Renal regulation of homeostasis

Acid-base balance and kidneys
Chemical buffers are capable of stopping increase in acids or bases. Buffers however are not capable of eliminating those acids and bases from body. Respiratory tract can eliminate (or cumulate) volatile carbonic acid by means of eliminating CO2 (or cumulate it). Only the kidneys are able to clean the body from non-volatile (metabolic) acids (i.e. phosphoric acid, sulphuric acid, uric acid, …). Thus preventing acidosis. In addition the kidneys are only organ that is efficiently capable of solving alkalosis (respiratory system btw offers another option, i.e. stop breathing).

The kidneys take part in maintaining the acid-base balance by means of:

1) Reabsorbing, excreting and producing bicarbonate

2) Excreting or producing H+

You should notice that loss of bicarbonate is the same as acquire of H+ and production of bicarbonate is the same as loss of H+. It is shown below that these processes are connected (e.g. excretion of H+ in proximal tubule is connected with reabsorption of HCO3– in the same place or excretion of H+ in distal tubule is connected with production of HCO3– in the same place). Next important concept is that higher bicarbonate concentration increases pH, lower bicarbonate concentration decreases pH.

In this section are in detail described basic processes as reabsorption of bicarbonate, new bicarbonate production, ammonium ion production, proton excretion in kidneys, bicarbonate secretion.

Bicarbonate reabsorption
Bicarbonate reabsorption takes place in proximal tubule cells. In glomerular ultrafiltrate there is filtered bicarbonate. To the lumen of the proximal tubule is transported H+. H+ is transported by Na+/H+ antiport  H+ reacts with HCO3– and H2CO3 is thus produced. H2CO3 split up into H2O and CO2. Water and carbon dioxide get through apical membrane of tubular cells. Inside these cells H2CO3 is again produced. H2CO3 dissociates into HCO3– and H+. Now their fates get different: (1) H+ becomes again substrate for Na+/H+ antiport and it is transported again to the lumen of the proximal tubule where it can “catch” another bicarbonate molecule. (2) Bicarbonate however traverse basolateral membrane into interstitial fluid (and then to the blood of the peritubular capillaries). Bicarbonate gets through basolateral membrane using either Na+/3 HCO3– cotransport, or anion exchanger (Cl–/HCO3– exchange).

Together it can be stated: for one secreted H+, one Na+ and one HCO3– are resorbed. Na+ is transported to the blood among other things by active transport – i.e. Na+/K+ ATPase.

New bicarbonate production (connected with H+ excretion)
New bicarbonate production takes place in intercalated cells type A of distal tubule and collecting duct. These cells absorb CO2 from the blood and inside the cells carbon dioxide reacts with water and carbonic acid is thus produced, catalysed by the enzyme carboanhydrase. Carbonic acid dissociates to H+ and HCO3–. H+ has totally different fate than bicarbonate: (1) H+ is excreted by the H-ATPase to the urine. This process is active, hence it consumes ATP. In order to eliminate as much H+ as possible it is necessary to buffer H+ in the urine. The most important buffers in the urine are ammonium and phosphate buffer. (2) Produced bicarbonate is transported to the blood in peritubular capillaries exchanged for Cl– (Cl–/HCO3– exchanger in basolateral membrane). Aldosterone stimulates H+ secretion (and therefore H+ excretion).

Ammonium ion excretion
This process uses ammonium generated in glutamine metabolism in tubular cells. For every metabolised glutamine two ammonium ions and two bicarbonates are produced. Bicarbonates are transported to the blood, whilst ammonium ions are excreted to the blood.

Proton excretion in the kidneys
Both bicarbonate resorption, and new bicarbonate production (both mentioned above) need transport of H+ (protons) to the tubules (protons are derived from carbonic acid dissociation). Precise mechanism is however quite different.

In the cells of the proximal tubule the transport of proton to the lumen is based on its exchange for Na+. On the basolateral membrane act Na+/K+-ATPase and HCO3–/Cl– exchanger.

In the intercalated cells type A (in the distal tubule and the collecting duct) the transport of proton to the lumen is based on active transport (H+-ATPase). Aldosterone promotes (1) excretion of H+ and K+ in the distal tubule and the collecting duct and (2) reabsorption of the sodium (and water).

The result of both described processes is generation of high concentration gradient for H+, i.e. in the urine there is thousand times higher concentration of protons than in the cells/blood. This thousand fold gradient is however maximal, thus the lowest achievable pH of the urine is 4,4 (40 μmol/l H+) – compare this value with value of the pH in blood: 7,4 (40 nmol/l H+).

Bicarbonate secretion
In conditions of rising pH (alkalosis) type B of the intercalated cells start to act. They secrete bicarbonate and gain H+. These mechanisms are absolutely inverse than processes described in the type A of the intercalated cells (see above). Even in alkalosis nephrons however excrete less bicarbonate than they retain.

We can summarize that extracellular pH is kept by the buffer systems and involved organs. These systems maintain pH value 7,36-7,44. The respiratory system modulates pCO2 and the kidneys modulate concentration of bicarbonate.

Final urine
Final urine is characteristically malodorous, clear, golden yellow liquid. Its specific gravity  varies between 1 003-1 038 kg/m3 and its pH between 4.4-8.0. It contains Na+ (100-250 mmol/l), K+ (25-100 mmol/l), Cl– (about 135 mmol/l), Ca2+, creatinine, vanillylmandelic acid (degradation product of catecholamines), uric acid, urea, etc. Healthy kidneys do not allow a significant amount of proteins and glucose to reach the final urine (they are almost completely reabsorbed). Presence of high amount of proteins and glucose in the final urine is a pathological finding. Normal diuresis is 1.5-2 l/day. Polyuria is diuresis higher than 2 l/day, oliguria lower than 0.5 l/day and anuria lower than 0.1 l/day.