The proximal convoluted tubule reabsorbs 65% of the filtered water, Na+, Cl, and K+. The epithelia of the proximal tubule have “leaky” tight junctions and can maintain only a small transepithelial membrane potential.

Most of the energy consumed by the proximal tubule is tied to Na+ reabsorption. On the apical surface, Na+ enters the cell by facilitated diffusion and can be inhibited by amiloride. The Na+/K+-ATPase on the basolateral surface prevents intracellular Na+ accumulation.

Glucose and amino acids are reabsorbed by Na+-coupled transport in the proximal tubule. A family of transport proteins on the apical surface of the epithelial cell uses the diffusion of Na+ down its electrochemical gradient as the energy source. Transport of glucose across the basolateral surface occurs by facilitated diffusion.

HCO3 is reabsorbed as major anion early in the proximal tubule through a variety of mechanisms. The apical Na+/H+ antiport secretes H+ into the lumen, where it combines with filtered HCO3 to form CO2. The CO2 can freely diffuse from the lumen into the cell, where it dissociates back to H+ and HCO3. The H+ is recycled and again secreted into the lumen.

The HCO3 is transported out of the cell across the basolateral surface by an HCO37Cl exchange. The H+ secretion causes the luminal pH to drop to 7.2 in the proximal tubule.

The reabsorption of Na+ and HCO3 causes a slight drop in the filtrate osmolarity. The osmotic gradient between the filtrate and the renal interstitial fluid, combined with the “leaky” tight junctions, allow water to be reabsorbed. This water reabsorption then causes an increase in the concentration of all the other filtrate components. This concentration gradient provides a driving force to allow reabsorption by diffusion.

K+ reabsorption in the proximal tubule is primarily paracellular, driven by a concentration gradient caused by water reabsorption. A small amount of K+ is actually secreted in late proximal tubule, but a net 70% of the filtered K+ load is reabsorbed in the proximal tubule. Cl is absorbed passively in later proximal tubule by both a chemical gradient and a transluminal electrical gradient.

The proximal tubule normally reabsorbs 100% of filtered glucose, amino acids, and small peptides. On the apical

surface, this movement is due to Na+-coupled cotransport. Consequently, amino acid and glucose reabsorption show saturation kinetics. The transport maximum for glucose is only about three times higher than the normal filtered load. If plasma glucose increases enough to increase the filtered load above this level, some of the filtered glucose will not be reabsorbed and will be excreted in the urine.

The cells of the proximal tubule also secrete organic acids and bases (transporter not shown). This secretion is the basis for the use of PAH for the clearance estimation of renal plasma flow. In addition, this secretion can be a major route for the elimination of certain drugs, such as penicillin, from the body.