682 SECTION VIII Renal Physiology
maintenance of the H+ concentration of the ECF. The mecha-
nisms regulating the composition of the ECF are particularly
important as far as this specific ion is concerned, because the
machinery of the cells is very sensitive to changes in H+ con-
centration. Intracellular H+ concentration, which can be mea-
sured by using microelectrodes, pH-sensitive fluorescent dyes,
and phosphorus magnetic resonance, is different from extra-
cellular pH and appears to be regulated by a variety of intra-
cellular processes. However, it is sensitive to changes in ECF
H+ concentration.
The pH notation is a useful means of expressing H+ concen-
trations in the body, because the H+ concentrations happen to
be low relative to those of other cations. Thus, the normal Na+
concentration of arterial plasma that has been equilibrated
with red blood cells is about 140 mEq/L, whereas the H+ con-
centration is 0.00004 mEq/L (Table 40–1). The pH, the nega-
tive logarithm of 0.00004, is therefore 7.4. Of course, a
decrease in pH of 1 unit, for example, from 7.0 to 6.0, repre-
sents a 10-fold increase in H+ concentration. It is important to
remember that the pH of blood is the pH of true plasma—
plasma that has been in equilibrium with red cells—because
the red cells contain hemoglobin, which is quantitatively one
of the most important blood buffers (see Chapter 36).
H
- BALANCE
The pH of the arterial plasma is normally 7.40 and that of
venous plasma slightly lower. Technically, acidosis is present
whenever the arterial pH is below 7.40, and alkalosis is
present whenever it is above 7.40, although variations of up to
0.05 pH unit occur without untoward effects. The H+ concen-
trations in the ECF that are compatible with life cover an ap-
proximately fivefold range, from 0.00002 mEq/L (pH 7.70) to
0.0001 mEq/L (pH 7.00).
Amino acids are utilized in the liver for gluconeogenesis,
leaving NH 4 + and HCO 3 – as products from their amino and
carboxyl groups (Figure 40–5). The NH 4 + is incorporated into
urea and the protons that are formed are buffered intracellu-
larly by HCO 3 – , so little NH 4 + and HCO 3 – escape into the cir-
culation. However, metabolism of sulfur-containing amino
acids produces H 2 SO 4 , and metabolism of phosphorylated
amino acids such as phosphoserine produces H 3 PO 4. These
strong acids enter the circulation and present a major H+ load
to the buffers in the ECF. The H+ load from amino acid metab-
olism is normally about 50 mEq/d. The CO 2 formed byCLINICAL BOX 40–1
Implications of Urinary pH Changes
Depending on the rates of the interrelated processes of
acid secretion, NH 4 + production, and HCO 3 – excretion, the
pH of the urine in humans varies from 4.5 to 8.0. Excretion
of urine that is at a pH different from that of the body fluids
has important implications for the body’s electrolyte and
acid–base economy. Acids are buffered in the plasma and
cells, the overall reaction being HA + NaH 3 → NaA + H 2 CO 3.
The H 2 CO 3 forms CO 2 and H 2 O, and the CO 2 is expired,
while the NaA appears in the glomerular filtrate. To the ex-
tent that the Na+ is replaced by H+ in the urine, Na+ is con-
served in the body. Furthermore, for each H+ ion excreted
with phosphate or as NH 4 +, there is a net gain of one HCO 3 –
ion in the blood, replenishing the supply of this important
buffer anion. Conversely, when base is added to the body
fluids, the OH– ions are buffered, raising the plasma HCO 3 –.
When the plasma level exceeds 28 mEq/L, the urine be-
comes alkaline and the extra HCO 3 – is excreted in the urine.
Because the rate of maximal H+ secretion by the tubules
varies directly with the arterial PCO 2 , HCO 3 – reabsorption
also is affected by the PCO 2. This relationship has been dis-
cussed in more detail in the text.TABLE 40–1 H+ concentration and pH of body fluids.
H+ ConcentrationmEq/L mol/L pH
Gastric HCI 150 0.15 0.8
Maximal urine
acidity0.03 3 × 10 –5 4.5PlasmaExtreme acidosis 0.0001 1 × 10 –7 7.0
Normal 0.00004 4 × 10 –8 7.4
Extreme alkalosis 0.00002 2 × 10 –8 7.7
Pancreatic
juice0.00001
1 × 10 –8 8.0FIGURE 40–5 Role of the liver and kidneys in the handling of
metabolically produced acid loads. Sites where regulation occurs
are indicated by asterisks. (Modified and reproduced with permission from
Knepper MA, et al: Ammonium, urea, and systemic pH regulation. Am J Physiol
1987;235:F199.)NH 4 + + HCO 3 − Glucose H 3 PO 4 + H 2 SO 4Amino acidsHPO 42 −H 2 PO 4 −H 2 PO 4 −HCO 3 −HCO 3 −NH 4 +NH 4 +H+H+SO 42 −SO 42 −UreaUreaGlutamineGlutamineα-Ketoglutarate* **LiverECFKidneyUrine