Monday, August 13, 2018

How does the kidney maintain the acid base balance of the blood?

The kidneys are ultimately responsible for balancing hydrogen ion gains and losses so as to maintain a relatively constant plasma H+ ion concentration. The kidneys eliminate or replenish H+ ions from the body by altering plasma bicarbonate concentration. When the plasma H+ ion concentration decreases (alkalosis), the kidney's homeostatic response is to excrete large quantities of bicarbonate. This increases plasma H+ ion concentration toward normal. In contrast, when plasma H+ ion concentration increases (acidosis), the kidneys do not excrete bicarbonate in the urine. Rather kidney tubular cells produce new bicarbonate and add it to the plasma.
Bicarbonate is completely filterable at the renal corpuscles and undergoes significant tubular reabsorption in the proximal tubule, ascending loop of Henle and cortical collecting ducts. Bicarbonate can also be secreted in the collecting ducts. Therefore,
HCO3- excretion = HCO3- filtered + HCO3- secreted- HCO3- reabsorbed.
Bicarbonate reabsorption is an active process. It depends on the tubular secretion of hydrogen ions, which combine in the lumen with filtered bicarbonates.
Inside the cell there is a combination of CO2 and H2O to form H2CO3, a reaction catalyzed by the enzyme carbonic anhydrase. The H2CO3 immediately dissociates to yield H+ and bicarbonate HCO3-. The HCO3- diffuses down its concentration gradient across the basolateral membrane into interstitial fluid and then into the blood. Simultaneously, the H+ is secreted into the lumen. Depending on the tubular segment, this secretion is achieved by some combination of primary H+ ATPase pumps, primary H+/K+ ATPase pumps and Na+/H+ counter transporters.
The secreted H+, however, is not excreted. Instead it combines in the lumen with a filtered HCO3- and generates CO2 and H2O, both of which can diffuse into the cell and be available for another cycle of H+ ion generation. The overall result is that the bicarbonate filtered from the plasma at the renal corpuscle has disappeared, but its place in the plasma has been taken by the bicarbonate that was produced inside the cell. In this manner, no net change in plasma bicarbonate concentration has occurred.
Now, the extra secreted H+ ions combine in the lumen with a filtered non bicarbonate buffer, usually HPO42-. The H+ ion is then excreted in the urine as part of an H2PO4- ion. When a secreted H+ ion combines in the lumen with a buffer other than bicarbonate, the overall effect is not merely one of bicarbonate conservation, but rather of addition to the plasma of a new bicarbonate. This raises the bicarbonate concentration of plasma and alkalinizes it.
There is a second mechanism by which the tubules contribute new bicarbonate to the plasma that involves not H+ ion secretion, but rather the renal production and secretion of ammonium ions (NH4+). Tubular cells mainly those of the proximal tubule, take up glutamine from both the glomerulus filtrate and peritubular plasma and metabolize it. In this process, both NH4+ and bicarbonate are formed inside the cells. The NH4+ is actively secreted via Na+/NH4+ counter transport into the lumen and excreted, while the bicarbonate moves into the peritubular capillaries and constitutes a new plasma bicarbonate.
The kidney normally contribute enough new bicarbonate to the blood by excreting H+ ions to compensate for the H+ ions from nonvolatile acids generated in the body.  



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