Henle, loop potassium reabsorption

The loop diuretics such as furosemide, torasemide and bumetanide act in the thick ascending loop of Henle, inhibiting the reabsorption of sodium, potassium and chloride ions. 

Hypercalcemia can be a medical emergency. Since the loop of Henle is an important site of calcium reabsorption, loop diuretics can be quite effective in promoting calcium diuresis. However, loop diuretics alone can cause marked volume contraction. If this occurs, loop diuretics are ineffective (and potentially counterproductive) because calcium reabsorption in the proximal tubule is enhanced. Thus, saline must be administered simultaneously with loop diuretics if an effective calcium diuresis is to be achieved. The usual approach is to infuse normal saline and furosemide (80-120 mg) intravenously. Once the diuresis begins, the rate of saline infusion can be matched with the urine flow rate to avoid volume depletion. Potassium may be added to the saline infusion as needed. 

Pathophysiology Non-potassium-sparing diuretics are the treatment of choice to reduce fluid retention and dyspnea. Acting at specific sites of nephrons, they inhibit sodium and water reabsorption. Loop diuretics act on the loop of Henle, producing a maximal diuretic effect equivalent to 20% to 25% of the filtered sodium load and promoting the free water clearance. Currently available loop diuretics include furosemide, bumetanide, torsemide, and ethacrynic acid. Because of their potency, they are generally effective in patients with advanced renal insufficiency (glomerular filtration rates <25 ml/min) (49). 

When the luminal fluid reaches the thick ascending limb of the loop of Henle, water no longer can freely move from the luminal fluid into the medullary interstitial space. Instead, this portion of the nephron is impermeable to water reabsorption and actively reabsorbs sodium, chloride, and potassium ions. Approximately 20-25% of filtered sodium and calcium ions are reabsorbed at this location. In addition, most, if not all, of the potassium ions reaching the thick limb of the loop of Henle are reabsorbed as well. Thus, as the luminal fluid passes through the ascending limb, the luminal fluid becomes more dilute. 

Loop or high-ceiling diuretics inhibit the transport of sodium in the ascending Loop of Henle and result in the excretion of sodium and water, potassium, calcium, and magnesium. Loop diuretics are more effective with inhibiting reabsorption of sodium than thiazides diuretics. 

Loop diuretics are the most potent diuretics, as evidenced by the fact that they increase peak fractional excretion of sodium (EeNa) to 20% to 25%. Thiazide- and potassium-sparing diuretics are less potent and increase peak FeNa to 3% to 5% and 1% to 2%, respectively. Although a large portion of the filtered sodium is reabsorbed in the proximal nephron, the efficacy of proximal-acting diuretics such as acetazolamide are limited by reabsorption of the excess fluid and sodium in the loop of Henle. 

Some of the rare causes of metabolic alkalosis due to potassium depletion are those found in subjects with either Cushing s syndrome, primary aldosteronism, or Bartter s syndrome. In Cushing s syndrome, the potassium ions and alkalosis are related to increased mineralocorticoid activity resulting from an increase in adrenocorticotropic hormone (ACTH), cortisol, deoxycorticosterone, and corticosterone. In primary aldosteronism, the effects of increased aldosterone are manifest on the distal tubule of the kidney. In Bartter s syndrome, the basic abnormality appears to be a defect in the reabsorption of chloride in the ascending limb of loop of Henle, leading to loss of potassium (12). 

Hydrochlorothiazide/triamterene is a diuretic combination. Hydrochlorothiazide inhibits reabsorption of sodium and chloride in the ascending loop of Henle and early distal tubules. Triamterene interferes with sodium reabsorption at the distal tubule. The combination provides additive diuretic activity and antihypertensive effects and minimizes potassium depletion. They are indicated in the treatment of edema or hypertension in patients who have, or are at risk of developing, hypokalemia. 

The mercurial diuretics essentially contain in an organic molecule. They usually inhibit sodium reabsorption in the proximal tubuler and ascending loop of Henle. There may be slight effect in the distal tubule where inhibition of chloride reabsorption also occurs. The mercurials have been foimd to enhance excretion though potassium loss is less than that produced by many other diuretics. However, the overall action of mercurial diuretics is invariably increased by acidification of urine. The mercurial diuretics are not very much used in clinical practices due to their pronormced and marked side-effects viz., mercurialism, hypersensitivity and excessive diuresis which may lead to electrolyte depletion and vascular complications. Most of the mercurials are administered by intramuscular route and the availability of orally active diru etics has limited their use. 

Figure 4.2 Site of diuretic actions. Thiazide diuretics inhibit sodium and chloride reabsorption in the thick ascending loop of Henle and the early distal tubule. Loop diuretics inhibit chloride reabsorption in the thick ascending loop of Henle. Potassium sparing diuretics inhibit potassium secretion and influence sodium excretion in the distal convoluted tubule. Mannitol osmotically inhibits water and sodium reabsorption throughout the nephron.

Hypermagnesuria is encountered in the case of metabolic and iatrogenic disorders, such as primary and secondary hyperaldosteronism (extracellular volume expansion), hypercalcemia (competition Ca/Mg at the thick ascending loop of Henle), hyperparathyroidism, and phosphate or potassium depletion. Hypermagnesuria may also result from tubulopathy, as the selective defect of the Mg tubular reabsorption (chromosome Hq23), Bartter s syndrome (thick ascending loop of Henle), or Gitelman s syndrome (distal convoluted tubule). 

While sodium reabsorption in the distal nephron, influenced by aldosterone, is particularly important because it can produce sodium-free urine and promote potassium loss, the great majority of renal sodium reabsorption occurs elsewhere about 25% in the loop of Henle and most in the proximal tubule. The loop is also a main site of magnesium reabsorption, hence the tendency for loop diuretics to cause hypomagnesemia. 

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