Question

Figure 12.6 Loop diuretics are drugs sometimes used to treat hypertension. These drugs inhibit the reabsorption of \(\mathrm{Na}^{+}\) and \(\mathrm{Cl}^{-}\) ions by the ascending limb of the loop of Henle. A side effect is that they increase urination. Why do you think this is the case?

Short answer

Question: Explain how loop diuretics lead to increased urination in patients taking these medications. Answer: Loop diuretics increase urination by inhibiting the reabsorption of Na+ and Cl- ions in the ascending limb of the loop of Henle in the nephron of the kidney. This reduces the ion concentration in the interstitial fluid, weakening the osmotic gradient responsible for water reabsorption. Consequently, less water is reabsorbed into the bloodstream, leading to increased urine production.

Step-by-step solution

Understand the loop of Henle

The loop of Henle is a portion of a nephron in the kidney. It plays a key role in the concentration and dilution of urine by adjusting the balance between the reabsorption of water and electrolytes such as sodium and chloride ions. The ascending limb of the loop of Henle is responsible for actively reabsorbing Na+ and Cl- ions into the interstitial fluid, which leads to passive water reabsorption by the descending limb.

The effect of loop diuretics

Loop diuretics inhibit the reabsorption of Na+ and Cl- ions by the ascending limb of the loop of Henle. This results in a decreased concentration of ions within the interstitial fluid surrounding the nephron.

Osmolality and water reabsorption

The normal ion concentration in the interstitial fluid creates an osmotic gradient that draws water out of the descending limb of the loop of Henle, leading to water reabsorption back into the bloodstream. Conversely, a decreased ion concentration due to the inhibition by loop diuretics weakens the osmotic gradient, which reduces the amount of water being reabsorbed into the body.

Increased urine production

Since the loop diuretics decrease the reabsorption of both Na+ and Cl- ions and subsequently water, it results in more water remaining in the nephron and ultimately being excreted. This leads to an increase in urine production, which is a side effect of loop diuretics. In conclusion, loop diuretics increase urination due to their inhibition of the reabsorption of Na+ and Cl- ions in the ascending limb of the loop of Henle. This decreases the concentration of ions in the interstitial fluid, which weakens the osmotic gradient, reducing the reabsorption of water into the bloodstream and leading to increased urine production.

Key concepts

Nephron Function

The nephron is the fundamental unit of the kidney, each kidney containing millions of these tiny, but incredibly significant structures. Their primary function is to filter blood and regulate water and soluble substances by filtering the blood, reabsorbing what is needed, and excreting the rest as urine.

It consists of a renal corpuscle and a renal tubule. The renal corpuscle performs the initial filtering of the blood, while the renal tubule, which includes components such as the proximal tubule, the loop of Henle, and the distal tubule, refines this filtrate by absorbing various substances back into the bloodstream and secreting others into the filtrate for elimination.

The process can be summarized in four key steps: filtration, reabsorption, secretion, and excretion. As the blood is filtered, water along with waste and other substances form a fluid called filtrate. Essential nutrients, minerals, and water are then reabsorbed from the filtrate back into the bloodstream. Additional waste is secreted into the filtrate, and finally, the refined filtrate (urine) is excreted out of the nephron through the collecting ducts to the bladder.

Loop of Henle

Sitting within the nephron, the loop of Henle is a hairpin-like structure that is critical for the body's ability to produce urine that is concentrated or diluted based on physiological needs. It extends from the proximal tubule and downwards into the medulla of the kidney, then ascends back toward the cortex.

The descending limb is permeable to water but not to salts. As the filtrate travels down, water is drawn out into the surrounding tissues, increasing the solute concentration of the filtrate. Alternatively, the ascending limb is impermeable to water and actively pumps out sodium and chloride ions, decreasing the filtrate's solute concentration.

Countercurrent Multiplication

The loop of Henle operates on a principle of countercurrent multiplication, a mechanism that amplifies the concentration gradients in the kidney medulla, allowing for the production of urine that is more concentrated than the blood. In essence, this system uses energy to create an environment where water can be withdrawn from the filtrate in a controlled manner, which concentrates the urine.

Osmolality and Water Reabsorption

Osmolality pertains to the concentration of solutes in a solution, dictating the movement of water. In the kidneys, particularly in the context of the loop of Henle, osmolality plays a pivotal role in water reabsorption. A high osmolality in the surrounding tissues of the nephron will pull water out of the tubule and back into the bloodstream.

As loop diuretics inhibit the reabsorption of sodium and chloride in the ascending limb, they disrupt the delicate balance created by the countercurrent multiplier system. The normal high osmolality of the interstitial fluid, which pulls water from the descending limb, is compromised. This reduction in osmolality means the water does not find the surrounding environment conducive for reabsorption and thus remains in the filtrate.

As a result of loop diuretics weakening the osmotic gradient, the kidney cannot reabsorb as much water, leading to an increase in the volume of urine produced. This is the underlying reason why patients prescribed with these medications experience increased urination, a side effect that serves its purpose in conditions such as hypertension, where the removal of excess fluid from the body can help lower blood pressure.