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before the distal nephron determines how much is sent on from the thick ascending limb, ie, delivered to the distal nephron Changes in upstream handling of sodium include changes in filtered load and reabsorption in prior segments Sodium delivery influences potassium secretion because more sodium delivered means more sodium taken up by principal cells; therefore, more sodium pumped out by the Na-K-ATPase, in turn causing more potassium to be pumped in The increased potassium can just recycle back to the interstitium, but the usual result is more potassium secretion (4) Distal nephron flow rate The role of flow rate in regulating potassium secretion is a story by itself Increased flow is detected by mechanosensitive elements of the principal cells This includes bending of the central cilium that protrudes from the apical surface into the tubule lumen.



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Bending of the central cilium initiates intracellular release of calcium and activation of BK channels Under most conditions, increased delivery of sodium is the chief cause of increased flow, because sodium is accompanied by water Thus increased delivery of sodium implies increased flow Increased flow has another effect By sweeping away potassium that reaches the tubule by secretion, luminal potassium concentration is kept low enough to preserve a favorable concentration gradient for secretion6 (5) Concentration of nonchloride anions In order for principal cells to secrete potassium there must be a route (channels) and a driving force (electrochemical gradient).





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Under conditions where the reabsorption of sodium is restricted because some of the luminal chloride has been replaced with anions that are not usually in high concentration and cannot accompany the sodium (because their permeability is less than that of chloride), one effect is a depolarization of the luminal membrane (usually described as increasing luminal negativity) This increases the driving force for potassium secretion We will discuss this further in the section on perturbations of potassium excretion (6) Dietary potassium The influence of dietary potassium on renal function is the most obvious regulator of potassium excretion, yet the least understood A major task of the kidneys is to maintain potassium balance by increasing and decreasing potassium excretion in parallel with dietary load The healthy kidneys do this very well.

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The problem is in understanding the signaling how do the kidneys know how much potassium a person has consumed Although large potassium loads can raise plasma potassium somewhat, the changes in excretion associated with diet do not seem to be accounted for on the basis of either changes in plasma potassium or the other identified factors However, the previously mentioned gastrointestinal signals influence not only the cellular uptake of potassium absorbed from the GI tract, but also renal handling of potassium, and seem to be one of the links between dietary load and excretion One of the manifestations of changing dietary loads is to regulate the distribution of ROMK channels between the luminal membrane and intracellular storage, ie, high-potassium diets lead to insertion of luminal channels and therefore higher potassium secretion In contrast, during periods of prolonged.

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