982b) but proteins such as horseradish peroxidase, myoglobin, bovine lactoperoxidase, haemoglobin, tyrosinase, lysozyme and Fab fragments of antiperoxidase antibody, which are readily reabsorbed by the proximal convoluted tubules, are rarely taken up by the glomerular epithelium in normal rats (Graham and Karnovsky, 1966;Graham and Kellermeyer, 1968;Ericson, 1968;Anderson, 1972;Oliver and Essner, 1978;Druet et al, 1978). Studies with graded dextrans (Caulfield and Farquhar, 1975) where low molecular weight fractions were accumulated less readily by glomerular epithelial cells than higher molecular weight fractions, indicate that this may in part be due to the relatively rapid passage of smaller proteins across the glomerular filter as suggested by Graham and Karnovsky (1966) and Venkatachalam, Cotran and Karnovsky (1 970) and that only large molecules which are restricted from entering Bowman's space at the level of the slit pore and therefore accumulate within the lamina rara externa can be taken up via the coated pits present in the epithelial cell surfaces abutting the GBM.…”

Glomerular Permeability to Protein Molecules – its Possible Structural Basis

“…Other studies using electron opaque tracers, such as colloidal lanthanum [10,16,35,40] as well as elucidating the phagocytic function of mesangial cells [13,36,40,41], A gel like consistency of the GBM was inferred from studies using intravenously injected globin [40]. Sizable aggregates of globin traversed the GBM without visibly deforming the latter.…”

“…To identify the structural equivalent of the glomerular permeability barrier, morphologists have relied on protein tracer molecules which can be visualized with the electron microscope [2,10,11,16,21,32,35,40,44,61], Although this approach has permitted certain structural-functional correlations to be made, the problem of defining the site of the filtration barrier in normal glomerular capillaries remains unresolved. The present review is restricted to those studies which have attempted to correlate ultrastructural-functional relationships of the glomerulus with its known permeability properties to proteins.…”