Hypokalemia (e.g., caused by a low-K+ diet or loss of K+ in diarrhea fluid) decreases K+ secretion via actions opposite those described for hyperkalemia. Hence hypokalemia inhibits Na+,K+-ATPase, decreases the electrochemical driving force for efflux of K+ across the apical membrane, reduces permeability of the apical membrane to K+ , and decreases plasma aldosterone levels.
Chronic hypokalemia (plasma [K+] < 3.5 mEq/L) occurs most often in patients who receive diuretics for hypertension. Hypokalemia also occurs in patients who vomit, undergo nasogastric suction, have diarrhea, abuse laxatives, or have hyperaldosteronism. Hypokalemia occurs because excretion of K+ by the kidneys exceeds dietary intake of K+ . Vomiting, nasogastric suction, diuretics, and diarrhea can all decrease ECF volume (ECFV), which in turn stimulates secretion of aldosterone (see ). Because aldosterone stimulates excretion of K+ by the kidneys, its action contributes to development of hypokalemia.
Chronic hyperkalemia (plasma [K+] > 5.0 mEq/L) occurs most frequently in individuals with reduced urine flow, low plasma aldosterone levels, and renal disease in which the glomerular filtration rate (GFR) falls below 20% of normal. In these individuals, hyperkalemia occurs because excretion of K+ by the kidneys is less than dietary intake of K+ . Less common causes of hyperkalemia occur in people with deficiencies in insulin, epinephrine, and aldosterone secretion or in people with metabolic acidosis caused by inorganic acids.
Chronically elevated (i.e., ≥24 hours) plasma aldosterone levels enhance secretion of K+ across principal cells in the late segment of the distal tubule and collecting duct (i.e., aldosterone-sensitive distal nephron [ASDN]) via five mechanisms (Fig. 36.7 ): (1) by increasing the amount of Na+,K+-ATPase in the basolateral membrane; (2) by increasing expression of the epithelial sodium channel (ENaC) in the apical cell membrane; (3) by elevating SGK1 (serum glucocorticoid-stimulated kinase) levels, which also increases expression of ENaC in the apical membrane and activates K+ channels; (4) by stimulating CAP1 (channelactivating protease, also called prostatin), which directly activates ENaC; and (5) by stimulating the permeability of the apical membrane to K+ . Aldosterone increases the permeability of the apical membrane to K+ by increasing the number of K+ channels in the membrane. However, the cellular mechanisms involved in this response are not completely known. Increased expression of Na+,K+-ATPase facilitates uptake of K+ across the basolateral membrane into cells and thereby elevates intracellular [K+]. The increase in the number and activity of Na+ channels enhances entry of Na+ into the cell from tubular fluid, an effect that depolarizes the apical membrane voltage. Depolarization of the apical membrane and increased intracellular [K+] enhance the electrochemical driving force for secretion of K+ from the cell into the tubule fluid. Taken together, these actions increase uptake of K+ into the cell across the basolateral membrane and enhance exit of K+ from the cell across the apical membrane. Secretion of aldosterone is increased by hyperkalemia and by angiotensin II (after activation of the renin-angiotensin system). Secretion of aldosterone is decreased by hypokalemia and natriuretic peptides released from the heart.
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis