The proximal tubule reabsorbs most of the filtered K+, whereas the distal nephron reabsorbs or secretes K+, depending on K+intake
Figure 37-5 summarizes the pattern of K+ transport along the nephron under conditions of low or normal/high K+ intake. In either case, the kidney filters K+ in the glomerulus and then extensively reabsorbs it along the proximal tubule (~80%) and the loop of Henle (~10%), so that only ~10% of the filtered K+ enters the distal convoluted tubule (DCT). Moreover, in either case, the medullary collecting duct (MCD) reabsorbs K+. The K+ handling depends critically on dietary K+ in five nephron segments: the DCT, the connecting tubule (CNT), the initial collecting tubule (ICT), the cortical collecting tubule (CCT), and the MCD.
FIGURE 37-5 K+ handling along the nephron. In A and B, the numbered yellow boxes indicate the fraction of the filtered load that various nephron segments reabsorb, whereas the red box in B indicates the fraction of the filtered load secreted by the ICT and CCT. The green boxes indicate the fraction of the filtered load that remains in the lumen at these sites. The values in the boxes are approximations that reflect the joint contributions of both juxtamedullary and superficial nephrons.
Low Dietary K+
When the body is trying to conserve K+, the “classic distal tubule” (i.e., DCT, CNT, and ICT) and CCT all reabsorb K+, so that only a small fraction of the filtered load (1% to 3%) appears in the urine (see Fig. 37-5A). In states of K+ depletion, this additional K+ reabsorption can be lifesaving by retrieving from the tubule lumen precious K+ that escaped reabsorption along the proximal tubule and loop of Henle. Despite the degree to which the kidneys can enhance K+ reabsorption, they cannot restrict K+ loss in the urine as effectively as they can restrict Na+ loss. Therefore, a negative K+ balance and hypokalemia may develop when K+ intake has been abnormally low for prolonged periods of time.
Normal or High Dietary K+
When external K+ balance demands that the kidneys excrete K+, the ICT, CCT, and the more proximal portion of the MCD secrete K+ into the tubule lumen (see Fig. 37-5B). Together, these segments, known as the distal K+ secretory system, account for most of the urinary excretion of K+. It is also this distal K+ secretory system that responds to many stimuli that modulate K+ excretion. Even at normal rates of K+ excretion (10% to 15% of the filtered load), the proximal tubules and loop of Henle first absorb very large amounts of K+ (~90% of the filtered load), so that the K+ appearing in the urine may largely represent K+ secreted by more distal segments of the nephron.
Medullary trapping of K+ helps to maximize K+ excretion when K+ intake is high
The kidney traps K+ in the medullary interstitium, with the interstitial [K+] being highest at the tip of the papilla and falling toward the cortex. This medullary K+ trapping is the result of three steps along the nephron. First, because interstitial [K+] rises toward the tip of the papilla, juxtamedullary nephrons, whose long loops of Henle dip into the inner medulla (p. 724), secrete K+ passively into the thin descending limb of the loop of Henle (tDLH). Indeed, analysis of fluid collected from the hairpin bend of the long loops of Henle of juxtamedullary nephrons shows that the amount of K+ delivered to the collection site at the hairpin bend can exceed not only the amount of K+ present at the end of the proximal tubule, but also the amount of K+ filtered. This K+ secretion by the tDLH is the first step of a process known as medullary K+recycling (Fig. 37-6).
FIGURE 37-6 Medullary recycling of K+ by juxtamedullary nephrons. IMCD, inner medullary collecting duct; OMCD, outer medullary collecting duct.
The second step of medullary K+ recycling is K+ reabsorption by the thin (tALH) and thick (TAL) ascending limbs, which deposit K+ in the medullary interstitium. This newly deposited interstitial K+contributes to the high interstitial [K+]. Together, the tALH and TAL of a juxtamedullary loop reabsorb more K+ than the descending limb secretes, so that net K+ reabsorption occurs along the loop and thereby contributes to medullary K+ trapping.
The third step of medullary K+ recycling is the reabsorption of K+ by the MCDs. Regardless of whether the distal K+-secretory system (ICT, CCT, early MCD) reabsorbs K+ (see Fig. 37-5A) or secretes K+ (see Fig. 37-5B), the medullary collecting ducts reabsorb some K+ and thereby contribute to medullary K+ trapping.
One would think that—with respect to K+ excretion—medullary K+ recycling is inefficient because K+ exits the ascending limb and MCD only to re-enter the nephron upstream, in the tDLH. However, medullary recycling and concomitant K+ trapping may be important in maximizing the excretion of K+ when K+ intake is high. Under these conditions, K+ secretion by the distal K+-secretory system is intense, so that luminal [K+] in the MCD may rise to ≥200 mM. Thus, enhanced K+ trapping in the medullary interstitium minimizes the [K+] difference between the MCD lumen and its peritubular environment, thus reducing the passive loss of K+ from the MCD.