This molecule contains 2 negatively-charged carboxylate groups so further metabolism of it in the cell results in the production of 2 HCO 3 - anions. This occurs if it is oxidised to CO 2 or if it is metabolised to glucose.
The pKa for ammonium is so high about 9. The subsequent situation with ammonium is complex. Most of the ammonium is involved in cycling within the medulla. The thick ascending limb of the loop of Henle is the important segment for removing ammonium. Some of the interstitial ammonium returns to the late proximal tubule and enters the medulla again ie recycling occurs.
A low pH greatly augments transfer of ammonium from the medullary interstitium into the luminal fluid as it passes through the medulla. The lower the urine pH, the higher the ammonium excretion and this ammonium excretion is augmented further if an acidosis is present. This augmentation with acidosis is 'regulatory' as the increased ammonium excretion by the kidney tends to increase extracellular pH towards normal. If the ammonium returns to the blood stream it is metabolised in the liver to urea Krebs-Henseleit cycle with net production of one hydrogen ion per ammonium molecule.
Note: Section 2. In chronic metabolic acidosis , there is also induction, through genomic effects on an acid pH i , of basolateral and mitochondrial glutamine transporters, of glutaminase, and other enzymes that participate in the oxidation of glutamine. These adaptations to chronic acidosis allow large amounts of ammonium to be excreted at any urine pH, even at pH 7.
The major buffer in urine is phosphate. At pH 7. For every proton secreted that titrates the phosphate in the lumen, there is generation of one molecule of bicarbonate that enters the circulation and helps restore the buffering capacity of the body. At this pH practically all phosphate has been converted to the diprotonated form. Diprotonated phosphates are excreted.
Conversely, it might be thought that hypoaldosteronism would be associated with a metabolic acidosis but this is very uncommon but may occur if there is coexistent significant interstitial renal disease.
Phosphate is the major component of titratable acidity. The amount of phosphate present in the distal tubule does not vary greatly. Consequently, changes in phosphate excretion do not have a significant regulatory role in response to an acid load. It has recently been established that a reduction in GFR is a very important mechanism responsible for the maintenance of a metabolic alkalosis. The filtered load of bicarbonate is reduced proportionately with a reduction in GFR.
This is very important in increasing renal acid excretion during a chronic metabolic acidosis. There is a lag period: the increase in ammonium excretion takes several days to reach its maximum following an acute acid load. Ammonium excretion increases with decreases in urine pH and this relationship is markedly enhanced with acidosis. How can the renal excretion of ammonium which has a pK of 9. One school says the production of ammonium from glutamine in the tubule cells results in production of alpha-ketoglutarate which is then metabolised in the tubule cell to new bicarbonate which is returned to the blood.
The net effect is the return of one bicarbonate for each ammonium excreted in the urine. Thus an increase in ammonium excretion as occurs in metabolic acidosis is an appropriate response to excrete more acid. The other school says this is not correct.
The key to understanding is said to lie in considering the role of the liver. Consider the following:. These are produced in equal amounts by neutral amino acids as each contains one carboxylic acid group and one amino group. The body now has two major problems:. The solution is to react the two together and get rid of both at once.
This process is hepatic urea synthesis Krebs-Henseleit cycle. The cycle consumes significant energy but solves both problems. The overall reaction in urea synthesis is:. The key thing here is that the acid-base implications of these 2 mechanisms are different.
For each ammonium converted to urea in the liver one bicarbonate is consumed. For each ammonium excreted in the urine, there is one bicarbonate that is not neutralised by it during urea synthesis in the liver. So overall, urinary excretion of ammonium is equivalent to net bicarbonate production -but by the liver! Indeed in a metabolic acidosis, an increase in urinary ammonium excretion results in an exactly equivalent net amount of hepatic bicarbonate produced from amino acid degradation available to the body.
So the true role of renal ammonium excretion is to serve as an alternative route for nitrogen elinination that has a different acid-base effect from urea production. The bicarbonates consumed in the production of glutamine and then released again with renal metabolism of ketoglutarate are not important as there is no net gain of bicarbonate. Finally: The role of urine pH in situations of increased acid secretion is worth noting. The urine pH can fall to a minimum value of 4.
Increased ammonium excretion increases steadily with decrease in urine pH and this effect is augmented in acidosis [This is the major and regulatory factor because it can be increased significantly]. As discussed also in section 2. Bicarbonate reabsorption is complete at low urinary pH so none is lost in the urine Such loss would antagonise the effects of an increased TA or ammonium excretion on acid excretion. The above discussion focuses on the 'traditional' approach to acid-base balance and a short-coming of that approach is that the explanations are wrong.
The Stewart approach see Chapter 10 provides the explanations and the insights into what is occurring. The urinary excretion of Cl - without excretion of an equivalent amount of strong ion results in a change in the SID or ' strong ion difference ' and it is this change which causes the change in plasma pH. See Chapter 10 for an introduction to the Stewart approach.
The renal mechanisms involved in acid-base balance can be difficult to understand so as a simplification we will consider the processes occurring in the kidney as involving 2 aspects: Proximal tubular mechanism Distal tubular mechanism. Note The differences in functional properties of the apical membrane from that of the basolateral membranes should be noted.
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