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Homeostatic mechanisms maintain plasma K+ concentration between 3.5 and 5.0 mM, despite marked variation in dietary K+ intake. In a healthy individual at steady state, the entire daily intake of potassium is excreted, ~90% in the urine and 10% in the stool; thus, the kidney plays a dominant role in potassium homeostasis. However, >98% of total-body potassium is intracellular, chiefly in muscle; buffering of extracellular K+ by this large intracellular pool plays a crucial role in the regulation of plasma K+ concentration. Changes in the exchange and distribution of intra- and extracellular K+ can thus lead to marked hypo- or hyperkalemia. A corollary is that massive necrosis and the attendant release of tissue K+ can cause severe hyperkalemia, particularly in the setting of acute kidney injury and reduced excretion of K+.
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Changes in whole-body K+ content are primarily mediated by the kidney, which reabsorbs filtered K+ in hypokalemic, K+-deficient states and secretes K+ in hyperkalemic, K+-replete states. Although K+ is transported along the entire nephron, it is the principal cells of the connecting segment (CNT) and cortical CD that play a dominant role in renal K+ secretion, whereas alpha-intercalated cells of the outer medullary CD function in renal tubular reabsorption of filtered K+ in K+-deficient states. In principal cells, apical Na+ entry via the amiloride-sensitive ENaC generates a lumen-negative potential difference, which drives passive K+ exit through apical K+ channels (Fig. 49-4). Two major K+ channels mediate distal tubular K+ secretion: the secretory K+ channel ROMK (renal outer medullary K+ channel; also known as Kir1.1 or KcnJ1) and the flow-sensitive “big potassium” (BK) or maxi-K K+ channel. ROMK is thought to mediate the bulk of constitutive K+ secretion, whereas increases in distal flow rate and/or genetic absence of ROMK activate K+ secretion via the BK channel.
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