as lactic acid and several other organic acids. Dissociation of
all of these acids yields anions and hydrogen ions. But simul-
taneously, the metabolism of a variety of organic anions
utilizes hydrogen ions and produces bicarbonate. Thus, the
metabolism of “nonvolatile” solutes both generates and uti-
lizes hydrogen ions. With the high-protein diet typical in the
United States, the generation of nonvolatile acids predomi-
nates in most people, and there is an average net production of
40 to 80 mmol of hydrogen ions per day.
A third potential source of the net gain or loss of hydro-
gen ions in the body occurs when gastrointestinal secretions
leave the body. Vomitus contains a high concentration of
hydrogen ions and so constitutes a source of net loss. In con-
trast, the other gastrointestinal secretions are alkaline. They
contain very little hydrogen ion, but their concentration of
bicarbonate is higher than in plasma. Loss of these ﬂ uids, as
in diarrhea, in essence constitutes a
of hydrogen ions.
Given the mass action relationship shown in equation 14–1,
when a bicarbonate ion is lost from the body, it is the same as
if the body had gained a hydrogen ion.
This is because loss of
the bicarbonate causes the reactions shown in equation 14–1
to be driven to the right, thereby generating a hydrogen ion
within the body. Similarly, when the body gains a bicarbonate
ion, it is the same as if the body had lost a hydrogen ion, as the
reactions of equation 14–1 are driven to the left.
Finally, the kidneys constitute the fourth source of net
hydrogen ion gain or loss. That is, the kidneys can either
remove hydrogen ions from the plasma or add them.
Buffering of Hydrogen Ions
in the Body
Any substance that can reversibly bind hydrogen ions is
Most hydrogen ions are buffered by extracel-
lular and intracellular buffers. The normal extracellular ﬂ
pH of 7.4 corresponds to a hydrogen ion concentration of
only 0.00004 mmol/L (40 nanomol/L). Without buffer-
ing, the daily turnover of the 40 to 80 mmol of H
from nonvolatile acids generated in the body from metabo-
lism would cause huge changes in body ﬂ
uid hydrogen ion
The general form of buffering reactions is:
Buffer + H
HBuffer is a weak acid in that it can dissociate to Buffer plus
or it can exist as the undissociated molecule (HBuffer).
concentration increases for any reason, the reac-
tion is forced to the right, and more H
is bound by Buffer
to form HBuffer
. For examp
le, when H
increased because of increased production of lactic acid, some
of the hydrogen ions combine with the body’s buffers, so the
hydrogen ion concentration does not increase as much as it
otherwise would have. Conversely, when H
decreases because of the loss of hydrogen ions or the addition
of alkali, equation 14–2 proceeds to the left and H
from HBuffer. In this manner, buffers stabilize H
tion against changes in either direction.
The major extracellular buffer is the CO
summarized in equation 14–1. This system also plays some role
in buffering within cells, but the major intracellular buffers are
phosphates and proteins. An example of an intracellular pro-
tein buffer is hemoglobin, as described in Chapter 13.
Note that buffering does not eliminate hydrogen ions
from the body or add them to the body; it only keeps them
“locked up” until balance can be restored. How balance is
achieved is the subject of the rest of our description of hydro-
gen ion regulation.
Integration of Homeostatic
The kidneys are ultimately responsible for balancing hydro-
gen ion gains and losses so as to maintain a relatively con-
stant plasma hydrogen ion concentration. Thus, the kidneys
normally excrete the excess hydrogen ions from nonvolatile
acids generated from metabolism—that is, all acids other than
carbonic acid. Moreover, if there is an additional net gain
of hydrogen ions due to increased production of these non-
volatile acids, to hypoventilation or respiratory malfunction,
or to loss of alkaline gastrointestinal secretions, the kidneys
increase the elimination of hydrogen ions from the body to
restore balance. Alternatively, if there is a net loss of hydrogen
ions from the body due to hyperventilation or vomiting, the
kidneys replenish these hydrogen ions.
Although the kidneys are the ultimate hydrogen ion
balancers, the respiratory system also plays a very important
homeostatic role. We have pointed out that hypoventilation,
respiratory malfunction, and hyperventilation can cause a
hydrogen ion imbalance. Now we emphasize that when a
hydrogen ion imbalance is due to a nonrespiratory cause, then
ventilation is reﬂ
exly altered so as to help compensate for the
imbalance. We described this phenomenon in Chapter 13 (see
Figure 13–38). An elevated arterial hydrogen ion concentra-
tion stimulates ventilation, which causes reduced arterial
and thus, by mass action, reduces hydrogen ion concentration.
Alternatively, a decreased plasma hydrogen ion concentration
inhibits ventilation, thereby increasing arterial
hydrogen ion concentration.
Thus, the respiratory system and kidneys work together.
The respiratory response to altered plasma hydrogen ion con-
centration is very rapid (minutes) and keeps this concentration
from changing too much until the more slowly responding
kidneys (hours to days) can actually eliminate the imbalance.
If the respiratory system is the actual cause of the hydrogen
ion imbalance, then the kidneys are the sole homeostatic
responder. Conversely, malfunctioning kidneys can create a
hydrogen ion imbalance by eliminating too little or too much
hydrogen ion from the body, and then the respiratory response
is the only one in control.
The kidneys eliminate or replenish hydrogen ions from the
body by altering plasma bicarbonate concentration. The key
to understanding how altering plasma bicarbonate concentra-