Ganong's Review of Medical Physiology, 23rd Edition

684 SECTION VIII Renal Physiology

reducing the already low plasma HCO 3 – and lowering the pH
toward normal.

METABOLIC ACIDOSIS

When acids stronger than HHb and the other buffer acids are
added to blood, metabolic acidosis is produced; and when the
free H+ level falls as a result of addition of alkali or removal of ac-
id, metabolic alkalosis results. Following the example from
Chapter 36, if H 2 SO 4 is added, the H+ is buffered and the Hb–,
Prot–, and HCO 3 – levels in plasma drop. The H 2 CO 3 formed is
converted to H 2 O and CO 2 , and the CO 2 is rapidly excreted via
the lungs. This is the situation in uncompensated metabolic aci-
dosis. Actually, the rise in plasma H+ stimulates respiration, so
that the PCO 2 , instead of rising or remaining constant, is reduced.
This respiratory compensation raises the pH even further. The
renal compensatory mechanisms then bring about the excretion
of the extra H+ and return the buffer systems to normal.

RENAL COMPENSATION

The anions that replace HCO 3 – in the plasma in metabolic ac-
idosis are filtered, each with a cation (principally Na+), thus
maintaining electrical neutrality. The renal tubular cells se-
crete H+ into the tubular fluid in exchange for Na+; and for
each H+ secreted, one Na+ and one HCO 3 – are added to the
blood. The limiting urinary pH of 4.5 would be reached rapid-
ly and the total amount of H+ secreted would be small if no
buffers were present in the urine to “tie up” H+. However, se-

creted H+ reacts with HCO 3 – to form CO 2 and H 2 O (bicarbo-

nate reabsorption); with HPO 4 2– to form H 2 PO 4 – ; and with

NH 3 to form NH 4 +. In this way, large amounts of H+ can be

secreted, permitting correspondingly large amounts of

HCO 3 – to be returned to (in the case of bicarbonate reabsorp-

tion) or added to the depleted body stores and large numbers

of the cations to be reabsorbed. It is only when the acid load is

very large that cations are lost with the anions, producing di-

uresis and depletion of body cation stores. In chronic acidosis,

glutamine synthesis in the liver is increased, using some of the

NH 4 + that usually is converted to urea (Figure 40–5), and the

glutamine provides the kidneys with an additional source of

NH 4 +. NH 3 secretion increases over a period of days (adapta-

tion of NH 3 secretion), further improving the renal compen-

sation for acidosis. In addition, the metabolism of glutamine

in the kidneys produces α-ketoglutarate, and this in turn is de-

carboxylated, producing HCO 3 – , which enters the blood-

stream and helps buffer the acid load (Figure 40–5).

The overall reaction in blood when a strong acid such as

H 2 SO 4 is added is:

2NaHCO 3 + H 2 SO 4 → Na 2 SO 4 + 2H 2 CO 3

For each mole of H+ added, 1 mole of NaHCO 3 is lost. The

kidney in effect reverses the reaction:

Na 2 SO 4 + 2H 2 CO 3 → 2NaHCO 3 + 2H+ + SO 4 2–

and the H+ and SO 4 2– are excreted. Of course, H 2 SO 4 is not

excreted as such, the H+ appearing in the urine as titratable

acidity and NH 4 +.

In metabolic acidosis, the respiratory compensation tends to

inhibit the renal response in the sense that the induced drop in

PCO 2 hinders acid secretion, but it also decreases the filtered

load of HCO 3 – and so its net inhibitory effect is not great.

METABOLIC ALKALOSIS

In metabolic alkalosis, the plasma HCO 3 – level and pH rise

(Figure 40–7). The respiratory compensation is a decrease in

ventilation produced by the decline in H+ concentration, and

this elevates the PCO 2. This brings the pH back toward normal

while elevating the plasma HCO 3 – level still further. The mag-

nitude of this compensation is limited by the carotid and aor-

tic chemoreceptor mechanisms, which drive the respiratory

center if any appreciable fall occurs in the arterial PO 2. In met-

abolic alkalosis, more renal H+ secretion is expended in reab-

sorbing the increased filtered load of HCO 3 – ; and if the

HCO 3 – level in plasma exceeds 26–28 mEq/L, HCO 3 – appears

in the urine. The rise in PCO 2 inhibits the renal compensation

by facilitating acid secretion, but its effect is relatively slight.

THE SIGGAARD–ANDERSEN

CURVE NOMOGRAM

Use of the Siggaard–Andersen curve nomogram (Figure 40–7)

to plot the acid–base characteristics of arterial blood is helpful

FIGURE 40–6 Acid–base nomogram showing changes in the
CO 2 (curved lines), plasma HCO 3 – , and pH of arterial blood in
respiratory and metabolic acidosis. Note the shifts in HCO 3 – and pH
as acute respiratory acidosis and alkalosis are compensated, produc-
ing their chronic counterparts. (Reproduced with permission from Cogan MG,
Rector FC Jr: Acid–base disorders. In: The Kidney, 4th ed. Brenner BM, Rector FC Jr
[editors]. Saunders, 1991.)

60

56

52

48

44

40

36

32

Ar terial plasma [HCO

− 3

] (meq/L)

28

24

20

16

12

8

4

0

7.00 7.10 7.20 7.30 7.40 7.50 7.60 7.70 7.80

Arterial blood pH

100 90 80 70 60 50 40 35 30 25 20

Arterial blood [H+] (nmol/L)

120 100 90 80 70 60 50 40

20

15

10

35

30

25

Acute

respiratory

alkalosis

Acute

respiratory

acidosis

Normal

Chronic

respiratory

alkalosis PCO 2 (mm Hg)

Metabolic

acidosis

Chronic

respiratory

acidosis

Meta-

bolic

alkalosis