The epithelial cells

The epithelial cells, or podocytes, are stellate cells which are applied closely to the outer aspect of the basement membrane of the capillary loops. The enlarged central portion of the cell contains the nucleus, numerous mitochondria, a lot of granular endoplasmic reticulum and a prominent Golgi apparatus.

The endoplasmic reticulum often has dilated cisternae that are filled with a dense material resembling basement membrane (Farquhar et al. 1961) and there is some evidence to suggest that the podocytes do, in fact, produce the basement membrane, which is in a state of continuous turnover.

From the central part of the cell, thick processes called trabeculae radiate out and wrap themselves round the circumference of one or, more commonly, several capillaries (Fig. 1.19).

Fig. 1.19: Scanning electron micrograph of capillary loops from a rat glomerulus. The cell body of a podocyte is seen on the right, its processes enveloping a capillary loop. Note the interdigitation of the foot processes. From Spinem (1974) by permission of the author and Academic Press Inc.

From the trabeculae, secondary processes arise and from these arise tertiary processes which are known as pedicels or foot processes. These interdigitate with the foot processes of neighbouring cells so that the capillary wall, in section, shows a row of foot processes of neighbouring cells of which alternate processes belong to the same cell.

The cytoplasm of the foot processes contains occasional vesicles which may open onto the surface. These can take up protein that has passed through the glomerular filter (Farquhar 1975) and may represent the ‘last line of defence’ in the filtration of large molecules. In addition, the foot processes contain a number of filaments which may be contractile, and also a system of microtubules whose function is unknown.

The bases of the foot processes are embedded in the basement membrane to a depth of 40-50 nm (Latta 1970) and they are connected at the level of the outer limit of the basement membrane by a thin membrane or diaphragm (Fig. 1.20).

Fig. 1.20: The filtration membrane of the glomerulus (rat). The foot processes (F) are connected at their bases by a thin membrane and are covered by a fuzzy cell coat. The basement membrane (B) and the fenestrated endothelium (E) are also visible.

The distance between the bases of the foot processes at the level of the diaphragm has been variously estimated at between 20 and 45 nm (there are probably species differences) and this is the narrowest part of the space between adjacent processes, at least in Specimens prepared by the usual techniques. This narrow cleft is called the slit pore and, because of the interdigitation of the foot processes,it has a very tortuous appearance in sections cut in a plane tangential to the capillary surface.

THE SLIT PORE

Since the glomerular filtrate has to pass through the slit pore in order to reach the urinary space, it and its diaphragm have been the subject of intensive study. Rodewald and Karnovsky (1974) examined the structure of the diaphragm in specially fixed rat and mouse kidneys and found that in these species the slit is 30-45 nm wide and is subdivided by a central longitudinal filament.

From the filament, a regular series of parallel cross-bridges run to each side of the slit, thus delineating a number of rectangular spaces measuring approximately 4 x 14 nm. The crossbridges alternate in position on either side of the filament, a bridge on one side of the filament lying opposite a space on the other, so that the whole slit has a remarkable zipper-like appearance.

It was suggested that the spaces or pores are the appropriate size and shape to function as a filtration barrier for large molecular weight proteins such as albumin. The zipper-like appearance has recently been confirmed in freeze-fractured specimens (Karnovsky & Ryan 1975).

Additional evidence for the importance of the pores in the slit diaphragm has been presented by Shea and Morrison (1975) who, in a stereological study of the rat kidney estimated the aggregate slit length per glomerulus to be approximately 65 cm of which approximately 49 cm lies opposite the fenestrated portion of the endothelium.

The total area of the pores of the slit diaphragm per 60,000 glomeruli (assuming that the pores occupy 26 per cent of the total slit area) is 3-96 cm2 of which 296 cm2 lies opposite the fenestrated endothelium. Calculation showed that this area is consistent with the proposal that the slit diaphragm plays a major part in determining the hydraulic conductivity of the glomerulus.

The foot processes are usually widest at their bases, their opposite ends being widely separated (Fig. 1.20) so that the slit pore is a relatively shallow aperture. It may well be, however, that this appearance is a fixation artifact produced by the shrinkage of all the parts of the foot processes that are not embedded in basement membrane (Latta 1970, Karnovsky & Ainsworth 1972). If this is true, the whole lateral aspects of the foot processes are parallel to each other and almost in contact during life, so that the depth of the slit pore corresponds to the total height of the foot processes.

THE CELL COAT

The surface of the foot processes is covered by a thick cell coat (‘fuzz coat’) consisting of a layer of polyanionic glycoprotein containing sialic acid (Fig. 1.20). This can be demonstrated with such stains as ruthenium red, colloidal iron and silver methenamine and the staining is abolished by treatment with neuraminidase.

The space between adjacent foot processes is thus lined by cell coat, but if the foot processes are indeed normally almost in contact along their lateral borders the gap between them would be narrow and completely occluded by the cell coat so that the glomerular filtrate would have to percolate through this active layer before reaching the urinary space.

The surface coat may therefore represent an important component of the filtration barrier, particularly by its repulsion of charged macromolecules (Chang et al. 1975), although it seems likely that its thickness may vary under different conditions. The subject has recently been reviewed by Latta et al. (1975).

Read the full article: The Anatomy of the Renal Circulation