Proximal convoluted tubule

The proximal tubule is the portion of the duct system of the nephron of the kidney which leads from Bowman's capsule to the loop of Henle.

Structure and appearance
The most distinctive characteristic of the proximal tubule is its brush border (or "striated border").

Brush border cell
The luminal surface of the epithelial cells of this segment of the nephron is covered with densely packed microvilli forming a border readily visible under the light microscope giving the brush border cell its name. The microvilli greatly increase the luminal surface area of the cells, presumably facilitating their resorptive function as well a putative flow sensing within the lumen.

The cytoplasm of the cells is densely packed with mitochondria, which are largely found in the basal region within the infoldings of the basal plasma membrane. The high quantity of mitochondria gives the cells an acidophilic appearance. The mitochondria are needed in order to supply the energy for the active transport of sodium ions out of the proximal tubule. Water passively follows the sodium out of the cell along its concentration gradient.

Cuboidal epithelial cells lining the proximal tubule have extensive lateral interdigitations between neighboring cells, which lend an appearance of having no discrete cell margins when viewed with a light microscope.

Agonal resorption of the proximal tubular contents after interruption of circulation in the capillaries surrounding the tubule often leads to disturbance of the cellular morphology of the proximal tubule cells, including the ejection of cell nuclei into the tubule lumen.

This has led some observers to describe the lumen of proximal tubules as occluded or "dirty-looking," in contrast to the "clean" appearance of distal tubules, which have quite different properties.

Divisions
The proximal tubule as a part of the nephron can be divided into two sections, pars convoluta and pars recta. Differences in cell outlines exist between these segments, and therefore presumably in function too.

Regarding ultrastructure, it can be divided into three segments, S1, S2, and S3:

Pars convoluta
'The "Pars convoluta" is the initial convoluted portion''.

'''In relation to the morphology of the kidney as a whole, the convoluted segments of the proximal tubules are confined entirely to the renal cortex.

Some investigators on the basis of particular functional differences have divided the convoluted part into two segments designated "S1" and "S2".

Pars recta
The "Pars recta" is the following straight (descending) portion.

Straight segments descend into the outer medulla. They terminate at a remarkably uniform level and it is their line of termination that establishes the boundary between the inner and outer stripes of the outer zone of the renal medulla.

As a logical extension of the nomenclature described above, this segment is sometimes designated as "S3".

Absorption
The proximal tubule regulates the pH of the filtrate by exchanging hydrogen ions in the interstitium for bicarbonate ions in the filtrate; furthermore, it is responsible for secreting organic acids, such as creatinine and other bases, into the filtrate.

Fluid in the filtrate entering the proximal convoluted tubule is reabsorbed into the peritubular capillaries. This is driven by sodium transport from the lumen into the blood by the Na+/K+ ATPase in the basolateral membrane of the epithelial cells. Sodium reabsorption is primarily driven by this antiporter. This is the most important transport mechanism in the PCT.

Secretion
Many types of medications are secreted in the proximal tubule. Further reading: Table of medication secreted in kidney

Most of the ammonium that is excreted in the urine is formed in the proximal tubule via the breakdown of glutamine to alpha-ketoglutarate. This takes place in two steps, each of which generates an ammonium anion: the conversion of glutamine to glutamate and the conversion of glutamate to alpha-ketoglutarate. The alpha-ketoglutarate generated in this process is then further broken down to form two bicarbonate anions, which are pumped out of the basolateral portion of the tubule cell by cotransport with sodium ions.

Pathophysiology in kidney disease
Proximal tubular epithelial cells (PTECs) have a pivotal role in kidney disease.

Malignant
Most renal cell carcinoma, the most common form of kidney cancer, arises from the convoluted tubules.

Non-malignant
Acute tubular necrosis occurs when PTECs are directly damaged by toxins such as antibiotics (e.g., gentamicin), pigments (e.g., myoglobin and sepsis (e.g., mediated by lipopolysaccharide from gram-negative bacteria). Renal tubular acidosis (proximal type) (Fanconi syndrome) occurs when the PTECs are unable to properly reabsorb glomerular filtrate so that there is increased loss of bicarbonate, glucose, amino acids, and phosphate.

PTECs also participate in the progression of tubulointerstitial injury due to glomerulonephritis, ischemia, interstitial nephritis, vascular injury, and diabetic nephropathy. In these situations, PTECs may be directly affected by protein (e.g., proteinuria in glomerulonephritis), glucose (in diabetes mellitus), or cytokines (e.g., interferon-γ and tumor necrosis factors). There are several ways in which PTECs may respond: producing cytokines, chemokines, and collagen; undergoing epithelial mesenchymal transdifferentiation; necrosis or apoptosis.