Quantifying Renal Acid-Base Excretion
Based on the principles discussed earlier, we can quan-titate the kidneys’ net excretion of acid or net addition or elimination of bicarbonate from the blood as follows.
Bicarbonate excretion is calculated as the urineflowrate multiplied by urinary bicarbonate concentration. This number indicates how rapidly the kidneys are removing HCO3– from the blood (which is the same as adding an H+ to the blood). In alkalosis, the loss of HCO3– helps return the plasma pH toward normal.
The amount of new bicarbonate contributed to the blood at any given time is equal to the amount ofH+ secreted that ends up in the tubular lumen with nonbicarbonate urinary buffers. As discussed previ-ously, the primary sources of nonbicarbonate urinary buffers are NH4+ and phosphate. Therefore, the amount of HCO3– added to the blood (and H+ excreted by NH4+) is calculated by measuring NH4+excretion (urine flow rate multiplied by urinary NH4+ concentration).
The rest of the nonbicarbonate, non-NH4+ buffer excreted in the urine is measured by determining a value known as titratable acid. The amount of titrat-able acid in the urine is measured by titrating the urine with a strong base, such as NaOH, to a pH of 7.4, the pH of normal plasma, and the pH of the glomerular filtrate. This titration reverses the events that occurred in the tubular lumen when the tubular fluid was titrated by excreted H+. Therefore, the number of mil-liequivalents of NaOH required to return the urinary pH to 7.4 equals the number of milliequivalents of H+ added to the tubular fluid that combined with phos-phate and other organic buffers. The titratable acid measurement does not include H+ in association with NH4+, because the pK of the ammonia-ammonium reaction is 9.2, and titration with NaOH to a pH of 7.4 does not remove the H+ from NH4+.
Thus, the net acid excretion by the kidneys can be assessed as
Net acid excretion = NH4+ excretion + Urinary titratable acid – Bicarbonate excretion
The reason we subtract bicarbonate excretion is that the loss of HCO3– is the same as the addition of H+ to the blood. To maintain acid-base balance, the net acid excretion must equal the nonvolatile acid production in the body. In acidosis, the net acid excretion increases markedly, especially because of increased NH4+ excre-tion, thereby removing acid from the blood. The net acid excretion also equals the rate of net HCO3– addi-tion to the blood. Therefore, in acidosis, there is a netaddition of HCO3– back to the blood as more NH4+ and urinary titratable acid are excreted.
In alkalosis, titratable acid and NH4+ excretion drop to 0, whereas HCO3– excretion increases. Therefore, inalkalosis, there is a negative net acid secretion. Thismeans that there is a net loss of HCO3– from the blood (which is the same as adding H+ to the blood) and that no new HCO3– is generated by the kidneys.
As discussed earlier, H+ secretion by the tubular epithelium is necessary for both HCO3– reabsorption and generation of new HCO3– associated with titrat-able acid formation. Therefore, the rate of H+secre-tion must be carefully regulated if the kidneys are to effectively perform their functions in acid-base home-ostasis. Under normal conditions, the kidney tubules must secrete at least enough H+ to reabsorb almost all the HCO3– that is filtered, and there must be enough H+ left over to be excreted as titratable acid or NH4+ to rid the body of the nonvolatile acids produced each day from metabolism.
In alkalosis, tubular secretion of H+ must be reduced to a level that is too low to achieve complete HCO3– reabsorption, enabling the kidneys to increase HCO3– excretion. In this condition, titratable acid and ammonia are not excreted because there is no excess H+ available to combine with nonbicarbonate buffers; therefore, there is no new HCO3– added to the urine in alkalosis. During acidosis, the tubular H+ secretion must be increased sufficiently to reabsorb all the filtered HCO3– and still have enough H+ left over to excrete large amounts of NH4+ and titratable acid, thereby contributing large amounts of new HCO3– to the total body extracellular fluid. Themost important stimuli for increasing H+ secretion by the tubules in acidosis are (1) an increase in PCO2 of the extracellular fluid and (2) an increase in H+ concentration of the extracellular fluid (decreased pH).
The tubular cells respond directly to an increase in PCO2 of the blood, as occurs in respiratory acidosis, with an increase in the rate of H+ secretion as follows: The increased PCO2 raises the PCO2 of the tubular cells, causing increased formation of H+ in the tubular cells, which in turn stimulates the secretion of H+. The second factor that stimulates H+ secretion is an increase in extracellular fluid H+concentration (decreased pH).
A special factor that can increase H+ secretion under some pathophysiologic conditions is excessive aldos-terone secretion. Aldosterone stimulates the secretion of H+ by the intercalated cells of the collecting duct. Therefore, oversecretion of aldosterone, as occurs in Conn’s syndrome, can cause excessive secretion of H+ into the tubular fluid and, consequently, increased amounts of bicarbonate added back to the blood. This usually causes alkalosis in patients with excessive aldosterone secretion.
The tubular cells usually respond to a decrease in H+ concentration (alkalosis) by reducing H+ secretion. The decreased H+ secretion results from decreased extracellular PCO2, as occurs in respiratory alkalosis, or from a decrease in H+ concentration per se, as occurs in both respiratory and metabolic alkalosis.
Table 30–2 summarizes the major factors that influ-ence H+ secretion and HCO3– reabsorption. Some of these are not directly related to the regulation of acid-base balance. For example, H+ secretion is coupled to Na+ reabsorption by the Na+-H+ exchanger in the proximal tubule and thick ascending loop of Henle. Therefore, factors that stimulate Na+ reabsorption, such as decreased extracellular fluid volume, may also secondarily increase H+ secretion.
Extracellular fluid volume depletion stimulates sodium reabsorption by the renal tubules and increases H+ secretion and HCO3– reabsorption through multiple mechanisms, including (1) increased angiotensin II levels, which directly stimulate the activ-ity of the Na+-H+ exchanger in the renal tubules, and (2) increased aldosterone levels, which stimulate H+ secretion by the intercalated cells of the cortical col-lecting tubules. Therefore, extracellular fluid volume depletion tends to cause alkalosis due to excess H+ secretion and HCO3– reabsorption.
Changes in plasma potassium concentration can also influence H+ secretion, with hypokalemia stimu-lating and hyperkalemia inhibiting H+ secretion in the proximal tubule. A decreased plasma potassium con-centration tends to increase the H+ concentration in the renal tubular cells. This, in turn, stimulates H+ secretion and HCO3– reabsorption and leads to alka-losis. Hyperkalemia decreases H+ secretion and HCO3– reabsorption and tends to cause acidosis.
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