Disorders of Potassium: Physiology

Fig. 14.1

Handling of K⁺ by various segments of the nephron; 60–80 % of K⁺ is reabsorbed by the proximal convoluted tubule (PCT) and about 25 % by the medullary thick ascending limb of Henle’s loop (TALH). Only 10 % of filtered K⁺ is delivered to the distal convoluted tubule (DCT). CCD, OMCD, and IMCD refer to cortical collecting, outer medullary collecting and inner medullary collecting ducts, respectively. Broken arrows denote K⁺ secretion into the late segment of the proximal tubule and descending thin limb of Henle’s loop (DTHL)

Proximal Tubule

K⁺ is freely filtered at the glomerulus. About 60–80 % of this filtered K⁺ is reabsorbed by the proximal tubule. Reabsorption of K⁺ is mostly passive and occurs via a K⁺ transporter. Also, passive reabsorption of K⁺ occurs through the paracellular pathway. This passive transport of K⁺ is coupled with Na⁺ and water transport. Volume expansion and osmotic diuretics (e.g., mannitol) inhibit this passive diffusion of Na⁺-coupled K⁺ transport.

Loop of Henle

In this segment of the nephron, both secretion and reabsorption of K⁺ occur. K⁺ enters the late segment of the proximal tubule and the descending thin limb of the Henle’s loop. This observation is based on evidence that the [K⁺] is higher in the lumen of the hairpin turn of the Henle’s loop than the plasma [K⁺], suggesting that K⁺ enters passively from the medullary interstitium.

The thick ascending limb of Henle’s loop actively reabsorbs K⁺. This segment also reabsorbs Na⁺ and Cl⁻. K⁺ reabsorption occurs mostly in the medullary thick ascending limb and could account for as much as 25 % of the filtered K⁺. The K⁺ transport in this segment of the nephron occurs by secondary active transport, as well as by passive diffusion through the paracellular pathway. The secondary active transport mechanism involves the cotransport of 1 Na⁺, 1 K⁺, and 2 Cl⁻ ions (Fig. 14.2). The driving force for this cotransport is provided by the Na/K-ATPase located in the basolateral membrane. This enzyme decreases the intracellular concentration of Na⁺, thereby creating a steep Na⁺ gradient across the apical membrane. In order to stimulate Na⁺ entry, K⁺ must leak back into the lumen. Indeed, K⁺ diffuses back into the lumen through K⁺ conductance channels, called renal outer medullary K (ROMK) channels, to provide a continuous supply of K⁺ ions for cotransport with Na⁺ and Cl⁻. Without this back-leak of K⁺, the low luminal K⁺ concentration would limit the reabsorption of Na⁺ and Cl⁻. This cotransport system is inhibited by the loop diuretics (furosemide, bumetanide, etc.).

Fig. 14.2

Cellular model for transepithelial K⁺ transport in the thick ascending limb of Henle’s loop. Thick broken arrows indicate diffusion of K⁺ via renal outer medullary K (ROMK) channels, and Cl⁻ channel

Three types of K⁺ channels have been identified: a low or small-conductance (SK) 30 pS channel, an intermediate 70 pS channel, and a high conductance calcium-activated maxi-K⁺ or BK (150 pS) channel. Only 30 pS (picosiemens) and 70 pS channels make up the ROMK and account for most of the K⁺ that diffuses into the lumen in the thick ascending Henle’s loop. The BK channel pumps out K⁺ in A (α) intercalated cells.

Distal Nephron

Distal Tubule

About 10 % of the filtered K⁺ reaches the distal tubule. The K⁺ secretion occurs in this segment because of low luminal Cl⁻ and high luminal Na⁺ concentration. In this segment, a luminal K/Cl cotransporter is responsible for K⁺ secretion (Fig. 14.3). This cotransporter operates in cooperation with a luminal Na/Cl cotransporter. It has been shown that delivery of Na⁺ to the distal tubule promotes secretion of K⁺ via the K/Cl cotransporter. Also, K⁺ secretion occurs via the ROMK channel. Thiazide diuretics (hydrochlorothiazide) inhibit Na/Cl cotransporter.

Fig. 14.3

Cellular model for transepithelial K⁺ transport in the distal tubule. Broken arrow indicates diffusion of K through conductance channel. ROMK is not shown

Connecting Tubule

The apical membrane of the connecting tubule cells contains Na⁺ (ENaC) and K⁺ (ROMK) conductance channels. The entry of Na⁺ via the ENaC creates a lumen-negative potential difference, which promotes K⁺ secretion via ROMK. The connecting tubule cells secrete K⁺ at a higher rate than the rate at which it is excreted in the urine. K⁺ secretion is sensitive to aldosterone.

Cortical Collecting Duct

The collecting duct is considered the major site for K⁺ secretion, although the early distal tubule and cortical collecting duct cells play an important role in K⁺ secretion. Two types of cells are found in this segment: principal cells and intercalated cells. Principal cells are the primary cells for K⁺ secretion. K⁺ enters the cell via Na/K-ATPase. K⁺ is reabsorbed across the lumen via the Na⁺ channel (ENaC). The principal cell possesses two secretory pathways for K⁺ in the apical membrane (Fig. 14.4a). One pathway is the ROMK channel and the other is the K/Cl cotransporter. As stated above, K⁺ secretion into the lumen occurs in association with a Na/K-ATPase located in the basolateral membrane, which pumps 2 K⁺ into and 3 Na⁺ ions out of the cell. Blockage of Na⁺ uptake by amiloride inhibits K⁺ secretion. Thus, K⁺ secretion is dependent on Na⁺ uptake from the lumen. The A-type intercalated cell is involved in K⁺ reabsorption. This cell reabsorbs K⁺ in exchange for H⁺ ion secretion via an H/K-ATPase (Fig. 14.4b). For each H⁺ ion secreted, one HCO₃ ⁻ is generated. Thus, the H/K-ATPase may participate in acid–base balance.

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