Late Distal Tubule and Cortical Collecting Tubule
The second half of the distal tubule and the subse-quent cortical collecting tubule have similar functional characteristics. Anatomically, they are composed of two distinct cell types, the principal cells and the inter-calated cells (Figure 27–11). The principal cells reab-sorb sodium and water from the lumen and secrete potassium ions into the lumen. The intercalated cells reabsorb potassium ions and secrete hydrogen ions into the tubular lumen.
Principal Cells Reabsorb Sodium and Secrete Potassium.
Sodium reabsorption and potassium secretion by the principal cells depend on the activity of a sodium-potassium ATPase pump in each cell’s basolateral membrane (Figure 27–12). This pump maintains a low sodium concentration inside the cell and, therefore, favors sodium diffusion into the cell through special channels.
The secretion of potassium by these cells from the blood into the tubular lumen involves two steps: (1) Potassium enters the cell because of the sodium-potassium ATPase pump, which maintains a high intracellular potassium concentration, and then (2) once in the cell, potassium diffuses down its con-centration gradient across the luminal membrane into the tubular fluid.
The principal cells are the primary sites of action of the potassium-sparing diuretics, including spirono-lactone, eplerenone, amiloride, and triamterene. Aldosterone antagonists compete with aldosterone for receptor sites in the principal cells and therefore inhibit the stimulatory effects of aldosterone on sodium reabsorption and potassium secretion. Sodium channel blockers directly inhibit the entry of sodium into the sodium channels of the luminal membranes and therefore reduce the amount of sodium that can be transported across the basolateral membranes by the sodium-potassium ATPase pump. This, in turn, decreases transport of potassium into the cells and ultimately reduces potassium secretion into the tubular fluid. For this reason the sodium channel blockers as well as the aldosterone antagonists decrease urinary excretion of potassium and act as potassium-sparing diuretics.
Intercalated Cells Avidly Secrete Hydrogen and Reabsorb Bicar-bonate and Potassium Ions. Hydrogen ion secretion bythe intercalated cells is mediated by a hydrogen-ATPase transport mechanism. Hydrogen is generated in this cell by the action of carbonic anhydrase on water and carbon dioxide to form carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions. The hydrogen ions are then secreted into the tubular lumen, and for each hydrogen ion secreted, a bicarbonate ion becomes available for reabsorption across the basolateral membrane. The intercalated cells can also reabsorb potassium ions.
The functional characteristics of the late distal tubule and cortical collecting tubule can be summarized as follows:
1. The tubular membranes of both segments are almost completely impermeable to urea, similar to the diluting segment of the early distal tubule; thus, almost all the urea that enters these segments passes on through and into the collecting duct to be excreted in the urine, although some reabsorption of urea occurs in the medullary collecting ducts.
2. Both the late distal tubule and the cortical collecting tubule segments reabsorb sodium ions, and the rate of reabsorption is controlled by hormones, especially aldosterone. At the same time, these segments secrete potassium ions from the peritubular capillary blood into the tubular lumen, a process that is also controlled by aldosterone and by other factors such as the concentration of potassium ions in the body fluids.
3. The intercalated cells of these nephron segments avidly secrete hydrogen ions by an active hydrogen-ATPase mechanism. This process is different from the secondary active secretion of hydrogen ions by the proximal tubule because it is capable of secreting hydrogen ions against a large concentration gradient, as much as 1000 to 1. This is in contrast to the relatively small gradient (4- to 10-fold) for hydrogen ions that can be achieved by secondary active secretion in the proximal tubule. Thus, the intercalated cells play a key role in acid-base regulation of the body fluids.
4. The permeability of the late distal tubule and cortical collecting duct to water is controlled by the concentration of ADH, which is also called vasopressin. With high levels of ADH, thesetubular segments are permeable to water, but in the absence of ADH, they are virtually impermeable to water. This special characteristic provides an important mechanism for controlling the degree of dilution or concentration of the urine.