679CHAPTER40
Acidification of the Urine
& Bicarbonate Excretion
OBJECTIVESAfter reading this chapter, you should be able to:
■
Outline the processes involved in the secretion of H
+
into the tubules and discuss
the significance of these processes in the regulation of acid–base balance.
■
Define acidosis and alkalosis, and give (in mEq/L and pH) the normal mean and the
range of H
+
concentrations in blood that are compatible with health.
■
List the principal buffers in blood, interstitial fluid, and intracellular fluid, and, using
the Henderson–Hasselbalch equation, describe what is unique about the bicarbo-
nate buffer system.
■
Describe the changes in blood chemistry that occur during the development of
metabolic acidosis and metabolic alkalosis, and the respiratory and renal compen-
sations for these conditions.
■
Describe the changes in blood chemistry that occur during the development of
respiratory acidosis and respiratory alkalosis, and the renal compensation for these
conditions.RENAL H
- SECRETION
The cells of the proximal and distal tubules, like the cells of the
gastric glands, secrete hydrogen ions (see Chapter 26). Acidi-
fication also occurs in the collecting ducts. The reaction that is
primarily responsible for H
- secretion in the proximal tubules
is Na–H exchange (Figure 40–1). This is an example of secon-
dary active transport; extrusion of Na
from the cells into the
interstitium by Na, K ATPase lowers intracellular Na
, and
this causes Na
to enter the cell from the tubular lumen, with
coupled extrusion of H
. The H
- comes from intracellular dis-
sociation of H
2
CO
3
, and the HCO
3
- that is formed diffuses
into the interstitial fluid. Thus, for each H
- ion secreted, one
Na
ion and one HCO
3
- ion enter the interstitial fluid.
Carbonic anhydrase
catalyzes the formation of H
2
CO
3
,
and drugs that inhibit carbonic anhydrase depress both secre-
tion of acid by the proximal tubules and the reactions which
depend on it.
Some evidence suggests that H
- is secreted in the proximal
tubules by other types of pumps, but the evidence for these
additional pumps is controversial, and in any case, their con-
tribution is small relative to that of the Na–H exchange mech-
anism. This is in contrast to what occurs in the distal tubules
and collecting ducts, where H
+
secretion is relatively indepen-
dent of Na
+
in the tubular lumen. In this part of the tubule,
most H
+
is secreted by an ATP-driven proton pump. Aldos-
terone acts on this pump to increase distal H
+
secretion. The I
cells in this part of the renal tubule secrete acid and, like the
parietal cells in the stomach, contain abundant carbonic
anhydrase and numerous tubulovesicular structures. There is
evidence that the H
+
-translocating ATPase that produces H
+
secretion is located in these vesicles as well as in the luminal
cell membrane and that, in acidosis, the number of H
+
pumps
is increased by insertion of these tubulovesicles into the lumi-
nal cell membrane. Some of the H
+
is also secreted by H–K
+
ATPase. The I cells contain
Band 3,
an anion exchange pro-
tein, in their basolateral cell membranes, and this protein may
function as a Cl/HCO
3
exchanger for the transport of HCO
3- to the interstitial fluid.
FATE OF H
+
IN THE URINEThe amount of acid secreted depends upon the subsequent
events in the tubular urine. The maximal H
+
gradient against
which the transport mechanisms can secrete in humans corre-
sponds to a urine pH of about 4.5; that is, an H
+
concentration in