Cortical collecting tubule

Potassium-Sparing Diuretics. Potassium-sparing diuretics act on the aldosterone-sensitive portion of cortical collecting tubules, and partially in the distal convoluted tubules of the nephron. The commonly used potassium-sparing diuretics are triamterene, amiloride, and spironolactone (Table 3). Spironolactone is a competitive aldosterone receptor antagonist, whereas triamterene and amiloride are not (44,45). 

Sodium reabsorption Much less than 10% of the filtered load of NaCl reaches the distal nephron. Regulation of Na uptake, occurring mainly in the principal cells of the cortical collecting tubule, is controlled by the steroid hormone aldosterone (see Section 4.4). The net effect of aldosterone is the reclamation of NaCl and potassium excretion in to the luminal fluid. 

Amiloride and triamterene-Am or 6e and triamterene not only inhibit sodium reabsorption induced by aldosterone, but they also inhibit basal sodium reabsorption. They are not aldosterone antagonists, but act directly on the renal distal tubule, cortical collecting tubule and collecting duct. They induce a reversal of polarity of the transtubular electrical-potential difference and inhibit active transport of sodium and potassium. Amiloride may inhibit sodium, potassium-ATPase. 

Cortical collecting tubule (CCT) Na+ reabsorption (2-5%) coupled to K+ and H+ secretion Variable2 Na channels (ENaC), channels,1 H transporter,1 aquaporins K+-sparing diuretics... 

Potassium-sparing diuretics prevent K+ secretion by antagonizing the effects of aldosterone at the late distal and cortical collecting tubules. Inhibition may occur by direct pharmacologic antagonism of mineralocorticoid receptors ( spironolactone, eplerenone ) or... 

Amiloride and triamterene are direct inhibitors of Na+ influx in the CCT (cortical collecting tubule). Triamterene is metabolized in the liver, but renal excretion is a major route of elimination for the active form and the metabolites. Because triamterene is extensively metabolized, it has a shorter half-life and must be given more frequently than amiloride (which is not metabolized). 

The mineralocorticoids influence salt and water metabolism and in general conserve sodium levels. They promote the resorption of sodium and the secretion of potassium in the cortical collecting tubules and possibly the connecting segment. They also elicit hydrogen secretion in the medullary collecting tubules (Figure 61.2). 

Stoner LC, Burg MB, Orloff J (1974) Ion transport in cortical collecting tubule effect of amiloride. Am J Physiol 227 453 159... 

Blot-Chabaud, M., Warrstok, F., Bon valet, J.-P., and Farman, N. (1990). Cell sodium induced recruitment of Na -K -ATPase pumps in rabbit cortical collecting tubules is aldosterone-dependent. J. Biol. Oiem. 265, 11676-11681. 

Fujii, Y Mujais, S. K and Kat, A, I (1989) Renal potassium adaptation Role of the Na -K pump in rat cortical collecting tubules. Aat.. Ph sioi. 256, F279-F284,... 

Concurrent acidosis in patients with trimethoprim-induced hyperkalemia is uncommon, which could be explained if the action of trimethoprim, like that of amiloride, is hmited to the cortical collecting tubule but does not affect the medullary collecting tubule, which has a large capacity to secrete hydrogen ions and may therefore prevent the development of acidosis. Predisposing factors for the rare adverse effect of renal tubular acidosis in this case may have been aldosterone deficiency or resistance, medullary dysfunction of sickle cell anemia, and renal insufficiency. All these factors could contribute to impaired renal handling of secretion of hydrogen ions (72). 

Ling BN, Eaton DC. Cyclosporin A inhibits apical secretory K-i-channels in rabbit cortical collecting tubule principal cells. Kidney Int 1993 44 974-984. 

This effect likely results from enhanced reabsorption in the cortical collecting tubule. 

The inhibitory effect of lithium on distal potassium secretion is likely to occur in the cortical collecting tubule where it decreases Na uptake and the transepi-thelial voltage (lumen-negative) that normally favors potassium secretion. 

CA is located both intracellularly (type II CA) and in the luminal bru.sh border membrane (type IV CA) of proximal convoluted tubule cells (Fig. 18-3A). Both of these site I locations are major targets of the CA inhibitors." This group of diuretics also inhibits intracellular CA in the intercalated cells of the connecting and cortical collecting tubules (i.e.. site 4 Fig. 18-6). 

Under normal conditions, approximately 180 L of glomerular ultrafiltrate are produced per day, the vast majority of which must be reabsorbed by the renal tubules to maintain homeostasis. Clinically, the renal tubule can be divided into three major sections the proximal tubule, Henle s loop, and the distal nephron, which includes the distal tubule, the cortical collecting tubule, and the medullary collecting ducts. In the proximal tubule, approximately 60% to 70% of the filtered load of water and solute is isovolemicaUy reabsorbed, as is the vast majority of filtered amino acids, glucose, and bicarbonate. 

Collecting duct Collecting system collecting duct Cortical collecting duct (CCD) Principal cells (+IC cells) Cortical collecting tubule (CCT)... 

Spielman WS, Sonnenburg WK, Allen ML, Arend U, Gerozissis K, Smith WL. Immunodissection and culture of rabbit cortical collecting tubule cells. Am J Physiol 1986 251 F348-F357. 

Other studies also support lithium s primary effect at the level of cyclic adenosine monophosphate generation [52, 53]. Though the greatest effect of arginine vasopressin is in the cortical collecting tubule, an argi-... 

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