number in this chapter found in parentheses after the reference.

Key References

American College of Cardiology/American Heart Association

Task Force on Practice Guidelines et al. ACC/AHA focused

update on perioperative beta-blockade. J Am Coll Cardiol. 2009;

54:2102. (5)

174 Section 1 General Care

American Society of Anesthesiologists Task Force on Neuraxial Opioids et al. Practice guidelines for the prevention, detection, and management of respiratory depression associated with

neuraxial opioid administration. Anesthesiology. 2009;110:218.

(129)

Apfel CFC et al. A factorial trial of six interventions for prevention of postoperative nausea and vomiting. N Engl J Med.

2004;350:2441. (94)

Gan TJ et al. Society for Ambulatory Anesthesia guidelines for

the management of postoperative nausea and vomiting. Anesth

Analg. 2007;105:1615. (81)

Horlocker TT et al. Executive summary: regional anesthesia in

the patient receiving antithrombotic or thrombolytic therapy:

American Society of Regional Anesthesia and Pain Medicine

Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med.

2010;35:102. (131)

McCaffery M, Pasero C. Pain Assessment and Pharmacologic

Management. St. Louis, MO: Elsevier Mosby. 2011. (136)

Neal JM et al. ASRA Practice advisory on the treatment of local

anesthetic systemic toxicity. Reg Anesth Pain Med. 2010;35:152.

(43)

Pasero C. Assessment of sedation during opioid administration

for pain management. J Perianesth Nurs. 2009;24:186. (110)

Weiskopf RB, Eger EI 2nd. Comparing the costs of inhaled anesthetics. Anesthesiology. 1993;79:1413.

Key Websites

Lipid Rescue. Resuscitation for cardiac toxicity. http://www.

lipidrescue.org.

Malignant Hyperthermia Association of the United States.

http://www.mhaus.org.

San Diego Patient Safety Council. Tool Kit. Patient Controlled Analgesia (PCA) Guidelines of Care for the Opioid

Na¨ıve Patient. December 2009. http://www.chpso.org/meds/

pcatoolkit.pdf. (114)

Acid–Base Disorders 9

Luis S. Gonzalez, III and Raymond W. Hammond

CORE PRINCIPLES

CHAPTER CASES

1 Acid–base analysis should proceed in a stepwise approach to avoid missing

complicated disorders that may not be readily apparent.

Case 9-1 (Question 1)

2 A normal anion gap metabolic acidosis is most commonly found in patients who

have either diarrhea or are receiving large amounts of isotonic crystalloid infusions.

A less common cause of a normal anion gap metabolic acidosis occurs with patients

who present with one of several types of renal tubular acidoses.

Case 9-1 (Questions 2–6)

3 A metabolic acidosis with an elevated anion gap is created by a disease process

that produces an acid, which is buffered by the major extracellular buffer,

bicarbonate. It is important to include a calculation of the anion gap in the workup

of all patients considered for acid–base analysis.

Case 9-2 (Questions 1–4)

4 Metabolic alkaloses can be classified according to a patient’s volume status and

responsiveness to the administration of chloride-containing solutions. A contraction

alkalosis, also called chloride-responsive alkalosis, is generally caused by diuretic

administration whereas a chloride-nonresponsive alkalosis may be caused by

glucocorticoid administration.

Case 9-3 (Questions 1–4)

5 A respiratory acidosis can be acute, chronic, or acute-on-chronic. The best way to

differentiate these disorders is with a careful patient history and review of previous

blood gas values looking for elevated carbon dioxide levels when a patient is at his

or her baseline.

Case 9-4 (Questions 1–4)

6 Unlike respiratory acidosis, most patients presenting with a respiratory alkalosis do

so acutely. There are a relatively small number of conditions that cause an acute

respiratory alkalosis, which can aid in the diagnosis when it is not apparent.

Case 9-5 (Questions 1–4)

7 Mixed metabolic and respiratory acid–base disorders occur commonly in acutely ill

patients. Acid–base analysis can assist in the diagnosis of clinically difficult cases.

Following a stepwise approach in the analysis of acid–base disorders should identify

all clinically important abnormalities.

Case 9-6 (Questions 1–3)

Understanding the etiology of a clinically important acid–base

disturbance is important because therapy generally should be

directed at the underlying cause of the disturbance rather

than merely the change in pH. Severe acid–base disorders can

affect multiple organ systems, including cardiovascular (impaired

contractility, arrhythmias), pulmonary (impaired oxygen delivery, respiratory muscle fatigue, dyspnea), renal (hypokalemia,

nephrolithiasis), or neurologic (decreased cerebral blood flow,

seizures, coma).

ACID–BASE PHYSIOLOGY

To protect body proteins, acid–base balance must be tightly controlled in an attempt to maintain a normal extracellular pH of

7.35 to 7.45 and an intracellular pH of approximately 7.0 to 7.3.1

This narrow range is maintained by complex buffer systems, ventilation to expel carbon dioxide (CO2), and renal elimination of

acids and reabsorption of bicarbonate (HCO−

3 ).2 At rest, about

200 mL of CO2, and even more during exercise, is transported

175

176 Section 1 General Care

Blood

Renal

Tubule Cell

Tubule

Lumen

CO2

CO2 CO2

HCO3

CO2 + H2O

H2CO3

HCO3 + H+

Na+

HCO3

HCO3

H2CO3

H+ +

+ H2O

Carbonic

Anhydrase

Carbonic

Anhydrase

FIGURE 9-1 Renal tubular bicarbonate

reabsorption.

from the tissues and excreted in the lungs.3 Although HCO−

3 is

responsible only for about 36% of intracellular buffering, it provides about 86% of the buffering activity in extracellular fluid

(ECF).1 Extracellular fluid contains approximately 350 mEq of

HCO−

3 , which buffers generated H+.

HCO−

3 + H+ ⇔ H2CO3 (Eq. 9-1)

Hydrogen ion (H+) combines with HCO−

3 and shifts the equilibrium of Eq. 9-1 to the right. In the proximal renal tubule lumen,

carbonic anhydrase catalyzes the dehydration of H2CO3 to CO2

and H2O, which are absorbed into the tubule cell, as illustrated

in Eq. 9-2 and in Figure 9-1. Within the tubule cell, H2O dissociates into H+ and OH−. The H+ is then secreted into the lumen

by a Na+–H+ exchanger. Carbonic anhydrase then catalyzes the

combination of OH− and CO2 to HCO−

3 , which is carried into

the circulation by a Na+HCO−

3 cotransporter.4

HCO−

3 + H+ ⇔ H2CO3

CA

⇔ CO2 (dissolved) + H2O (Eq. 9-2)

To maintain acid–base balance, the kidney must reclaim and

regenerate all the filtered HCO−

3 . The daily amount that must be

reabsorbed can be calculated by the product of the glomerular

filtration rate (GFR) and the HCO−

3 concentration in ECF (180

L/day GFR×24 mEq/L HCO−

3 =4,320 mEq/day).1 The proximal

tubule reabsorbs about 85% of the filtered HCO−

3 . The loop of

Henle and the distal tubule reabsorb about 10%.5 Acid salts, such

as HPO−

4 (pKa of 6.8), that have a pKa greater than the pH of the

urine (titratable acids) can accept a proton and be excreted as

the acid, thus regenerating an HCO−

3 anion.5 Sulfuric acid and

other acids with a pKa less than 4.5 are not titratable. Protons

from these acids must be combined with another buffer to be

secreted. Glutamine deamination in proximal tubular cells forms

NH3, which accepts these protons. In the collecting tubule, the

NH+

4 produced is lipid insoluble, trapping it in the lumen and

causing its excretion, eliminating the proton, and allowing for

regeneration of HCO−

3 .

4–6 Figure 9-2 is a simplified illustration

of the buffering of these acids.

The daily metabolism of carbohydrates and fats generates

about 15,000 mmol of CO2. Although CO2 is not an acid,

it reversibly combines with H2O to form carbonic acid (i.e.,

H2CO3). Respiration prevents the accumulation of volatile acid

through the exhalation of CO2. Metabolism of proteins and fats

results in several fixed acids and bases. Amino acids such as lysine

and arginine have a net positive charge and serve as acids. Compounds such as glutamate, aspartate, and citrate have a negative

charge. In general, animal proteins contain more sulfur and phosphates, producing an acidic diet. Vegetarian diets consist of more

organic anions, resulting in a more alkaline diet.7 Normally, fatty

acids are metabolized to HCO−

3 ; however, during starvation or

diabetic ketoacidosis, they may be incompletely oxidized to acetoacetate and β-hydroxybutyric acid.6 The typical diet generates

a net nonvolatile acid load of about 70 to 100 mEq of H+ (1.0–

1.5 mEq/kg) per day.1,8 Renal excretion of 70 mEq in 2 L of urine

each day would require a pH of 1.5. Because the kidney cannot

produce a pH less than 4.5, most of this fixed acid load must

be buffered. The primary buffers for renal net acid excretion

Blood

Renal

Tubule Cell

Tubule

Lumen

CO2 CO2 + H2O

H2CO3

+ H+

Na+

Carbonic

Anhydrase

HPO4

2

H+ H+ + HPO4

2

NH3 H+ + NH3 NH4

Excreted in

Urine

NH3 Glutamate +

Glutamine

H2PO4

+

HCO3 HCO3

Na+

FIGURE 9-2 Renal tubular

hydrogen ion excretion.

177Acid–Base Disorders Chapter 9

TABLE 9-1

Normal Arterial Blood Gas Values

ABGs Normal Range

pH 7.36–7.44

Pao2 90–100 mm Hg

Paco2 35–45 mm Hg

HCO−

3 22–26 mEq/L

ABG, arterial blood gas.

are NH−

3 /NH+

4 and titratable buffers, such as HPO−

4 /H2PO2−

4 ,

as mentioned earlier.7 The correct assessment of acid–base disorders begins with an evaluation of appropriate laboratory data

and an understanding of the physiologic mechanisms responsible

for maintaining a normal pH.

Laboratory Assessment

Laboratory data used to evaluate acid–base status are arterial pH,

arterial carbon dioxide tension (Paco2), and serum bicarbonate

(HCO−

3 ).9–11 These values are obtained routinely with an arterial

blood gas (ABG) determination. Acid–base abnormalities occur

when the concentration of Paco2 (an acid) or HCO−

3 (a base)

is altered. ABG measurements also include the arterial oxygen

tension (Pao2); however, this value does not directly influence

decisions regarding acid–base abnormalities. Normal ABG values

are listed in Table 9-1. When arterial pH is less than 7.35, the

patient is considered acidemic, and the process that caused acid–

base imbalance is called acidosis. Conversely, when the arterial

pH is greater than 7.45, the patient is considered alkalemic, and

the causative process is alkalosis. The process is further defined

as respiratory in cases of an inappropriate elevation or depression

of Paco2 or metabolic with an inappropriate rise or fall in serum

HCO−

3 .

Acid–base balance is normally maintained by the primary

extracellular buffer system of HCO−

3 /CO2. Components of this

buffer system are measured routinely to assess acid–base status.

Other extracellular buffers (e.g., serum proteins, inorganic

phosphates) and intracellular buffers (e.g., hemoglobin, proteins, phosphates), however, also contribute significant buffering

activity.1,7–10 Serum electrolytes are obtained to calculate the

anion gap, an estimate of the unmeasured cations and anions

in serum. The anion gap helps determine the probable cause of

a metabolic acidosis.6,10,12–28 Urine pH, electrolytes, and osmolality help to further differentiate among the possible causes of

metabolic acidosis.10,29–33

Acid–Base Balance, Carbon Dioxide

Tension, and Respiratory Regulation

In aqueous solution, carbonic acid (i.e., H2CO3 formed

through the reaction described in Eq. 9-1) reversibly dehydrates

to form carbon dioxide (CO2) and water (H2O) as shown in

Eq. 9-2.

The enzyme carbonic anhydrase (CA), present in red blood

cells, renal tubular cells, and other tissues, catalyzes the interconversion of carbonic acid and carbon dioxide. Some of the carbon

dioxide produced by dehydration of carbonic acid remains dissolved in plasma, but most exists as a volatile gas:

HCO−

3 + H+ ⇔ H2CO3

CA

⇔ CO2 (dissolved) + H2O

↑↓ (Eq. 9-3)

k × CO2 (gas)

In Eq. 9-3, k is a solubility constant that has a value of approximately 0.03 in plasma at body temperature.2,33 Virtually all

the carbonic acid in body fluids is in the form of carbon dioxide. The Paco2, a measure of carbon dioxide gas, is therefore

directly proportional to the amount of carbonic acid in the

HCO−

3 /H2CO3 buffer system. The normal range for Paco2 is

35 to 45 mm Hg.

The lungs can rapidly exhale large quantities of carbon dioxide and thereby contribute significantly to the maintenance of

a normal pH. Carbon dioxide formed through the reaction

described in Eq. 9-3 diffuses easily from tissues to capillary blood

and from pulmonary capillary blood into the alveoli where it is

exhaled from the body.3 Pulmonary ventilation is regulated by

peripheral chemoreceptors (located in the carotid arteries and

the aorta) and central chemoreceptors (located in the medulla).

The peripheral chemoreceptors are activated by arterial acidosis, hypercarbia (elevated Paco2), and hypoxemia (decreased

Pao2). Central chemoreceptors are activated by cerebrospinal

fluid (CSF) acidosis and by elevated carbon dioxide tension in

the CSF.3 Activation of these chemoreceptors stimulates the respiratory control center in the medulla to increase the rate and

depth of ventilation, which results in increased exhalation of

carbon dioxide.

BICARBONATE AND RENAL CONTROL

As described in the Acid–Base Physiology section, the kidneys are

responsible for regulating the serum bicarbonate concentration.

This is accomplished through two important and interrelated

functions. First, they must reabsorb the bicarbonate that undergoes glomerular filtration and is present in the renal tubular fluid.

Second, the kidneys must excrete hydrogen ions released from

nonvolatile acids. Both functions are important in preventing

systemic acidosis.

One mechanism of bicarbonate reabsorption in the proximal

renal tubule is illustrated in Figure 9-1. Carbonic anhydrase catalyzes intracellular formation of carbonic acid (H2CO3) from

carbon dioxide (CO2) and water in the renal tubular cell. The

carbonic acid then dissociates to form H+ and HCO−

3 . The H+

ion is secreted into the lumen of the tubule in exchange for a

sodium ion (Na+), and the bicarbonate from the renal tubule

cell is reabsorbed into the capillary blood.

Inside the lumen, carbonic acid is re-formed from secreted

H+ and filtered HCO−

3 . Carbonic anhydrase present inside the

lumen (on the brush border membrane of the cell) catalyzes

conversion of carbonic acid to carbon dioxide, which can readily

diffuse back into the blood. Thus, the net result is reabsorption

of sodium and bicarbonate. Although a hydrogen ion is secreted

into the lumen in this process, no net excretion of acid occurs

because of the reabsorption of carbon dioxide.4–6 Figure 9-2

illustrates H+ excretion by the kidney. This process was also

discussed in the Acid–Base Physiology section.

In clinical practice, the serum bicarbonate concentration usually is estimated from the total carbon dioxide content when

the serum concentration of electrolytes are ordered on an electrolyte panel or calculated from the pH and Paco2 on an ABG

determination. These estimations of the serum bicarbonate concentration are more convenient than directly measuring serum

bicarbonate. The total carbon dioxide content that is reported

on serum electrolyte panels is determined by acidifying serum

to convert all the bicarbonate to carbon dioxide and measuring

the partial pressure of CO2 gas. Approximately 95% of the total

carbon dioxide content is bicarbonate. The serum bicarbonate

concentration reported on ABG results is calculated from the

patient’s pH and Paco2 using the Henderson–Hasselbalch equation (Eq. 9-4). This calculated bicarbonate concentration should

be within 2 mEq/L of the measured total carbon dioxide. The

178 Section 1 General Care

normal range of serum bicarbonate using these methods is 22 to

26 mEq/L.10

BICARBONATE/CARBONIC ACID RATIO

The relationship between the pH and the concentrations of the

acid–base pairs in buffer systems is described by the Henderson–