In the absence of ROMK, the reabsorption of NaCl by the TAL is reduced, resulting in the loss of NaCl in urine. This reduction also decreases the positive voltage that drives the reabsorption of K+ by this nephron segment. As a result, urinary excretion of K+ increases, even when the cortical collecting duct is unable to secrete the normal amount of K+ due to a lack of ROMK channels. However, in ROMK knockout mice, the cortical collecting duct still secretes K+ through the flow and Ca++-dependent BK K+ channel in the apical membrane of principal cells.

Inhibiting Na+,K+-ATPase augments the flow of tubular fluid along the ASDN. Inhibition of water and NaCl reabsorption by the proximal tubule also decreases effective circulating volume (ECFV) and stimulates the secretion of aldosterone. Additionally, chronic acidosis caused by inorganic acids increases plasma [K+], which further stimulates aldosterone secretion. These factors contribute to an increase in K+ secretion. The effects of acidosis on cell [K+] and apical membrane permeability are offset by the rise in tubular fluid flow, plasma [K+], and aldosterone levels.

Metabolic acidosis can either inhibit or stimulate excretion of K+ depending on the duration of the disturbance. Acute metabolic alkalosis stimulates excretion of K+, while chronic metabolic alkalosis, especially in association with ECFV contraction, significantly increases renal K+ excretion due to increased levels of aldosterone.

Glucocorticoids also increase urinary K+ excretion by increasing GFR, which enhances the urinary flow rate, a potent stimulus of K+ excretion, and by stimulating SGK1 activity.

The rate of urinary K+ excretion is often determined by simultaneous changes in hormone levels, acid-base balance, or the flow rate of tubule fluid. The powerful effect of flow can either enhance or oppose the response of the ASDN to hormones and changes in acid-base balance. This interaction is beneficial in the case of hyperkalemia as it enhances K+ excretion and restores K+ homeostasis. However, in alkalosis, changes in flow and acid-base status can alter K+ homeostasis in a detrimental manner.
Fig. 36.7 ). In the absence of ROMK, reabsorption of NaCl by the TAL is reduced, which leads to loss of NaCl in urine. Reduction of NaCl reabsorption by the TAL also reduces the positive transepithelial luminal voltage, which is the driving force for reabsorption of K+ by this nephron segment. Thus the reduction in paracellular K+ reabsorption by the TAL increases urinary K+ excretion even when the cortical collecting duct is unable to secrete the normal amount of K+ because of a lack of ROMK channels. The cortical collecting duct, however, does secrete K+ even in ROMK knockout mice via the flow and Ca++-dependent BK K+ channel expressed in the apical membrane of principal cells.
inhibiting Na+,K+-ATPase. Hence the flow of tubular fluid is augmented along the ASDN. Inhibition of water and NaCl reabsorption by the proximal tubule also decreases ECFV and thereby stimulates secretion of aldosterone. In addition, chronic acidosis caused by inorganic acids increases plasma [K+], which stimulates secretion of aldosterone. The rise in tubular fluid flow, plasma [K+], and aldosterone levels offsets the effects of acidosis on cell [K+] and apical membrane permeability, and K+ secretion rises. Thus metabolic acidosis may either inhibit or stimulate excretion of K+ , depending on the duration of the disturbance. As noted, acute metabolic alkalosis stimulates excretion of K+ . Chronic metabolic alkalosis, especially in association with ECFV contraction, significantly increases renal K+ excretion because of the associated increased levels of aldosterone.
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis • Fig. 36.10 Acute versus chronic effect of metabolic acidosis on excretion of K+. See text for details. ECV, effective circulating volume. ˛ Na+,K+-ATPase activity ˛ K+ permeability of apical membrane ˛ Apical membrane K+ gradient Metabolic acidosis Acute Chronic Distal tubule and collecting duct principal cells ˜ Na+,K+-ATPase activity ˜ K+ permeability of apical membrane ˜ K+ secretion ˜ K+ excretion Skeletal muscle cell Proximal tubule cell ˛ H+/K+ exchange ˜ NaCl and H2O reabsorption ˜ ECV ˛ Plasma [K+] ˛ Tubule fluid flow rate Distal tubule and collecting duct principal cells ˛ Aldosterone ˛ Aldosterone ˛ K+ secretion ˛ K+ excretion
Glucocorticoids increase urinary K+ excretion. This effect is mediated in part by an increase in GFR, which enhances the urinary flow rate, a potent stimulus of K+ excretion, and by stimulation of SGK1 activity (see earlier).
As discussed, the rate of urinary K+ excretion is frequently determined by simultaneous changes in hormone levels, acid-base balance, or the flow rate of tubule fluid ( 36.1 ). The powerful effect of flow often enhances or opposes the response of the ASDN to hormones and changes in acid-base balance. This interaction can be beneficial in the case of hyperkalemia, in which the increase in flow enhances excretion of K+ and thereby restores K+ homeostasis. However, this interaction can also be detrimental, as in the case of alkalosis, in which changes in flow and acid-base status alter K+ homeostasis.