The left panel of Fig. 36.4 shows that the kidneys cannot decrease the excretion of K+ to the same extent as they can for Na+ (i.e., 0.2%). Consequently, individuals on a K+-deficient diet can develop hypokalemia. The overall rate of urinary K+ excretion is determined by the variable magnitude and direction of K+ transport by the distal tubule and collecting duct.

Fig. 36.5A depicts the cellular mechanisms of K+ secretion by principal cells in the late segment of the distal tubule and collecting duct. Fig. 36.5B shows the cellular mechanism of K+ secretion by α-intercalated cells in the same tubular segment. α-intercalated cells have low levels of Na+,K+-ATPase in the basolateral membrane. Depletion of K+ stimulates the H+,K+-ATPase (HKA) in α-intercalated cells, increasing K+ reabsorption.

In individuals with advanced renal disease, the kidneys cannot eliminate ingested K+, leading to elevated plasma [K+]. Hyperkalemia resulting from this impairs the resting membrane potential by making the voltage less negative. This decrease in potential reduces the excitability of neurons, cardiac cells, and muscle cells by inactivating fast Na+ channels, which are crucial for the depolarization phase of the action potential (see Fig. 36.1). Sudden and severe increases in plasma [K+] can cause cardiac arrest and death.

In contrast, hypertensive patients taking diuretic drugs often excrete more urinary K+ than their dietary intake. This negative K+ balance leads to hypokalemia. The decline in extracellular [K+] hyperpolarizes the resting cell membrane, making the voltage more negative. This reduces the excitability of neurons, cardiac cells, and muscle cells. Severe hypokalemia can result in paralysis, cardiac arrhythmias, and death. Additionally, hypokalemia can impair the kidneys' ability to concentrate urine and stimulate renal production of NH4+, affecting acid-base balance.

Maintaining high intracellular [K+], low extracellular [K+], and a high [K+] gradient across cell membranes is essential for various cellular functions.

CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis discusses the secretion of K+ from blood into the tubule lumen by principal cells and α-intercalated cells in the late segment of the distal tubule and the collecting duct. This secretion involves the uptake of K+ from blood through the basolateral membrane by Na+,K+-ATPase and the diffusion of K+ from the cell into tubular fluid via K+ channels (ROMK and BK). A K+/Cl− symporter (KCC1) in the apical plasma membrane also secretes K+. Na+,K+-ATPase establishes a high intracellular [K+] that drives the exit of K+ across the apical membrane through K+ channels. Although K+ channels are present in the basolateral membrane as well, K+ mainly exits the cell through the apical membrane and enters the tubular fluid. This occurs because the electrochemical gradient of K+ across the apical membrane favors its movement into the tubular fluid, and the permeability of the apical membrane to K+ is higher than that of the basolateral membrane. K+ secretion through the apical membrane via the K+/Cl− symporter is driven by the concentration gradient of K+ between the cell and tubular fluid. The three main factors controlling the rate of K+ secretion by the late segment of the distal tubule and the collecting duct are: 1. the activity of Na+,K+-ATPase, 2. the concentration gradient of K+ between the cell and tubular fluid, and 3. the permeability of the apical membrane to K+.
Fig. 36.4 , left panel). The kidneys cannot reduce K+ excretion to the same low levels as they can for Na+ (i.e., 0.2%). Therefore hypokalemia can develop in individuals placed on a K+-deficient diet. Because the magnitude and direction of K+ transport by the distal tubule and collecting duct are variable, the overall rate of urinary K+ excretion is determined by these tubular segments.
Cellular Mechanism of K+ Secretion by Principal Cells and Intercalated Cells
Fig. 36.5A illustrates the cellular mechanisms of K+ secretion by principal cells in the late segment of the distal • Fig. 36.5 Cellular mechanism of K+ secretion by principal cells (A) and α-intercalated cells (B) in the late segment of the distal tubule and collecting duct. α-Intercalated cells contain very low levels of Na+,K+-ATPase in the basolateral membrane (not shown). K+ depletion increases K+ reabsorption by α-intercalated cells by stimulating the H+,K+-ATPase (HKA).
In individuals with advanced renal disease, the kidneys are unable to eliminate ingested K+ from the body. Therefore plasma [K+] rises. The resulting hyperkalemia reduces the resting membrane potential (i.e., the voltage becomes less negative), and this reduced potential decreases the excitability of neurons, cardiac cells, and muscle cells by inactivating fast Na+ channels, which are critical for the depolarization phase of the action potential (see
Fig. 36.1 ). Severe rapid increases in plasma [K+] can lead to cardiac arrest and death. In contrast, in patients taking diuretic drugs for hypertension, urinary K+ excretion often exceeds dietary K+ intake. Accordingly K+ balance is negative and hypokalemia develops. This decline in extracellular [K+] hyperpolarizes the resting cell membrane (i.e., the voltage becomes more negative) and reduces the excitability of neurons, cardiac cells, and muscle cells. Severe hypokalemia can lead to paralysis, cardiac arrhythmias, and death. Hypokalemia can also impair the ability of the kidneys to concentrate urine and can stimulate renal production of NH4 + , which affects acid-base balance (see ). Therefore maintenance of high intracellular [K+], low extracellular [K+], and a high [K+] gradient across cell membranes is essential for a number of cellular functions.
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis tubule and the collecting duct. Secretion from blood into the tubule lumen is a two-step process: (1) uptake of K+ from blood across the basolateral membrane by Na+,K+-ATPase and (2) diffusion of K+ from the cell into tubular fluid via K+ channels (ROMK and BK). A K+/ Cl− symporter (KCC1) in the apical plasma membrane also secretes K+ . Na+,K+-ATPase creates a high intracellular [K+] that provides the chemical driving force for exit of K+ across the apical membrane through K+ channels. Although K+ channels are also present in the basolateral membrane, K+ preferentially leaves the cell across the apical membrane and enters the tubular fluid. K+ transport follows this route for two reasons. First, the electrochemical gradient of K+ across the apical membrane favors its downhill movement into tubular fluid. Second, the permeability of the apical membrane to K+ is greater than that of the basolateral membrane. Therefore K+ preferentially diffuses across the apical membrane into tubular fluid. K+ secretion across the apical membrane via the K+/Cl− symporter is driven by the favorable concentration gradient of K+ between the cell and tubular fluid. The three major factors that control the rate of K+ secretion by the late segment of the distal tubule and the collecting duct are: 1.
the activity of Na+,K+-ATPase 2.