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Ao de la Diversificacin Productiva y del Fortalecimiento de la Educacin

Universidad Nacional Mayor de San Marcos

Facultad de Medicina
Unidad de Postgrado
Maestra de Fisiologa


Alumna: Anselma Pardo Villafranca

Docente: Dr. Hugo Cebreros



It is essential for the body to control the concentration of free protons (hydrogen
ions) in the ECF. Although most substances regulated by renal processes exist
at plasma levels in the millimolar range or greater, the normal hydrogen ion
is a seemingly miniscule 40 nanomolar (1 nanomole is 1 millionth of a
millimole). Even though very small, this level is crucial for body function. Proteins
contain titratable groups that reversibly bind hydrogen ions. As sites on membrane
proteins protonate and deprotonate in response to changes in extracellular pH,
the resulting alteration of local charge density affects the shape, and therefore
the behavior of those proteins. The plasma levels of hydrogen ions are constantly
being altered by a number of processes, including (1) metabolism of ingested food,
(2) secretions of the gastrointestinal (GI) tract, (3) de novo generation of acids and
bases from metabolism of stored fat and glycogen, and (4) changes in the production
of carbon dioxide.
The essence of the physiological response to these changes comes down to
2 processes: (1) matching the excretion of acid-base equivalents to their input, that
is, maintaining balance, and (2) regulating the ratio of weak acids to their conjugate
bases in buffer systems. Buffer systems limit changes in pH to a small range.
The 2 processes of excreting acids and bases, and regulating physiological buffer
concentrations are intimately related, but they are not identical. It is possible to be
in balance even though buffer ratios are inappropriate.

Central Role of H+:

The Brnsted/Lowry Formulation
A wide array of molecules contains hydrogen atoms that may dissociate in
solution, yielding H+. Once dissociated, these same molecules become sites
for potential recombination with H+. This cycle of dissociation and recombination
led to the following definitions by Brnsted and Lowry (3,4). An
acid is any molecular species that can function as a proton donor (i.e., that
can dissociate an H+). A base is a proton acceptor (i.e., a compound that
can bind to and remove H+ from solution). The anion remaining when an
acid (HA) gives up H+ is termed the conjugate base (A-) of that acid,
because it becomes a potential proton acceptor. These concepts are illustrated
by the following formula:

This simple formula provides the basis for measurement of acidity, that
is, the amount of free H+ released from HA at equilibrium in any given setting,
and avoids the confusion that arose with other approaches to describing the

acidbase status of the body fluids such as defining cations as bases and anions
as acids (6,7). The relative ease with which a given molecule in a given milieu
dissociates H+ under equilibrium conditions is a measure of acid strength. In
the mixture of weak acids that comprise biological fluids, the concentration of
H+ ([H+]) is vanishingly small in comparison to HA and A_, and its measurement
requires the use of the pH electrode. The technique for measuring [H+] in
biological solutions, and its nomenclature, is described below.

Units of Measurement: [H] and pH

The degree of acidity of a solution is a measure of the activity of H in that
solution. Because H activity in chemical solutions can range so widely and
because small changes have such a large impact on enzyme reactions,
Srensen (8) developed the pH unit to describe acidity and set the standards
for its measurement. He defined pH as the negative logarithm of hydrogen
ion concentration, [H]:
pH _log10H_

Because pH is a logarithm, it has no units. [H] in this equation is

expressed in mol or equivalents per liter.
Srensen measured pH using an electrode that generates a voltage
proportional to the difference in H activity, aH , rather than [H],
between a test solution and a standard solution. Unfortunately, his standard
was based on a value for aH corrected for ionic interaction that
did not precisely reflect activity. A later correction was introduced, but
in fact a precise definition of aH is not possible with electrode technology
(9). Thus, while pH is a highly accurate and reproducible measure of
acidity, it is not an exact measure of either aH or [H]. These two
entities are related as follows:
aH gH H_ 3
In this equation, gH is the activity coefficient for H. The value for
gH is directly related to the temperature and inversely related to the ionic
strength of the solution (9). In biological solutions of interest to physiologists
and clinicians, gH is close to 1.0 and varies only very slightly because
temperature and ionic strength are both closely regulated. As a result (and
because there is no completely precise measure of either), [H] and aH are
used interchangeably in human acidbase analyses. Unless otherwise noted,
[H] will be used throughout this book instead of aH when this measure
rather than pH is used to denote acidity. Because of the very low concentrations
found in biological fluids, [H] is expressed in nanoequivalents per liter
(nEq=L), rather than in equivalents or milliequivalents. To convert the measured
pH to [H] in nEq=L, the following formula is used:
H_ 109_pH 4
The use of pH units to assess acidity is well established among chemists
because it allows the wide range of [H] encountered to be designated
by a manageable numerical scale (pH 014). The range encountered in living
biological systems is considerably narrower, however, and some acidbase
experts have advocated using [H] rather than pH to evaluate clinical
acidbase problems (2,10). The relationship between pH and [H] over

the range of values of interest is shown in Fig. 1 and Table 1. This conversion
has two main virtues. The first is to make manipulation of the Henderson
Hasselbalch equation (see later) simpler by removing logarithms, and
the second is to call attention to the impact of changes in acidity on mass
balance in any quantitative analysis (1). The two modes of assessing acidity
are used interchangeably in this book.
Hydrogen Ion Activity in Water: Law of Mass Action
In his discussion of the milieu interieur or inner environment of the
body fluids, Claude Bernard (12) stated, Water is the first indispensable
condition of every vital manifestation . . . . The properties of this remarkable
molecule are therefore worthy of consideration. Because of its structure,
water behaves as a dipole with a weak positive charge in the region of
the hydrogen atoms and a weak negative charge in the region of the
oxygen atom. This property of water causes substances whose atoms are
kept together primarily by electrostatic bonds to dissociate into their
component ions when they dissolve in it. In addition, this property of water
causes it to dissociate slightly into H and OH_. Although this dissociation
is minute, it can be measured with the pH electrode. Water dissociation
follows the law of mass action. According to this principle, the cycle
of dissociation and recombination is a continuous and reversible process:
HOH $ H OH_ 5
The H in Eq. (5) actually combines with an undissociated HOH to
produce a hydronium ion, H3O, but by convention the symbol H is used
to designate hydrogen ions in solution (9). At any given moment, a particular
molecule is either dissociated or recombined. The fraction of all such
molecules in one or the other state is stable at equilibrium because the more
molecules dissociate [movement to the right-hand side of Eq. (5)], the stronger
the drive for recombination (movement to the left-hand side), and vice
versa. At equilibrium, conditions are defined as follows:
H_ _ OH__=HOH_ K

This equation states that at equilibrium the ratio of the concentration
products of the opposing reactions is a predictable value (K0
HOH). K0
HOH is
not a constant, but varies with temperature. Because the high concentration
of undissociated water ([HOH] 55.5 M) varies negligibly in dilute
solutions, the equation simplifies to
H_ _ OH__ K

10_14 7
The prime symbol indicates that concentrations rather than activities

are used, and the concentration of HOH is included in the value of K. At

25_C, K0 is 10_14. In pure water, [H] [OH_] and therefore [H] is equal
to the square root of 10_14 or 10_7. Thus, pH 7.0, defined as neutrality. In
body fluids, the pH optimum is 7.40 at 37_C, defined by functionality rather
than equivalence of [H] and [OH_]. The ability of water to dissolve ionic
compounds reflects the development of electrostatic linkages between water
molecules and the cations and anions of the solute. For example, when NaCl
is placed in water, Cl_ bonds weakly with the positive pole and Na bonds

weakly with the negative pole of the water molecule.

Sistema buffer

A buffer system serves the useful purpose

of limiting the change in pH upon addition of other acids or bases. When another
acid is added, most of the hydrogen ions released by that acid combine with the
conjugate base of the buffer system, greatly restricting the increase in free hydrogen
ions. Similarly, when another base is added, most of the free hydrogen ions
removed by the base are replaced by hydrogen ions that dissociate from the acid
of the buffer system.
In any buffer system, the ratio of the acid to its conjugate base fixes the free
aqueous concentration of hydrogen ion (which is only a trivial fraction of the
of either the acid or base). This relation is shown in Equation 9-2 or in
the more familiar pH form (the Henderson-Hasselbalch equation) in Equation 9-3.
We should emphasize that buffer systems in the body do not eliminate added acid
or base equivalents, but only limit the effect of the equivalents on blood pH. In
the face of persistent imbalance between input and output, the acid or base component
of the buffer is gradually reduced in concentration as it is converted to
the other component. Eventually acid or base equivalents added to the body, even
though transiently associated with blood buffers, must be excreted by the kidneys
to maintain balance.
Buffer systems exist in the extracellular fluid, the intracellular fluid (the cytosol
of the various cells in the body), and the matrix of bone. Although these buffers
are in different compartments, they communicate with each other. Phosphate
and albumin are important buffers in the ECF. Hemoglobin in red blood cells
is an important intracellular buffer, since changes in plasma pH lead to uptake
or release of protons from red blood cells. For several reasons, the most important
buffer system in the body turns out to be the CO2-bicarbonate buffer system.
Fortunately, we can understand the role of buffers in acid-base balance by looking
at this single buffer system alone and ignore the others because all buffer systems
must have ratios of weak acid to conjugate base that result in the same pH.

Quantitation of Buffer Effect on Acidity

Figure 2 depicts the titration curves of three buffers: acetic acid=acetate, uric
acid=monourate, and monobasic phosphate=dibasic phosphate. The midpoint
of each of the curves denotes the setting in which the concentrations
of the acid and its conjugate base are equal. From Eqs. (9) and (10), one
can see that when these concentrations are equal, [H] K0 or pH pK0 .

As illustrated in Fig. 2, the buffering ability or capacity is also the greatest

when pH pK0 .
The capacity of a specific buffer to resist a change in pH is defined as
its buffer value (b), the first derivative of the titration curve:
b dacid or base=dpH 14
Buffer value is conventionally expressed as mol=L or mmol=L of strong acid
or base added per unit change in pH. Given the curves in Figure 2, it is
apparent that b varies with pH and reaches a maximum when pH pK0 .
This unit of measure has been named the slyke, in honor of Donald D.
Van Slyke (15), a pioneer in the study of acids and bases in biological fluids.
In a seminal paper, he deduced that b is a function of the concentration of
the weak acid in a solution (C), the K0 (or pK0 ) of the buffer, and the prevailing
[H] (16). He also showed that for any weak acid, the maximal value for
b (i.e., when [H] K0 or pH pK0 ) is 0.575. Thus, if one added HCl to the
30mM phosphate solution discussed earlier at a starting pH of 6.8 (the pK0
for H2PO4
_=HPO4 2_
), 0.575 _ 30 or 17.25 mmol of HCl would be required to
lower pH by 1 unit, to 5.8.
Complex Solutions Containing Multiple Buffers
The buffer value of a solution containing more than one buffer is equal to
the additive effects of all buffers in the solution. In solutions containing multiple
buffers with pK0 values that are reasonably close to one another, or one
that contains a complex buffer with multiple dissociation constants (e.g.,
hemoglobin), the titration curve may approach linearity over the range of
pH values of interest. In this setting, b can be approximated by a single
value (see later). Blood, extracellular and intracellular fluids are examples
of such complex solutions. In the extracellular compartment, the principal
buffers are carbonic acid, phosphate, and proteins. Hemoglobin, although
located within red cells, is considered by convention as one of the proteins
contributing to extracellular buffering. The intracellular compartment is
more complex (see Chapter 2), comprised of multiple subcompartments
containing different proteins, and both inorganic and organic phosphates.
Carbonic acid is also an important intracellular buffer.
Isohydric Principle
Although most biological solutions contain a variety of simple and complex
buffers, such solutions have only a single value for [H] at any given time if
they are well mixed and homogeneous. It follows from Eq. (9) above that





In such a complex solution, the equilibrium value for [H] is determined
by the composite effect of the concentrations of the buffer pairs
and their respective dissociation constants. The beauty of this formulation
is that one can quickly and easily determine the value for [H] in a given
solution from a knowledge of the K0 and concentrations of just one acid
and its conjugate base in the system. Thus, regardless of the complexity of

the solution evaluated, the Brnsted=Lowry approach provides a powerful

means for analysis of its acidbase status by focusing on a single buffer.
The buffer system most commonly used for this analysis in biological fluids
is carbonic acid=bicarbonate. It should be emphasized, however, that any
buffer pair would serve the purpose. The features of carbonic acid that make
it such a powerful buffer are discussed below.

Describe el pH de los compartimientos corporales y explica los principales sistemas amortiguadores y el equilibrio