Kidney and acid- base physiology:part 1

As we move up the ladder, I feel that it is the right time to discuss the role of kidney in maintaining the acid base balance. Just as the gut is important for HCO₃^-  secretion , kidney plays a role in hydrogen ion removal from the body. Each day the bicarbonate loss in the faeces imparts an acid load (Net endogenous acid production, NEAP) to the body which is in a way made up for by the kidney’s acid secretion (Renal net acid excretion, RNAE).

Thus a balance is reached in normal physiological conditions when NEAP equals the RNAE.

As I was about to start with this topic, I found that sodium-potassium transport is invariably linked to and coexists with the H⁺/HCO₃^- movement in/out of the tubular cells. I felt that this is the right time when I highlight the site of action of various diuretics too.

The normal HCO₃^- in plasma is about 24 meq/l and GFR is 180 l/day, so the filtered load of the bicarbonate is about (180*24=4300 meq/day). Approximately 80 % of the HCO₃^- is reabsorbed in the proximal tubule (PT) with the thick ascending limb (ThAL) and distal convoluted tubule (DT) contributing to additional 16 % reabsorption. The remaining bicarbonate is reabsorbed by the collecting duct (CD).

The following diagram depicting the reabsorption of the various ions at basolateral surface and secretion at the apical luminal surface is self -explanatory.

The salient features of the events at (proximal tubule) PT are as follows:

1. Main transporter for H⁺ ion secretion at the PT are H⁺ - ATPase and Na⁺/H⁺ antiporter (exchanger; NHE3).

2. The NHE3  is responsible for driving approximately 2/3 of HCO₃^-  reabsorption at the corresponding basolateral surface; rest 1/3 is contributed by the H⁺ - ATPase.

3.      The H+ are generated inside the cell by the activity of Carbonic anhydrase (II).

4.    Carbonic anhydrase (IV) is present in the brushborder at the apical surface also where it catalyses the production of H₂O and CO₂ from the luminal carbonic acid.

5.      Thus the bicarbonate in the tubular fluid are neutralized by the H⁺ secreted at the apical surface inside the lumen and there is actually no change in the pH of the tubular fluid.

6.      The HCO₃^- which is reabsorbed at the basolateral surface is actually a new molecule; for one H⁺ secreted from the cell, one molecule of HCO₃^- is reabsorbed in the blood.

7.      The HCO₃^- transporters at the basolateral surface are 3HCO₃^--Na⁺ symporter (NBCe1) mainly and HCO₃^-/Cl^- exchanger (to some extent).

8.      The Na⁺ entering the cell by NHE3 at the apical surface is extruded out by Na⁺-K⁺ ATPase athe basolateral surface.

9.      The Na⁺ movement inside the cell at the apical surface is also coupled with glucose cotransport (SGLT-1, SGLT-2 at late and early PT respectively). At the basolateral surface, the carrier for the facilitated diffusion of glucose are  GLUT-2,GLUT-1 at early and late PT respectively).

10.  The glucose, lactate, phosphates and amino acids are completely reabsorbed in the PT.

11.     The K⁺ and Cl^- entering the cell are extruded or reabsorbed at the basolateral surface by separate K⁺-Cl^- cotransporter.

12.     Na⁺, K⁺, Cl^- are also reabsorbed through paracellular pathways and the lateral surface of the PT cells have selective K⁺ channels for the K⁺ ion movement into the cells.

13.     More water is reabsorbed in the early PT as compared to Cl^- so Cl^- concentration goes on increasing and is reltively higher in the late PT. This creates a concentration gradient for the Cl^- ions which diffuse to the interior through paracellular pathway leaving the lumen slightly positive. This positivity then drags the Na⁺ to diffuse in the blood.

14.     Thus about 67% of filtered Na⁺, K⁺, Cl^- are reabsorbed at the PT along with water.