Physiology and Mechanism of Action of Diuretics

Mechanism of Action of Diuretics

The Nephron is made up of the Bowman's capsule, the proximal convoluted tubule (where a large amount of about 65% or 2/3rds of sodium and water reabsorption occurs). If there is a diuretic that inhibits the reabsorption of sodium and water in the proximal convoluted tubule, then you can be sure that a large number of sodium and water will be eliminated from the body. ,. Carbonic anti-hydrase inhibitors is a drug that works in the proximal convoluted tubule which aids the reaction of carbon dioxide and water into bicarbonate, thereby allowing the excretion of water and sodium.. Another part of the kidney tubule is the Loop of Henle. The loop of Henle is made with a thin descending, and a thin ascending limb. At the descending limb of Henle's, water is reabsorbed, and on the ascending limb of the loop of Henle, about 25% of sodium, and water are reabsorbed., . At the ascending limb of the loop of Henle, drugs such as Loop Diuretics act in that the ascending limb of the loop of Henle to reduce sodium, chloride reabsorption. .

The water and sodium in the Nephron continue to move from the Loop of Henle if it is not reabsorbed to reach the Distal Convoluted Tubule. In the distal convoluted tubule which is made up of the late distal convoluted tubule and the early distal convoluted tubule where water and sodium are reabsorbed. About 5% of Sodium and water are reabsorbed each, at both distal convoluted tubules. Also, in the Distal Convoluted Tubule, there are drugs that work to inhibit the reabsorption of Sodium, Chlorine, and water from the tubule are the Thiazide Diuretics in the early, and Potassium Sparing Diuretics in the late Distal Convoluted Tubule.

It is important to know that at a different site of the kidney tubules, sodium and water are reabsorbed at different percentages, and at the distal tubule, relatively the late distal convoluted tubule, reabsorption is dependent on antidiuretic hormone Aldosterone, and Antidiuretic Hormone (ADH) for water reabsorption.

Mannitol is another type of Osmotic Diuretic which is poorly reabsorbed in the glomerulus in the Nephron. Mannitol is a solute molecule that gets filtered out across the glomerulus, which creates an osmotic gradient which pulls water into the convoluted tube, allowing the water to go down the tubule, causing Diuresis..

Physiology of Action of Diuretics

Filtrates such as Bicarbonate, and Sodium move from the Bowman's capsule into the proximal convoluted tubule where the sodium is reabsorbed and hydrogen protons are returned into the tubule. The proton combines with the carbonate to form carbonic acid, which disassociates with the help of a catalyst known as Carbonic anhydrase into lipid-soluble Co2 and Water. ,. The CO2 is moved across the membrane, which is then converted into Bicarb, then absorbed into the bloodstream and chloride is moved into the membrane of the tubule. Also, the sodium (Na+) in the cell of the basal lateral membrane is pumped out while potassium (K+) is pumped into the cell., . With Drugs Such as Carbonic Anhydrase inhibitor, the carbonic anhydrase enzyme will be inhibited which prevents the stimulation of CO2 and Water to become Carbonic acid which will reduce the amount of proton, the amount of bicarb reabsorbed, preventing sodium being reabsorbed. So Bicarbs are not reabsorbed, protons are not excreted, and Bicarbs cannot be converted into CO2 and Water to be reabsorbed, stopping the entire cycle and causing the loss of Sodium, Water and excessive Bicarb in Urine. , , .

At the Ascending loop of Henle, there is a transporter known as the Sodium Potassium 2 chloride (Na-K-2Cl) cotransporter, which allows Sodium (Na+), chloride (Cl-), and Potassium (K+) into the cell from the lumen. With the Sodium inside the cell in a lower concentration. The sodium and chloride are pushed into the bloodstream while Potassium (K+) which is from the bloodstream goes into the cell. Potassium in the cell keeps building up, increasing the potassium in the cell. The potassium leaves the cell into the lumen through the potassium transporter creating positive charges. Magnesium and Calcium which are charged in the lumen move through the tubular cells into the bloodstream., , , . Loop diuretics inhibits the Sodium Potassium 2 chloride (Na-K-2Cl) cotransporter preventing sodium, and chloride from being reabsorbed, having much sodium, chloride and water being lost in the urine. , .

The Early distal convoluted tubule also absorbed some nutrients. There is a transporter in the Early distal convoluted tubule known as the Sodium Chloride co-transporter which allows both sodium (Na+) and chloride (Cl-) to be absorbed from the lumen into the membrane of the cell and the chloride gets into the bloodstream through the chloride transporter, while the sodium-potassium ATPase which allows for sodium to leave the membrane and going into the bloodstream and the ATPase allows potassium into the membrane. Also, calcium is absorbed, and it is controlled by the parathyroid hormone into the membrane. At the basal lateral membrane, the calcium is expelled into the blood while allowing sodium into the cell.. Thiazide diuretic is a sodium chloride co-transporter inhibitor which does not allow sodium and chloride reabsorption, thereby causing the loss of sodium, chloride and water..

Conclusion

This post is just the beginning of explaining Diuretics. I have been able to explain the physiology of diuretics and diuresis in the Bowman's capsule, Ascending Loop of Henle, and the Early Distal Convoluted Tubule. I will be writing on the Late distal convoluted tubule, and other paths of renal and diuretic physiology, and will explain each of the diuretic drugs.