Potassium, Calcium, and Phosphate Homeostasis

K ⁺ Homeostasis

Potassium (K ⁺ ) is the most abundant cation in the body. The vast majority of total body K ⁺ is located intracellularly (98%) where the [K ⁺ ] is 150 mEq/L. Only 2% of total body K ⁺ exists in the ECF at a concentration of approximately 4 mEq/L. The large [K ⁺ ] difference across cell membranes (≈146 mEq/L) is maintained by the Na ⁺ ,K ⁺ -ATPase. The [K ⁺ ] gradient is important in maintaining the potential difference across cell membranes and is critical for the excitability of nerve and muscle cells, as well as for the contractility of cardiac, skeletal, and smooth muscle cells ( Fig. 36.1 ). Skeletal muscles contain the largest single pool of K ⁺ in the body. In an adult, the skeletal muscles contain approximately 225 times more K+ than all extracellular compartments in the body. Moreover, due to the large number of Na ⁺ ,K ⁺ -ATPase pumps and K ⁺ channels, skeletal muscles possess a huge capacity for K ⁺ exchange. Despite wide fluctuations of the dietary K ⁺ load, [K ⁺ ] remains remarkably constant in the intracellular fluid (ICF) and extracellular fluid (ECF). A [K ⁺ ] in ECF that exceeds 5.0 mEq/L constitutes hyperkalemia. Conversely, a [K ⁺ ] in ECF of less than 3.5 mEq/L constitutes hypokalemia. During hypokalemia, skeletal muscle cells release K ⁺ to preserve [K ⁺ ] in the ECF leading to total body K ⁺ depletion.

IN THE CLINIC

Cardiac arrhythmias can result from hyperkalemia and hypokalemia. The electrocardiogram (ECG; Fig. 36.2 ) (also see Chapter 16 ) monitors the electrical activity of the heart and is a fast and reliable method to determine whether changes in plasma [K ⁺ ] influence the heart function. The first sign of hyperkalemia is the appearance of tall, thin T waves on the ECG. Further increases in plasma [K ⁺ ] prolong the PR interval, depress the ST segment, and lengthen the QRS interval of the ECG. As 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 of the ECG.

K ⁺ absorbed from 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):

Rapid (seconds to minutes) intracellular uptake of K ⁺ is essential to prevent life-threatening hyperkalemia. Excretion of K ⁺ by the kidneys is relatively slow (hours). Maintaining total body [K ⁺ ] constant requires that almost all the K ⁺ absorbed from the GI tract is eventually excreted by the kidneys. The colon is responsible for the remaining small fraction of K+ excretion, and in patients with end-stage kidney disease the colon may increase fecal K ⁺ excretion.

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 ; see Fig. 36.3 ) by stimulating Na ⁺ ,K ⁺ -ATPase and the Na ⁺ /K ⁺ /2Cl ⁻ and Na ⁺ /Cl ⁻ cotransporters in these cells. Acute stimulation of K ⁺ uptake (i.e., within minutes) is mediated by increased activity of existing Na ⁺ ,K ⁺ -ATPase and the Na ⁺ /K ⁺ /2Cl ⁻ and Na ⁺ /Cl ⁻ cotransporters, whereas a chronic increase in K ⁺ uptake (i.e., within hours to days) is mediated by increased abundance 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.

Alterations in Plasma [K ⁺ ]

Hyperkalemia usually develops when the amount of K ⁺ , either enteral (dietary or bleeding into the GI tract) or parenteral (intravenous administration or hemolysis), exceeds the ability of intracellular uptake and the kidneys to excrete K ⁺ (see Box 36.1 ). Hypokalemia usually develops when intracellular K ⁺ uptake and renal K ⁺ loss exceeds K ⁺ intake (dietary or intravenous) (see Box 36.1 ). In some situations (see later), changes in the distribution of K ⁺ between the ECF and ICF alone can result in acute and clinically relevant disturbances of plasma [K ⁺ ].