The collecting duct begins in the cortex and descends through the medulla to the tip of the papilla. It can be divided into cortical, outer medullary, and inner medullary segments (see Fig. 116-2 ). There is remarkable cellular heterogeneity along the collecting duct.

The cortical collecting duct (CCD) can be subdivided into the initial collecting tubule and the medullary ray portion. The CCD is composed of principal cells and intercalated cells. The principal cells, which represent approximately two thirds of the total cell population, have a light-staining cytoplasm and relatively few organelles but prominent infoldings of the basal plasma membrane. The intercalated or “dark” cells constitute approximately a third of the cells in the CCD.

There is evidence for the presence of two distinct configurations of intercalated cells in the CCD, type A and type B. Type A or α cells have prominent microprojections on the apical plasma membrane and extensive tubulovesicular structures in the apical cytoplasm. Type B or β cells have a denser cytoplasm, more mitochondria, more spherical vesicular structures in the cytoplasm, and a larger basolateral membrane surface area. The type B cell is localized to the CCD.

The outer medullary collecting duct (OMCD) is composed of both principal cells and intercalated cells. The latter represent a third of the cells in the OMCD and resemble the type A cells in the CCD.

The inner medullary collecting duct (IMCD) is subdivided into two regions: the initial IMCD, located in the outer third of the inner medulla, and the terminal IMCD, situated in the distal two thirds of the inner medulla (see Fig. 116-2 ). The initial IMCD is formed mainly of principal cells and a few intercalated cells, whereas the terminal IMCD is composed of one cell type, the IMCD cell.


The collecting duct is the final site in the renal tubule that modifies the volume and solute composition of the tubule fluid.

Water Transport

AQP-2, AQP-3, and AQP-4 function as molecular water channels in the collecting duct (see Fig. 116-9 ). AQP-2 is located predominantly in the apical plasma membrane of all principal cells and IMCD cells, whereas AQP-3 is found in the basolateral membrane throughout the collecting duct system from the cortex to the papillary tip. AQP-4 is limited to the basolateral plasma membrane of principal cells in the inner stripe of the outer medulla and the basolateral plasma membrane of IMCD cells in the outer third of the inner medulla. In all segments of the collecting duct, osmotic water permeability is controlled largely by vasopressin. In the absence of vasopressin, only the papillary collecting duct manifests some residual permeability. In the presence of vasopressin, the principal cells and all cells in the IMCD are highly permeable to water (see Fig. 116-9 ). It should be emphasized that in vasopressin-induced antidiuresis, the bulk of the tubule fluid is actually reabsorbed in the CCD.

Proton and Bicarbonate Transport

The entire collecting duct is involved in proton transport and the “fine-tuning” of acid secretion by the kidney. The presence of high levels of carbonic anhydrase II in the intercalated cells suggested initially that they were involved in urine acidification. Immunocytochemical studies have localized a vacuolar-type H+-ATPase in the apical membrane and a Cl-/HCO3- exchanger in the basolateral membrane of type A intercalated cells ( Fig. 116-10A ). These findings implicate the type A cell in proton or hydrogen ion secretion in the CCD. The immunolocalization of H+-ATPase to the basolateral membrane of type B cells and the functional evidence for an apical Cl-/HCO3- exchanger in these cells provide evidence that type B intercalated cells are involved in bicarbonate secretion (see Fig. 116-10B ). Recent immunolocalization of a Cl-/HCO3- exchanger in the apical membrane of type B cells confirms the functional evidence for Cl-/HCO3- exchange.

FIGURE 116-10  Diagrams illustrating the transport characteristics of type A (left) and type B (right) intercalated cells of the cortical collecting duct. c.a. = carbonic anhydrase.  (Used with permission from Madsen KM, Verlander JW, Kim J, Tisher CC: Morphological adaptation of the collecting duct to acid-base disturbances. Kidney Int 1991;33:S57–S63.)

The intercalated cells in the OMCD are responsible for hydrogen ion secretion, which is an active mineralocorticoid-stimulated, sodium-independent process driven in part by H+-ATPase. The IMCD is also involved in urine acidification. Acid-secreting intercalated cells are present in the initial IMCD, and microcatheterization studies have documented a decrease in luminal pH along the IMCD.

Urea Transport

The cortical and outer medullary segments of the collecting duct are largely impermeable to urea in the presence and absence of vasopressin. In the terminal IMCD, urea reabsorption occurs by means of a vasopressin-sensitive, phloretin-inhibitable, facilitated transport pathway that helps maintain a high urea concentration in the deep inner medulla to facilitate urea recycling, which is important for maximum urine concentration (see Fig. 116-9 ).

Sodium and Potassium Transport

Virtually all sodium transport and much of the potassium transport in the collecting duct are controlled by aldosterone. Although it is this region of the renal tubule that “fine-tunes” sodium excretion, it is estimated that less than 10% of the filtered load of sodium is controlled by aldosterone. The target for aldosterone is the principal cell. This hormone increases sodium reabsorption by increasing the number of sodium channels in the apical plasma membrane of the principal cell. The sodium channels permit electrogenic sodium entry down a concentration gradient, which creates a lumen-negative potential difference. The increase in intracellular sodium concentration stimulates basolateral Na+,K+-ATPase activity to maintain a concentration gradient for sodium entry while increasing the intracellular potassium concentration. Potassium secretion across the luminal membrane through aldosterone-sensitive potassium channels is also enhanced by the lumen-negative potential difference. Conditions that increase plasma aldosterone levels enhance sodium absorption and potassium secretion.

The kidney is chiefly responsible for maintaining potassium homeostasis. The total body potassium content of a 70-kg individual is estimated to be approximately 3500 mEq, 98 to 99% of which resides in the intracellular compartment at a concentration of 125 mEq/L. The concentration of potassium in the extracellular fluid ranges from 3.5 to 4.5 mEq/L. Each day approximately 720 mEq of potassium (4.0 mEq/L × 180 L) is filtered, whereas only 10 to 15% is excreted in urine by an individual with normal body potassium stores. In general, potassium excretion equals potassium ingestion. With a normal potassium intake of approximately 100 mEq/day, the kidney excretes all but about 10 mEq. Approximately 70% of the filtered load of potassium is reabsorbed in the proximal tubule, and another 15 to 20% is reabsorbed in the loop of Henle. The kidney can respond quickly to increase potassium excretion 10-fold when potassium intake is increased. With potassium deprivation, however, it takes up to 14 days to reach a new steady state, a period of time sufficient for a considerable potassium deficit to develop.

The collecting duct is also responsible for fine-tuning potassium excretion. As noted earlier, the principal cells secrete potassium under the control of mineralocorticoids, whereas intercalated cells reabsorb potassium. Several factors influence renal potassium secretion, including the rate of distal tubule fluid flow, acid-base balance, aldosterone, and the electronegativity of the distal tubule. The flow dependence of potassium secretion in the collecting duct is well documented. With an increase in flow (such as that induced by diuretics), there is a parallel increase in sodium delivery to the collecting duct, which facilitates sodium reabsorption and potassium secretion. With metabolic acidosis and to a lesser extent with respiratory acidosis, potassium secretion is suppressed. An opposite effect is observed in metabolic alkalosis. With an increase in the circulating aldosterone level (such as induced by hyperkalemia), there is a parallel increase in the exchange of sodium for potassium by the principal cells that leads to enhanced potassium secretion. Finally, an increase in the lumen-negative potential, a decrease in the luminal potassium concentration, an increase in the intracellular potassium concentration, and an increase in luminal membrane permeability to potassium all favor potassium secretion by the principal cell.

The kidney also can protect against hypokalemia. The presence of H+,K+-ATPase has been documented in the intercalated cell of the collecting duct, and data suggest that with potassium deprivation there is enhanced reabsorption of potassium in exchange for protons in these cells.

Intercalated cells also help maintain potassium balance by the collecting duct. During states of potassium deprivation, an H+,K+-ATPase located in the apical cell membrane facilitates potassium reabsorption in exchange for hydrogen ions throughout the CCD and OMCD.