Medical Physiology, 3rd Edition

Cellular Mechanisms of K+ Absorption and Secretion

Overall net transepithelial K+ movement is absorptive in the small intestine and secretory in the colon

The gastrointestinal tract participates in overall K+ balance, although compared with the kidneys, the small intestine and large intestine play relatively modest roles, especially in healthy individuals.

The pattern of intestinal K+ movement parallels that of the kidney: (1) the intestines have the capacity for both K+ absorption and secretion, and (2) the intestines absorb K+ in the proximal segments but secrete it in the distal segments.

Dietary K+ furnishes 80 to 120 mmol/day, whereas stool K+ output is only ~10 mmol/day. The kidney is responsible for disposal of the remainder of the daily K+ intake (see p. 795). Substantial quantities of K+ are secreted in gastric, pancreatic, and biliary fluid. Therefore, the total K+ load presented to the small intestine is considerably greater than that represented by the diet. The concentration of K+ in stool is frequently >100 mM. This high stool [K+] is the result of several factors, including both colonic K+ secretion and water absorption, especially in the distal part of the colon.

K+ absorption in the small intestine probably occurs via solvent drag

Experiments in which a plasma-like solution perfused segments of the intestine have established that K+ is absorbed in the jejunum and ileum of the small intestine and is secreted in the large intestine. Although the small intestine absorbs substantial amounts of K+, no evidence has been presented to suggest that K+ absorption in the jejunum and ileum is an active transport process or even carrier mediated. Thus, K+absorption in the small intestine is probably passive, most likely a result of solvent drag (i.e., pulled along by bulk water movement; see p. 908), as illustrated in Figure 44-6A. Although changes in dietary Na+and K+ and alterations in hydration influence K+ movement in the colon, similar physiological events do not appear to affect K+ absorption in the small intestine.

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FIGURE 44-6 Cellular mechanisms of K+ secretion and absorption. A, In the small intestine, K+ absorption occurs via solvent drag. B, Throughout the colon, passive K+ secretion occurs via tight junctions, driven by a lumen-negative transepithelial voltage. C, Throughout the colon, active K+ secretion is transcellular. D, In the distal colon, active K+ absorption is transcellular. The thickness of the arrows in the insets indicates the relative magnitude of K+ flux in different segments.

Passive K+ secretion is the primary mechanism for net colonic secretion

In contrast to the small intestine, the human colon is a net secretor of K+. This secretion occurs by two mechanisms: a passive transport process that is discussed in this section and an active process that is discussed in the next. Together, these two K+ secretory pathways are greater than the modest component of active K+ absorption in the distal part of the colon and thus account for the overall secretion of K+ by the colon.

Passive K+ secretion, which is the pathway that is primarily responsible for overall net colonic K+ secretion, is driven by the lumen-negative Vte of 15 to 25 mV. The route of passive K+ secretion is predominantly paracellular, not transcellular (see Fig. 44-6B). Because Vte is the primary determinant of passive K+ secretion, it is not surprising that passive K+ secretion is greatest in the distal end of the colon, where Vte difference is most negative. Similarly, increases in the lumen-negative Vte that occur as an adaptive response to dehydration—secondary to an elevation in aldosterone secretion (see the next section)—result in an enhanced rate of passive K+ secretion. Information is not available regarding the distribution of passive K+ secretion between surface epithelial and crypt cells.

Active K+ secretion is also present throughout the large intestine and is induced both by aldosterone and by cAMP

In addition to passive K+ secretion, active K+ transport processes—both secretory and absorptive—are also present in the colon. However, active transport of K+ is subject to considerable segmental variation in the colon. Whereas active K+ secretion occurs throughout the colon, active K+ absorption is present only in the distal segments of the large intestine. Thus, in the rectosigmoid colon, active K+ absorption and active K+secretion are both operative and appear to contribute to total-body homeostasis.

The model of active K+ secretion in the colon is quite similar to that of active Cl secretion (see Fig. 44-5) and is also parallel to that of active K+ secretion in the renal distal nephron (see p. 799). The general paradigm of active K+ transport in the colon is a “pump-leak” model (see Fig. 44-6C). Uptake of K+ across the basolateral membrane is a result of both the Na-K pump and the Na/K/Cl cotransporter (NKCC1), which is energized by the low [Na+]i that is created by the Na-K pump. Once K+ enters the cell across the basolateral membrane, it may exit either across the apical membrane (K+ secretion) or across the basolateral membrane (K+ recycling). The cell controls the extent to which secretion occurs, in part by K+ channels present in both the apical and the basolateral membranes. When apical K+ channel activity is less than basolateral channel activity, K+ recycling dominates. Indeed, in the basal state, the rate of active K+ secretion is low because the apical K+ channel activity is minimal in comparison with the K+ channel activity in the basolateral membrane.

It is likely that aldosterone stimulates active K+ secretion in surface epithelial cells of the large intestine, whereas cAMP enhances active K+ secretion in crypt cells. In both cases, the rate-limiting step is the apical BK K+ channel, and both secretagogues act by increasing K+ channel activity.

Aldosterone

The mineralocorticoid aldosterone enhances overall net K+ secretion by two mechanisms. First, it increases passive K+ secretion by increasing Na-K pump activity and thus increasing electrogenic Na+ absorption (see Fig. 44-3D). The net effects are to increase the lumen-negative Vte and to enhance passive K+ secretion (see Fig. 44-6B). Second, aldosterone stimulates active K+ secretion by increasing the activity of both apical K+ channels and basolateral Na-K pumps (see Fig. 44-6C).

cAMP and Ca2+

VIP and cholera enterotoxin both increase [cAMP]i and thus stimulate K+ secretion. Increases in [Ca2+]i—induced, for example, by serotonin (or 5-hydroxytryptamine [5-HT])—also stimulate active K+ secretion. In contrast to aldosterone, neither of these second messengers has an effect on the Na-K pump; rather, they increase the activity of both the apical and the basolateral K+ channels. Because the stimulation of K+channels is greater at the apical than at the basolateral membrane, the result is an increase in K+ exit from the epithelial cell across the apical membrane (i.e., secretion). Stimulation of K+ secretion by cAMP and Ca2+, both of which also induce active Cl secretion (see Fig. 44-5), contributes to the significant fecal K+ losses that occur in many diarrheal diseases.

Active K+ absorption takes place only in the distal portion of the colon and is energized by an apical H-K pump

As noted above, not only does the distal end of the colon actively secrete K+, it also actively absorbs K+. The balance between the two processes plays a role in overall K+ homeostasis. Increases in dietary K+enhance both passive and active K+ secretion (see Fig. 44-6B, C). However, dietary K+ depletion enhances active K+ absorption (see Fig. 44-6D). The mechanism of active K+ absorption appears to be an exchange of luminal K+ for intracellular H+ across the apical membrane, mediated by an H-K pump (see pp. 117–118). The colonic H-K pump is ~60% identical at the amino-acid level to both the Na-K pump and the gastric parietal-cell H-K pump. Thus, active colonic K+ absorption occurs via a transcellular route, in contrast to the paracellular route that characterizes K+ absorption in the small intestine (see Fig. 44-6A). The mechanism of K+ exit across the basolateral membrane may involve K/Cl cotransport. Not known is whether active K+ secretion (see Fig. 44-6C) and active K+ absorption (see Fig. 44-6D) occur in the same cell or in different cells.

 

SMALL INTESTINE

LARGE INTESTINE

Length (m)

6

2.4

Area of apical plasma membrane (m2)

~200

~25

Folds

Yes

Yes

Villi

Yes

No

Crypts or glands

Yes

Yes

Microvilli

Yes

Yes

Nutrient absorption

Yes

No

Active Na+ absorption

Yes

Yes

Active K+ secretion

No

Yes