Loop diuretics

Diuretics are medications that act on the kidneys to increase production of urine - and therefore, eliminates water from the body. There are 5 main types of diuretics - carbonic anhydrase inhibitors; osmotic diuretics; thiazide and thiazide-like diuretics; potassium sparing diuretics; and last but not least, loop diuretics - which we’ll get intimately acquainted with during this video.

Now, the basic unit of the kidney is called a nephron, and each nephron is made up of a glomerulus, which filters the blood. Blood enters the glomerulus with the afferent arteriole, and exits the glomerulus from the efferent arteriole. The filtered content then goes through the renal tubule, where excess waste, and molecules (such as ions and water), are removed or filtered through an exchange between the tubule and the peritubular capillaries. So the renal tubule plays a huge role in secretion and reabsorption of fluid and ions - such as sodium, potassium, and chloride - in order to maintain homeostasis, or the balance of fluid and ions in our body. The renal tubule has a few segments of its own: the proximal convoluted tubule; the U-shaped loop of Henle, with a thin descending, a thin ascending limb, and a thick ascending limb; and finally, the distal convoluted tubule, which empties into the collecting duct, which collects the urine.

Different kinds of diuretics act on different segments of the renal tubule. Now, loop diuretics - as you might have guessed - act on the loop of Henle. To be more specific, they mainly target the thick ascending limb. The thick ascending limb is impermeable to water and it is lined with cuboidal cells that have Na+K+2Cl- cotransporters on the apical surface. These transporters reabsorb sodium, potassium, and chloride from inside the thick ascending limb back into the blood. As such, they shuttle one sodium into the cell, down its concentration gradient, and that powers the movement of one potassium and two chlorides into the cell as well. Think of it as a revolving door where sodium is the guy doing all the pushing, and one potassium and two chlorides just follow him in. This way, approximately 25% of the filtered sodium is reabsorbed in the loop of Henle, mostly in the thick ascending limb. Now, on the basolateral side of the tubule cell, a Na/K ATPase uses energy in the form of ATP to pump three sodium ions into the interstitial fluid in exchange for letting two potassium ions into the cell. This helps to maintain the low sodium concentration inside the cell. Finally, both chloride and potassium move from the cell back into the lumen of the thick ascending limb, through special channels on the apical side of the cells that simply “leak” these ions passively. Funnily enough, the passive movement of potassium generates an electrochemical gradient that increases the reabsorption of calcium and magnesium through a paracellular pathway - meaning, these ions don’t use any channels, but rather they sneak between two epithelial cells and go back in the bloodstream. Now that’s a lot of activity for such a tiny cell!