The distribution of K+ across cell membranes is influenced by the osmolality of plasma. When the osmolality of ECF increases, cells release more K+ into the extracellular space, leading to an increase in plasma [K+]. A 10 mOsm/kg H2O elevation in plasma osmolality can cause plasma [K+] to increase by 0.4 to 0.8 mEq/L. In patients with diabetes mellitus who do not take insulin, plasma [K+] is often elevated due to the lack of insulin and the increase in plasma [glucose], which raises plasma osmolality. Conversely, hypoosmolality has the opposite effect on plasma [K+]. These changes in osmolality-related plasma [K+] are linked to alterations in cell volume. As plasma osmolality increases, water leaves cells, causing cells to shrink and intracellular [K+] to rise. The rise in intracellular [K+] drives K+ to exit cells, leading to an increase in plasma [K+]. A decrease in plasma osmolality has the opposite effect. Hyperkalemia can occur due to cell lysis, which releases intracellular K+ into the ECF. Conditions such as severe trauma, tumor lysis syndrome, rhabdomyolysis, and gastric ulcers can cause cell destruction and subsequent release of K+ into the ECF, leading to hyperkalemia. Exercise also increases K+ release from skeletal muscle cells, with the degree of exercise determining the extent of hyperkalemia. The kidneys play a major role in K+ balance by excreting 90% to 95% of ingested dietary K+. Despite variations in dietary intake, urinary excretion remains balanced with intake. While small amounts of K+ are lost through feces and sweat, the kidneys' excretion of K+ is more significant. K+ secretion from blood into tubular fluid by cells in the distal tubule and collecting duct system is the primary determinant of urinary K+ excretion.
The osmolality of plasma also influences the distribution of K+ across cell membranes. An increase in the osmolality of ECF enhances the release of K+ by cells and thus increases extracellular [K+]. Plasma [K+] may increase by 0.4 to 0.8 mEq/L with a 10 mOsm/kg H2O elevation in plasma osmolality. In patients with diabetes mellitus who do not take insulin, plasma [K+] is often elevated, in part because of the lack of insulin and in part because of the increase in plasma [glucose] (i.e., from a normal value of ≈ 100 mg/ dL to as high as ≈ 1200 mg/dL in some cases), which increases plasma osmolality. Hypoosmolality has the opposite action. The alterations in plasma [K+] associated with changes in osmolality are related to changes in cell volume. For example, as plasma osmolality increases, water leaves cells because of the osmotic gradient across the plasma membrane (see
Chapter 1).
Water leaves cells until the intracellular osmolality equals that of ECF. This loss of water shrinks cells and causes [K+] in cells to rise. The rise in intracellular [K+] provides a driving force for the exit of K+ from cells. This sequence increases plasma [K+]. A fall in plasma osmolality has the opposite effect.
Cell lysis causes hyperkalemia as a result of addition of intracellular K+ to ECF. Severe trauma (e.g., burns) and some conditions such as tumor lysis syndrome (i.e., chemotherapy-induced destruction of tumor cells) and rhabdomyolysis (i.e., destruction of skeletal muscle) destroy cells and release K+ and other cell solutes into ECF. In addition, gastric ulcers may cause seepage of red blood cells into the GI tract. The blood cells are digested, and the K+ released from the cells is absorbed and can cause hyperkalemia.
More K+ is released from skeletal muscle cells during exercise than during rest. The ensuing hyperkalemia depends on the degree of exercise. In people walking slowly, plasma [K+] increases by 0.3 mEq/L. With vigorous exercise, plasma [K+] may increase by 2.0 or more mEq/L.
K+ Excretion by the Kidneys
The kidneys play a major role in maintaining K+ balance. As illustrated in
Fig. 36.3 the kidneys excrete 90% to 95% of the K+ ingested in the diet. Excretion equals intake even when intake increases by as much as 10-fold. This balance in urinary excretion and dietary intake underscores the importance of the kidneys in maintaining K+ homeostasis. Although small amounts of K+ are lost each day in feces and sweat (≈5%–10% of the K+ ingested in the diet), except during severe diarrhea this amount is essentially constant, is not regulated, and therefore is relatively less important than the K+ excreted by the kidneys. K+ secretion from blood into tubular fluid by cells of the distal tubule and collecting duct system is the key factor in determining urinary K+ excretion (
Fig. 36.4