Regulation of Acid Base Balance pdf - The Body Fluids and Kidneys

sium, lithium, and so forth—with a highly basic ion such as a hydroxyl ion (OH

formed by the combination of one or more of the alkaline metals—sodium, potas-

are often used synonymously. An

The terms

bases.

proteins in the other cells of the body are among the most important of the body’s

. The protein hemoglobin in the red blood cells and

as bases, because some of the amino acids that make up proteins have net negative

. The proteins in the body also function

to form H

. Likewise, HPO

to form H

. For example, HCO

). Likewise, carbonic acid (H

to as acids. An example is hydrochloric acid (HCl), which ionizes in water to form

A hydrogen ion is a single free proton released from a hydrogen atom. Molecules

various cell functions.

) concentration. Thus,

, which averages only 0.00004 mEq/L. Equally important, the

lar fluid (142 mEq/L) is about 3.5 million times as great as the normal concen-

is kept at a low level. For example, the concentration of sodium in extracellu-

Compared with other ions, the H

hydrogen concentration alter virtually all cell and body functions.

concentration. Therefore, changes in

Precisely Regulated

Hydrogen Ion Concentration Is

body fluids.

), one of the key components of acid-base control systems in the

secretion and renal reabsorption, production, and excretion of bicarbonate

concentration are discussed, with special emphasis on the control of renal

In this chapter, the various mechanisms that contribute to the regulation of

ple acid-base buffering mechanisms involving the blood, cells, and lungs that are

by the kidneys. There are also multi-

removal. However, precise control

as is true for other ions, the kidneys play a key role

from the body. And,

body. For instance, to achieve homeostasis, there

Regulation of Acid-Base Balance

383

Regulation of hydrogen ion (H

) balance is similar

in some ways to the regulation of other ions in the

must be a balance between the intake or production
of H

and the net removal of H

in regulating H

of extracellular fluid H

concentration involves

much more than simple elimination of H

essential in maintaining normal H

concentrations in both the extracellular and

the intracellular fluid.

ions (HCO

–

Precise H

regulation is essential because the activities of almost all enzyme

systems in the body are influenced by H

concentration of the body fluids normally

tration of H

normal variation in H

concentration in extracellular fluid is only about one mil-

lionth as great as the normal variation in sodium ion (Na

the precision with which H

is regulated emphasizes its importance to the

Acids and Bases—Their Definitions
and Meanings

containing hydrogen atoms that can release hydrogen ions in solutions are referred

hydrogen ions (H

) and chloride ions (Cl

–

) ionizes

in water to form H

and bicarbonate ions (HCO

–

A base is an ion or a molecule that can accept an H

–

is a

base because it can combine with H

is a base

because it can accept an H

–

charges that readily accept H

base and alkali

alkali is a molecule

–

between 6.0 and 7.4. Hypoxia of the tissues and poor

. Depending on the type of cells, the

person can live more than a few hours is about 6.8, and

pH rises above 7.4. The lower limit of pH at which a

is 7.4, a person is considered to have

(Table 30–1). Because the normal pH of arterial blood

The normal pH of arterial blood is 7.4, whereas the

concentration, and a high pH

concentration; therefore, a low pH

From this formula, one can see that pH is inversely

(0.00000004 Eq/L). Therefore, the normal pH is

] is 40 nEq/L

For example,

the normal [H

scale, using pH units. pH is related to the actual H

because these small numbers are cumbersome, it is cus-

concentration normally is low, and

as 10 nEq/L to as high as 160 nEq/L without causing

conditions, the H

are only about 3 to 5 nEq/L, but under extreme

of about 0.00004 mEq/L (40 nEq/L). Normal variations

cussed earlier, the blood H

Normal Hydrogen Ion Concentration and pH of Body Fluids

base.

tion are weak acids and bases. The most important ones

. Most of the acids and bases in the extracel-

O). A typical weak base is

, which reacts

from a solution. A typical example is OH

and, therefore, quickly removes these

. A strong base is one that reacts rapidly and

with less vigor. An example is

therefore, release H

acids have less tendency to dissociate their ions and,

in solution. An example is HCl. Weak

Strong and Weak Acids and Bases.

acidosis.

, which is referred

from the body fluids, in

typical bases. For similar reasons, the term

to remove it from solution; they are, therefore,

The base portion of these molecules reacts quickly with

384

Unit V

The Body Fluids and Kidneys

alkalosis

refers to excess removal of H

contrast to the excess addition of H

to as

A strong acid is one that

rapidly dissociates and releases especially large
amounts of H

strongly with H

–

with H

to form water (H

HCO

–

because it binds with H

much more weakly than

does OH

–

lular fluid that are involved in normal acid-base regula-

that we discuss in detail are H

and bicarbonate

and Changes That Occur in Acidosis and Alkalosis.

As dis-

concentration is normally

maintained within tight limits around a normal value

concentration can vary from as low

death.

Because H

tomary to express H

concentration on a logarithm

con-

centration by the following formula (H

concentration

] is expressed in equivalents per liter):

= –log [0.00000004]

= 7.4

related to the H

corresponds to a high H

corresponds to a low H

concentration.

pH of venous blood and interstitial fluids is about 7.35
because of the extra amounts of carbon dioxide (CO

)

released from the tissues to form H

in these fluids

acidosis when the

pH falls below this value and to have alkalosis when the

the upper limit is about 8.0.

Intracellular pH usually is slightly lower than plasma

pH because the metabolism of the cells produces acid,
especially H

pH of intracellular fluid has been estimated to range

blood flow to the tissues can cause acid accumulation
and decreased intracellular pH.

log H

log

[ ]

= -

[ ]

ful of the acid-base regulatory systems.

hours to several days, they are by far the most power-

compared with the other defenses, over a period of

can eliminate the excess acid or base from the body.

kidneys,

slowly responding third line of defense, the

These

from the body.

therefore, H

The second line of defense, the

of a second to minimize these changes. Buffer systems

concentration, the

When there is a change in H

normal during acidosis or alkalosis.

excrete either acid or alkaline urine, thereby readjust-

kidneys,

uid; and (3) the

(and, therefore, H

respiratory center,

tion; (2) the

the body fluids,

chemical acid-base buffer systems of

alkalosis: (1) the

There are three primary systems that regulate the H

Buffers, Lungs, and Kidneys

Hydrogen Ion Concentration:

In the remainder of this chapter, we discuss the reg-

The H

cells of the stomach mucosa, as discussed in Chapter 64.

excreting acids or bases at variable rates.

cussed later, the kidneys play a major role in correcting

uid. As dis-

The pH of urine can range from 4.5 to 8.0, depending

on the acid-base status of the extracellular fl

abnormalities of extracellular fluid H

concentration by

An extreme example of an acidic body fluid is the

HCl secreted into the stomach by the oxyntic (parietal)

concentration in these cells is about 4 million

times greater than the hydrogen concentration in blood,
with a pH of 0.8.

ulation of extracellular fluid H

concentration.

Defenses Against Changes in

concentration in the body fluids to prevent acidosis or

which immediately combine with acid

or base to prevent excessive changes in H

concentra-

which regulates the

removal of CO

) from the

extracellular fl

which can

ing the extracellular fluid H

concentration toward

buffer systems of the body fluids react within a fraction

do not eliminate H

from or add them to the body

but only keep them tied up until balance can be re-
established.

respiratory system,

also acts within a few minutes to eliminate CO

and,

first two lines of defense keep the H

con-

centration from changing too much until the more

Although the kidneys are relatively slow to respond

Table 30–1

Urine

uid

4.5

Venous blood

4.5

Arterial blood

4.0

Concentration (mEq/L)

pH and H

Concentration of Body Fluids

Extracellular fluid

¥ 10

–5

7.40

¥ 10

–5

7.35

Interstitial fl

¥ 10

–5

7.35

Intracellular fl

¥ 10

–3

to 4

¥ 10

–5

6.0 to 7.4

¥ 10

–2

to 1

¥ 10

–5

4.5 to 8.0

Gastric HCl

160

0.8

, as

uid. NaHCO

salt, occurs predominantly as sodium bicarbonate

The second component of the system, bicarbonate

O to form H

with H

epithelial cells of the renal tubules, where CO

released; carbonic anhydrase is also present in the

dant in the walls of the lung alveoli, where CO

is present. This enzyme is especially abun-

This reaction is slow, and exceedingly small amounts

with H

, and (2) a bicarbonate salt, such as NaHCO

tion that contains two ingredients: (1) a weak acid,

The bicarbonate buffer system consists of a water solu-

Bicarbonate Buffer System

The action of acid-base buffers can perhaps best be

cause huge changes in body

mally is only about 0.00004 mEq/L. Without buffering,

example, about 80 milliequivalents of hydrogen is

amounts of acids produced by the body each day. For

The importance of the body

buffer. In this way, changes in H

shifts toward the left, and H

concentration decreases, the reaction

the buffer, as long as buffer is available. Conversely,

reaction is forced to the right, and more H

concentration increases, the

. When the H

In this example, a free H

The general form of the buffering reaction is

Buffering of Hydrogen Ions

Regulation of Acid-Base Balance

Chapter 30

385

in the Body Fluids

A buffer is any substance that can reversibly bind H

combines with the buffer to

form a weak acid (H buffer) that can either remain as
an unassociated molecule or dissociate back to buffer
and H

binds to

when the H

is released from the

concentration are

minimized.

fluid buffers can be

quickly realized if one considers the low concentration
of H

in the body fluids and the relatively large

either ingested or produced each day by metabolism,
whereas the H

concentration of the body fluids nor-

the daily production and ingestion of acids would

fluid H

concentration.

explained by considering the buffer system that is
quantitatively the most important in the extracellular
fluid—the bicarbonate buffer system.

is formed in the body by the reaction of CO

of H

are formed unless the enzyme carbonic

anhydrase

reacts

ionizes weakly to form small amounts of H

and HCO

–

(NaHCO

) in the extracellular fl

ionizes almost completely to form HCO

–

and Na

follows:

NaHCO

HCO

æ Æ

H C

HCO

æÆ æ

H O

H CO

carbonic
anhydrase

¨ææ

ææ

æ Æ

ææ

Buffer H

H Buffer

æÆ æ

æ Æ

solution, the

This equation indicates that in an H

For any acid, the concentration of the acid relative

From mass balance considerations, the concentrations

, are ionized to some extent.

All acids, including H

Quantitative Dynamics of the

expiration. The rise in blood HCO

of CO

levels in the blood to decrease, but the decreased CO

The net result, therefore, is a tendency for the CO

with H

it reacts with NaOH), causing more CO

time, the concentration of H

replaces the strong base NaOH. At the same

. Thus, the weak base

In this case, the OH

base, such as sodium hydroxide (NaOH), is added to

The opposite reactions take place when a strong

from the

ulates respiration, which eliminates the CO

O. The excess CO

, which in

O production. From these reactions, one

is formed, causing increased

As a result, more H

bicarbonate buffer solution, the increased H

When a strong acid such as HCl is added to the

, the H

Now, putting the entire system together, we have the

following:

Because of the weak dissociation of H

concentration is extremely small.

released

from the acid (HCl

Æ H

+ Cl

–

) is buffered by HCO

–

≠H

+ HCO

–

Æ H

Æ CO

+ H

and H

can see that H

from the strong acid HCl reacts with

HCO

–

to form the very weak acid H

turn forms CO

and H

greatly stim-

extracellular fluid.

the bicarbonate buffer solution.

NaOH

+ H

Æ NaHCO

+ H

–

from the NaOH combines with

to form additional HCO

–

NaHCO

decreases (because

to combine

O to replace the H

in the blood inhibits respiration and decreases the rate

–

that occurs

is compensated for by increased renal excretion of
HCO

–

Bicarbonate Buffer System

of H

and HCO

–

are proportional to the concentration

of H

to its dissociated ions is defined by the dissociation
constant K

¢.

(1)

amount of free H

is equal to

(2)

H CO

HCO

¢ ¥

H CO

HCO

¢ =

H CO

HCO

æÆ æ

æ Æ

≠

NaOH

H O

H CO

HCO

æ Æ

H O

H CO

HCO

–

Ï Ì Ó

æÆ æ

æ Æ

æ æ

æÆ æ

causes the pH to rise, shifting the acid-base balance

From the Henderson-Hasselbalch equation, it is

and with it, one can calculate the pH of a solution if

For the bicarbonate buffer system, the pK is 6.1, and

ator and denominator in the last term, using the law of

Rather than work with a negative logarithm, we can

Therefore,

of that equation, which yields

Therefore, we can express the H

similar manner.

The dissociation constant can be expressed in a

rather than in actual concentrations. Recall that pH is

As discussed earlier, it is

measured. Therefore, equa-

0.03 mmol/mm Hg at body temperature.This means that

conditions, the solubility coef

; under physiologic

of CO

. Fortunately, the amount

dissolved in solution. However, most clinical labo-

The dissociation constant (K) for equation 3 is only

. Therefore, equation 2

. However, the CO

The concentration of undissociated H

386

Unit V

The Body Fluids and Kidneys

cannot be

measured in solution because it rapidly dissociates into
CO

and H

O or to H

and HCO

–

dissolved in the blood is directly proportional to the
amount of undissociated H

can be rewritten as

(3)

about

400

of the dissociation constant (K

¢) of equation

2 because the proportionality ratio between H

and

is 1:400.

Equation 3 is written in terms of the total amount of

ratories measure the blood CO

tension (P

) rather

than the actual amount of CO

in the blood is a linear function of P

times

the solubility coefficient for CO

ficient for CO

0.03 millimole of H

is present in the blood for each

millimeter of mercury P

tion 3 can be rewritten as

(4)

Henderson-Hasselbalch Equation.

customary to express H

concentration in pH units

defined as pH

= –log H

= –log K

concentration in

equation 4 in pH units by taking the negative logarithm

(5)

(6)

change the sign of the logarithm and invert the numer-

logarithms to yield

(7)

equation 7 can be written as

(8)

Equation 8 is the Henderson-Hasselbalch equation,

the molar concentration of HCO

–

and the P

are

known.

apparent that an increase in HCO

–

concentration

0 03

log

HCO

0 03

HCO

(

)

log

0 03

HCO

(

)

log

0 03

log

log H

= -

(

)

HCO

0.03

HCO

(

)

HCO

Hasselbalch equation. When acid is added, it is buffered

increasing the pH, as is evident from the Henderson-

to CO

bonate buffer system. When base is added to the system,

components of the buffer system are equal, the pH of

log of 1, which is equal to 0. Therefore, when the two

equal, the right-hand portion of equation 8 becomes the

When the concentrations of these two components are

to CO

Figure 30

Bicarbonate Buffer System Titration Curve.

respiratory alkalosis.

by a decrease in P

respiratory acidosis,

bolic alkalosis.

bolic acidosis,

disorders. Therefore, acidosis caused by a primary

centration, they are referred to as

When disturbances of acid-base balance result from

impaired, thus altering either the bicarbonate concen-

lungs and the kidneys, and acid-base disorders occur

from the coordinated efforts of both of these organs, the

. Normal physiologic acid-base homeostasis results

plasma, and by decreasing respiration, the lungs elevate

from the

rate of respiration, the lungs remove CO

controlled by the rate of respiration.

by the kidneys, whereas the P

later,

uid. As discussed

uid, provides

The Henderson-Hasselbalch equation, in addition to

decrease, shifting the acid-base balance toward acidosis.

toward alkalosis. An increase in P

causes the pH to

defining the determinants of normal pH regulation and
acid-base balance in the extracellular fl
insight into the physiologic control of acid and base
composition of the extracellular fl

the bicarbonate concentration is regulated mainly

in extracellular fluid is

By increasing the

when one or both of these control mechanisms are

tration or the P

of extracellular fluid.

a primary change in extracellular fluid bicarbonate con-

metabolic acid-base

decrease in bicarbonate concentration is termed meta-

whereas alkalosis caused by a primary

increase in bicarbonate concentration is called meta-

Acidosis caused by an increase in P

is called

whereas alkalosis caused

is termed

–1 shows

the changes in pH of the extracellular fluid when the
ratio of HCO

–

in extracellular fluid is altered.

the solution is the same as the pK (6.1) of the bicar-

part of the dissolved CO

is converted into HCO

–

causing an increase in the ratio of HCO

–

and

Acid added

Per cent of buffer in form of

and CO

100

Per cent of buffer in form of

HCO

Base added

100

Normal

operating

point in body

) are altered.

extracellular fluid when the percentages of buffer in the form of

Titration curve for bicarbonate buffer system showing the pH of

Figure 30–1

HCO

–

and CO

(or H

become maximally effective.

For this reason, the buffer

changes in extracellular pH.

the pH in intracellular fluid to change when there are

diffuse through all the cell membranes.

, however, can rapidly

occurs in the red blood cells. CO

uid, except for rapid equilibrium that

through the cell membrane, although these ions

There is a slight amount of diffusion of H

uid pH changes.

uid, nevertheless changes approxi-

The pH of the cells, although slightly lower than in

within the cells.

body because of their high concentrations, especially

Intracellular Buffers

Proteins: Important

uid. Also, the pH of intracellular

uid does, bringing the operating

ing power of the phosphate system, and (2) the tubular

centrated in the tubules, thereby increasing the buffer-

reasons: (1) phosphate usually becomes greatly con-

important in the tubular fluids of the kidneys,

cellular buffer,

concentration of the bicarbonate buffer. Therefore,

uid is low, only about 8 per cent of the

buffering power. However, its concentration in the

The phosphate buffer system has a pK of 6.8, which

, causing only a slight increase in

base, NaH

In this case, a strong base, NaOH, is traded for a weak

buffer system, the OH

When a strong base, such as NaOH, is added to the

, and the decrease in pH is minimized.

The result of this reaction is that the strong acid, HCl,

HCl is added to a mixture of these two substances, the

. When a strong acid such as

The main elements of the phosphate buffer system

uids.

uid buffer, it plays a major

Phosphate Buffer System

by the lungs.

lungs, as discussed later. As a result of this regulation,

, are regulated, respectively, by the kidneys and the

that the two elements of the buffer system, HCO

body. This apparent paradox is due mainly to the fact

Despite these characteristics, the bicarbonate buffer

, are not great.

system, CO

low and the buffering power is poor. Second, the con-

. For this reason, this system operates on

bonate buffer system is 6.1. This means that there is

uid is about 7.4, whereas the pK of the bicar-

be powerful, for two reasons: First, the pH of the extra-

From the titration curve shown in Figure 30

Buffer.

changes the pH considerably.

system. With low concentrations of the buffers, only a

The absolute concentration of the buffers is also an

system has no more buffering power.

, the

these limits, the buffering power rapidly diminishes.

extends from a pH of about 5.1 to 7.1 units. Beyond

of the pK, which for the bicarbonate buffer system

the pH is near the pK of the system. The buffer system

system. This means that the change in pH for any given

part of the curve, where the pH is near the pK of the

Second, the buffer system is most effective in the central

1, several points are apparent. First,

curve in Figure 30

From the titration

to CO

, which is then converted into dissolved CO

Regulation of Acid-Base Balance

Chapter 30

387

by HCO

–

decreasing the ratio of HCO

–

and decreasing

the pH of the extracellular fluid.

“Buffer Power” Is Determined by the Amount and Relative Con-
centrations of the Buffer Components.

–

the pH of the system is the same as the pK when each
of the components (HCO

–

and CO

) constitutes 50 per

cent of the total concentration of the buffer system.

amount of acid or base added to the system is least when

is still reasonably effective for 1.0 pH unit on either side

And when all the CO

has been converted into HCO

–

or when all the HCO

–

has been converted into CO

important factor in determining the buffer power of a

small amount of acid or base added to the solution

Bicarbonate Buffer System Is the Most Important Extracellular

–1,

one would not expect the bicarbonate buffer system to

cellular fl

about 20 times as much of the bicarbonate buffer
system in the form of HCO

–

as in the form of dis-

solved CO

the portion of the buffering curve where the slope is

centrations of the two elements of the bicarbonate

and HCO

–

system is the most powerful extracellular buffer in the

–

and

the pH of the extracellular fluid can be precisely con-
trolled by the relative rate of removal and addition of
HCO

–

by the kidneys and the rate of removal of CO

Although the phosphate buffer system is not impor-
tant as an extracellular fl
role in buffering renal tubular fluid and intracellular
fl

are H

–

and HPO

hydrogen is accepted by the base HPO

and con-

verted to H

–

HCl

+ Na

HPO

Æ NaH

+ NaCl

is replaced by an additional amount of a weak acid,
NaH

–

is buffered by the H

–

form additional amounts of HPO

+ H

NaOH

+ NaH

Æ Na

HPO

+ H

pH.

is not far from the normal pH of 7.4 in the body fluids;
this allows the system to operate near its maximum

extracellular fl

the total buffering power of the phosphate system in
the extracellular fluid is much less than that of the
bicarbonate buffering system.

In contrast to its rather insignificant role as an extra-

the phosphate buffer is especially

for two

fluid usually has a considerably lower pH than
the extracellular fl
range of the buffer closer to the pK (6.8) of the
system.

The phosphate buffer system is also important in

buffering intracellular fluid because the concentration
of phosphate in this fluid is many times that in the
extracellular fl

fluid is

lower than that of extracellular fluid and therefore is
usually closer to the pK of the phosphate buffer
system compared with the extracellular fluid.

Proteins are among the most plentiful buffers in the

the extracellular fl
mately in proportion to extracellular fl

and HCO

–

require several hours to come to equilibrium with the
extracellular fl

This diffusion

of the elements of the bicarbonate buffer system causes

systems within the cells help prevent changes in the
pH of extracellular fluid but may take several hours to

uids and blood, and the

metabolic processes. After it is formed, it diffuses from

Balances Metabolic Formation of CO

, thus also increasing H

concentration. Conversely, decreased

uid, which, by mass action,

tion by the lungs. An increase in ventilation eliminates

The second line of defense against acid-base distur-

Respiratory Regulation

The implication of this principle is that any condition

the bases of the three buffer systems.

, and A

, HA

respective acids, HA

time. This phenomenon is called the

uid, the

tions of all the systems. Therefore, whenever there is a

all work together, because H

uids. However, they

We have been discussing buffer systems as though they

in Equilibrium with the Same

in a Common Solution Are

Isohydric Principle: All Buffers

the cells, another factor that contributes to their

lular acid-base abnormalities.

However, except for the red blood cells, the slowness

most of this results from the intracellular proteins.

cal buffering of the body fluids is inside the cells, and

Approximately 60 to 70 per cent of the total chemi-

tant buffer, as follows:

In the red blood cell, hemoglobin (Hb) is an impor-

388

Unit V

The Body Fluids and Kidneys

with which H

and HCO

–

move through the cell mem-

branes often delays for several hours the maximum
ability of the intracellular proteins to buffer extracel-

In addition to the high concentration of proteins in

buffering power is the fact that the pKs of many of
these protein systems are fairly close to 7.4.

Hydrogen Ion Concentration

operated individually in the body fl

is common to the reac-

change in H

concentration in the extracellular fl

balance of all the buffer systems changes at the same

isohydric principle

and is illustrated by the following formula:

, K

are the dissociation constants of three

, A

are the

concentrations of the free negative ions that constitute

that changes the balance of one of the buffer systems
also changes the balance of all the others because the
buffer systems actually buffer one another by shifting
H

back and forth between them.

of Acid-Base Balance

bances is control of extracellular fluid CO

concentra-

from extracellular fl

reduces the H

ventilation increases CO

con-

centration in the extracellular fluid.

Pulmonary Expiration of CO

is formed continually in the body by intracellular

the cells into the interstitial fl

HHb

æ Æ

æÆ æ

tion, doubling the ventilation rate raises the pH to

uid by about 0.23. If the pH

the rate of alveolar ventilation. Note that increasing

Figure 30

tion also increase, thereby lowering extracellular

increases, the H

As discussed previously, when CO

lower the alveolar ventilation rate, the higher the P

; conversely, the

alveolar ventilation, the lower the P

uid is the rate of alveolar ventilation. The higher the

Increasing Alveolar Ventilation

uid decreases. Therefore, changes in

is blown off from the lungs, and the P

. If the rate of pulmonary ventilation is increased,

Conversely, a decreased metabolic rate lowers the

increases,

of 40 mm Hg.

uid, corresponding to a P

atmosphere by pulmonary ventilation. About 1.2 mol/

owing blood transports it to the lungs, where it dif-

fl
fuses into the alveoli and then is transferred to the

L of dissolved CO

normally is in the extracellular

If the rate of metabolic formation of CO

the Pco

of the extracellular fluid is likewise increased.

Pco

in the

extracellular fl
either pulmonary ventilation or the rate of CO

for-

mation by the tissues can change the extracellular fluid
Pco

Decreases Extracellular Fluid
Hydrogen Ion Concentration and
Raises pH

If the metabolic formation of CO

remains constant,

the only other factor that affects Pco

in extracellular

concentration

concentration and H

concentra-

fluid pH.

–2 shows the approximate changes in

blood pH that are caused by increasing or decreasing

alveolar ventilation to about twice normal raises the
pH of the extracellular fl
of the body fluids is 7.40 with normal alveolar ventila-

Normal

0.5

1.0

1.5

2.0

2.5

pH change in body fluids

0.3

0.4

0.5

0.1

0.2

0.1

Rate of alveolar ventilation

(normal = 1)

decreased rate of alveolar ventilation, expressed as times normal.

Change in extracellular fluid pH caused by increased or

Figure 30–2

stances, the kidneys represent the sole remaining phys-

increased ventilation are blunted. In these circum-

Also, the ability to respond to metabolic aci-

acidosis.

uid and a tendency toward

; this causes a buildup of CO

severe emphysema, decreases the ability of the lungs

example, an impairment of lung function, such as

concentration. For

concentration. However,

in H

We have discussed thus far the role of the

Impairment of Lung Function Can Cause Respiratory Acidosis.

nism as by the chemical buffers.

uid combined. That is, one to two times as much

general, the overall buffering power of the respiratory

responding kidneys can eliminate the imbalance. In

Buffering Power of the Respiratory System.

response occurs within 3 to 12 minutes.

return the pH to a value of about 7.2 to 7.3. This

pH falls from 7.4 to 7.0, the respiratory system can

of 1 to 3. That is, if the H

feedback gain

50 and 75 per cent, corresponding to a

pH. Ordinarily, the respiratory mechanism for con-

Efficiency of Respiratory Control of Hydrogen Ion Concen-

becomes depressed, alveolar ventilation decreases, and

tration falls below normal, the respiratory center

tion back toward normal. Conversely, if H

and alveolar ventilation increases. This decreases the

above normal, the respiratory system is stimulated,

That is, whenever the H

concentration, the respi-

stimulates respiration, and because increased alveolar

ratory System.

stimulates the ventilation rate. Therefore, the respira-

) in the blood also decreases, which

concentration), the amount of oxygen

ventilation rate decreases, owing to an increase in pH

levels of pH. The reason for this is that as the alveolar

ventilation rate. As one can see from the graph, the

plasma pH rises above 7.4, this causes a decrease in the

7.4 to the strongly acidic value of 7.0. Conversely, when

alveolar ventilation. Thus, Figure 30

uids, but the H

Alveolar Ventilation

times normal, one can easily understand how much the

can change markedly, from as low as 0 to as high as 15

the pH to 6.95. Because the alveolar ventilation rate

is, if the pH is 7.4 at a normal alveolar ventilation,

tion to one fourth normal reduces the pH by 0.45. That

about 7.63. Conversely, a decrease in alveolar ventila-

Regulation of Acid-Base Balance

Chapter 30

389

reducing the ventilation to one fourth normal reduces

pH of the body fluids can be changed by the respira-
tory system.

Increased Hydrogen Ion
Concentration Stimulates

Not only does the alveolar ventilation rate influence
H

concentration by changing the Pco

of the body

concentration affects the rate of

–3 shows that the

alveolar ventilation rate increases four to five times
normal as the pH decreases from the normal value of

change in ventilation rate per unit pH change is much
greater at reduced levels of pH (corresponding to ele-
vated H

concentration) compared with increased

(decreased H

added to the blood decreases and the partial pressure
of oxygen (P

tory compensation for an increase in pH is not nearly
as effective as the response to a marked reduction in
pH.

Feedback Control of Hydrogen Ion Concentration by the Respi-

Because increased H

concentration

ventilation decreases the H

ratory system acts as a typical negative feedback con-
troller of H

concentration.

concentration increases

in extracellular fluid and reduces H

concentra-

concen-

concentration increases back toward normal.

tration.

Respiratory control cannot return the H

concentration all the way back to normal when a dis-
turbance outside the respiratory system has altered

trolling H

concentration has an effectiveness between

concentration is suddenly

increased by adding acid to the extracellular fluid and

Respiratory reg-

ulation of acid-base balance is a physiologic type of
buffer system because it acts rapidly and keeps the H

concentration from changing too much until the slowly

system is one to two times as great as the buffering
power of all other chemical buffers in the extracellu-
lar fl
acid or base can normally be buffered by this mecha-

normal res-

piratory mechanism as a means of buffering changes

abnormalities of respi-

ration can also cause changes in H

to eliminate CO

in the

extracellular fl

respiratory

dosis is impaired because the compensatory reduc-
tions in P

that would normally occur by means of

iologic mechanism for returning pH toward normal
after the initial chemical buffering in the extracellular
fluid has occurred.

≠[H

]

Æ ≠Alveolar ventilation

ØP

–

7.0

7.1

7.2

7.3

7.4

7.5

7.6

Alveolar ventilation (normal = 1)

pH of arterial blood

Effect of blood pH on the rate of alveolar ventilation.

Figure 30–3

ows into the distal tubules and collecting ducts. In the

tubule, so that only a small amount of bicarbonate

bonate reabsorbed, an H

tion along the tubule. Keep in mind that for each bicar-

Henle. Figure 30

Renal Tubules

Secretion of Hydrogen Ions

discussed in the next few sections.

accomplished through the same basic mechanism, as

, and

, (2) reabsorption of filtered HCO

centration through three fundamental mechanisms: (1)

Thus, the kidneys regulate extracellular fluid H

uid. This reduces the extracellular

and produce new bicarbonate, which is added back to

In acidosis, the kidneys do not excrete bicarbonate

uid. Therefore, in alkalosis, the removal of

uid, this loss of

excretion of bicarbonate. Because HCO

ltered bicarbonate, thereby increasing the

concentration (alkalosis), the kidneys fail to reab-

When there is a reduction in the extracellular

uid each day.

body of the nonvolatile acids produced each day, for a

ltered bicarbonate. Then an additional

before it can be reabsorbed, 4320 mil-

secretion by the tubules.

As discussed later, both the reabsorption of bicar-

sorbed from the tubules, thereby conserving the

L); under normal conditions, almost all this is reab-

volatile acids. Each day the kidneys

loss of bicarbonate in the urine, a task that is quanti-

is renal excretion. The kidneys must also prevent the

fore, cannot be excreted by the lungs. The primary

and, there-

from the metabolism of proteins.These acids are called

about 80 milliequivalents of nonvolatile acids, mainly

As discussed previously, each day the body produces

there will be a net loss of base.

versely, if more HCO

uid. Con-

ltered, there will

epithelial cells, thus removing acid from the blood. If

removes base from the blood. Large numbers of H

tubules, and if they are excreted into the urine, this

excrete acidic or basic urine is as follows: Large

The overall mechanism by which the kidneys

either an acidic or a basic urine. Excreting an acidic

The kidneys control acid-base balance by excreting

Renal Control of

390

Unit V

The Body Fluids and Kidneys

Acid-Base Balance

urine reduces the amount of acid in extracellular fluid,
whereas excreting a basic urine removes base from the
extracellular fluid.

numbers of HCO

–

are filtered continuously into the

are

also secreted into the tubular lumen by the tubular

more H

is secreted than HCO

–

is fi

be a net loss of acid from the extracellular fl

–

is filtered than H

is secreted,

nonvolatile because they are not H

mechanism for removal of these acids from the body

tatively more important than the excretion of non-

filter about 4320

milliequivalents of bicarbonate (180 L/day

¥ 24 mEq/

primary buffer system of the extracellular fluid.

bonate and the excretion of H

are accomplished

through the process of H

Because the HCO

–

must react with a secreted H

form H

liequivalents of H

must be secreted each day just to

reabsorb the fi
80 milliequivalents of H

must be secreted to rid the

total of 4400 milliequivalents of H

secreted into the

tubular fl

fluid

sorb all the fi

–

normally

buffers hydrogen in the extracellular fl
bicarbonate is the same as adding an H

to the extra-

cellular fl
HCO

–

raises the extracellular fluid H

concentration

back toward normal.

into the urine but reabsorb all the filtered bicarbonate

the extracellular fl
fluid H

concentration back toward normal.

con-

secretion of H

(3) production of new HCO

. All these processes are

and Reabsorption of
Bicarbonate Ions by the

Hydrogen ion secretion and bicarbonate reabsorption
occur in virtually all parts of the tubules except the
descending and ascending thin limbs of the loop of

–4 summarizes bicarbonate reabsorp-

must be secreted.

About 80 to 90 per cent of the bicarbonate reab-

sorption (and H

secretion) occurs in the proximal

85%

(3672 mEq/day)

>4.9%
(215 mEq/day)

(1 mEq/day)

4320 mEq/day

10%

(432 mEq/day)

reabsorbed per day under normal

tubular segments are shown, as well

percentages of the filtered load of

ent segments of the renal tubule. The

Reabsorption of bicarbonate in differ-

Figure 30–4

bicarbonate absorbed by the various

as the number of milliequivalents

conditions.

ltered into the tubules. The

from the tubules, although

The net effect of these reactions is

is also formed and released back

lial cells, an HCO

Thus, each time an H

exchange.

two mechanisms: (1) Na

peritubular capillary blood. The transport of HCO

; the

molecule. This

anhydrase, to generate a new H

O, under the in

fore, it instantly diffuses into the tubular cell, where it

can move easily across the tubular membrane; there-

O. The CO

secreted by the tubular cells. The H

This reabsorption of HCO

as shown in Figure 30

, which eventually becomes CO

directly reabsorbed. Instead, HCO

membranes of the renal tubular cells; therefore,

Hydrogen Ions in the Tubules

Filtered Bicarbonate Ions Are

secreted into the tubular lumen, an

and the peritubular capillary blood. The net result is

The HCO

basolateral membrane. The gradient for Na

lished by the sodium-potassium ATPase pump in the

with the carrier protein. The Na

same time, an H

in the luminal border of the cell membrane; at the

rior of the cell, it

sodium-hydrogen counter-transport. That is, when an

. The H

, which dissociates into HCO

O to form

carbonic anhydrase,

, under the in

epithelial cells. CO

achieves bicarbonate reabsorption. The secretory

Figure 30

lecting tubules and collecting ducts.

the tubules. This mechanism, however, does not estab-

bonate is reabsorbed in this manner, requiring about

lateral membrane. More than 90 per cent of the bicar-

adenosine triphosphatase (ATPase) pump in the baso-

This gradient is established by the sodium-potassium

exchanger protein, and the energy for H

5. This secondary active secretion of H

Figure 30

by sodium-hydrogen counter-transport, as shown in

segment of the ascending loop of Henle, and the early

The epithelial cells of the proximal tubule, the thick

in the Early Tubular Segments

by Secondary Active Transport

Hydrogen Ions Are Secreted

segments accomplish this task differently.

, but different tubular

and collecting duct. As discussed previously, the mech-

ltered bicarbonate is reabsorbed, and the remain-

thick ascending loop of Henle, another 10 per cent of

Regulation of Acid-Base Balance

Chapter 30

391

the fi
der of the reabsorption takes place in the distal tubule

anism by which bicarbonate is reabsorbed also
involves tubular secretion of H

distal tubule all secrete H

into the tubular fluid

–

is coupled with the transport of Na

into the cell at

the luminal membrane by the sodium-hydrogen

secretion

against a concentration gradient is derived from the
sodium gradient favoring Na

movement into the cell.

3900 milliequivalents of H

to be secreted each day by

lish a very high H

concentration in the tubular fluid;

the tubular fluid becomes very acidic only in the col-

–5 shows how the process of H

secretion

process begins when CO

either diffuses into the

tubular cells or is formed by metabolism in the tubular

fluence of the enzyme

combines with H

–

and H

is secreted from the cell into the tubular lumen by

moves from the lumen of the tubule to the inte-

first combines with a carrier protein

in the interior of the cells combines

moves into the cell

down a concentration gradient that has been estab-

move-

ment into the cell then provides the energy for moving
H

in the opposite direction from the interior of the

cell to the tubular lumen.

–

generated in the cell (when H

dissoci-

ates from H

) then moves downhill across the

basolateral membrane into the renal interstitial fluid

that for every H

HCO

–

enters the blood.

Reabsorbed by Interaction with

Bicarbonate ions do not readily permeate the luminal

HCO

–

that is filtered by the glomerulus cannot be

–

is reabsorbed by

a special process in which it first combines with H

form H

and H

–5.

–

is initiated by a reaction

in the tubules between HCO

–

filtered at the glomeru-

lus and H

formed then dissociates into CO

and H

recombines with H

fluence of carbonic

in turn dissociates to form HCO

–

and H

HCO

–

then diffuses through the basolateral mem-

brane into the interstitial fluid and is taken up into the

across the basolateral membrane is facilitated by

-HCO

–

co-transport and (2)

–

-HCO

–

is formed in the tubular epithe-

into the blood.
“reabsorption” of HCO

–

the HCO

–

that actually enters the extracellular fluid

is not the same as that fi
reabsorption of filtered HCO

–

does not result in net

secretion of H

because the secreted H

combines with

the filtered HCO

–

and is therefore not excreted.

HCO

Tubular cells

Tubular

ATP

HCO

Renal

interstitial

fluid

Renal

interstitial

fluid

lumen

Carbonic
anhydrase

of hydrogen ion secretion occurs in the proximal tubule, the thick

reabsorption in exchange for hydrogen ions secreted. This pattern

sociates to form carbon dioxide and water; and (3) sodium ion

combination with hydrogen ions to form carbonic acid, which dis-

the renal tubule; (2) tubular reabsorption of bicarbonate ions by

Cellular mechanisms for (1) active secretion of hydrogen ions into

Figure 30–5

ascending segment of the loop of Henle, and the early distal
tubule.

metabolism each day, about 2667 liters of urine would

can be excreted. To excrete the

urine formed, a maximum of only about 0.03 mil-

mEq/L, or 0.03 mEq/L. Thus, for each liter of

is about 4.5, corresponding to an H

urine. The reason for this is that the minimal urine pH

uid, only a small part of the

When H

the Tubule—A Mechanism

and Ammonia Buffers in

Hydrogen Ions with Phosphate

limit of pH that can be achieved in normal kidneys.

uid to about 4.5, which is the lower

as 900-fold in the collecting tubules. This decreases the

However, H

can be reduced to only about 6.7, although large

about threefold to fourfold, and the tubular

imal tubules, H

tant in forming a maximally acidic urine. In the prox-

secreted, this mechanism is impor-

instead of by counter-transport, as occurs in the early

proximal tubules. The main difference is that H

is reabsorbed, similar to the process in the

hydrogen-ATPase mechanism. For each H

, which is secreted into the tubule by means of the

, which is reabsorbed into the blood, plus

into HCO

, and (2) the H

to form H

tubule and in the collecting tubules. Hydrogen ion

diphosphate.

derived from the breakdown of ATP to adenosine

ATPase. The energy required for pumping the H

c protein, a hydrogen-transporting

brane of the tubular cell, where H

6. It occurs at the luminal mem-

shown in Figure 30

The mechanism for primary active H

loop of Henle, and early distal tubule.

ferent from those discussed for the proximal tubule,

The characteristics of this transport are dif-

through the remainder of the tubular system, the

Distal and Collecting Tubules

Ions in the Intercalated Cells of Late

Primary Active Secretion of Hydrogen

and eventually excreted as salts. Thus, the basic mech-

passes into the urine. The excess H

In acidosis, there is excess H

alkalosis.

into the urine, which helps correct the metabolic

cannot be reabsorbed; therefore, the excess

urine, as occurs in metabolic alkalosis, the excess

When there is an excess of HCO

other urinary buffers, especially phosphate and

metabolism. As discussed later, most of this H

excreted in the urine. This excess H

The titration process is not quite exact because there

each other in the tubules.

O. Therefore, it is said that HCO

form CO

almost equal, and they combine with each other to

is about 4320 mEq/day. Thus, the

secretion is about 4400 mEq/day, and the rate of

Under normal conditions, the rate of tubular

Tubules.

Bicarbonate Ions Are “Titrated” Against Hydrogen Ions in the

392

Unit V

The Body Fluids and Kidneys

fil-

tration by HCO

–

quantities of these two ions entering the tubules are

and H

–

and H

normally “titrate”

is usually a slight excess of H

in the tubules to be

(about 80 mEq/

day) rids the body of nonvolatile acids produced by

not excreted as free H

but rather in combination with

ammonia.

–

over H

in the

HCO

–

HCO

–

is left in the tubules and eventually excreted

relative to HCO

–

causing complete reabsorption of the bicarbonate;
the excess H

buffered in the tubules by phosphate and ammonia

anism by which the kidneys correct either acidosis or
alkalosis is incomplete titration of H

against HCO

–

leaving one or the other to pass into the urine and be
removed from the extracellular fluid.

Beginning in the late distal tubules and continuing

tubular epithelium secretes H

by primary active

transport.

secretion is

–

is transported

directly by a specifi

Primary active secretion of H

occurs in a special

type of cell called the intercalated cells of the late distal

secretion in these cells is accomplished in two steps:
(1) the dissolved CO

in this cell combines with H

then dissociates

–

secreted,

an HCO

–

moves

across the luminal membrane by an active H

pump

parts of the nephron.

Although the secretion of H

in the late distal tubule

and collecting tubules accounts for only about 5 per
cent of the total H

concentration can be increased only

fluid pH

amounts of H

are secreted by this nephron segment.

concentration can be increased as much

pH of the tubular fl

Combination of Excess

for Generating “New”
Bicarbonate Ions

is secreted in excess of the bicarbonate fil-

tered into the tubular fl
excess H

can be excreted in the ionic form (H

) in the

concentration

of 10

–4.5

liequivalent of free H

80 milliequivalents of nonvolatile acid formed by

have to be excreted if the H

remained free in

solution.

Tubular

Tubular cells

ATP

Carbonic
anhydrase

HCO

Renal

interstitial

fluid

Renal

interstitial

fluid

lumen

secreted along with the hydrogen ion.

each hydrogen ion secreted, and a chloride ion is passively

membrane of the intercalated epithelial cells of the late distal and

Primary active secretion of hydrogen ions through the luminal

Figure 30–6

collecting tubules. Note that one bicarbonate ion is absorbed for

9). Here, H

(Figure 30

In the collecting tubules, the addition of NH

constitutes new bicarbonate.

generated by this process

metabolized in the proximal tubules, two NH

capillaries. Thus, for each molecule of glutamine

, into the inter-

brane, along with the reabsorbed Na

in exchange for sodium, which is reabsorbed. The

the tubular lumen by a counter-transport mechanism

. The NH

Once inside the cell, each molecule of glutamine is

the loop of Henle, and distal tubules (Figure 30

cells of the proximal tubules, thick ascending limb of

olism of amino acids in the liver. The glutamine deliv-

from glutamine, which comes mainly from the metab-

). Ammonium ion is synthesized

by the Ammonia Buffer System

and Generation of New Bicarbonate

. Therefore, much of the

phate is reabsorbed, and only about 30 to 40 mEq/day

Under normal conditions, much of the

. This demonstrates one of the

, the net effect is addition of a new

Therefore, whenever an H

by the blood, rather than merely a replace-

case, the HCO

excretion from that discussed previously. In this

There is one important difference in this sequence

), carrying with it

, it can be

to form H

and other tubular buffers. After the H

, any excess H

has been reabsorbed and is no longer avail-

. However, once all

uid, most of the

tubules is the same as described earlier. As long as

to the blood. The process of H

Figure 30

phosphate buffer system. Therefore, in the tubules, the

slightly acidic, and the urine pH is near the pK of the

is about 6.8. Under normal conditions, the urine is

uid buffer, it is much more effective

uid. Therefore, although phosphate is not an impor-

. Both become concentrated in the tubular

The phosphate buffer system is composed of HPO

and Generates New Bicarbonate

Phosphate Buffer System Carries

two sections, we discuss the mechanisms by which

uid in acidosis. In the next

, thereby helping to replenish the HCO

uid, the kidneys not

that can also enter the blood. Thus, when there

, and this results in the generation of new

in the urine, they combine with buffers other

secreted, as discussed earlier. But when there are

When H

weak buffer systems, such as urate and citrate, that are

phate buffer and ammonia buffer. There are other

uid. The most important buffers are phos-

The excretion of large amounts of H

Regulation of Acid-Base Balance

Chapter 30

393

(on occasion

as much as 500 mEq/day) in the urine is accomplished
primarily by combining the H

with buffers in the

tubular fl

much less important.

is titrated in the tubular fluid with HCO

–

this results in the reabsorption of one HCO

–

for each

excess H

than HCO

–

HCO

–

is excess H

in the extracellular fl

only reabsorb all the filtered HCO

–

but also generate

new HCO

–

lost from the extracellular fl

phosphate and ammonia buffers contribute to the gen-
eration of new HCO

–

Excess Hydrogen Ions into the Urine

and H

–

fluid because of their relatively poor reabsorption and
because of the reabsorption of water from the tubular
fl
tant extracellular fl
as a buffer in the tubular fluid.

Another factor that makes phosphate important as

a tubular buffer is the fact that the pK of this system

phosphate buffer system normally functions near its
most effective range of pH.

–7 shows the sequence of events by which

is excreted in combination with phosphate buffer

and the mechanism by which new bicarbonate is added

secretion into the

there is excess HCO

–

in the tubular fl

secreted H

combines with HCO

–

the HCO

–

able to combine with H

can combine

with HPO

combines with HPO

–

excreted as a sodium salt (NaH

the excess hydrogen.

of H

–

that is generated in the tubular cell

and enters the peritubular blood represents a net gain
of HCO

–

ment of filtered HCO

–

secreted into the tubular lumen combines with a buffer
other than HCO

HCO

to the blood

mechanisms by which the kidneys are able to replen-
ish the extracellular fluid stores of HCO

–

filtered phos-

is available for buffering H

buffering of excess H

in the tubular fluid in acidosis

occurs through the ammonia buffer system.

Excretion of Excess Hydrogen Ions

A second buffer system in the tubular fluid that is even
more important quantitatively than the phosphate
buffer system is composed of ammonia (NH

) and the

ammonium ion (NH

ered to the kidneys is transported into the epithelial

–8).

metabolized in a series of reactions to ultimately form
two NH

and two HCO

–

is secreted into

HCO

–

is transported across the basolateral mem-

stitial fluid and is taken up by the peritubular

are

secreted into the urine and two HCO

–

are reabsorbed

into the blood. The HCO

–

to the

tubular fluids occurs through a different mechanism

–

is secreted by the tubular

Tubular

Tubular cells

ATP

NaHPO

HCO

NaH

Carbonic
anhydrase

Renal

interstitial

fluid

Renal

interstitial

fluid

lumen

that reacts with a secreted hydrogen ion.

). Note that a new bicarbonate ion is returned to the

Buffering of secreted hydrogen ions by filtered phosphate

Figure 30–7

(NaHPO

–

blood for each NaHPO

–

Bicarbonate excretion

Thus, the

reaction is 9.2, and titration with NaOH to a pH of 7.4

, because the pK of the ammonia-ammonium

phate and other organic buffers. The titratable acid

. Therefore, the number of mil-

ltrate. This titration reverses the events that occurred

pH of normal plasma, and the pH of the glomerular

with a strong base, such as NaOH, to a pH of 7.4, the

The amount of titrat-

The rest of the nonbicarbonate, non-NH

and phosphate. Therefore, the

ously, the primary sources of nonbicarbonate urinary

nonbicarbonate urinary buffers. As discussed previ-

to the blood). In alkalosis, the loss of

This number indicates how rapidly the kidneys are

follows.

net excretion of acid or net addition

Based on the principles discussed earlier, we can quan-

Acid-Base Excretion

new bicarbonate during chronic acidosis.

This also pro-

chronic acidosis, the dominant mechanism by which

Therefore, with

increase to as much as 500 mEq/day.

chronic acidosis,

generated by the kidneys. However,

normal conditions,

buffering; a decrease in H

stimulates renal glutamine metabolism and, therefore,

excreted, a new HCO

For each

tubular lumen and eliminated in the urine.

, the NH

to form NH

with NH

; therefore, once the H

diffuse into the tubular lumen. However, the luminal

, which can easily

, which is then excreted. The col-

to form NH

membrane into the lumen, where it combines with

394

Unit V

The Body Fluids and Kidneys

lecting ducts are permeable to NH

membrane of this part of the tubules is much less per-
meable to NH

has reacted

is trapped in the

is generated and added to

the blood.

Chronic Acidosis Increases NH

Excretion.

One of the most

important features of the renal ammonium-ammonia
buffer system is that it is subject to physiologic control.

An increase in extracellular fluid H

concentration

increases the formation of NH

and new HCO

–

to be

used in H

concentration

has the opposite effect.

Under

the amount of H

elimi-

nated by the ammonia buffer system accounts for
about 50 per cent of the acid excreted and 50 per cent
of the new HCO

–

with

the rate of NH

excretion can

acid is eliminated is excretion of NH

vides the most important mechanism for generating

Quantifying Renal

titate the kidneys’
or elimination of bicarbonate from the blood as

Bicarbonate excretion is calculated as the urine flow

rate multiplied by urinary bicarbonate concentration.

removing HCO

–

from the blood (which is the same as

adding an H

HCO

–

helps return the plasma pH toward normal.

The amount of new bicarbonate contributed to

the blood at any given time is equal to the amount of
H

secreted that ends up in the tubular lumen with

buffers are NH

amount of HCO

–

added to the blood (and H

excreted

by NH

) is calculated by measuring NH

excretion (urine flow rate multiplied by urinary NH

concentration).

buffer

excreted in the urine is measured by determining a
value known as titratable acid.
able acid in the urine is measured by titrating the urine

fi
in the tubular lumen when the tubular fluid was
titrated by excreted H

liequivalents of NaOH required to return the urinary
pH to 7.4 equals the number of milliequivalents of H

added to the tubular fluid that combined with phos-

measurement does not include H

in association with

does not remove the H

from NH

net acid excretion by the kidneys can be

assessed as

Net acid excretion

= NH

excretion

+ Urinary

titratable acid –

Glutamine

Tubular

Renal

interstitial

fluid

Renal

interstitial

fluid

lumen

Proximal

tubular cells

Proximal

tubular cells

Glutamine

2HCO

2NH

are returned

are produced and secreted and two HCO

is secreted into the lumen by a

) by proximal

Production and secretion of ammonium ion (NH

Figure 30–8

tubular cells. Glutamine is metabolized in the cell, yielding NH

and bicarbonate. The NH

sodium-NH

pump. For each glutamine molecule metabolized,

two NH

–

to the blood.

Tubular

ATP

Carbonic
anhydrase

Renal

interstitial

fluid

Renal

interstitial

fluid

lumen

Collecting

tubular cells

Collecting

tubular cells

HCO

+ Cl

tubular cells and returned to the blood.

is formed in the

excreted, a new HCO

excreted. For each NH

reacts with secreted hydrogen ions to form NH

lecting tubules. Ammonia diffuses into the tubular lumen, where it

Buffering of hydrogen ion secretion by ammonia (NH

Figure 30–9

) in the col-

, which is then

–

reabsorption and tends to cause acidosis.

losis. Hyperkalemia decreases H

the renal tubular cells. This, in turn, stimulates H

proximal tubule. A decreased plasma potassium con-

secretion, with hypokalemia stimu-

lecting tubules. Therefore, extracellular

(2) increased aldosterone levels, which stimulate H

exchanger in the renal tubules, and

angiotensin II levels, which directly stimulate the activ-

through multiple mechanisms, including (1) increased

uid volume, may also

Therefore, factors that stimulate Na

proximal tubule and thick ascending loop of Henle.

base balance. For example, H

reabsorption. Some of

Table 30

in both respiratory and metabolic alkalosis.

concentration per se, as occurs

, as occurs in respiratory alkalosis, or

The decreased H

The tubular cells usually respond to a decrease in H

amounts of bicarbonate added back to the blood. This

uid and, consequently, increased

s syndrome, can cause excessive secretion of H

Therefore, oversecretion of aldosterone, as occurs in

terone secretion. Aldosterone stimulates the secretion

. The

cells, which in turn stimulates the secretion of H

of the tubular cells,

The increased P

of the blood, as occurs in respiratory acidosis,

The tubular cells respond directly to an increase in

secretion by

acid, thereby contributing large amounts of new

urine in alkalosis. During acidosis, the tubular H

therefore, there is no new HCO

excretion. In this condition, titratable acid and

reabsorption, enabling the kidneys to increase HCO

In alkalosis, tubular secretion of H

ltered, and there must be enough

ostasis. Under normal conditions, the kidney tubules

able acid formation. Therefore, the rate of H

As discussed earlier, H

Regulation of Renal Tubular Hydrogen

is generated by the kidneys.

This

alkalosis, there is a negative net acid secretion.

Therefore, in

excretion increases.

to 0, whereas HCO

In alkalosis, titratable acid and NH

back to the blood as more NH

Therefore, in acidosis, there is a net

tion, thereby removing acid from the blood. The net

markedly, especially because of increased NH

in the body. In acidosis, the net acid excretion increases

the blood. To maintain acid-base balance, the net acid

The reason we subtract bicarbonate excretion is that

Regulation of Acid-Base Balance

Chapter 30

395

the loss of HCO

–

is the same as the addition of H

excretion must equal the nonvolatile acid production

excre-

acid excretion also equals the rate of net HCO

–

addi-

tion to the blood.
addition of HCO

–

and

urinary titratable acid are excreted.

excretion drop

–

means that there is a net loss of HCO

–

from the blood

(which is the same as adding H

to the blood) and that

no new HCO

–

Ion Secretion

secretion by the tubular

epithelium is necessary for both HCO

–

reabsorption

and generation of new HCO

–

associated with titrat-

secre-

tion must be carefully regulated if the kidneys are to
effectively perform their functions in acid-base home-

must secrete at least enough H

to reabsorb almost all

the HCO

–

that is fi

left over to be excreted as titratable acid or NH

to rid the body of the nonvolatile acids produced each
day from metabolism.

must be reduced

to a level that is too low to achieve complete HCO

–

ammonia are not excreted because there is no excess
H

available to combine with nonbicarbonate buffers;

–

added to the

secretion must be increased sufficiently to reabsorb
all the filtered HCO

–

and still have enough H

left

over to excrete large amounts of NH

and titratable

HCO

–

to the total body extracellular fluid. The

most important stimuli for increasing H

the tubules in acidosis are (1) an increase in P

of the extracellular fluid and (2) an increase in H

concentration of the extracellular fluid (decreased
pH).

with an increase in the rate of H

secretion as follows:

raises the P

causing increased formation of H

in the tubular

second factor that stimulates H

secretion is an

increase in extracellular fluid H

concentration

(decreased pH).

A special factor that can increase H

secretion under

some pathophysiologic conditions is excessive aldos-

of H

by the intercalated cells of the collecting duct.

Conn’

into the tubular fl

usually causes alkalosis in patients with excessive
aldosterone secretion.

concentration (alkalosis) by reducing H

secretion.

secretion results from decreased

extracellular P

from a decrease in H

–2 summarizes the major factors that influ-

ence H

secretion and HCO

–

these are not directly related to the regulation of acid-

secretion is coupled

to Na

reabsorption by the Na

-H

exchanger in the

reabsorption,

such as decreased extracellular fl
secondarily increase H

secretion.

Extracellular fluid volume depletion stimulates

sodium reabsorption by the renal tubules and
increases H

secretion and HCO

–

reabsorption

ity of the Na

-H

secretion by the intercalated cells of the cortical col-

fluid volume

depletion tends to cause alkalosis due to excess H

secretion and HCO

–

reabsorption.

Changes in plasma potassium concentration can

also influence H

lating and hyperkalemia inhibiting H

secretion in the

centration tends to increase the H

concentration in

secretion and HCO

–

reabsorption and leads to alka-

secretion and HCO

–

Table 30–2

Factors That Increase or Decrease H

Secretion and HCO

Secretion and

Decrease H

Reabsorption by the Renal Tubules

Increase H

Secretion and

HCO

–

Reabsorption HCO

–

Reabsorption

≠ P

CO2

Ø P

CO2

≠ H

Ø HCO

–

Ø H

≠ HCO

–

Ø Extracellular fluid volume

≠ Extracellular fluid volume

≠ Angiotensin II

Ø Angiotensin II

≠ Aldosterone

Ø Aldosterone

Hypokalemia

Hyperkalemia

losis, HCO

and is, therefore, excreted in the urine. Thus, in alka-

uid. The net effect of this is an excess of

bolic or respiratory abnormalities, there is still an

in Renal Tubular Fluid

concentration), as is evident from the Henderson-

increases, causing a rise in pH (a decrease in H

to CO

opposite to those that occur in acidosis. In alkalosis,

The compensatory responses to alkalosis are basically

and Increased Excretion

Secretion of Hydrogen Ions

Alkalosis—Decreased Tubular

Renal Correction of

bicarbonate to the extracellular fluid, helps minimize

, and renal compensation, which, by adding new

tions include increased ventilation rate, which reduces

However, in this case, the primary abnormality is a

metabolic acidosis,

, thereby returning the

The rise in HCO

the extracellular fluid by the kidneys.

, caused by the addition of new bicarbonate to

, which is the initial cause of the acidosis.

concentration, and an increase in

there is a reduction in pH, an increase in

acidosis,

cussed in the next section. Note that in

respiratory and metabolic alkalosis, which are dis-

Table 30

helping to correct the acidosis.

, also

acidosis is metabolically mediated, additional com-

the extracellular pH and corrects the acidosis. If the

with the Henderson-Hasselbalch equation, helps raise

of the bicarbonate buffer system, which, in accordance

uid. This increases the bicarbonate part

Thus, with chronic acidosis, the increased secretion

; this, in turn, contributes up to 500 mEq/day of

can be excreted in the urine, mainly in the form of

severe chronic acidosis, as much as 500 mEq/day of H

uid. With

, which

regardless of whether it is respiratory or metabolic,

As discussed previously, with chronic acidosis,

, which stimulates H

In respiratory acidosis, the excess H

This decreased

over HCO

In metabolic acidosis, an excess of H

dosis, the kidneys reabsorb all the

. Thus, in aci-

renal tubules, causing complete reabsorption of HCO

uid. As a result, there is an excess of H

in Renal Tubular Fluid

respiratory acidosis.

, the acidosis is referred

metabolic acidosis.

, the acidosis is

uid decreases, thereby decreasing pH. If this ratio

to CO

Hasselbalch equation, we can see that acidosis occurs

Referring to equation 8,

the Henderson-

, we can

Hydrogen Ions and Addition

Increased Excretion of

Renal Correction of Acidosis—

396

Unit V

The Body Fluids and Kidneys

of Bicarbonate Ions to the
Extracellular Fluid

Now that we have described the mechanisms by which
the kidneys secrete H

and reabsorb HCO

–

explain how the kidneys readjust the pH of the extra-
cellular fluid when it becomes abnormal.

when the ratio of HCO

–

in the extracellular

fl
decreases because of a fall in HCO

–

referred to as

If the pH falls

because of an increase in P

to as

Acidosis Decreases the Ratio of
HCO

Both respiratory and metabolic acidosis cause a
decrease in the ratio of HCO

–

to H

in the renal

tubular fl

in the

–

and still leaving additional H

available to combine

with the urinary buffers NH

and HPO

filtered HCO

–

and

contribute new HCO

–

through the formation of NH

and titratable acid.

–

occurs in the tubular fluid primarily because of
decreased filtration of HCO

filtration

of HCO

–

is caused mainly by a decrease in the extra-

cellular fluid concentration of HCO

–

in the tubular

fluid is due mainly to the rise in extracellular fluid
P

secretion.

there is an increase in the production of NH

further contributes to the excretion of H

and the addi-

tion of new HCO

–

to the extracellular fl

new HCO

–

that is added to the blood.

of H

by the tubules helps eliminate excess H

from

the body and increases the quantity of HCO

–

in the

extracellular fl

pensation by the lungs causes a reduction in P

–3 summarizes the characteristics associ-

ated with respiratory and metabolic acidosis as well as

respiratory

extracellular fluid H

The

compensatory response is an increase in plasma
HCO

–

helps offset the increase in P

plasma pH toward normal.

there is also a decrease in pH

and a rise in extracellular fluid H

concentration.

decrease in plasma HCO

–

. The primary compensa-

the initial fall in extracellular HCO

concentration.

of Bicarbonate Ions

the ratio of HCO

–

in the extracellular fluid

Hasselbalch equation.

Alkalosis Increases the Ratio of
HCO

Regardless of whether the alkalosis is caused by meta-

increase in the ratio of HCO

–

to H

in the renal

tubular fl
HCO

–

that cannot be reabsorbed from the tubules

–

is removed from the extracellular fluid by

Table 30–3

≠

≠≠

≠

ØØ

≠

ØØ

≠

≠≠

≠

Normal

7.4

40 mEq/L

40 mm Hg

24 mEq/L

Characteristics of Primary Acid-Base Disturbances

HCO

–

Respiratory acidosis

Respiratory alkalosis

Metabolic acidosis

Metabolic alkalosis

, whereas metabolic disorders are initiated by an increase or decrease in

). Note that

The primary event is indicated by the double arrows (

≠≠ or ØØ

respiratory acid-base disorders are initiated by an increase or decrease in
P

HCO

–

tents alone would cause loss of acid and a tendency

Vomiting of gastric con-

Vomiting of Intestinal Contents.

serious and can cause death, especially in young

urine. This form of metabolic acidosis is particularly

from the body, which has the same

large amounts of bicarbonate, and diarrhea results in

The gastrointestinal secretions normally contain

feces.

cause of metabolic acidosis.

s syndrome.

impair tubular function, such as Fanconi

of renal tubular acidosis include chronic renal failure,

uids. Some causes

are excreted, so that there is

an alkaline urine. In these cases, inadequate amounts of

establish a normal acidic urine, causing the excretion of

in the urine, or (2)

sorption, causing loss of HCO

types: (1) impairment of renal tubular HCO

, or both. These disorders are generally of two

This type of acidosis results from

Renal Tubular Acidosis.

bolic acidosis are the following.

uids. Some speci

uids, which has the same effect as adding an acid to the

infusion of acids, and (4) loss of base from the body

excess quantities of metabolic acids in the body, (3)

acids normally formed in the body, (2) formation of

causes: (1) failure of the kidneys to excrete metabolic

uids. Metabolic acidosis can result from several general

The term

Metabolic Acidosis Results from

alkalosis. Again, the major means for compensation are

content of the air stimulates respiration, which causes

when a person ascends to high altitude. The low oxygen

person becomes alkalotic.

pathological conditions. However, a psychoneurosis can

the lungs. Rarely does this occur because of physical

from Increased Ventilation and

Respiratory Alkalosis Results

for the disorder.

the kidneys, which require several days to compensate

In respiratory acidosis, the compensatory responses

alveolar air, can cause respiratory acidosis.

brane surface area, as well as any factor that interferes

pneumonia, emphysema, or decreased pulmonary mem-

medulla oblongata can lead to respiratory acidosis.Also,

For example, damage to the respiratory center in the

acidosis.

an abnormality in respiration, it is called

sulting in acidosis. Because the acidosis is caused by

concentration, thus re-

uid. This causes

From the previous discussion, it is obvious that any

by Decreased Ventilation and

Respiratory Acidosis Is Caused

Acid-Base Disorders

excretion, which helps compen-

, and

tions are decreased ventilation, which raises P

In metabolic alkalosis, the primary compensa-

urine.

to react with, and it is excreted in the

uid. The excess HCO

uid pH toward normal. In addition, the

tion rate, which increases P

This is

The cause of metabolic alkalosis, however, is a rise in

metabolic alkalosis,

caused by increased renal excretion of HCO

Therefore, the compensatory

rection of the alkalosis.

reabsorbed and is excreted in the urine. This results in

Therefore, the HCO

uid. Consequently, there is not

secretion by the renal tubules. The

The reduction in P

, caused by hyperventi-

sis,

piratory and metabolic alkalosis. In

Table 30

uid. This helps return the H

renal excretion, which has the same effect as adding an

Regulation of Acid-Base Balance

Chapter 30

397

to the extracellular fl

concentration and pH back toward normal.

–3 shows the overall characteristics of res-

respiratory alkalo-

there is an increase in extracellular fluid pH and a

decrease in H

concentration. The cause of the alkalo-

sis is a decrease in plasma P

lation.

then leads to a decrease

in the rate of H

decrease in H

secretion reduces the amount of H

the renal tubular fl
enough H

to react with all the HCO

–

that is filtered.

–

that cannot react with H

is not

a decrease in plasma HCO

–

concentration and cor-

response to a primary reduction in P

in respiratory

alkalosis is a reduction in plasma HCO

concentration,

there is also an increase in

plasma pH and a decrease in H

concentration.

the extracellular fluid HCO

–

concentration.

partly compensated for by a reduction in the respira-

and helps return the

extracellular fl
increase in HCO

–

concentration in the extracellular

fluid leads to an increase in the filtered load of HCO

–

which in turn causes an excess of HCO

–

over H

secreted in the renal tubular fl

–

in the tubular fluid fails to be reabsorbed because
there is no H

increased renal HCO

sate for the initial rise in extracellular fluid HCO

concentration.

Clinical Causes of

Increased P

factor that decreases the rate of pulmonary ventilation
also increases the P

of extracellular fl

an increase in H

and H

respiratory

Respiratory acidosis can occur from pathological

conditions that damage the respiratory centers or
that decrease the ability of the lungs to eliminate CO

obstruction of the passageways of the respiratory tract,

with the exchange of gases between the blood and the

available are (1) the buffers of the body fluids and (2)

Decreased P

Respiratory alkalosis is caused by overventilation by

occasionally cause overbreathing to the extent that a

A physiologic type of respiratory alkalosis occurs

excess loss of CO

and development of mild respiratory

the chemical buffers of the body fluids and the ability
of the kidneys to increase HCO

–

excretion.

Decreased Extracellular Fluid
Bicarbonate Concentration

metabolic acidosis refers to all other types of

acidosis besides those caused by excess CO

in the body

addition of metabolic acids to the body by ingestion or

fl
body fl

fic conditions that cause meta-

a defect in renal secretion of H

or in reabsorption of

HCO

–

reab-

–

inability of the renal tubular H

secretory mechanism to

titratable acid and NH

net accumulation of acid in the body fl

insufficient aldosterone secretion (Addison’s disease),
and several hereditary and acquired disorders that

’

Diarrhea.

Severe diarrhea is probably the most frequent

The cause of this acidosis is

the loss of large amounts of sodium bicarbonate into the

the loss of HCO

–

effect as losing large amounts of bicarbonate in the

children.

alkalosis.

acidosis, whereas a pH greater than 7.4 indicates

is acidosis or alkalosis. A pH less than 7.4 indicates

ining the pH, one can determine whether the disorder

10. By exam-

several steps, as shown in Figure 30

The diagnosis of simple acid-base disorders involves

plasma bicarbonate concentration, and P

three measurements from an arterial blood sample: pH,

proper diagnosis. The simple acid-base disorders

Disorders

Clinical Measurements and

monohydrochloride.

gerous. Another substance used occasionally is

highly toxic, and this procedure can be dan-

occasionally is infused intravenously, but NH

tion in the acidic direction. Ammonium chloride

reaction liberates HCl, which immediately reacts with

portion is converted by the liver into urea. This

chloride is absorbed into the blood, the ammonia

can be administered by mouth. When the ammonium

ammonium chloride

For the treatment of alkalosis,

the molecules are metabolized in the body, leaving the

The lactate and gluconate portions of

sodium gluconate.

are often used instead, such as

physiologic effects of such treatment, other substances

intravenously, but because of the potentially dangerous

toward normal. Sodium bicarbonate can also be infused

the bicarbonate buffer system, thereby increasing pH

can be ingested by mouth. The sodium

To neutralize excess acid, large amounts of

cumstances, various agents can be used to neutralize the

impaired lung function or kidney failure. In these cir-

cult, especially in chronic diseases that cause

the condition that caused the abnormality. This is often

The best treatment for acidosis or alkalosis is to correct

or Alkalosis

Treatment of Acidosis

ulcer.

bicarbonate, for the treatment of gastritis or peptic

alkalosis is ingestion of alkaline drugs, such as sodium

pyloric sphincter muscles.

losis. This type of alkalosis occurs especially in neonates

stomach mucosa. The net result is a loss of acid from the

nal contents, causes loss of the HCl secreted by the

tents alone, without vomiting of the lower gastrointesti-

Vomiting of the gastric con-

Vomiting of Gastric Contents.

metabolic alkalosis.

its increased excretion by the kidneys and, therefore,

lecting tubules. This increased secretion of H

alkalosis develops. As discussed previously, aldosterone

are secreted by the adrenal glands, a mild metabolic

When large amounts of aldosterone

development of alkalosis, characterized by increased

bicarbonate reabsorption. These changes lead to the

secretion, the enhanced sodium reabsorption also

from these parts of the nephrons.

distal and collecting tubules. This leads to increased

along the tubules, usually causing increased

as follows.

dosis, but some of the causes of metabolic alkalosis are

from the body, this results in metabolic alkalosis. Meta-

When there is excess retention of HCO

Metabolic Alkalosis Is Caused

associated with severe metabolic acidosis.

uids. Thus, chronic renal failure can be

kidneys. In addition, the decreased glomerular

markedly, there is a buildup of the anions of weak acids

. When kidney function declines

cylics (aspirin) and methyl alcohol (which forms formic

certain acidic poisons. Some of these include acetylsali-

ingested in normal foods. However, severe metabolic

times as much as 500 mmol/day.

large amounts of acid are excreted in the urine, some-

acidosis. In an attempt to compensate for this acidosis,

acid levels can rise very high, causing severe metabolic

glucose. With severe diabetes mellitus, blood acetoacetic

some of the fats are split into acetoacetic acid, and this

use of glucose for metabolism is prevented. Instead,

cient insulin, the normal

diabetes). In the absence of suf

acidosis.

occurs, causes loss of bicarbonate and results in meta-

deeper in the gastrointestinal tract, which sometimes

highly acidic. However, vomiting large amounts from

398

Unit V

The Body Fluids and Kidneys

toward alkalosis because the stomach secretions are

bolic acidosis in the same way that diarrhea causes

Diabetes Mellitus.

Diabetes mellitus is caused by lack of

insulin secretion by the pancreas (type I diabetes) or
by insufficient insulin secretion to compensate for
decreased sensitivity to the effects of insulin (type II

is metabolized by the tissues for energy in place of

Ingestion of Acids.

Rarely are large amounts of acids

acidosis occasionally results from the ingestion of

acid when it is metabolized).

Chronic Renal Failure

in the body fluids that are not being excreted by the

filtration

rate reduces the excretion of phosphates and NH

which reduces the amount of bicarbonate added back
to the body fl

by Increased Extracellular Fluid
Bicarbonate Concentration

–

or loss of H

bolic alkalosis is not nearly as common as metabolic aci-

Administration of Diuretics (Except the Carbonic Anhydrase
Inhibitors).

All diuretics cause increased flow of fluid

flow in the

reabsorption of Na

Because the sodium reabsorption here is coupled with
H

leads to an increase in H

secretion and an increase in

extracellular fluid bicarbonate concentration.

Excess Aldosterone.

promotes extensive reabsorption of Na

from the distal

and collecting tubules and at the same time stimulates
the secretion of H

by the intercalated cells of the col-

leads to

extracellular fluid and development of metabolic alka-

who have pyloric obstruction caused by hypertrophied

Ingestion of Alkaline Drugs.

A common cause of metabolic

diffi

excess acid or base in the extracellular fluid.

sodium

bicarbonate
bicarbonate is absorbed from the gastrointestinal tract
into the blood and increases the bicarbonate portion of

sodium lactate and

sodium in the extracellular fluid in the form of sodium
bicarbonate and thereby increasing the pH of the fluid
toward normal.

the buffers of the body fluids to shift the H

concentra-

lysine

Analysis of Acid-Base

Appropriate therapy of acid-base disorders requires

described previously can be diagnosed by analyzing

–

increased above the normal value of 40 mm Hg. This is

is absent, and P

However, the respiratory compensation that would

the patient is acidotic, and there appears to be a meta-

50 mm Hg. In this example,

7 mEq/L, and plasma P

lowing values: pH 7.15, plasma HCO

Hg to 25 mm Hg.

acidosis, with appropriate respiratory compensation

25 mm Hg. With these values, one can look at the

concentration 12.0 mEq/L, and plasma P

patient yields the following values: pH 7.30, plasma

For example, assume that the arterial plasma from a

an acid-base disorder.

mind, the acid-base diagrams can be used as a quick

is a simple acid-base disorder. With this reservation in

always

be a mixed acid-base disorder.

lie outside the shaded area, this suggests that there may

Conversely, if the values for pH, bicarbonate, or P

suggests that there is a simple acid-base disturbance.

ratory disorders. If a value is within the shaded area, this

response, which is 6 to 12 hours for the ventilatory com-

When using this diagram, one must assume that suf-

tory disorders.

within the normal range. The shaded areas of the

balch equation. The central open circle shows normal

concentration, and P

acid-base diagram, pH, HCO

of acidosis or alkalosis, as well as its severity. In this

11. This diagram can be used to determine the type

to use an acid-base nomogram, as shown in Figure

mixed acidosis. This could occur, for example, in a

Therefore, this disorder would be categorized as a

, one would suspect a respiratory compo-

. However, if the low plasma

compensation, a low P

concentration and, after appropriate respiratory

ated, this would also be accompanied by a low plasma

rized as acidotic. If the disorder was metabolically medi-

For example, a patient with low pH would be catego-

more underlying causes for the acid-base disturbance.

This means that there are two or

acid-base disorder.

mixed

this occurs, the abnormality is referred to as a

panied by appropriate compensatory responses. When

In some instances, acid-base disorders are not accom-

Use of the Acid-Base Nomogram

Complex Acid-Base Disorders and

, and increased P

sis, one would expect to find increased pH, increased

concentration in the plasma. In simple metabolic alkalo-

, and decreased HCO

increased pH, decreased P

simple respiratory alkalosis, one would expect to find

Therefore, in

metabolic component to the alkalosis.

, there must be a

respiratory component to the alkalosis. If the rise in pH

, there must be a

that there is an increase in plasma pH. If the increase in

sis involve the same basic steps. First, alkalosis implies

The procedures for categorizing the types of alkalo-

concentration, and a reduction in P

sis, one would expect to find a low pH, a low plasma

Therefore, in simple metabolic acido-

pensation, in contrast to respiratory acidosis, in which

component to the acidosis. In simple metabolic acidosis,

concentration, there must be a metabolic

concentration. Therefore, if a low pH is associated with

in plasma pH. However, with metabolic acidosis, the

For metabolic acidosis, there would also be a decrease

, and increased

be reduced plasma pH, increased P

Therefore, the

component to the acidosis. After renal compensation,

is increased, there must be a respiratory

, it is 24 mEq/L. If the

about 40 mm Hg, and for HCO

concentration. The normal value for P

The second step is to examine the plasma P

Regulation of Acid-Base Balance

Chapter 30

399

and

HCO

–

disorder has been characterized as acidosis and the
plasma P

the plasma HCO

–

concentration in respiratory acidosis

would tend to increase above normal.
expected values for a simple respiratory acidosis would

plasma HCO

–

concentration after partial renal

compensation.

primary abnormality is a decrease in plasma HCO

–

a low HCO

–

the P

is reduced because of partial respiratory com-

is increased.

HCO

after

partial respiratory compensation.

pH is associated with decreased P

is associated with increased HCO

–

plasma HCO

for Diagnosis

HCO

–

pH and low HCO

–

concentration are associated with

elevated P

nent to the acidosis as well as a metabolic component.

patient with acute HCO

–

loss from the gastrointestinal

tract because of diarrhea (metabolic acidosis) who also
has emphysema (respiratory acidosis).

A convenient way to diagnose acid-base disorders is

30–

–

values intersect according to the Henderson-Hassel-

values and the deviations that can still be considered

diagram show the 95 per cent confidence limits for the
normal compensations to simple metabolic and respira-

ficient time has elapsed for a full compensatory

pensations in primary metabolic disorders and 3 to 5
days for the metabolic compensations in primary respi-

It is important to recognize that an acid-base value

within the shaded area does not

mean that there

means of determining the specific type and severity of

HCO

–

diagram and find that this represents a simple metabolic

that reduces the P

from its normal value of 40 mm

A second example would be a patient with the fol-

–

concentration

bolic component because the plasma HCO

–

concentra-

tion is lower than the normal value of 24 mEq/L.

normally reduce P

is slightly

Metabolic

Respiratory

Arterial blood sample

pH?

Alkalosis

Acidosis

>7.4

<7.4

HCO

>24 mEq/L

Pco

<40 mm Hg

Pco

>40 mm Hg

Pco

<40 mm Hg

HCO

<24 mEq/L

HCO

>24 mEq/L

HCO

<24 mEq/L

Pco

>40 mm Hg

Respiratory

compensation

Respiratory

compensation

Metabolic

Renal

compensation

Renal

compensation

of the figure, one should suspect a mixed acid-base disorder.

responses are markedly different from those shown at the bottom

Analysis of simple acid-base disorders. If the compensatory

Figure 30–10

bolic acidosis.

4. By calculating the anion gap,

are shown in Table 30

. Some examples of metabolic aci-

ketoacids, is associated with an increased plasma anion

nonvolatile acids (besides HCl), such as lactic acid or

culated anion gap. Metabolic acidosis caused by excess

, there must be increased levels of

hyperchloremic metabolic acidosis.

anion gap will remain normal, and this is often referred

, the

increase to maintain electroneutrality. If plasma Cl

sodium concentration is unchanged, the concentration

is reduced. If the plasma

dosis, the plasma HCO

different causes of metabolic acidosis. In metabolic aci-

The plasma anion gap is used mainly in diagnosing

cations, and the anion gap ranges between 8 and

albumin, phosphate, sulfate, and other organic anions.

potassium, and the major unmeasured anions are

unmeasured cations include calcium, magnesium, and

or if unmeasured cations fall. The most important

The anion gap will increase if unmeasured anions rise

108

[Cl

[HCO

and unmeasured cations, and is estimated as

. The

, and the anions are usually Cl

measured in the clinical laboratory. The cation normally

However, only certain cations and anions are routinely

fore, there is no real

must be equal to maintain electrical neutrality. There-

The concentrations of anions and cations in plasma

Use of Anion Gap to Diagnose

base disorders.

ate concentrations. In a clinical setting, the patient

, and plasma bicarbon-

tributing to abnormal pH, P

The acid-base diagram serves as a quick way to assess

400

Unit V

The Body Fluids and Kidneys

consistent with a mixed acid-base disturbance con-
sisting of metabolic acidosis as well as a respiratory
component.

the type and severity of disorders that may be con-

’s

history and other physical findings also provide impor-
tant clues concerning causes and treatment of the acid-

Acid-Base Disorders

“anion gap” in the plasma.

measured is Na

–

and

HCO

–

“anion gap” (which is only a diagnostic

concept) is the difference between unmeasured anions

Plasma anion gap

= [Na

] –

–

] –

–

]

= 144 –

–

= 10 mEq/L

Usually the unmeasured anions exceed the unmeasured

16 mEq/L.

–

of anions (either Cl

–

or an unmeasured anion) must

–

increases in proportion to the fall in plasma HCO

–

to as

If the decrease in plasma HCO

–

is not accompanied

by increased Cl

–

unmeasured anions and therefore an increase in the cal-

gap because the fall in HCO

–

is not matched by an

equal increase in Cl

–

dosis associated with a normal or increased anion gap

–

one can narrow some of the potential causes of meta-

Table 30–4

Metabolic Acidosis Associated with Normal or Increased

Aspirin (acetylsalicylic acid)

Addison

Chronic renal failure

Carbonic anhydrase inhibitors

Lactic acidosis

Renal tubular acidosis

Diabetes mellitus (ketoacidosis)

Diarrhea

(Normochloremia)

(Hyperchloremia)

Increased Anion Gap

Normal Anion Gap

Plasma Anion Gap

’s disease

poisoning

Methanol poisoning
Ethylene glycol poisoning
Starvation

110

120

100 90

7.40

7.50

7.60

7.70

7.80

Arterial plasma [HCO

] (mEq/L)

7.30

7.20

7.10

7.00

Arterial blood pH

Chronic

respiratory

acidosis

Metabolic

alkalosis

Acute

respiratory

alkalosis

Metabolic

acidosis

Acute

respiratory

acidosis

Chronic

respiratory

alkalosis

Normal

Pco

(mm Hg)

Pco

(mm Hg)

Base Disorders in the Kidney, 3rd

base disorder. (Adapted from

lying outside the shaded areas,

respiratory disorders. For values

for the normal compensations

show the approximate limits

shaded areas in the nomogram

status in normal people. The

approximate limits for acid-base

central open circle shows the

arterial blood pH, arterial plasma

Figure 30–11

Acid-base nomogram showing

HCO

–

, and P

values. The

caused by simple metabolic and

one should suspect a mixed acid-

Cogan MG, Rector FC Jr: Acid-

ed. Philadelphia: WB Saunders,
1986.)

Endocr Metab Disord 4:343, 2003.

White NH: Management of diabetic ketoacidosis. Rev

York: Raven Press, 2000, pp 2055-2072.

Physiology and Pathophysiology, 3rd ed. New

metabolic alkalosis. In Seldin DW, Giebisch G (eds): The

Wesson DE, Alpern RJ, Seldin DW: Clinical syndromes of

duct. J Nephrol 15(Suppl 5):S112, 2002.

Wagner CA, Geibel JP: Acid-base transport in the collecting

balance by the lung. Nephron Physiol 93:61, 2003.

Madias NE, Adrogue HJ: Cross-talk between two organs:

285:F811, 2003.

acid and base in humans. Am J Physiol Renal Physiol

Lemann J Jr, Bushinsky DA, Hamm LL: Bone buffering of

Laffey JG, Kavanagh BP: Hypocapnia. N Engl J Med 347:43,

Nephrol 13:2178, 2002.

Karet FE: Inherited distal renal tubular acidosis. J Am Soc

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Igarashi I, Sekine T, Inatomi J, Seki G: Unraveling the molec-

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Physiology and Pathophysiology, 3rd ed. New

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Regulation of Acid-Base Balance

Chapter 30

401

References

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Kidney—