Renal Physiology: Secretion

After two fairly lengthy posts on reabsorption, this post on secretion should be relatively short!

Most of the secretion that I'm going to talk about occurs in the distal tubule, but that's not to say that secretion doesn't take place anywhere else- as mentioned in one of my pharmacology posts, active secretion of many drugs and other organic compounds occurs in the proximal tubule via specific carriers.

Potassium Secretion

Just like in the proximal tubule, there are Na⁺/K⁺ pumps in the distal tubule. However, while the proximal tubule has K⁺ channels in the basolateral membrane, the distal tubule has K⁺ channels in the luminal membrane. That means that the K⁺ that is pumped in by the Na⁺/K⁺ pumps is secreted into the tubule, rather than being released back into the blood.

Why is it important to control the secretion of K⁺? Well, K⁺ is important in the action potentials of nerves and muscles. If there is too much K⁺, the muscles and nerves can become over-excitable, and if there is too little K⁺, the muscles and nerves have a reduced excitability, leading to muscle weakness and so forth.

K+ secretion can be controlled by aldosterone. As mentioned in my previous post, aldosterone increases the number of Na⁺/K⁺ pumps as well as Na⁺ channels. It also increases K⁺ channels. An increased K⁺ in the blood can directly increase aldosterone secretion from the adrenal cortex, which in turn increases K⁺ secretion via the pumps and channels in the distal tubule.

Kidneys and Acid-Base Balance

As you should know by now, the main pH buffer system of the blood goes something like this:

CO₂ + H₂O <--> H₂CO₃ <--> H⁺ + HCO₃^-

This buffer system is regulated by the lungs, which regulate CO₂ levels as explained here, and the kidneys, which regulate HCO₃^- levels. Since this is a post on renal physiology, let's have a look at how the kidneys regulate HCO₃^-!

HCO₃^- is filtered and must be reabsorbed. (Yes, I know I said this post was going to be about secretion. I lied.) The reabsorption of HCO₃^- is kinda unique. There are no carriers for HCO₃^-, so HCO₃^- must react with H⁺ to form CO₂ and H₂O. CO₂ can then diffuse into the cell. Within the cell, it undergoes the reverse reaction (i.e. CO₂ and H₂O become H⁺ and HCO₃^-), facilitated by the enzyme carbonic anhydrase. (Carbonic anhydrase was also mentioned when I wrote about the respiratory system.) The HCO₃^- can then pass through the basolateral membrane via HCO₃^-/Cl^- antiports. (Antiports transport two substances in opposite directions. Also, you probably won't have to know that last little detail about which antiports transport HCO₃^- - it wasn't in the lecture, but it was in the textbook.)

What about the extra H⁺ in the cell? Well, that is pumped out into the lumen, where it can react with more HCO₃^- and make the cycle start over again. Since too much H⁺ can damage the epithelial layer of the lumen, H⁺ is usually co-secreted with weak bases like NH₃ and NaPO₄^-.

These mechanisms allow the kidneys to help prevent the body from being too damaged by respiratory acidosis (build-up of CO₂) or respiratory alkalosis (not enough CO₂). You see, CO₂ from the blood can also diffuse into the cells of the tubule and carry out the carbonic anhydrase-catalysed reaction, resulting in H⁺ and HCO₃^-. The H⁺ is then pumped into the tubule, where it reacts with all of the HCO₃^- and causes all of it to become reabsorbed. When CO₂ levels drop, this process doesn't happen so more HCO₃^- is lost in the urine.

And that's it for renal physiology! Only two small topics to go!