HYDROGEN ION HOMEOSTASIS
"Life is a struggle, not against sin, not against the Money Power, not against malicious animal magnetism, but against hydrogen ions."
Mencken was neither a physician nor physiologist, but he knew the importance of hydrogen ions. Enzyme systems operate at an optimal hydrogen ion concentration ([H+]), and variation from this optimal can markedly affect enzyme activity. For the blood plasma, optimal [H+] is 40 nanomoles/L. As shown in Table 71, the importance of H+ is out of proportion to its minuscule concentration.
Strictly speaking, hydrogen ions are protons and do not exist in the naked state in body fluids; instead they react with water (H20) to form hydronium ions, such as H30+ and H5O2+. For clinical purposes H+ can be used to represent these hydrated protons. Because [H+] is so critical to enzyme function yet the absolute concentration is small and difficult to manipulate, the concept of pH was developed and is now universally used to represent [H+].*
CONCEPT OF pH
The pH is the negative logarithm of the hydrogen ion concentration ([H+]):
A pH of 7.4 represents a [H+] of 40 nmoles/L, or 4 x 105 moles/L (for univalent ions, mmoles/ L equal mEq/L). By definition pH does not have units.
|Table 71. Plasma ion concentrations|
|*K+, Potassium ion; Ca++, calcium ion; Mg++, magnesium ion; Na+, sodium ion.|
Since pH is the negative log of [H+], the lower the pH, the greater the [H+] and hence the greater the acidity; the higher the pH, the lower the [H+] and the greater the alkalinity (or the less the acidity). Use of a logarithmic expression also means that a pH change of one whole unit, e.g., from 7.0 to 8.0, represents a tenfold change in [H+] .
|Table 72. pH and hydrogen ion concentration|
Table 72 shows the relationship between pH and the relative
acidity of the blood. A pH change from 7.40 to 7.30 represents
a 25% increase in blood [H+]. A similar numerical change
of conventional measurement, such as an increase in serum uric
acid from 7.3 mg% to 7.4 mg%, represents only a 1.4% increase.
The range of normal arterial pH (7.36 to 7.44) encompasses approximately two standard deviations of the normal population; anything outside this range is considered abnormal. Clinically, the "safe" range for pH is approximately 7.30 to 7.52; within this range, pH per se is not usually lifethreatening. A pH outside this range is potentially lifethreatening because of altered enzymatic activity and enhanced myocardial irritability, and direct steps should be taken to return the pH to normal. Although 7.30 to 7.52 may at first seem a narrow range, it represents a [H+] ranging from 50 to 30 nmoles/L or a change from the normal 40 nmoles/L of plus or minus 25%. A similar range for serum sodium is 175 to 105 mEq/L!
A buffer system counteracts the effects of adding acid or alkali to the blood. The resulting pH change is less than if the buffer were not present. Blood contains two basic buffer systems: bicarbonate and nonbicarbonate. Each consists of a weak acid or acids and their conjugate base or bases.
The bicarbonate system buffers the effects of fixed acids and alkalies that are added to the blood; the acid component is H2CO3 and the base is HCO3-. The nonbicarbonate system consists mainly of proteins and phosphates and serves to buffer changes in carbon dioxide. These two systems are represented by the equations in Fig. 71. Since the nonbicarbonate system is a heterogeneous group of compounds, the acid component is represented by HBuf and the base by Buf. Note that carbon dioxide is part of an open system, since any buildup in plasma (aqueous or dissolved CO2) can be excreted by healthy lungs.
Fig. 71. Bicarbonate and nonbicarbonate buffer
system. The two systems are in equilibrium with each other.
The bicarbonate and nonbicarbonate buffer systems are in equilibrium with each other. Measuring the components of either system will give the hydrogen ion concentration ([H+]) or the pH of the blood. However, since the nonbicarbonate system is a heterogeneous group of molecules, it is easier to measure the bicarbonate buffer components in order to determine pH.
An extremely small quantity of H2C03 is present in the blood compared with dissolved CO2 (approximately 1 to 400). Since H2CO3 is in equilibrium with dissolved CO2, the latter (measured as PaCO2) can be used as the acid component in calculating pH. Therefore measurement of HCO3- and PaCO2 will provide the pH.
The HendersonHasselbalch equation relates blood pH to the components of the bicarbonate buffer system, as shown in Equation 2.
where pK is the negative log of the dissociation constant of carbonic
acid and has the value 6.1. The pH of the blood is equal to the
pK of the bicarbonate buffer system plus the logarithm of the
following ratio bicarbonate concentration ([HCO3-])
over 0.03 times the arterial partial pressure of carbon dioxide
(PaCO2). The constant 0.03 converts PaCO2
from mm Hg to mmoles/L. Inserting normal values gives 7.4, the
normal blood pH.
It is not necessary to memorize the full HendersonHasselbalch
equation to intelligently manage acidbase disorders. It
is important to understand that pH reflects a ratio of HCO3-
The bicarbonate buffer system is the most important of the body's buffer systems for several reasons. This system provides the major way to buffer the additions of fixed acid and alkali to the blood. Since one of its components is carbon dioxide, the system is open, i.e., the respiratory system allows for excretion of huge amounts of carbon dioxide. Also, since carbon dioxide is readily diffusible across all cell membranes, the results of buffering can be reflected quickly in intracellular compartments.
Since there are three variables in the bicarbonate buffer system (Equation 2), measurement of any two will define the third. The body preferentially wants to maintain normal pH and does so by altering the numerator (HCO3-) or denominator (PaCO2) of the HendersonHasselbalch equation as necessary.
DOES THE PATIENT HAVE AN ACIDBASE DISORDER?
It is important to recognize when a patient has an acidbase disorder since that recognition is the first step toward diagnosis and therapy. If any of the three variables in the HendersonHasselbalch equation are abnormal, the answer to this question is yes. Any acidbase derangement will be reflected in one or more components of the bicarbonate system: pH, PaCO2, HCO3- (see the box on p. 20 for the range of normal values).
A single abnormal component, even without knowledge of the other two, always indicates an acidbase disorder. This is particularly important since an abnormal HCO3- is often found in venous blood (as part of the serum electrolytes measurement) without a concomitant blood gas measurement. An abnormal HCO3- value alone cannot define or diagnose an acidbase disorder but nonetheless points to its presence. For example, an elevated HCO3- suggests either metabolic alkalosis or respiratory acidosis.
|Clinical problem 1|
|A 79yearold woman was hospitalized for dehydration and for cellulitis in her left leg. She received meperidine (Demerol) for pain and diazepam (Valium) for agitation. On the third hospital day she was found to be lethargic and unarousable. Review of her serum electrolytes measurements over the 3 days revealed the following information:|
Day Serum HCO3-
1 35 mEq/L
2 36 mEq/L
3 36 mEq/L
No blood gas analysis was obtained until Day 3. What probably happened to this woman?
CALCULATED VS. MEASURED HCO3-
Incorrect therapeutic decisions can occur if blood gas values are accepted at face value. They should always be examined for physiologic correctness, particularly when considering acidbase disorders, which seem prone to misdiagnosis. For example, a PaCO2 of 49 mm Hg, pH of 7.35, and HCO3- of 16 mEq/L may be interpreted as a metabolic acidosis (low pH and low HCO3-) when in fact there is a transcription error: the HCO3- should be 26 and cannot possibly be 16 if the pH is 7.35 and the PaCO2 is 49 mm Hg.
Such errors can be avoided if it is remembered that HCO3-, PaCO2, and pH must satisfy the HendersonHasselbalch equation. If PaCO2 and pH have been measured, arterial HCO3- can be calculated and does not have to be measured. The HCO3- is routinely measured as one of the serum electrolytes (on venous blood), and this measurement can pose a problem when a comparison is made with the blood gas HCO3-. Often, the measured venous HCO3- does not agree with the arterial HCO3- that has been calculated from the HendersonHasselbalch equation. When this happens there are several possible reasons as shown in the box below.
|POSSIBLE REASONS FOR MEASURED VENOUS HCO3- NOT AGREEING WITH CALCULATED ARTERIAL HCO3-|
Note that the pK of 6.1, on which the calculated HCO3-
is based, may vary among patients. The significance of such variation
is somewhat controversial (Hood and Campbell, 1981). At most,
the variation is slight (+ 0.012 for extreme conditions) and would
not account for the wide discrepancy often found between measured
venous HCO3- and calculated arterial HCO3-.
|Clinical problem 2|
A 54yearoldman is hospitalized with congestive heart failure. His arterial blood pH is 7.52, PcO2 is 44 mm Hg, and HCO3- is 34 mEq/L. Measured venous HCO3- is 24 mEq/L. What is his acidbase status?
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