After a meal, potassium (K+) that is absorbed by the gastrointestinal (GI) tract quickly enters the extracellular fluid (ECF) within minutes. If the K+ from a normal meal were to stay in the ECF compartment, the plasma concentration of K+ would increase by 2.4 mEq/L. However, to prevent dangerous hyperkalemia, it is essential for cells to take up the absorbed K+. The process of excreting all the K+ absorbed by the GI tract through the kidneys takes about 6 hours.

The regulation of plasma K+ levels involves several hormones, such as epinephrine, insulin, and aldosterone. These hormones increase the uptake of K+ into various cells, including skeletal muscle, liver, bone, and red blood cells. They achieve this by stimulating specific transporters and enzymes in these cells. Acute stimulation of K+ uptake occurs within minutes and is mediated by increased activity of existing transporters, while chronic stimulation happens within hours to days and involves an increase in the quantity of transporters. The rise in plasma K+ concentration following K+ absorption triggers the release of insulin, aldosterone, and epinephrine, whereas a decrease in plasma K+ inhibits their release. Insulin and epinephrine act quickly, while aldosterone takes about an hour to stimulate K+ uptake into cells.

Catecholamines, such as epinephrine, influence the distribution of K+ across cell membranes by activating specific receptors. Stimulation of α-adrenoceptors releases K+ from cells, particularly in the liver, while stimulation of β2-adrenoceptors promotes K+ uptake by cells. For instance, β2-adrenoceptor activation after exercise plays a role in preventing hyperkalemia. The plasma K+ increase after a meal rich in K+ is higher in individuals pretreated with propranolol, a β-adrenoceptor antagonist. Moreover, the release of epinephrine during stress can rapidly decrease plasma K+ levels.

Insulin also stimulates the uptake of K+ into cells. The significance of insulin is demonstrated by two observations: first, the rise in plasma K+ after a K+-rich meal is greater in patients with diabetes mellitus due to insulin deficiency, and second, insulin (along with glucose to prevent hypoglycemia) can be administered intravenously to correct hyperkalemia. Insulin is the most crucial hormone involved in shifting K+ into cells following K+ ingestion. In patients with chronic kidney disease, although insulin-stimulated glucose uptake into cells is impaired, insulin stimulation of K+ uptake into cells remains normal.
After a meal the K+ absorbed by the gastrointestinal (GI) tract enters the ECF within minutes (Fig. 36.3 ). If the K+ ingested during a normal meal (≈33 mEq) were to remain in the ECF compartment (14 L), plasma [K+] would increase by 2.4 mEq/L (33 mEq added to 14 L of ECF):
Equation 36.1 14L = 2 4. mEq after a meal is relatively slow (hours), uptake of K+ by cells is essential to prevent life-threatening hyperkalemia. Maintaining total body [K+] constant requires that all the K+ absorbed by the GI tract eventually be excreted by the kidneys. This process requires about 6 hours.
Regulation of Plasma [K+]
Several hormones, including epinephrine, insulin, and aldosterone, increase uptake of K+ into skeletal muscle, liver, bone, and red blood cells (Box 36.1
Fig. 36.3 ) by stimulating Na+,K+-ATPase, the 1Na+/1K+/2Cl− symporter, and the Na+/Cl− symporter in these cells. Acute stimulation of K+ uptake (i.e., within minutes) is mediated by increased activity of existing Na+,K+-ATPase, 1Na+/1K+/2Cl− , and Na+/Cl− transporters, whereas a chronic increase in K+ uptake (i.e., within hours to days) is mediated by an increase in the quantity of Na+,K+-ATPase. The rise in plasma [K+] that follows K+ absorption by the GI tract stimulates secretion of insulin from the pancreas, release of aldosterone from the adrenal cortex, and secretion of epinephrine from the adrenal medulla (see
Fig. 36.3 ). In contrast, a decrease in plasma [K+] inhibits release of these hormones. Whereas insulin and epinephrine act within a few minutes, aldosterone requires about an hour to stimulate uptake of K+ into cells.
• BOX 36.1 Major Factors, Hormones, and Drugs Influencing Distribution of K+Between Intracellular and Extracellular Fluid Compartments
Physiological: Keep Plasma [K+] Constant
Pathophysiological: Displace Plasma [K+] From Normal
CHAPTER 36 Potassium, Calcium, and Phosphate Homeostasis
Catecholamines affect the distribution of K+ across cell membranes by activating α-and β2-adrenergic receptors. Stimulation of α-adrenoceptors releases K+ from cells, especially in the liver, whereas stimulation of β2-adrenoceptors promotes K+ uptake by cells.
For example, activation of β2-adrenoceptors after exercise is important in preventing hyperkalemia. The rise in plasma [K+] after a K+-rich meal is greater if the patient has been pretreated with propranolol, a β-adrenoceptor antagonist. Furthermore, release of epinephrine during stress (e.g., myocardial ischemia) can rapidly lower plasma [K+].
Insulin also stimulates uptake of K+ into cells. The importance of insulin is illustrated by two observations. First, the rise in plasma [K+] after a K+-rich meal is greater in patients with diabetes mellitus (i.e., insulin deficiency) than in healthy people. Second, insulin (and glucose to prevent insulin-induced hypoglycemia) can be infused to correct hyperkalemia. Insulin is the most important hormone that shifts K+ into cells after ingestion of K+ in a meal. In patients with chronic kidney disease, although insulin-stimulated glucose uptake into cells is impaired, insulin stimulation of K+ uptake into cells is normal.