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Blood, Sweat, and Buffers: pH Regulation During Exercise

Key Concepts:

 Exercise and how it affects the body

 How buffering works
 Quantitative: Equilibrium Constants
 Qualitative: Le Châtelier's Principle
 Le Châtelier's Principle
 Direction of Equilibrium Shifts
 Application to Blood pH

How Does Exercise Affect the Body?

Many people today are interested in exercise as a way of improving their health and physical abilities. But there is
also concern that too much exercise, or exercise that is not appropriate for certain individuals, may actually do
more harm than good. Exercise has many short-term (acute) and long-term effects that the body must be capable
of handling for the exercise to be beneficial. When we exercise, our heart rate, systolic blood pressure, and cardiac
output (the amount of blood pumped per heart beat) all increase. Blood flow to the heart, the muscles, and the
skin increase. The body's metabolism becomes more active, producing CO 2 and H+ in the muscles. We breathe
faster and deeper to supply the oxygen required by this increased metabolism. Eventually, with strenuous exercise,
our body's metabolism exceeds the oxygen supply and begins to use alternate biochemical processes that do not
require oxygen. These processes generate lactic acid, which enters the blood stream. As we develop a long-term
habit of exercise, our cardiac output and lung capacity increase, even when we are at rest, so that we can exercise
longer and harder than before. Over time, the amount of muscle in the body increases, and fat is burned as its
energy is needed to help fuel the body's increased metabolism.

Chemical Changes in the Blood During Exercise

During exercise, the muscles use up oxygen as they convert chemical energy in glucose to mechanical energy. This
O2 comes from hemoglobin in the blood. CO 2 and H+ are produced during the breakdown of glucose, and are
removed from the muscle via the blood. The production and removal of CO 2 and H+, together with the use and
transport of O2, cause chemical changes in the blood. These chemical changes, unless offset by other physiological
functions, cause the pH of the blood to drop. If the pH of the body gets too low (below 7.4), a condition known as
acidosis results. This can be very serious, because many of the chemical reactions that occur in the body, especially
those involving proteins, are pH-dependent. Ideally, the pH of the blood should be maintained at 7.4. If the pH
drops below 6.8 or rises above 7.8, death may occur. Fortunately, we have buffers in the blood to protect against
large changes in pH.
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Figure 1

This figure highlights some of the major acute (short-

term) effects on the body during exercise.

How Chemicals Are Exchanged in the Body

All cells in the body continually exchange chemicals (e.g., nutrients, waste products, and ions) with the external
fluid surrounding them. This external fluid, in turn, exchanges chemicals with the blood being pumped throughout
the body. A dominant mode of exchange between these fluids (cellular fluid, external fluid, and blood) is diffusion
through membrane channels, due to a concentration gradient associated with the contents of the fluids. Hence,
the chemical composition of the blood (and therefore of the external fluid) is extremely important for the cell. If,
for instance, the pH of the blood and external fluid is too low (too many H + ions), then an excess of H+ ions will
enter the cell. As mentioned above, maintaining the proper pH is critical for the chemical reactions that occur in
the body. In order to maintain the proper chemical composition inside the cells, the chemical composition of the
fluids outside the cells must be kept relatively constant. This constancy is known in biology as homeostasis.
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Figure 2

This is a schematic diagram showing the flow of

species across membranes between the cells, the
extracellular fluid, and the blood in the capillaries.

The body has a wide array of mechanisms to maintain homeostasis in the blood and extracellular fluid. The most
important way that the pH of the blood is kept relatively constant is by buffers dissolved in the blood. Other
organs help enhance the homeostatic function of the buffers. The kidneys help remove excess chemicals from the
blood. It is the kidneys that ultimately remove (from the body) H + ions and other components of the pH buffers
that build up in excess. Acidosis that results from failure of the kidneys to perform this excretory function is known
as metabolic acidosis. However, excretion by the kidneys is a relatively slow process, and may take too long to
prevent acute acidosis resulting from a sudden decrease in pH (e.g., during exercise). The lungs provide a faster
way to help control the pH of the blood. The increased-breathing response to exercise helps to counteract the pH-
lowering effects of exercise by removing CO 2, a component of the principal pH buffer in the blood. Acidosis that
results from failure of the lungs to eliminate CO 2 as fast as it is produced is known as respiratory acidosis.

Questions on Chemical Changes in Blood During Exercise and How Chemicals Are Exchanged in the Body

1. Why does exercise generate H+?

2. How can H+ generated in muscle cells during exercise affect the pH of the blood throughout the body (i.e.,
how does the concentration of H+ in the muscle cells affect the concentration of H + in the blood)?

How Buffers Work: A Quantitative View

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The kidneys and the lungs work together to help maintain a blood pH of 7.4 by affecting the components of the
buffers in the blood. Therefore, to understand how these organs help control the pH of the blood, we must first
discuss how buffers work in solution.

Acid-base buffers confer resistance to a change in the pH of a solution when hydrogen ions (protons) or hydroxide
ions are added or removed. An acid-base buffer typically consists of a weak acid, and its conjugate base (salt).
Buffers work because the concentrations of the weak acid and its salt are large compared to the amount of
protons or hydroxide ions added or removed. When protons are added to the solution from an external source,
some of the base component of the buffer is converted to the weak-acid component (thus using up most of the
protons added); when hydroxide ions are added to the solution (or, equivalently, protons are removed from the
solution), protons are dissociated from some of the weak-acid molecules of the buffer, converting them to the
base of the buffer (and thus replenishing most of the protons removed). However, the change in acid and base
concentrations is small relative to the amounts of these species present in solution. Hence, the ratio of acid to
base changes only slightly. Thus, the effect on the pH of the solution is small, within certain limitations on the
amount of H+ or OH- added or removed.

The Carbonic-Acid-Bicarbonate Buffer in the Blood

By far the most important buffer for maintaining acid-base balance in the blood is the carbonic-acid-bicarbonate
buffer. The simultaneous equilibrium reactions of interest are

. (1)

We are interested in the change in the pH of the blood; therefore, we want an expression for the concentration of
H+ in terms of an equilibrium constant and the concentrations of the other species in the reaction (HCO 3-, H2CO3,
and CO2).

To more clearly show the two equilibrium reactions in the carbonic-acid-bicarbonate buffer, Equation 1 is rewritten
to show the direct involvement of water:

(10
)

Carbonic acid (H2CO3) is the acid and water is the base. The conjugate base for H 2CO3 is HCO3- (bicarbonate ion).
Carbonic acid also dissociates rapidly to produce water and carbon dioxide, as shown in the equilibrium on the
right of Equation 10. This second process is not an acid-base reaction, but it is important to the blood's buffering
capacity, as we can see from Equation 11, below.

(11)
.

Notice that Equation 11 is in a similar form to the Henderson-Hasselbach equation. Equation 11 does not meet the
strict definition of a Henderson-Hasselbach equation, because this equation takes into account a non-acid-base
reaction (i.e., the dissociation of carbonic acid to carbon dioxide and water), and the ratio in parentheses is not the
concentration ratio of the acid to the conjugate base. However, the relationship shown in Equation 11 is frequently
referred to as the Henderson-Hasselbach equation for the buffer in physiological applications.

In Equation 11, pK is equal to the negative log of the equilibrium constant, K, for the buffer (Equation 12).
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(12)
where K=Ka/K2 (from Equation 10).

This quantity provides an indication of the degree to which HCO 3- reacts with H+ (or with H3O+ as written in
Equation 10) to form H2CO3, and subsequently to form CO2 and H2O. In the case of the carbonic-acid-bicarbonate
buffer, pK=6.1 at normal body temperature.

Derivation of the pH Equation for the Carbonic-Acid-Bicarbonate Buffer

We may begin by defining the equilibrium constant, K 1, for the left-hand reaction in
Equation 10, using the Law of Mass Action:

(13)
.
Ka (see Equation 9, above) is the equilibrium constant for the acid-base reaction that is
the reverse of the left-hand reaction in Equation 10. It follows that the formula for K a is

(14)
.
The equilibrium constant, K2, for the right-hand reaction in Equation 10 is also defined
by the Law of Mass Action:

(15)
.
Because the two equilibrium reactions in Equation 10 occur simultaneously, Equations
14 and 15 can be treated as two simultaneous equations. Solving for the equilibrium
concentration of carbonic acid gives

. (16)
Rearranging Equation 16 allows us to solve for the equilibrium proton concentration in
terms of the two equilibrium constants and the concentrations of the other species:

(17)
.
Because we are interested in the pH of the blood, we take the negative log of both
sides of Equation 17:

(18)
,

Recalling the definitions of pH and pK (Equations 2 and 12, above), Equation 18 can be
rewritten using more conventional notation, to give the relation shown in Equation 11,
which is reproduced below:
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As shown in Equation 11, the pH of the buffered solution (i.e., the blood) is dependent only on the ratio of the
amount of CO2 present in the blood to the amount ofHCO3- (bicarbonate ion) present in the blood (at a given
temperature, so that pK remains constant). This ratio remains relatively constant, because the concentrations of
both buffer components (HCO3- and CO2) are very large, compared to the amount of H+ added to the blood during
normal activities and moderate exercise. When H+ is added to the blood as a result of metabolic processes, the
amount of HCO3- (relative to the amount of CO2) decreases; however, the amount of the change is tiny compared
to the amount of HCO3- present in the blood. This optimal buffering occurs when the pH is within approximately 1
pH unit from the pK value for the buffering system, i.e., when the pH is between 5.1 and 7.1.

However, the normal blood pH of 7.4 is outside the optimal buffering range; therefore, the addition of protons to
the blood due to strenuous exercise may be too great for the buffer alone to effectively control the pH of the
blood. When this happens, other organs must help control the amounts of CO 2 and HCO3- in the blood. The lungs
remove excess CO2 from the blood (helping to raise the pH via shifts in the equilibria in Equation 10), and the
kidneys remove excess HCO3- from the body (helping to lower the pH). The lungs' removal of CO 2 from the blood is
somewhat impeded during exercise when the heart rate is very rapid; the blood is pumped through the capillaries
very quickly, and so there is little time in the lungs for carbon dioxide to be exchanged for oxygen.

Figure 3

This figure shows the major organs that help control

the blood concentrations of CO2 and HCO3-, and thus
help control the pH of the blood.

Removing CO2 from the blood helps increase the pH.

Removing HCO3- from the blood helps lower the pH.
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Why the Optimal Buffering Capacity Is at pH=pK

Why is the buffering capacity of the carbonic-acid-bicarbonate buffer highest when the pH is close to the pK value,
but lower at normal blood pH? The answer to this question lies in the shape of the titration curve for the buffer,
which is shown in Figure 4, below.

Titration Curve for the Bicarbonate-Buffer System

It is possible to plot a titration curve for this buffer system. In this plot, the vertical axis shows the pH of the
buffered solution (in this case, the blood). The horizontal axis shows the composition of the buffer: on the left-
hand side of the plot, most of the buffer is in the form of carbonic acid or carbon dioxide, and on the right-hand
side of the plot, most of the buffer is in the form of bicarbonate ion. Note that as acid is added, the pH decreases
and the buffer shifts toward greater H2CO3 and CO2 concentration. Conversely, as base is added, the pH increases
and the buffer shifts toward greater HCO 3- concentration (Equation 10).

Figure 4

This is the titration curve for the carbonic-acid-bicarbonate buffer. Note that
the pH of the blood (7.4) lies outside the region of greatest buffering capacity
(green).

Note: The percent buffer in the form of HCO3- is given by the formula:

(19)

The slope of the curve is flattest where the pH is equal to the pK value (6.1) for the buffer. Here, the buffering
capacity is greatest because a shift in the relative concentrations of bicarbonate and carbon dioxide produces only
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a small change in the pH of the solution. However, at pH values higher than 7.1, the slope of the curve is much
higher. Here, a shift in the relative concentrations of bicarbonate and carbon dioxide produces a large change in
the pH of the solution. Hence, at the physiological blood pH of 7.4, other organs must help to control the amounts
of HCO3- and CO2 in the blood to keep the pH relatively constant, as described above.

Other pH-Buffer Systems in the Blood

Other buffers perform a more minor role than the carbonic-acid-bicarbonate buffer in regulating the pH of the
blood. The phosphate buffer consists of phosphoric acid (H 3PO4) in equilibrium with dihydrogen phosphate ion
(H2PO4-) and H+. The pK for the phosphate buffer is 6.8, which allows this buffer to function within its optimal
buffering range at physiological pH. The phosphate buffer only plays a minor role in the blood, however, because
H3PO4 and H2PO4- are found in very low concentration in the blood. Hemoglobin also acts as a pH buffer in the
blood. Hemoglobin protein can reversibly bind either H + (to the protein) or O2 (to the Fe of the heme group), but
that when one of these substances is bound, the other is released (as explained by the Bohr effect). During
exercise, hemoglobin helps to control the pH of the blood by binding some of the excess protons that are
generated in the muscles. At the same time, molecular oxygen is released for use by the muscles.

Questions on How Buffers Work: A Quantitative View

3. If blood had a normal pH of 6.1 instead of 7.2, would you expect exercise to result in heavy breathing? 
Justify your answer.

4. How would a graph like that found in Figure 4 differ for the phosphate buffer system?

Equilibrium Shifts: A Qualitative View

The above discussion treats changes in pH quantitatively. These changes in pH can be described qualitatively, also.
A qualitative view is very useful for predicting how the pH will change in response to external conditions (such as
exercise). The principle used for this qualitative view is known as Le Châtelier's Principle.

Le Châtelier's Principle

When a reactant or product of an equilibrium reaction is added to a solution that is at equilibrium, the added
species will react to change the concentrations of the reactants and products in the solution until a new
equilibrium is established. This process is known as a shift in the equilibrium. In 1884, Henri Le Châtelier developed
a rule to predict how a system in equilibrium will shift when the conditions of the system are changed. Although
this rule can oversimplify the changes that occur in certain situations, it is a powerful and useful tool for predicting
the direction of an equilibrium shift. Le Châtelier's Principle states that "if a change in conditions ([an external]
'stress') is imposed on a system at equilibrium, the equilibrium position will shift in a direction that tends to
reduce that change in conditions" (Zumdahl, 208). For example, if the concentration of one of the products of an
equilibrium reaction is increased in a solution that was at equilibrium (prior to the concentration increase), the
equilibrium will shift so as to reduce the concentration of the product, i.e.,more reactant will be generated. Of
course, the reverse equilibrium shift would occur when the concentration of a product is decreased. The effect of a
temperature change can also be predicted by Le Châtelier's Principle. (In the case of a change in temperature, the
equilibrium constant actually changes.) If a reaction is exothermic, "heat" is treated as a "product" (e.g., A + B -> C
+ D + "heat"). If a reaction is endothermic, "heat" is treated as a "reactant" (e.g., "heat" + A + B -> C + D). Increasing
the temperature can be thought of as increasing the amount of "heat" in the reaction. Examples of external
stresses and the equilibrium shifts predicted by Le Châtelier's Principle are shown in the purple table below.
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External Stress Predicted Equilibrium Shift

Change in pressure Affects gases only.
Concentration of reactant(s) Equilibrium shifts toward products (to the
increased right).
Concentration of product(s) increased Equilibrium shifts toward reactants (to the left).
Temperature increased
Equilibrium shifts toward reactants (to the left).
(exothermic reaction)
Temperature increased Equilibrium shifts toward products (to the
(endothermic reaction) right).

Example: Removal of Bicarbonate by the Kidneys

Le Châtelier's Principle can be used to explain how the kidneys help prevent excessively high pH (a condition
known as alkalosis). When the pH of the blood is too high, the kidneys remove bicarbonate ion (HCO 3-) from the
blood. As the kidneys decrease the blood's concentration of HCO 3-, the equilibrium reaction in Equation 10 is
shifted toward the left to compensate for the loss in HCO 3-, according to Le Châtelier's Principle. When the
equilibrium shifts to the left, more H+ ions are generated together with HCO3- ions. As a result, the pH decreases.

Questions on Equilibrium Shifts: A Qualitative View

5. An emergency medical team evaluates an Olympic athlete and determines that she has alkalosis. What
component of the carbonic-acid-bicarbonate buffer would the athlete be given to decrease the pH of the
blood?

6. Hyperventilation (very rapid and deep breathing, which reduces the concentration of CO 2 in the blood)
causes dizziness.
a. How does hyperventilation affect the pH of the blood (i.e., is the pH increased or decreased as a
result of hyperventilation)? Briefly, explain your answer in terms of equilibrium shifts.
b. The normal first-aid treatment for hyperventilation is to have the patient breathe into a paper
bag. Briefly, explain why this treatment works and tell what effect the paper-bag treatment has
on the pH of the blood.

Summary: What Happens to the Blood During Exercise?

When you exercise, many processes work together to determine how the pH of the blood will change.

The following steps outline the processes that affect the buffers in the blood during exercise.

 Hemoglobin carries O2 from the lungs to the muscles through the blood.

 The muscles need more O2 than normal, because their metabolic activity is increased during exercise. The
amount of oxygen in the muscle is therefore depleted in the muscles, setting up a concentration gradient
between the muscle cells and the blood in the capillaries. Oxygen diffuses from the blood to the muscles,
via this concentration gradient.
 The muscles produce CO2 and H+ as a result of increased metabolism, setting up concentration gradients
in the opposite direction from the O2 gradient.
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 The CO2 and H+ flow from the muscles to the blood, via these concentration gradients.
 The buffering action of hemoglobin picks up the extra H + and CO2.
 If the amounts of H+ and CO2 exceed the capacity of hemoglobin, they affect the carbonic acid equilibrium
(Equation 10), as predicted by Le Châtelier's Principle or the quantitative treatment in terms of
equilibrium constants. As a result, the pH of the blood is lowered, causing acidosis.
 The lungs and kidneys respond to pH changes by removing CO2, HCO3-, and H+ from the blood.

Hence, the body has developed finely-tuned chemical processes (based on buffering and acid-base equilibria) that
work in combination to handle the changes that exercise produces.

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