An increase in plasma insulin, epinephrine, or aldosterone prompts the movement of K+ into cells and reduces plasma [K+]. Conversely, a decrease in plasma levels of these hormones has the opposite effect, increasing plasma [K+]. The kidneys regulate the amount of K+ in the body. K+ balance is achieved when dietary intake and urinary output (plus output by the GI tract) are equal. Excretion of K+ by the kidneys is controlled by plasma [K+], aldosterone, and AVP. Aldosterone, similar to catecholamines and insulin, facilitates the uptake of K+ into cells. An elevation in aldosterone levels causes hypokalemia, while a decline in aldosterone levels leads to hyperkalemia. Aldosterone also stimulates urinary K+ excretion, thus influencing plasma [K+]. Factors like metabolic acidosis, metabolic alkalosis, respiratory alkalosis, and respiratory acidosis affect the movement of K+ between intracellular fluid (ICF) and extracellular fluid (ECF), resulting in the development of hypokalemia or hyperkalemia. Metabolic acidosis increases plasma [K+], while metabolic alkalosis decreases it. Respiratory alkalosis causes hypokalemia, but respiratory acidosis has minimal impact on plasma [K+]. Inorganic acids contribute more to an increase in plasma [K+] compared to organic acids. Acidosis inhibits transporters that accumulate K+ inside cells, while also promoting movement of H+ into cells. The reciprocal movement of H+ and K+ across cell membranes maintains electroneutrality. Metabolic alkalosis has the opposite effect, with plasma [K+] decreasing as K+ moves into cells and H+ exits. Organic acids, although causing metabolic acidosis, do not significantly contribute to hyperkalemia. The reduced ability of organic acids to cause hyperkalemia may be attributed to their entry into cells with H+ or their stimulation of insulin secretion, which promotes movement of K+ into cells and counteracts the direct effect of acidosis.
• Fig. 36.3 Overview of K+homeostasis. An increase in plasma insulin, epinephrine, or aldosterone stimulates movement of K+into cells and decreases plasma [K+], whereas a fall in plasma concentration of these hormones has the opposite effect and increases plasma [K+]. The amount of K+in the body is determined by the kidneys. An individual is in K+balance when dietary intake and urinary output (plus output by the GI tract) are equal. Excretion of K+by the kidneys is regulated by plasma [K+], aldosterone, and AVP. Diet 100 mEq of K+/day Feces 5–10 mEq of K+/day Urine 90–95 mEq of K+/day Intestinal absorption 90 mEq of K+/day Extracellular fluid 65 mEq of K+ Tissue stores 3435 mEq of K+ Insulin Epinephrine Aldosterone Plasma [K+] AVP Aldosterone
Aldosterone, like catecholamines and insulin, also promotes uptake of K+ into cells. A rise in aldosterone levels (e.g., primary aldosteronism) causes hypokalemia, whereas a fall in aldosterone levels (e.g., Addison’s disease) causes hyperkalemia. As discussed later and as illustrated in
Fig.
36.3 , aldosterone also stimulates urinary K+ excretion. Thus aldosterone alters plasma [K+] by acting on uptake of K+ into cells and altering urinary K+ excretion.
Box 36.1 ). These factors are not involved in regulation of plasma [K+] but rather alter the movement of K+ between the intracellular fluid (ICF) and ECF and thus cause development of hypokalemia or hyperkalemia.
Metabolic acidosis increases plasma [K+], whereas metabolic alkalosis decreases it. Respiratory alkalosis causes hypokalemia. In contrast, respiratory acidosis has little or no effect on plasma [K+]. Metabolic acidosis produced by addition of inorganic acids (e.g., HCl, H2SO4) increases plasma [K+] much more than an equivalent acidosis produced by accumulation of organic acids (e.g., lactic acid, acetic acid, ketoacids). The reduced pH (i.e., increased [H+]) promotes movement of H+ into cells and the reciprocal movement of K+ out of cells to maintain electroneutrality. This effect of acidosis occurs in part because acidosis inhibits the transporters that accumulate K+ inside cells, including Na+,K+-ATPase and the 1Na+/1K+/2Cl− symporter. In addition, movement of H+ into cells occurs as the cells buffer changes in [H+] of the ECF (see
Chapter 37).
As H+ moves across cell membranes, K+ moves in the opposite direction, and thus cations are neither gained nor lost across cell membranes. Metabolic alkalosis has the opposite effect; plasma [K+] decreases as K+ moves into cells and H+ exits.
Although organic acids produce a metabolic acidosis, they do not cause significant hyperkalemia. Two explanations have been suggested for the reduced ability of organic acids to cause hyperkalemia. First, the organic anion may enter the cell with H+ and thereby eliminate the need for K+-H+ exchange across the membrane. Second, organic anions may stimulate insulin secretion, which moves K+ into cells. This movement may counteract the direct effect of the acidosis, which moves K+ out of cells.