Faculty version with model answers

Acid-Base Balance
Bruce M. Koeppen, M.D., Ph.D.
University of Connecticut Health Center

Introduction:
Analysis of acid-base disorders requires measurement of arterial blood gases, and in particular the Pco2 and
pH. In addition, it is often necessary to measure (or calculate) the [HCO3-] of plasma, and what is termed
the anion gap.
Blood gases: Arterial blood gases allow analysis of the critical components of the CO2/HCO3- buffer
system.
CO2 + H2O ? H
? 2CO3 ? H + + HCO3It is from this relationship that the Henderson-Hasselbalch equation is derived:
pH = pK' + log

[HCO 3 ]
Pco2

or

pH = 6.1 + log

[HCO 3 ]
0.03Pco2

Where: pK is the apparent pK of the reaction of CO2 and H2O; and is equivalent to a solubility constant for
CO2 on plasma. The values of 6.1 for the pK and 0.03 for are specific for plasma at 37o C. The normal
range for these parameters is as follows:
Pco2
Po2
pH
[HCO3-]

=
=
=
=

33 - 44 mmHg
(40 mmHg)*
75 - 105 mmHg (100 mmHg)
7.35 - 7.45
(7.40)
22 - 28 mEq/L (24 mEq/L)

* Normal value used for the problems in this conference.

Acid-base disorders resulting from a primary alteration in the Pco2 are termed respiratory disorders, while
those resulting from a primary alteration in the [HCO3-] are termed metabolic disorders.
Anion gap: When acid is added to the body fluids, the [H+] increases (pH decreases), and the [HCO3-]
decreases. In addition, the concentration of the anion, which is associated with the acid, will increase. This
change in the [anion] provides a convenient way to analyze and help determine the cause of an acid-base
disturbance by calculating what is termed the anion gap. The anion gap represents the difference between
the concentration of the major plasma cation (Na+) and the major plasma anions (Cl- and HCO3-), and
reflects the concentration of anions other than Cl- and HCO3- that must be present to balance the
concentration of Na+.
Anion Gap = [Na+] - ([Cl-] + [HCO3-])
Under normal conditions the calculated anion gap is in the range of 8 - 16 mEq/L. An anion gap (i.e., a
difference between the concentration of cations and anions) does not actually exist. All cations are
balanced by anions. The gap simply reflects the parameters that are measured. In reality:
[Na+] + [unmeasured cations] = [Cl-] + [HCO3-] + [unmeasured anions]

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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If the anion of the acid is Cl-, the anion gap will be normal (i.e., the decrease in [HCO3-] is matched by an
increase in [Cl-]. The metabolic acidosis associated with diarrhea or renal tubular acidosis has a normal
anion gap. In contrast, if the anion of the non-volatile acid is not Cl- (e.g., lactate,
-hydroxybutyrate, etc.), the anion gap will increase (i.e., the decrease in [HCO3-] is not matched by an
increase in the [Cl-], but rather by an increase in the [unmeasured anion]). The anion gap is increased in
the metabolic acidosis associated with renal failure, diabetes (ketoacidosis), lactic acidosis, or the ingestion
of large quantities of aspirin. Thus, calculation of the anion gap is a useful way to identify the etiology of a
metabolic acidosis.
Approach to analyzing acid-base disorders: The following simplified approach can be used to analyze
clinical acid-base disturbances.
Ar ter ia l b lo o d sam p le

p H < 7 .4 0

p H > 7 .4 0

Alk a l o s is

Acid o s is
[ HCO 3 -] < 2 4 m Eq / L

Pco 2 > 4 0 m m Hg

[HCO 3 -] > 2 4 m Eq / L

Pco 2 < 4 0 m m Hg

Meta b o lic
Ac id o sis

Res p ir a to r y
Ac id o s is

Met ab o lic
Al k a l o s is

Res p ir at o r y
Alk a l o s is

Pco 2 < 4 0 m m Hg

[HCO3 - ] > 2 4 m Eq / L

Pco 2 > 4 0 m m Hg

[HCO3 -] < 2 4 m Eq / L

Resp ir at or y co m p en sa tio n

1.2 mm Hg Pco2
per 1 mEq/L in [HCO3-]

Ren al co m p en s atio n

Re sp ir a to r y com p en sat io n

3.5 mEq/L [HCO3-]

0.7 mm Hg Pco2
per 10 mm Hg in Pco2 per 1 mEq/L in [HCO3-]

Ren al co m p en sat io n

4 - 5 mEq/L [HCO3-]
per 10 mmHg in Pco2

Recommended Reading:
pp. 133 - 154. Koeppen and Stanton: Renal Physiology, 3rd ed., Mosby, 2001.

1.

In order to stay in acid-base balance a 70 kg man must excrete 1mEq/kg/day of acid in the
urine. If the urine contained no buffers, and if the minimum pH of urine is 4.0, how much acid
could this man excrete if his urine output was 1 L/day? What impact would this have on his
ability to maintain acid-base balance?
The [H+] of a pH 4.0 solution is 0.1 mEq/L. This would be the amount of acid this man could
excrete in the urine if he had no urinary buffers. Obviously, he would quickly develop a
metabolic acidosis because of the large imbalance between the amount of non-volatile acid

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produced versus the amount of acid excreted in the urine. Another way to emphasize the
importance of urinary buffers is to calculate the volume of urine that would have to be excreted
in order to maintain acid-base balance. If the urine contained no buffers the 70 mEq/day of acid
acid would need to be excreted as free H+. Since the minimum urine pH is 4.0 (0.1 mEq/L),
urine output would need to be (70 mEq/day x 0.1 mEq/L = 700 L/day). This exceeds the GFR
by several times (GFR = 180 L/day). Note: The major urinary buffer is phosphate, ammonia is
technically not a urinary buffer, although it is referred to in this manner in many textbooks (see
below).

2.

A 40 year old man has profuse diarrhea for 2 days. At the end of this time the following
laboratory data are obtained (his body weight is 60 kg).
Serum [Na+]
+

Serum [K ]
Serum [Cl-]
3

Serum [HCO ]

140 mEq/L (nl = 135 147 mEq/L)

3.0 mEq/L (nl = 3.5 5.0 mEq/L)

110 mEq/L (nl = 95 105 mEq/L)

15 mEq/L (nl = 22 28 mEq/L)

A. What will be the mechanisms by which his body will compensate for the decreased
serum [HCO3-] in this man?
Anion Gap = [Na+] ([Cl-] + [HCO3-]) or 140 (110 + 15) = 15 mEq/L
This man has developed a metabolic (normal anion gap) metabolic acidosis as a result of the
loss of HCO3- in the diarrhea fluid. The loss of HCO3- is equivalent to the addition of acid to the
body. The body has basically three lines of defense to minimize the impact of acid-base
disturbances on body fluid pH these are described below.
Chemical buffering: The initial line of defense for a metabolic acidosis is chemical buffering of
the acid. This will have already occurred in this man during the course of the development of his
metabolic acidosis. Chemical buffering occurs both extracellularly and intracellularly (for a
metabolic acidosis approximately 50% will be buffered in the ECF and 50% will be buffered in
the ICF). Chemical buffering occurs rapidly (seconds to minutes). Note that this minimizes the
effect of the loss of HCO3- on body fluid pH, but will not correct the acid-base disorder.
Respiratory mechanisms: The acidosis resulting from the loss of HCO3- will stimulate the
medullary respiratory centers and increase the ventilatory rate. This will result in a decrease in
the Pco2, which will minimize the change in the pH (see Henderson-Hasselbalch equation).
Note that this response will not correct the acid-base disorder but simply minimize (or
compensate for) the change in pH. This is illustrated later in the problem. The Pco2 in an
individual is determined by both the rate of CO2 production (Vco2), and alveolar ventilation (Va)
as indicated below:
Pco2 = (Vco2/Va) x K

(where: K = constant)

Thus, reducing the Pco2 by 1/2 (i.e., from 40 mmHg to 20 mmHg) requires a doubling of alveolar
ventilation. Generally, the limits of the respiratory response are dictated by lung mechanics
and the maximum rate of ventilation. In a young person, Pco2 can be reduced to near 10
mmHg. However, most adults cannot reduce the Pco2 below 15 - 20 mmHg. It can also be
noted that hypoventilation can rarely increase the Pco2 above 60 mm Hg (in an otherwise
normal individual), because at this point the hypoventilation will reduce the Po2 to a level that

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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the hypoxia will increase the ventilatory rate. Respiratory compensation occurs in the time
frame of minutes to hours.
Renal mechanisms: In response to the acidosis, the kidneys will increase the secretion of H+
(this will happen quickly and occurs at the level of the proximal tubule, thick ascending limb and
collecting duct). The response of the cells to increase their H+ secretion is triggered by
intracellular acidification (this intracellular acidification occurs in both respiratory and metabolic
acidosis). The intracellular acidification produces a more favorable electrochemical gradient for
H+ secretion across the apical cell membrane. It also causes the insertion of more H+ and
HCO3- transporters into the membrane (apical and/or basolateral depending on the transporter).
Although increased H+ secretion by the nephron is an important component to the response to
acidosis, by itself it is of limited value since so little H+ can be secreted as free H+ (see
question #1). Therefore, there must also be increased availability of urine buffers. The primary
urine buffer is phosphate (as mentioned previously, and as described below, NH4+ is technically
not a urine buffer although many textbooks still use this designation), and there is an increase
in phosphate excretion with acidosis. However, there is limited capacity to increase the
availability of urine buffers.
Quantitatively, the most important response of the kidney to acidosis is to increase the
synthesis and excretion of NH4+. By this process, new HCO3- is generated by the kidney and
returned to the systemic circulation. NH4+ is derived from the metabolism of glutamine in the
cells of the proximal tubule (1 molecule of glutamine yields 2 NH4+ ions and 1 molecule of ketoglutarate, with further metabolism of the -ketoglutarate yielding 2 HCO3- ions). The NH4+ is
secreted into the tubular fluid by the Na+/H+ antiporter (substituting for H+), and the HCO3- is
returned to the circulation. It is important to emphasize that excretion of the NH4+ is critical for
this process to result in the generation of new HCO3- . If the NH4+ is not excreted, it will be
returned to the systemic circulation, and metabolized to urea by the liver with the generation of
2 H+. Thus, it will negate the generation of HCO3- from?
-ketoglutarate. Effective excretion of
+
NH4 requires adequate acidification of the tubular fluid in the collecting duct. Normally, a
significant portion of the NH4+ secreted into the proximal tubular fluid is reabsorbed by the thick
ascending limb of Henles loop (paracellularly driven by the lumen positive voltage, and as a
substitute ion for K+ on the Na+-2Cl--K+ symporter). The NH4+ accumulates in the medullary
interstitium (in equilibrium with NH3). The NH3 then diffuses into the lumen of the collecting duct
(non-ionic diffusion), where, if protonated, it becomes trapped (diffusion trapping), and then
excreted. If collecting duct H+ secretion is impaired NH4+ excretion will decline, more NH4+ will
be returned to the systemic circulation, and no new HCO3- will be generated (there is a one-toone relationship between the amount of NH4+ excreted and the amount of new HCO3-
generated). The reactions involved in the metabolism of glutamine are stimulated by acidosis,
again triggered by cellular acidification. The time course for this stimulation of glutamine
metabolism is hours to days. Therefore, renal compensation consists of enhanced excretion of
acid (excreted with urine buffers such as phosphate) and increased production and excretion of
NH4+ (NH4+ excretion serving as a marker of new HCO3- generation from glutamine metabolism
in the proximal tubule). If this individual stops losing HCO3-, the increased excretion of acid by
the kidneys will eventually correct the acidosis. However, if the HCO3- loss is ongoing the renal
response, like the respiratory response will only work to minimize (or compensate for) the
decrease in pH.
Additional background information: The students may ask why diarrhea results in loss of
HCO3-. In a very simplified manner; the stomach secretes H+, while all portions of the intestine
secrete HCO3-. Under normal conditions there is slightly more HCO3- secreted into the lumen of
the intestine each day then there is H+ secreted into the stomach. Thus, the net impact of the
GI tract on acid-base balance each day is the excretion of 20 40 mEq/day of HCO3- (addition

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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of an equivalent amount of H+ to the ECF). As a result the feces are alkaline, and increased
fecal loss due to diarrhea results in the development of a metabolic acidosis.
This patient also presented with hypokalemia. This too is a result of increased K+ loss in the
feces. K+ is normally secreted into the lumen of the colon. With increased fecal loss
significant amounts of K+ can excreted by this route leading to the development of hypokalemia.

B. If the mans serum [HCO3-] was 24 mEq/L prior to the onset of his diarrhea, how much
HCO3- did he lose in his feces? (Hint: HCO3- is located in both the ECF and ICF,
although the ICF concentration is less than that of the ECF concentration. To estimate
the total amount of HCO3- in the body fluids assume that the volume of distribution of
HCO3- is 50% of body weight or 30 L).

Calculations:
Volume of distribution for HCO3- = 60 kg x 0.5 = 30L
Initial total body HCO3- content = 30 L x 24 mEq/L = 720 mEq
New total body HCO3- content = 30 L x 15 mEq/L = 450 mEq
HCO3- loss = 720 mEq 450 mEq = 270 mEq

C. Estimate the ECF pH if respiratory compensation did not occur in this individual. (i.e.,
assume that the Pco2 is fixed at its normal value of 40 mmHg).
Calculations: Using the Henderson-Hasselbalch equation with a Pco2 of 40 mmHg and a
[HCO3-] of 14 mEq/L, the calculated pH is:
pH = 6.1 + Log(15/(0.03 x 40)
= 6.1 + Log(12.50)
= 6.1 + 1.097
= 7.20

D. Estimate the Pco2 and ECF pH after appropriate respiratory compensation.

Calculations:
The Pco2 can be determined from the scheme on page 2. Appropriate respiratory
compensation for a metabolic acidosis is: 1.2 mmHg decrease in Pco2 for each 1 mEq/L
decrease in serum [HCO3-]. The decrease in serum [HCO3-] from its normal value is 9 mEq/L.
Therefore the Pco2 should decrease by 11 mmHg (9 x 1.2 = 10.8), and the expected Pco2 is 40
mmHg 11 mmHg = 29 mmHg.
Pco2

= ___29____ mmHg

The new expected ECF pH with this degree of respiratory compensation is:

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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pH = 6.1 + Log(15/(0.03 x 29)

= 6.1 + Log(17.86)
= 6.1 + 1.24
= 7.35
ECF pH = __7.34___
This new pH is only slightly below the normal value as a result of the respiratory compensation.
Thus potentially deleterious effects of acidemia are minimized.

3.

Simple acid-base disorders can be diagnosed using the scheme outlined above (see page 2).
What simple acid-base disorders are represented by the following arterial blood gas
determinations (distinguish between acute and chronic respiratory acid-base disorders)?

Normal

pH
7.40

[HCO3-]
mEq/L
24

Pco2
(mm Hg)
40

7.23

10

25

Metabolic Acidosis

7.46

30

44

Metabolic Alkalosis

7.37

28

50

Chronic Respiratory Acidosis

7.66

22

20

Acute Respiratory Alkalosis

7.34

26

50

Acute Respiratory Acidosis

7.58

18

20

Chronic Respiratory Alkalosis

Diagnosis

Distinguish between acute and chronic respiratory acid-base disorders. Acute disorders reflect the fact
that renal compensation has not yet occurred. While chronic respiratory disorders include the renal
compensatory response.

4.

An 18 year old man with insulin-dependent (Type I) diabetes mellitus is seen in the emergency
department. He reports not taking his insulin during the previous 24 hours because he did not
feel well and was not eating. He now has weakness, nausea, thirst, and frequent urination.
His blood pressure is 100/60 mmHg supine and 80/50 erect. His pulse rate increases from
100/min. supine to 110/min. when erect. On physical examination he is found to have deep
and rapid respiration (Kussmal respiration). At 1 AM the following laboratory data are
obtained:
Plasma [Na+]

= 130 mEq/L (nl = 135 - 147 mEq/L)

Serum [Cl ]

= 95 mEq/L (nl = 95 - 105 mEq/L)

Plasma [K ]

= 6.5 mEq/L (nl = 3.5 - 5.0 mEq/L

3

Plasma [HCO ]

7 mEq/L (nl = 22 - 28 mEq/L)

Blood pH

= 6.99 (nl = 7.35 - 7.45)

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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Arterial Pco2

= 18 mmHg (nl = 33 - 44 mm Hg)

Plasma [glucose]

= 600 mg/dL (nl = 70 - 110 mg/dL)

Urine contains glucose and ketones (nl = absent)

The diagnosis of diabetic ketoacidosis is made, and the man is admitted to the hospital. Saline
is administered intravenously, and insulin therapy begun. The results of therapy are
illustrated below.

Time

Serum [K+ ]

Plasma pH

(mEq/L)

Serum [HCO3-]

Serum [glucose]

(mEq/L)

(mg/dL)

1:00 AM

6.5

6.99

600

3:00 AM

4.5

7.10

12

400

4:00 AM

4.0

7.16

14

300

5:00 AM

3.5

7.20

16

250

7:00 AM

3.2

7.24

18

200

A. What type of acid-base disorder does this man have? What is the anion gap, and what
is its significance?
The acid-base disorder of this man is a metabolic acidosis. In the absence of insulin the
metabolism of fats and carbohydrates is altered such that non-volatile acids (ketoacids) are
produced. The non-volatile acids are rapidly buffered by cellular and extracellular buffers.
Buffering in the extracellular fluid results in a decrease in the plasma [HCO3-], which lowers the
pH. The deep rapid breathing reflects the respiratory compensation (Pco2 is lowered).
The anion gap is calculated using the following formula (normal value is 8 16 mEq/L):
Anion Gap = [Na+] - ([Cl-] + [HCO3-]) or 130 (95 + 7) = 28 mEq/L
The anion gap is elevated because of the presence of unmeasured anions, in this case the
anions would be the ketoacids such as acetoacetate, -hydroxybutyrate, etc.

B. What can you conclude about K+ balance in this man?

Despite the hyperkalemia in this man, he is probably K+ depleted. The K+ depletion is a result
of K+ shifts out of the cells (see below) and enhanced K+ excretion because of the glucose
induced osmotic diuresis (i.e., increased urinary flow rate increases K+ secretion in the
collecting duct).
Hyperkalemia is this man is a result of a shift of K+ out of cells (e.g., skeletal muscle) into the
extracellular fluid. This shift occurs because of the lack of insulin and the hypertonicity of the

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ECF secondary to the elevated [glucose]. The acidosis is probably not a major contributing
factor to the development of hyperkalemia in this situation. When acidosis is induced by
mineral acids (e.g., HCl) movement of H+ into cells during the process of intracellular buffering
results in a shift of K+ out of the cell into the ECF. However, with organic acidosis, as occurs in
this situation, the cellular buffering of the organic acids does not result in a significant shift of K+
out of the cell.
The polyuria is a result of an osmotic diuresis induced by glucose (also the ketoacids).
Normally, all of the filtered load of glucose is reabsorbed by the proximal tubule. However, in
this man the filtered load of glucose exceeds the reabsorptive capacity of the proximal tubule.
Consequently, the non-reabsorbed glucose will remain in the lumen of the proximal tubule
where it will act as an osmotically active particle. As NaCl and water are reabsorbed by the
proximal tubule, the concentration of the non-reabsorbed glucose will increase. With this
increase in glucose concentration, an osmotic gradient opposite to that generated by the NaCl
reabsorptive process is developed. Because reabsorption of water by the proximal tubule
depends on an osmotic pressure gradient (lumen osmolality less than interstitial fluid
osmolality), the presence of glucose in the tubular fluid will reduce the osmotic gradient and
thereby water reabsorption. The glucose-induced osmotic diuresis will increase the delivery of
NaCl and water to the distal tubule and cortical collecting duct which stimulates K+ secretion at
these sites. As a result, K+ excretion from the body will be increased. In addition, ketoacids
(anions) are excreted with a cation (Na+ and K+). Thus, some additional K+ will be excreted
because of the high excretion rate of the ketoacids. Increased K+ excretion together with the
shift of K+ from the ICF to the ECF noted above (secondary to the insulin deficiency and
hyperosmolality) will lead to progressive whole body K+ depletion. Accordingly, an increase in
serum [K+] is not always indicative of positive K+ balance. This man is in negative K+ balance,
and is at risk for the development of hypokalemia when insulin is administered and the
metabolic abnormalities are corrected (see 5.C.).

C. Explain why the serum [K+ ] fell during the first hour of treatment.
The serum [K+] fell for several reasons. Insulin causes K+ to move into cells. The mechanism
responsible for this effect of insulin appears to be related to stimulation of the Na+-K+-ATPase.
With increased activity of the Na+-K+-ATPase, K+ uptake into the cell is enhanced. In addition,
insulin's effect on glucose metabolism will lower the serum [glucose]. As a consequence, the
osmolality of the ECF will decrease, and cause additional K+ to move into cells. Finally,
administration of fluids will re-expand the ECF, and dilute the K+ in this compartment. For all of
these reasons, K+ is usually administered during the course of treatment so as not to have
hypokalemia develop. It is usually administered once there was evi dence of adequate urine
output in response to the fluid administration, and serum [K+] falls to less than 5.5 mEq/L. With
normal renal function, fluid and electrolyte therapy should be tailored so that correction occurs
gradually.

5.

A previously healthy 28-year old is seen in the emergency room with right side flank pain.
Shortly after arrival, he passes a small kidney stone. He denies any significant previous renal
or gastrointestinal problems. There is a family history of kidney stones. The results of
laboratory tests done in the emergency room include the following:

Plasma [Na+]
+

Plasma [K ]

137 mEq/L (nl = 135 - 147 mEq/L)

3.1 mEq/L (nl = 3.5 - 5.0 mEq/L)

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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Plasma [Cl-]

=
3

Plasma [HCO ]

Arterial pH

Arterial Pco2

Urine pH

111 mEq/L (nl = 95 - 105 mEq/L)

13 mEq/L (nl = 22 - 28 mEq/L)
7.28 (nl = 7.35 - 7.45)
28 mm Hg (nl = 33 - 44 mm Hg
6.4

A. What is the acid base disorder, and what is its most likely cause?
This is a metabolic acidosis with a normal anion gap. The two most frequent causes for nonanion gap acidoses are defects in renal acid excretion (renal tubular acidosis), or loss of HCO3from the body (e.g., diarrhea). In this case, the relatively alkaline urine pH in the presence of
systemic acidosis suggests a defect in renal acid excretion. Normally, the urine should be
maximally acidic with this degree of systemic acidosis. The most likely diagnosis is distal
renal tubular acidosis (i.e., a defect in H+ secretion or H+ permeability of the distal tubule and
collecting duct). The renal stone which brought this man to the physician, is probably a
calcium-containing stone, since the solubility of calcium is reduced in alkaline urine.

B. What is the mechanism for the decreased serum [HCO3-] in this man?
This is a case of type I (distal) renal tubular acidosis, where the defect is an inability of the
distal nephron to maximally acidify the urine. Because of this defect, there is decreased
excretion of NH4+, net acid excretion (see page 2) is less than non-volatile acid production, and
metabolic acidosis (non-anion gap) develops. This accounts for the decrease in this mans
serum [HCO3-].
The production and excretion of NH4+ is reviewed in the diagram shown below. Note the
important role acidification of the collecting duct plays in getting the NH4+ from the medullary
interstitium into the urine (non-ionic diffusion and diffusion trapping).

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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Na+

Na+

Glutamine
H+
2NH 4 + + A=
NH3
2HCO3 NH4

NH4 +

NH4 +

NH4 +
NH3
+
H+

NH3
+
H+

H+
ATP

NH4 +

NH4 +

HCO3 CA

Cl-

CO2 + H 2 O

If there is inadequate acidification of the tubular fluid by the collecting duct, the NH4+ reabsorbed
by the thick ascending limb of the loop of Henle will be returned to the circulation, and
metabolized to urea. In that process H+ is generated.

6.

A 50 year old man with a history of a duodenal ulcer is admitted to the hospital after several
days of intermittent vomiting. His physical examination reveals signs of volume depletion
(orthostatic changes in blood pressure, sunken eyes, flat neck veins, and poor skin turgor).
Laboratory tests reveal:
Serum [Na+]
+

Serum [K ]

140 mEq/L (nl = 135 - 147 mEq/L)

3.0 mEq/L (nl = 3.5 - 5.0 mEq/L)

98 mEq/L (nl = 95 - 105 mEq/L)

Serum [Cl ]
3

Serum [HCO ]

32 mEq/L (nl = 22 - 28 mEq/L)

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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Arterial pH

Arterial Pco2

Urine [Na+]

7.47 (nl = 7.35 - 7.45)

45 mm Hg (nl = 33 - 44 mm Hg)

5 mEq/L

Urine [Cl ]

5 mEq/L

Urine [K+]

40 mEq/L

Urine pH

5.5

A. What is the acid-base disorder?

The acid-base disorder is a metabolic alkalosis secondary to loss of gastric acid due to
vomiting.
B. How do you explain the urine electrolyte excretion pattern (why are the urine
concentrations of Na + and Cl - low, and why is the urine acidic)? What do these values
tell you about the renal response to the metabolic alkalosis?
This man is volume depleted. The volume depletion accounts for the observed urinary
electrolyte excretion pattern (low urinary NaCl excretion and high urinary K+ excretion).
Moreover, the volume depletion prevents the kidneys from excreting HCO3-, as would be
expected in the presence of a metabolic alkalosis not associated with volume depletion.
Volume depletion has the following effects on the kidneys. First, the GFR and thus the filtered
load of HCO3- are decreased. Second, proximal tubule reabsorption is enhanced so virtually all
the filtered HCO3- will be reabsorbed. This response of the proximal tubule is in defense of the
volume depletion, and directed at NaCl retention. It is mediated by several factors:
Increased activity of the sympathetic nervous system. Renal sympathetic nerves
innervate the cells of the proximal tubule, and stimulate the reabsorption of Na+. The
cellular mechanisms are not known, but appear to be mediated via 1-adrenoceptors.
Increased activity of the renin-angiotensin-aldosterone system. A-II acts directly on the
cells of the proximal tubule to stimulate Na+ reabsorption (and H+ secretion via the
Na+/H+ antiporter). A-II exerts its effect on the cells of the proximal tubule via AT1
receptors.
Alteration in the peritubular Starling forces. With the decreased ECV, the GFR
decreases and the filtration fraction increases. This in turn decreases the hydrostatic
pressure and increases the oncotic pressure in the peritubular capillaries, and thereby
enhances overall reabsorption of fluid by the proximal tubule (included in that fluid is
HCO3-).
Because aldosterone secretion will be stimulated by volume depletion (through reninangiotensin-aldosterone system), there will also be a stimulation of H+ secretion by the
collecting duct. Aldosterone directly stimulates the intercalated cell to secrete H+. This
response is thought to involve the insertion of H+-ATPase (and perhaps also H+/K+-ATPase) into
the apical membrane. In addition, aldosterone stimulates Na+ reabsorption by the principal
cells. Since this process is electrogenic, the transepithelial voltage of the collecting duct
hyperpolarizes (i.e., becomes more lumen negative). This change in voltage favors H+ secretion
by the H+-ATPase, which is also electrogenic. Taken together the kidneys are unable to excrete
HCO3-, because they must retain Na+ and water in response to the volume depletion. Urine pH
is acidic because HCO3- excretion does not occur, and collecting duct H+ secretion is
enhanced.

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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C. How do you explain this mans hypokalemia?

The activation of the renin-angiotensin-aldosterone system also results in enhanced K+
secretion by the principal cells of the collecting duct. As a result hypokalemia, as seen in this
man develops. The alkalosis may also contribute to the hypokalemia by causing K+ to shift into
the cells.

D. How would you treat this man in order to correct his acid-base disorder?
The most effective way to treat this man is to correct his volume depletion by the administration
of isotonic saline. Such therapy will turn off the signals outlined above that prevent the kidneys
from excreting HCO3- . Once the volume status is corrected the renin-angiotensin-aldosterone
system will be suppressed from its activated state, and the stimulatory effect of aldosterone on
collecting duct K+ secretion will be reduced. However, in the short-term, and despite the
suppression of the renin-angiotensin-aldosterone system, K+ will be excreted with the HCO3-.
Thus, K+ loss will continue for a period of time even after the volume depletion is corrected.

7.

A 12 year old girl presents to the emergency room with an acute asthmatic attack. Initial
arterial blood gas values on room air are:
Serum [HCO3-]

22 mEq/L (nl = 22 - 28 mEq/L)

Arterial pH

Arterial Pco2

Arterial Po2 (room air) =

7.55 (nl = 7.35 - 7.45)

28 mm Hg (nl = 33 - 44 mm Hg)
60 mm Hg (nl = 75 - 105 mm Hg)

A. What was the acid-base disorder when she presented to the emergency room?
The initial acid-base disorder is a respiratory alkalosis. This results from increased ventilatory
rate secondary to the hypoxemia. The increased ventilatory rate in response to the hypoxemia
results in a decrease in the Pco2, and therefore the development of a respiratory alkalosis.
Note: CO2 diffuses approximately 20 times faster than O2 across the alveolar wall. This allows
the Pco2 to be reduced by hyperventilation, while the same degree of hyperventilation cannot
raise the Po2 in this setting (i.e., bronchospasm).

Five hours later after receiving appropriate therapy (including 40% O2 by mask), she is tired
and has quiet breath sounds on auscultation. Repeat arterial blood gases are obtained.
Serum [HCO3-]

22.4 mEq/L (nl = 22 - 28 mEq/L)

Arterial pH

Arterial Pco2

7.32 (nl = 7.35 - 7.45)

45 mm Hg (nl = 33 - 44 mm Hg)

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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Arterial Po2 (room air) =

60 mm Hg (nl = 75 - 105 mm Hg)

B. What is the acid-base disorder after therapy, and how do you account for the change
in the patients condition?
After therapy the acid-base disorder is a respiratory acidosis. This reflects decreased
ventilation secondary to fatigue (she has had labored breathing for 5 hours). With decreased
ventilation (i.e., moving less air into and out of the lungs, because both the respiratory rate and
the depth of each breath is reduced) CO2 will be retained, thus raising the Pco2. Note: The Po2
is unchanged despite the fact that she is receiving supplemental O2 (40% O2). Without this
supplemental O2, her hypoxemia would have worsened. The decreased lung sounds (i.e., little
wheezing) is a result of decreased air movement as well as some relief of the bronchospasm.
Because of fatigue, she may need to be placed temporarily on a respirator.

8.

A 48 year old man is admitted to the hospital with renal failure secondary to diabetes mellitus.
The following laboratory data is obtained.
Serum [Na+]

Serum [K+]

Serum [Cl ]
Serum [HCO3-]
Serum [creatinine]

=
=
=

135 mEq/L (nl = 135 - 147 mEq/L)

5.2 mEq/L (3.5 5.0 mEq/L)
100 mEq/L (nl = 95 - 105 mEq/L)
15 mEq/L (nl = 22 28 mEq/L)
8.2 mg/dL (nl = 0.6 1.2 mg/dL)

A. What is the acid-base disorder, and what is the anion gap?

This is a metabolic acidosis, with an elevated anion gap. The anion gap is: 135 (100 + 15) =
20 mEq/L. The acidosis is a result of the reduced excretion of net acid by the kidney,
secondary to the renal failure. Because of the loss of renal tissue, there is inadequate
production and excretion of ammonium.

B. How much HCO3- would have to be administered to this man in order to normalize his
serum [HCO3-] to 24 mEq/L (assume a body weight of 55 kg)? Once normalized, and
assuming he continues to have the same daily production of non-volatile acid, how
much HCO3- would have to be administered on a daily basis to maintain a normal
serum [HCO3-]?
The same approach as used in question 1 (i.e. assume the volume of distribution of HCO3- is
50% of body weight), would be used here to calculate the HCO3- deficit in this man, and thus
the amount of HCO3- that would have to be administered to correct his serum [HCO3-] is 247.5
mEq.
Calculations:
Volume of distribution for HCO3- = 55 kg x 0.5 = 27.5 L
Initial total body HCO3- content = 27.5 L x 15 mEq/L = 412.5 mEq

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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Desired body HCO3- content = 27.5 L x 24 mEq/L = 660 mEq

HCO3- need = 660 mEq 412.5 mEq = 247.5 mEq

In order to maintain a normal serum [HCO3-] an amount of HCO3- would have to be administered
each day to balance non-volatile acid production. If non-volatile acid production is estimated as
1 mEq/kg/day, then his non-volatile acid production is 55 mEq/day, and he would need to
receive the same daily dose of HCO3-.

Bruce M. Koeppen, M.D., Ph.D., University of Connecticut Health Center

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