PROXIMAL TUBULE

The proximal tubule receives urine from Bowman’s space. It plays a major role in the transport of material from the urine back into the blood (reabsorption) and vice versa (secretion). In humans, the entire proximal tubule is approximately 14 mm long. It is divided into two sections: the proximal convoluted tubule (pars convoluta) and the proximal straight tubule (pars recta). The latter forms the first part of the loop of Henle.

In rats, the proximal tubule is often subdivided into S1 (first two thirds of the convoluted part), S2 (last third of the convoluted part and initial portion of the straight part), and S3 (remainder of the straight part); however, these distinctions are generally not made in humans.

The proximal tubule contains cuboidal to low columnar cells arranged over a tubular basement membrane. These cells possess an eosinophilic cytoplasm, and their round nuclei are usually situated near the cell base. Their other histologic features differ according to the particular region under consideration.

PROXIMAL CONVOLUTED TUBULE

The proximal convoluted tubule (PCT) is the major site of solute reabsorption in the nephron. An extensive microvillous brush border on the apical plasma membrane projects into the lumen and dramatically increases the available surface area for solute transport. On light microscopy, the lumen often appears collapsed or indistinct owing to the presence of the brush border, which should be readily seen. Distal tubules and collecting ducts, in contrast, lack a brush border and thus appear more widely patent.

The lateral and basal borders of PCT cells are thrown into extensive processes that interdigitate with infoldings of adjoining cells; as a result, lateral cell borders are indistinct on light microscopy sections. These basolateral processes increase the surface area available for transport across the basolateral cell membrane. They are replete with additional mitochondria to support active transport processes. The complex extracellular area between these folds is known as the basolateral intercellular space. It is closed by the tubular basement membrane, which separates the tubular epithelium from the interstitium and peritubular capillaries.

Junctional complexes connect neighboring cells near their apical surface. These consist of a tight junction (zonula occludens) and an intermediate junction (zonula adherens). Although tight junctions are critical for maintaining the barrier between the tubular lumen and interstitium, a small number of discontinuities permits some molecules to be reabsorbed through a paracellular route.

PCT cells are rich with mitochondria, which provide energy for solute transport. These are arranged perpendicular to the cell base and resemble vertical striations on some histologic sections. These cells also possess a prominent rough endoplasmic reticulum and Golgi apparatus near the apical membrane.

PCT cells contain evidence of extensive endocytosis near the apical plasma membrane, including coated pits, invaginations, and endosomes. Numerous lysosomes are also present to process and degrade a subset of the incoming material. Endocytosis appears to be most important for the reabsorption of filtered proteins, as it is up-regulated in conditions that damage the normal glomerular filtration barrier.

PROXIMAL STRAIGHT TUBULE

The cells of the proximal straight tubule differ from those of the PCT in several important respects. The microvilli are shorter and sparser, endocytotic figures are less frequent, mitochondria are sparser, and the basolateral processes and infoldings are smaller and less elaborate. These morphologic differences reflect the smaller amount of reabsorption that occurs across these cells.