Potassium secretion

The kidney contains the major site of renin synthesis, the juxtaglomerular cells in the wall of the afferent arteriole. From these cells, renin is secreted not only into the circulation but also into the renal interstitium. Moreover, the enzyme is produced albeit in low amounts by proximal tubular cells. These cells also synthesize angiotensinogen and ACE. The RAS proteins interact in the renal interstitium and in the proximal tubular lumen to synthesize angiotensin II. In the proximal tubule, angiotensin II activates the sodium/hydrogen exchanger (NHE) that increases sodium reabsorption. Aldosterone elicits the same effect in the distal tubule by activating epithelial sodium channels (ENaC) and the sodium-potassium-ATPase. Thereby, it also induces water reabsotption and potassium secretion. 

As nephron mass decreases, both the distal tubular secretion and GI excretion are increased because of aldosterone stimulation. Functioning nephrons increase FEK up to 100% and GI excretion increases as much as 30% to 70% in CKD,30 as a result of aldosterone secretion in response to increased potassium levels.30 This maintains serum potassium concentrations within the normal range through stages 1 to 4 CKD. Hyperkalemia begins to develop when GFR falls below 20% of normal, when nephron mass and renal potassium secretion is so low that the capacity of the GI tract to excrete potassium has been exceeded.30... 

Potassium secretion is enhanced by aldosterone. As the concentration of K+ ions in the extracellular fluid increases, the secretion of aldosterone from the adrenal cortex also increases. The mechanism of action of aldosterone involves an increase in the activity of the Na+, K+ pump in the basolateral membrane. Furthermore, aldosterone enhances formation of K+ channels in the luminal membrane. 

Hydrocortisone exhibits anti-shock, anti-allergy, and anti-inflammatory action. It raises sugar content in the blood, increases potassium secretion, and lowers sodium excretion from the body. It exhibits anti-metaboUc action and reduces histamine synthesis in the body. 

To maintain electroneutrality during potassium secretion, the ion transport mechanism involves co-transport of K and Cl , as shown in Step 4, Details of the... 

The pathway of potassium secretion by the principal cell is diagrammed in Figure 10.14). The pumps and channels are those involved in sodium resorption... 

Wright, F S., Slriedner, N., Fowler, N. B-, and Giebisch, G. (1971). Potassium secretion by distal tubule after potassium adaptation. Anr. J. Pfrysrol. 221,437-446. 

Mild and uncomplicated hyperkalemia is commonly observed in patients taking ciclosporin and is generally prevented by a low potassium diet. A reduction in distal nephron potassium secretion and tubular flow rate, with insensitivity to exogenous mineralocorticoids, and leakage of cellular potassium into the extracellular fluid are possible mechanisms (SED-13, 1124) (64). 

With the widespread use of lithium in the treatment of affective disorders, many questions have centered on its long-term effect on the kidneys. Of particular interest is the action of lithium at distal nephron sites where it inhibits water transport, hydrogen secretion, and possibly potassium secretion as well [10,11]. The most common side effect of chronic lithium therapy is an impairment of renal concentrating abihty [11]. Lithium therapy is also associated with side effects... 

The inhibitory effect of lithium on distal potassium secretion is likely to occur in the cortical collecting tubule where it decreases Na uptake and the transepi-thelial voltage (lumen-negative) that normally favors potassium secretion. 

Bhandari S, Hunter M. Inward rectifier renal potassium channel (ROMK), the low-conductance channels for potassium secretion. Nephrol Dial Transplant 1998 13 3019-23. 

The kidney is the primary route of potassium elimination. Potassium is freely filtered with almost all of it being reabsorbed passively in the proximal tubule and the thick ascending limb of the loop of Henle. Therefore urinary potassium excretion is primarily determined by potassium secretion from the luminal cells of the distal tubule and collecting duct. The normal daily amount of potassium excreted in the urine is generally 40 to 90 mEq/L, but it can vary based on dietary intake, serum potassium concentration, and aldosterone activity. 

Aldosterone is a mineralocorticoid that is secreted from the adrenal glands in response to high serum potassium concentrations. Aldosterone promotes potassium excretion through the kidneys. Aldosterone works at the distal tubule and collecting duct to promote the reabsorption of sodium and water in exchange for potassium. The net result is potassium secretion into the urine. Aldosterone may also have extrarenal activity by stimulating cellular Na -K -ATPase pump activity. ... 

Tubular Unresponsiveness to Aldosterone Certain medical conditions, such as sickle cell anemia, systemic lupus erythematosus, and amyloidosis, can produce a defect in tubular potassium secretion, possibly as the result of an alteration in the aldosterone-binding site. The exact mechanism of the tubular unresponsiveness is unknown. 

Hyperkalemic distal (type IV) RTA resulting from generalized distal tubule defects is less common than hyporeninemic hypoaldosteronism, but is more common than classic distal (type I) RTA. Patients with this defect have impaired tubular potassium secretion in addition to impaired urinary acidification (urine pH >5.5 despite acidemia or acid loading). Urinary obstruction is the most frequent cause of this disorder, which may also be associated with sickle-cell nephropathy, systemic lupus erythematosus, HIV nephropathy, analgesic abuse nephropathy, amyloidosis, renal transplant rejection, and chronic cyclosporine nephrotoxicity. 

The metabolic acidosis associated with hyperkalemic distal (type IV) RTA with hyporeninemic-hypoaldosteronemia that is often seen in patients with diabetes meUitus may be corrected by the treatment of hyperkalemia alone (see Chap. 50). The use of supplemental alkali (1 to 2 mEq/kg per day) to increase sodium intake and stimulate distal tubular potassium secretion may be beneficial. A minority of patients require the administration of pharmacologic amounts of fludrocortisone." Type TV RTA resulting from a generalized distal tubular disorder often responds to low doses of alkali (1.5 to 2.0 mEq/kg per day). ° Corrections of the acidosis along with modest dietary potassium restriction (to 1 mEq/kg per day) wfll often result in the maintenance of serum potassium levels of 5 mEq/L or less. 

Posttraumatic secretion of aldosterone has also been measured. Increased quantities were found to be present during surgery, and in the urine subsequently (D3, HI 7, Zl). Also, the aldosterone antagonist spironolactone will abolish postoperative sodium retention without affecting potassium secretion, illustrating the dependence of sodium displacements after surgery on the hormone (J2, M8). 

Potassium depletion has been reported in hyperparathyroidism (B9). This would be expected if there was impaired hydrogen ion secretion into the renal tubule such impairment may be associated with a compensatory increase in potassium secretion in exchange for sodium. Magnesium depletion has also been described, and parathyroidectomy is followed by magnesium retention (Bl). It is thought that these effects may be the result of the action of the hormone on bone (F6). 

Potassium sparing diuretics Aktoslerone inhibitors or inhlbilors cH tubular potassium secretion... 

On the basis of maximum weight gain in weanling male rats, the requirement for potassium was found to be 2.3 gkg diet DM (Bieri 1977). Potassium-depleted rats developed a low appetite, which was reversed by prior intragastric repletion with potassium (Adam and Dawborn 1972b). Potassium depletion produces a preference in potassium-deficient rats (Adam 1973). Potassium depletion stimulates potassium absorption in the rafs distal colon, while potassium secretion remains unaffected (Wolffram et al. 1985). Potassium deficiency in rabbits resulted in a severe and rapidly progressing muscular dystrophia and diarrhea (induced coccidiosis) by a lack both of potassium intake and conservation of potassium by the kidneys (McDowell 1992). 

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