The establishment of a transtubular osmotic gradient by solute reabsorption, such as NaCl and Na+-glucose, drives water reabsorption in the renal tubules. This occurs as Na+ and organic solutes, along with HCO3− and Cl−, are reabsorbed from the tubular fluid into the lateral intercellular spaces, reducing the osmolality of the tubular fluid and increasing the osmolality of the intercellular space. Due to the high permeability of the proximal tubule to water, mainly due to the presence of aquaporin water channels (AQP1) in the apical and basolateral membranes, water is reabsorbed by osmosis across the cells. The tight junctions in the proximal tubule also contribute to water reabsorption through the paracellular pathway. The accumulation of fluid and solutes in the intercellular space leads to an increase in hydrostatic pressure, forcing fluid and solutes into the capillaries. Additionally, the elevated protein oncotic pressure in the peritubular capillaries facilitates the uptake of fluid and solutes into the capillary. The transport of solutes, including Na+, Cl−, and organic solutes, into the intercellular space establishes the osmotic gradient that drives water reabsorption across the proximal tubule. This occurs because certain transporters and Na+,K+-ATPase located on the lateral cell membranes deposit these solutes between cells. Furthermore, diffusion across the tight junction also allows some NaCl to enter the intercellular space through the paracellular pathway. As water flows across the transcellular and paracellular pathways, certain solutes like K+ and Ca++ are entrained in the reabsorbed fluid and are thus reabsorbed by solvent drag. The reabsorbed fluid in the proximal tubule is slightly hyperosmotic compared to plasma. However, the difference in osmolality is minimal, leading to the description of proximal tubule reabsorption as isosmotic, with approximately 67% of both the filtered load of solute and water being reabsorbed. Importantly, changes in Na+ reabsorption directly impact the reabsorption of water and other solutes in the proximal tubule. This is particularly relevant during volume depletion, as increased Na+ reabsorption by the proximal tubule is accompanied by a parallel increase in HCO3− reabsorption, potentially contributing to metabolic alkalosis known as volume contraction alkalosis.
Table 34.5 ). The driving force for water reabsorption is a transtubular osmotic gradient established by reabsorption of solute (e.g., NaCl, Na+-glucose). Reabsorption of Na+ along with organic solutes, HCO3 − , and Cl− from tubular fluid into the lateral intercellular spaces reduces the osmolality of the tubular fluid and increases the osmolality of the lateral intercellular space. The osmotic gradient across the proximal tubule established by these transport processes is only a few mOsm/L (
Fig. 34.4 ). Because the proximal tubule is highly permeable to water, primarily owing to expression of aquaporin water channels (AQP1) in the apical and basolateral membranes, water is reabsorbed across cells by osmosis. In addition the tight junctions in the proximal tubule are also water permeable, so some water is also reabsorbed across the paracellular pathway between proximal tubular cells. Accumulation of fluid and solutes within the lateral intercellular space increases hydrostatic pressure in this compartment. The increased hydrostatic pressure forces fluid and solutes into the capillaries.
2In addition, protein oncotic pressure in the peritubular capillaries (πpc) is elevated because of the process of glomerular filtration (see ). The elevated πpc facilitates uptake of fluid and solute into the capillary.
•Fig. 34.4 Routes of reabsorption of water and solute across the proximal tubule. Transport of solutes, including Na+ , Cl− , and organic solutes, into the lateral intercellular space increases the osmolality of this compartment, which establishes the driving force for osmotic reabsorption of water across the proximal tubule. This occurs because some Na+,K+-ATPase and some transporters of organic solutes, HCO3− , and Cl− are located on the lateral cell membranes and deposit these solutes between cells. Furthermore, some NaCl also enters the lateral intercellular space via diffusion across the tight junction (i.e., paracellular pathway). An important consequence of osmotic water flow across the transcellular and paracellular pathways in the proximal tubule is that some solutes, especially K+ and Ca++ , are entrained in the reabsorbed fluid and thereby reabsorbed by the process of solvent drag.
reabsorption in the proximal tubule. The reabsorbed fluid is slightly hyperosmotic relative to plasma. However, this difference in osmolality is so small it is commonly said that proximal tubule reabsorption is isosmotic (i.e., ≈67% of both the filtered load of solute and water are reabsorbed). Indeed, there is little difference in the osmolality of tubular fluid at the start and end of the proximal tubule. An important consequence of osmotic water flow across the proximal tubule is that some solutes, especially K+ and Ca++ , are entrained in the reabsorbed fluid and thereby reabsorbed by the process of solvent drag (see
Fig. 34.4 ). Reabsorption of virtually all organic solutes, Cl− and other ions, and water is coupled to Na+ reabsorption. Therefore changes in Na+ reabsorption influence reabsorption of water and other solutes by the proximal tubule. This point will be discussed later, notably in , and is especially relevant during volume depletion when increased Na+ reabsorption by the proximal tubule is accompanied by a parallel increase in HCO3 − reabsorption, which can contribute to metabolic alkalosis (i.e., volume contraction alkalosis).