Overview of the Role of the Kidneys in Acid-Base Balance

The kidneys have two main ways to maintain acid-base balance: their cells reabsorb bicarbonate HCO3− from the urine back to the blood and they secrete hydrogen (H+) ions into the urine. By adjusting the amounts reabsorbed and secreted, they balance the bloodstream’s pH.

Our kidneys filter blood continuously by distributing the blood that comes into the kidney to millions of tiny functional units called nephrons. Each nephron is made up of the glomerulus, or a tiny clump of capillaries, where blood filtration starts. When blood passes through a glomerulus, about one fifth of the plasma leaves the glomerular capillaries and goes into the renal tubule. The renal tubules function to reabsorb the good stuff like water and electrolytes and leave behind the bad stuff like waste products and acid. The renal tubule is a structure with several segments: the proximal convoluted tubule, the U-shaped loop of Henle with a thin descending and a thick ascending limb, and the distal convoluted tubule, which goes back up again, before emptying into the collecting duct, which collects the final urine.

Each of these tubules is lined by brush border cells which have two surfaces. One is the apical surface that faces the tubular lumen and is lined with microvilli, which are tiny little projections that increase the cell’s surface area to help with solute reabsorption. The other is the basolateral surface, which faces the peritubular capillaries, which run alongside the nephron.

So with bicarbonate reabsorption, as the filtrate leaves the glomerulus, it first goes through the proximal convoluted tubule. At first, this filtrate contains the same concentration of electrolytes as the plasma it came from. But when a molecule of bicarbonate approaches the apical surface of the brush border cell it binds to hydrogen secreted by the brush border cell in exchange for a sodium ion from the tubule to form carbonic acid. At that point, an enzyme called carbonic anhydrase type 4 that lurks in the tubule in the microvilli kind of like a shark, swims along and splits the carbonic acid into water and carbon dioxide.

Unlike charged bicarbonate anions, which are stuck in the tubule, the water and carbon dioxide happily diffuse across the membrane into cells where carbonic anhydrase type 2 facilitates the reverse reaction, combining them to form carbonic acid, which dissolves into bicarbonate and hydrogen. A sodium bicarbonate cotransporter on the basolateral surface snatches up the bicarbonate and a nearby sodium, and shuttles both into the blood. Alternatively, a bicarbonate chloride exchanger exchanges bicarbonate (HCO3- ) with chloride (Cl-) leaving the bloodstream to enter the cells. All this chemical trickery effectively moves 99.9% of the filtered bicarbonate that’s in the tubule back into the bloodstream.

Hydrogen (H+) ions, with their positive charge don’t naturally want to pass through cell membranes out into the urine. They need to be pushed out. There are 2 mechanisms. One mechanism is sodium-hydrogen countertransport. A carrier protein in the apical wall binds a hydrogen H+ ion from the cell and a sodium Na+ ion in the tubular fluid. The higher concentration of sodium in the tubular fluid turns the carrier protein like a little revolving door to push the H+ out and bring the Na+ in. Remember this is in the proximal tubule, but in the distal convoluted tubule and collecting ducts there’s another mechanism that involves alpha-intercalated cells. These cells have a different pump that uses the energy of ATP to push hydrogen H+ ions into the tubule.

However, the urine can hold only so many free hydrogen H+ ions because the pH would quickly drop too low, and the tubules can’t maintain a urine pH below about 4.5. So, to get around this limit and hold more hydrogen H+ ions, the urine contains chemical buffers, which bind the hydrogen ions and prevent the pH from dropping too low. The most important is the ammonia buffer system, in which the kidney’s uses a process called ammoniagenesis. Ammoniagenesis begins when the proximal convoluted tubule cells break down amino acids such as glutamine into ammonia NH3. The ammonia is lipid soluble so it diffuses freely into the tubule, where it combines with a hydrogen ion to form an ammonium NH4+ ion. Ammonium NH4+ combines with chloride Cl- in the urine. Because ammonium chloride is only weakly acidic, the urine pH doesn’t drop much even though it now contains a lot of hydrogen H+ ions. Most of this ammonium NH4+ is lost in the urine, which helps the kidneys get rid of a large amount of hydrogen H+.

A second buffer system uses phosphate. Monohydrogen phosphate HPO42- enters the tubule from the plasma. It is poorly reabsorbed from the tubules, so it concentrates there. It acts as a buffer by combining with secreted hydrogen ions to form dihydrogen phosphate H2PO4- which is then peed out in the urine.

All right, as a quick recap, the kidneys help maintain pH balance of the blood. In the nephron, the proximal convoluted tubule cells are able to reabsorb the bicarbonate HCO3− ions, and cells in the proximal, as well as distal convoluted tubule and collecting ducts, cells secrete hydrogen H+ ions that are carried out into the urine using the ammonia and phosphate buffer system.