Regulation of Potassium Balance

Overview of K ⁺ Homeostasis

Total body K ⁺ is 50 mEq/kg of body weight, or 3500 mEq for a person weighing 70 kg. A total of 98% of the K ⁺ in the body is located within cells, where its average [K ⁺ ] is 150 mEq/L. A high intracellular [K ⁺ ] is required for many cell functions, including cell growth and division and volume regulation. Only 2% of total body K ⁺ is in the ECF, where its normal concentration is approximately 4 mEq/L. [K ⁺ ] in the ECF that exceeds ∼5.0 mEq/L constitutes hyperkalemia . Conversely, [K ⁺ ] in the ECF of less than ∼3.5 mEq/L constitutes hypokalemia .

In the Clinic

Hypokalemia is one of the most common electrolyte disorders in clinical practice and can be observed in as many as 20% of hospitalized patients. The most common causes of hypokalemia include administration of diuretic drugs (see Chapter 10 ), surreptitious vomiting (i.e., bulimia), and severe diarrhea. Gitelman syndrome (a genetic defect in the Na ⁺ -Cl ^– symporter in the apical membrane of distal tubule cells) also causes hypokalemia (see Chapter 4 , Table 4.3 ). Hyperkalemia also is a common electrolyte disorder and is seen in 1%–10% of hospitalized patients. Hyperkalemia often is seen in patients with renal failure, in persons taking drugs such as angiotensin-converting enzyme inhibitors and K ⁺ -sparing diuretics (see Chapter 10 ), in persons with hyperglycemia (i.e., high blood sugar), and in the elderly. Pseudohyperkalemia , a falsely high plasma [K ⁺ ], is caused by traumatic lysis of red blood cells while blood is being drawn. Red blood cells, like all cells, contain K ⁺ , and lysis of red blood cells releases K ⁺ into the plasma, artificially elevating the plasma [K ⁺ ].

The large concentration difference of K ⁺ across cell membranes (approximately 146 mEq/L) is maintained by the Na ⁺ -K ⁺ -adenosine triphosphatase (ATPase). This K ⁺ gradient is important in maintaining the potential difference across cell membranes. Thus K ⁺ is critical for the excitability of nerve and muscle cells and for the contractility of cardiac, skeletal, and smooth muscle cells ( Fig. 7.1 ).

In the Clinic

Cardiac arrhythmias are produced by both hypokalemia and hyperkalemia. The electrocardiogram (ECG; Fig. 7.2 ) monitors the electrical activity of the heart and is a quick and easy way to determine whether changes in plasma [K ⁺ ] influence the heart and other excitable cells. In contrast, measurements of the plasma [K ⁺ ] by the clinical laboratory require a blood sample, and values often are not immediately available. The first sign of hyperkalemia is the appearance of tall, thin T waves on the ECG. Further increases in the plasma [K ⁺ ] prolong the PR interval, depress the ST segment, and lengthen the QRS interval on the ECG. Finally, as the plasma [K ⁺ ] approaches 10 mEq/L, the P wave disappears, the QRS interval broadens, the ECG appears as a sine wave, and the ventricles fibrillate (i.e., manifest rapid, uncoordinated contractions of muscle fibers). Hypokalemia prolongs the QT interval, inverts the T wave, and lowers the ST segment on the ECG.

After a meal, the K ⁺ absorbed by the gastrointestinal tract enters the ECF within minutes ( Fig. 7.3 ). If the K ⁺ ingested during a normal meal (≈33 mEq) were to remain in the ECF compartment (14 L), the plasma [K ⁺ ] would increase by 2.4 mEq/L (33 mEq added to 14 L of ECF):

This rise in the plasma [K ⁺ ], which could have deleterious effects on the electrical activity of the heart and other excitable tissues, is prevented by the rapid uptake (within minutes) of K ⁺ into cells. Because the excretion of K ⁺ by the kidneys after a meal is relatively slow (within hours), the uptake of K ⁺ by cells is essential to prevent life-threatening hyperkalemia. Maintaining total body K ⁺ constant requires all the K ⁺ absorbed by the gastrointestinal tract to eventually be excreted by the kidneys. This process requires about 6 hours.

Regulation of Plasma [K ⁺ ]

Several hormones, including epinephrine , insulin , and aldosterone , increase K ⁺ uptake into skeletal muscle, liver, bone, and red blood cells by stimulating Na ⁺ -K ⁺ -ATPase, the Na ⁺ -K ⁺ -2Cl ^– symporter, and the Na ⁺ -Cl ^– symporter in these cells ( Box 7.1 ; see Fig. 7.3 ). Acute stimulation of K ⁺ uptake (i.e., within minutes) is mediated by an increase in the activity of existing Na ⁺ -K ⁺ -ATPase, Na ⁺ -K ⁺ -2Cl ^– , and Na ⁺ -Cl ^– transporters, whereas the chronic increase in K ⁺ uptake (i.e., within hours to days) is mediated by an increase in the quantity of Na ⁺ -K ⁺ -ATPase. A rise in the plasma [K ⁺ ] that follows K ⁺ absorption by the gastrointestinal tract stimulates insulin secretion from the pancreas, aldosterone release from the adrenal cortex, and epinephrine secretion from the adrenal medulla. In contrast, a decrease in the plasma [K ⁺ ] inhibits the release of these hormones. Whereas insulin and epinephrine act within a few minutes, aldosterone requires about 1 hour to stimulate K ⁺ uptake into cells.