Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 40Acidification of the Urine & Bicarbonate Excretion 683

metabolism in the tissues is in large part hydrated to H 2 CO 3
(see Chapter 36), and the total H+ load from this source is over
12,500 mEq/d. However, most of the CO 2 is excreted in the
lungs, and only small quantities of the H+ remain to be excreted
by the kidneys. Common sources of extra acid loads are strenu-
ous exercise (lactic acid), diabetic ketosis (acetoacetic acid and
β-hydroxybutyric acid), and ingestion of acidifying salts such as
NH 4 Cl and CaCl 2 , which in effect add HCl to the body. Failure
of diseased kidneys to excrete normal amounts of acid is also a
cause of acidosis. Fruits are the main dietary source of alkali.
They contain Na+ and K+ salts of weak organic acids, and the
anions of these salts are metabolized to CO 2 , leaving NaHCO 3
and KHCO 3 in the body. NaHCO 3 and other alkalinizing salts
are sometimes ingested in large amounts, but a more common
cause of alkalosis is loss of acid from the body as a result of
vomiting of gastric juice rich in HCl. This is, of course, equiva-
lent to adding alkali to the body.

BUFFERING

Buffering is of key importance in maintaining H+ homeosta-
sis. It is defined in Chapter 1 and discussed in Chapter 36 in
the context of gas transport, with an emphasis on roles for
proteins, hemoglobin and the carbonic anhydrase system in
the blood. Carbonic anhydrase is also found in high concen-
tration in gastric acid-secreting cells (see Chapter 26) and in
renal tubular cells (see Chapter 38). Carbonic anhydrase is a
protein with a molecular weight of 30,000 that contains an
atom of zinc in each molecule. It is inhibited by cyanide, azide,
and sulfide. The sulfonamides also inhibit this enzyme, and
sulfonamide derivatives have been used clinically as diuretics
because of their inhibitory effects on carbonic anhydrase in
the kidney (see Chapter 38).
Buffering in vivo is, of course, not limited to the blood. The
principal buffers in the blood, interstitial fluid, and intracellu-
lar fluid are listed in Table 40–2. The principal buffers in cere-
brospinal fluid (CSF) and urine are the bicarbonate and
phosphate systems. In metabolic acidosis, only 15–20% of the
acid load is buffered by the H 2 CO 3 –HCO 3 – system in the
ECF, and most of the remainder is buffered in cells. In meta-
bolic alkalosis, about 30–35% of the OH– load is buffered in
cells, whereas in respiratory acidosis and alkalosis, almost all
the buffering is intracellular.

In animal cells, the principal regulators of intracellular pH

are HCO 3 – transporters. Those characterized to date include

the Cl–HCO 3 – exchanger AE1 (formerly band 3), three Na+–

HCO 3 – cotransporters, and a K+–HCO 3 – cotransporter.

SUMMARY

When a strong acid is added to the blood, the major buffer re-

actions are driven to the left. The blood levels of the three

“buffer anions” Hb– (hemoglobin), Prot– (protein), and

HCO 3 – consequently drop. The anions of the added acid are

filtered into the renal tubules. They are accompanied (“cov-

ered”) by cations, particularly Na+, because electrochemical

neutrality is maintained. By processes that have been dis-

cussed above, the tubules replace the Na+ with H+ and in so

doing reabsorb equimolar amounts of Na+ and HCO 3 – , thus

conserving the cations, eliminating the acid, and restoring the

supply of buffer anions to normal. When CO 2 is added to the

blood, similar reactions occur, except that since it is H 2 CO 3

that is formed, the plasma HCO 3 – rises rather than falls.

RENAL COMPENSATION TO

RESPIRATORY ACIDOSIS

AND ALKALOSIS

As noted in Chapter 36, a rise in arterial PCO 2 due to decreased

ventilation causes respiratory acidosis and conversely, a de-

cline in PCO 2 causes respiratory alkalosis. The initial changes

shown in Figure 40–6 are those that occur independently of

any compensatory mechanism; that is, they are those of un-

compensated respiratory acidosis or alkalosis. In either situa-

tion, changes are produced in the kidneys, which then tend to

compensate for the acidosis or alkalosis, adjusting the pH to-

ward normal.

HCO 3 – reabsorption in the renal tubules depends not only

on the filtered load of HCO 3 – , which is the product of the glo-

merular filtration rate (GFR) and the plasma HCO 3 – level, but

also on the rate of H+ secretion by the renal tubular cells, since

HCO 3 – is reabsorbed by exchange for H+. The rate of H+ secre-

tion—and hence the rate of HCO 3 – reabsorption—is propor-

tional to the arterial PCO 2 , probably because the more CO 2 that

is available to form H 2 CO 3 in the cells, the more H+ can be

secreted. Furthermore, when the PCO 2 is high, the interior of

most cells becomes more acidic. In respiratory acidosis, renal

tubular H+ secretion is therefore increased, removing H+ from

the body; and even though the plasma HCO 3 – is elevated,

HCO 3 – reabsorption is increased, further raising the plasma

HCO 3 –. This renal compensation for respiratory acidosis is

shown graphically in the shift from acute to chronic respiratory

acidosis in Figure 40–6. Cl– excretion is increased, and plasma

Cl– falls as plasma HCO 3 – is increased. Conversely, in respira-

tory alkalosis, the low PCO 2 hinders renal H+ secretion, HCO 3 –

reabsorption is depressed, and HCO 3 – is excreted, further

TABLE 40–2 Principal buffers in body fluids.

Blood H 2 CO 3 ←→ H+ + HCO 3 –

HProt ←→ H+ + Prot–

HHb ←→ H+ + Hb–

Interstitial fluid H 2 CO 3 ←→ H+ + HCO 3 –

Intracellular fluid HProt ←→ H+ + Prot–

H 2 PO 4 – (^) ←→ H+ + HPO 4 2–