section 39.5
Acid-Base Balance
935
FIGURE 39-6
Reclamation of bicarbonate. The filtered Na+ is reabsorbed by the
proximal tubular cell in exchange for H+. The filtered HCOJ is converted
to H
2
O and CO
2
catalyzed by the luminal carbonic anhydrase IV (CAIV).
CO
2
diffuses in the tubular cell where it is hydrated to H
2
CO
3
by carbonic
anhydrase II and dissociated to H+ and HCOJ. Three molecules of HCO
3
and one of Na+ are transported to the peritubular capillary by the
basolateral cotransporter.
in exchange for Na+ from the tubular fluid (an energy-
dependent process mediated by Na+, H+-ATPase) com-
bines with HCO^ to form CO
2
and water. The C 0
2
dif-
fuses into the tubular cells, where it is rehydrated to H
2
CO
3
by carbonic anhydrase and dissociates to bicarbonate and
H+. The HC0
3
diffuses into the bloodstream, resulting in
reclamation of bicarbonate (Figure 39-6).
The formation of H
2
CO
3
, from H+ and HCO^ in the
tubular lumen is catalyzed by the membrane-bound isoen-
zyme of carbonic anhydrase (CAIV). CAIV is located on
the brush border lining the lumen of the proximal tubules
of the kidney. The C 0
2
diffuses into the tubular cells where
it is rehydrated to H
2
CO
3
by a different isoenzyme of car-
bonic anhydrase, namely, carbonic anhydrase II (CAII).
HC07 is transported from the cytosol of the proximal
tubular cell to peritubular capillary blood by a basolateral
cotransporter, which transports three molecules of HCO^
and one of Na+. An inherited CAII deficiency is an autoso-
mal recessive disorder causing renal tubular acidosis and
osteopetrosis. The latter is due to lack of H+ production
required for bone remodeling processes (Chapter 37). The
proximal tubular mechanism for reclamation of HCO,
becomes saturated at approximately 26 mEq HCO
3
/L. At
higher levels, HCOIT appears in the distal tubule and may
be excreted in urine. Under conditions of elevated PCO
2
,
H+ secretion is more active, possibly owing to intracellular
acidosis. In proximal renal tubular acidosis, HCO^ reab-
sorption is impaired and saturation occurs at a lower con-
centration (about 16-18 mEq/L), so that plasma [HC0
3
J
is low while urine pH may be high because of the presence
of HCO
3
".
Na+/H+ exchange may also be coupled to formation
of H
2
PO
4
from HPO
4
- in the lumen (Figure 39-7). This
coupling is of particular importance in distal tubules and
acidifies the urine to a maximum pH of about 4.4. The
FIGURE 39-7
Hydrogen ion secretion and Na+/H+ exchange coupled to the conversion
of HPOj- to H
2
PO
4
in the distal tubule lumen. CA, carbonic anhydrase.
proximal tubule cannot maintain an H+ gradient of more
than one pH unit between the lumen and the intracellular
fluid. The H
2
PO
4
present (termed the “titratable acidity”)
can be measured by titrating the urine to pH 7 (pK
2
for
H
3
PO
4
= 6.2). Normal values for titratable acidity are
16-60 mEq/24 h, depending on the phosphate load.
Generation of ammonia from glutamine and its excre-
tion as NH
4
is an important mechanism for elimination
of protons, particularly during severe metabolic acidosis,
when it becomes a significant mode of nitrogen excretion.
Most renal glutamine is derived from muscle (Chapters
17 and 22). Glutamine provides two molecules of NH3:
glutaminase
Glutamine + H20 --------
>
glutamate- +
NH
3
+ H+(?=^ NH
4
)
and
glutamate
dehydrogenase
,
Glutamate-
N A D H
N A D H + H +
a -
ketoglutarate2- + NH3 + H+ (<
* NHJ)
The ratio of [NH
3
]/[NH
4
] depends on intracellular pH;
however, the NH
3
readily diffuses into the tubular lumen
and there forms an ammonium ion that is no longer able to
pass freely through the membranes and remains “trapped”
in the urine, where it is associated with the dominant coun-
terion (Figure 39-8). Protons produced in these reactions
are consumed when a-ketoglutarate is either completely
oxidized or converted to glucose. Thus, they do not add
to the existing “proton burden” due to severe acidosis (see
also Chapters 13 and 15).
Disorders of Acid-Base Balance
These disorders are classified according to their cause
and the direction of the pH change into respiratory acido-
sis, metabolic acidosis, respiratory alkalosis, or metabolic
alkalosis. Any derangement of acid-base balance elicits
