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.