From the Guidelines
Inhibiting sodium reabsorption increases water output because it creates an osmotic gradient that prevents water from being reabsorbed in the kidneys, leading to increased urine volume. This is based on the understanding that sodium and water movement in the kidneys are closely linked through osmosis, as described in the 2013 ACCF/AHA guideline for the management of heart failure 1. When diuretics, such as furosemide or thiazides, block sodium reabsorption in the kidney tubules, sodium remains in the tubular fluid instead of being transported back into the bloodstream.
The mechanism of action of diuretics, as outlined in the guideline, involves inhibiting the reabsorption of sodium or chloride at specific sites in the renal tubules, including the loop of Henle and the distal portion of the tubule 1. This creates an osmotic gradient that draws water with it through osmosis, resulting in greater urine volume. The increased sodium excretion disrupts the kidney's concentration gradient, further reducing its ability to concentrate urine.
Key points to consider include:
- Diuretics are recommended in patients with heart failure who have evidence of fluid retention, unless contraindicated, to improve symptoms 1
- Loop diuretics, such as furosemide, have emerged as the preferred diuretic agents for use in most patients with heart failure 1
- The use of inappropriately low doses of diuretics will result in fluid retention, while the use of inappropriately high doses will lead to volume contraction, increasing the risk of hypotension and renal insufficiency 1
From the FDA Drug Label
Hydrochlorothiazide blocks the reabsorption of sodium and chloride ions, and it thereby increases the quantity of sodium traversing the distal tubule and the volume of water excreted. Investigations into the mode of action of Furosemide tablets have utilized micropuncture studies in rats, stop flow experiments in dogs and various clearance studies in both humans and experimental animals It has been demonstrated that Furosemide tablets inhibits primarily the absorption of sodium and chloride not only in the proximal and distal tubules but also in the loop of Henle.
Inhibiting the reabsorption of sodium increases water output because sodium and water are reabsorbed together in the kidneys. When sodium reabsorption is blocked, water reabsorption is also decreased, resulting in an increase in the amount of water excreted in the urine. This is the mechanism by which diuretics like hydrochlorothiazide and furosemide work to increase urine production [2] [3].
- Key points: + Inhibition of sodium reabsorption decreases water reabsorption + Decreased water reabsorption increases water excretion + Diuretics like hydrochlorothiazide and furosemide work by inhibiting sodium reabsorption
From the Research
Mechanism of Diuretics
- Diuretics work by inhibiting sodium reabsorption in the renal tubules, which leads to an increase in urinary sodium and water excretion 4.
- The inhibition of sodium reabsorption in the early distal convoluted tubule by thiazides and thiazide-like agents, and in the thick ascending limb of the loop of Henle by loop diuretics, results in increased sodium and water excretion 5.
Effect on Water Output
- The net effect of inhibiting sodium reabsorption is an increase in urinary sodium and water excretion, which leads to increased water output 4.
- Loop diuretics, such as furosemide, are particularly effective in increasing water output by inhibiting sodium and chloride reabsorption in the thick ascending limb of the loop of Henle 5, 6.
Clinical Implications
- Diuretics are widely used to treat hypertension and are effective in reducing blood pressure by increasing sodium and water excretion 5, 7.
- The choice of diuretic and dosage depends on the individual patient's needs and the severity of their condition, with loop diuretics being used in patients with renal failure or severe heart failure 5, 6.