T Pco2

0 PCo2

T H+, 0 hco3-

0 H+, T hco3-

0 Extracellular fluid volume

T Extracellular fluid volume

T Angiotensin II

0 Angiotensin II

T Aldosterone

0 Aldosterone



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 influence 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 activity 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 collecting 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 stimulating and hyperkalemia inhibiting H+ secretion in the proximal tubule. A decreased plasma potassium concentration 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.

Renal Correction of Acidosis— Increased Excretion of Hydrogen Ions and Addition of Bicarbonate Ions to the Extracellular Fluid

Now that we have described the mechanisms by which the kidneys secrete H+ and reabsorb HCO3-, we can explain how the kidneys readjust the pH of the extracellular fluid when it becomes abnormal.

Referring to equation 8, the Henderson-Hasselbalch equation, we can see that acidosis occurs when the ratio of HCO3- to CO2 in the extracellular fluid decreases, thereby decreasing pH. If this ratio decreases because of a fall in HCO3-, the acidosis is referred to as metabolic acidosis. If the pH falls because of an increase in Pco2, the acidosis is referred to as respiratory acidosis.

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