The Role of Ammonium Excretion
What happens next to ammonium is somewhat complex. So before continuing , let us re-examine the rational behind ammonium excretion.
Now remember; free hydrogen ions are not filtered by the kidney. Instead, they are secreted into the tublar fluid. Because free hydrogens cannot be excreted in the urine easily, there are excreted with weak acids such as H2PO4- which function as urinary buffers. Now in the presence of an increased acid load, the phospate ions are used up and the kidney then increases its production of ammonium .
Notice that ammonium, not ammonia is produced in the proximal tubule. Therefore you might ask yourself, how does ammonium production increase hydrogen excretion if it cannot bind to hydrogen ions secreted in the proximal tubular lumen?
The answer to this is somewhat controversial in the literature. Below is one school of thought that has gained popularity.
As was mentioned previously, new bicarbonate ions are produced during ammoniagenesis. The generation of new bicarbonate ions conceptually is akin to inceased hydrogen excretion. Therefore the real function of ammoniagenesis is not as a urinary buffer of hydrogen ions as is commonly inaccurately described. The real function of ammoniagensis is to increase the generation of new bicarbonate ions.
For simplicity, this rational will be the basis of the remaining discussion on ammonium excretion.
Ammonium before it is excreted is first re-absorbed in the thick ascending limb, circulated in the medullary interstitium and then pumped back in the collected tubule as ammonia. In the collecting tubule, ammonia then takes up hydrogen ions secreted into the lumen by intercalated cells, to form ammonium.
Now the second question you might ask is why so many steps leading to the same result?
In order for ammoniagenesis to be effective in the generation of new HCO3-, the NH4+ produced must be excreted in the urine. If NH4+ were to enter the circulation, it would end up in the liver where metabolism would lead to the formation of urea
as showed in the following equation:
NH4+ + 2 HCO3- => urea + CO2 + 3 H2O
Notice that the formation of urea consumes 2 molecules of bicarbonate. Therefore, in essence, the bicarbonate generated in the proximal tubule would be negated or cancelled out, and ammoniagenesis would not increase net acid excretion.
As mentioned previously, NH4+ secreted in the proximal tubule is in equilibrium with a small quantity of NH3. This NH3 is capable of diffusing out of the lumen into the peritubular capillaries. If this were allowed to continually happen, a large quantity of ammonium would be lost to the circulation and its metabolism in the liver would consume the HCO3- generated.
This effect is minimized by having an acidic urine ph which keeps NH4+ in its protonated form. However, the urine does not become maximally acidified until the collecting tubule where secretion of hydrogen ions by intercalated cells significantly reduce the urine pH. Therefore the kidney prevents loss of ammonium by reabsorbing NH4+ in the thick ascending limb and pumping it into the collecting duct where the urine pH is very low, facilitating ammonia in its protonated form. This process is enhanced during periods of acidosis when hydrogen secretion by the intercalated cells is significantly increased.
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