CHAPTER 54 

TRADITIONAL ACID-BASE ANALYSIS

Kate Hopper, BVSc, PhD, DACVECC

KEY POINTS
SAMPLE COLLECTION AND HANDLING
• Traditional acid-base analysis uses the Henderson-Hasselbalch Before further discussion of acid-base analysis, it is important to
equation to evaluate the blood pH as a direct consequence of the appreciate the potential for preanalytical error if inappropriate
PCO2, bicarbonate, and base excess. sample collection or handling occurs. The site of sample collection
• Blood pH is a measure of hydrogen ion concentration and is
dependent on the ratio of bicarbonate to PCO2.
affects acid-base variables. In healthy research dogs there was a sta-
• PCO2 behaves as an acid in the body and represents the tistically significant difference in pH, PCO2, PO2, and bicarbonate
respiratory contribution to acid-base balance. concentration when arterial values were compared with venous
• Bicarbonate, base excess, and TCO2 are all representations of the values. pH and PCO2 were also different between jugular and cephalic
metabolic contribution to acid-base balance. venous samples (see Appendix 1).8 These differences are relatively
• The anion gap is a diagnostic tool that may help identify the small, and for the purpose of acid-base analysis, venous samples have
cause of a metabolic acidosis.
been found to be an adequate replacement for arterial values in criti-
• The treatment of most acid-base disorders is focused on
resolution of the underlying disease. cally ill human patients.9,10 In states of poor peripheral perfusion,
• Sodium bicarbonate therapy is primarily indicated for the peripheral venous samples can have elevations in PCO2 and lactate
treatment of metabolic acidoses associated with kidney disease concentration, which will contribute to lower pH values that may not
and diarrhea-associated loss of bicarbonate. be representative of central venous or arterial values.10
Other sources of preanalytical error for acid-base analysis include
time delays between sample collection and sample analysis; exposure
to air, which will allow PCO2 to equilibrate to a lower value; and
Regulation of hydrogen ion concentration within physiologically inappropriate dilution of the blood sample with liquid anticoagulant
acceptable limits is essential. The evaluation of acid-base balance is such as sodium heparin.11 Any bubbles in the sample should be
an integral aspect of managing critically ill and injured patients. immediately removed. If a delay of greater than 15 minutes between
Clinically, adequate assessment of acid-base abnormalities requires sample collection and analysis is anticipated, the sample should be
an understanding of the etiology and magnitude of changes in order maintained under airtight conditions and immersed in ice water.12,13
to guide further diagnostic and therapeutic interventions. Acid-base
balance has been a focus of research and discussion in the medical TRADITIONAL APPROACH
literature since the beginning of the twentieth century.1-5
The normal concentration of hydrogen ions is very small (40 The traditional approach is based on the Henderson-Hasselbalch
nanomoles/L) compared with other ions in the body, such as sodium equation (Box 54-1) for carbonic acid (H2CO3) and uses pH, the
(145 million nanomoles/L in the dog).6 By convention, the concen- partial pressure of carbon dioxide (PCO2), and bicarbonate concen-
tration of hydrogen ions is described as pH, a dimensionless measure tration (HCO3−). From this equation it is clear that pH has a direct
that is calculated as the negative logarithm of the hydrogen ion activ- relationship with bicarbonate concentration and an inverse relation-
ity and allows the representation of a wide range of hydrogen ion ship with PCO2. Modern blood gas machines measure the hydrogen
concentrations in a simplified manner. The pH scale ranges from 0 ion activity and PCO2 of a blood or plasma sample and use the
for a 1 molar solution of hydrogen ion to 14 for a 10−14 molar solu- Henderson-Hasselbalch (HH) equation to derive the concentration
tion.4 The hydrogen ion concentration considered compatible with of bicarbonate. The base excess (BE) and anion gap (AG) parameters
life for a mammalian system ranges from 10 to 160 nanomoles/L, have been added to the traditional approach to improve its diagnostic
which correlates with a pH from 8 to 6.8, respectively.7 A blood pH utility.
below the normal range for the species is considered an acidemia and The body relies on three major processes to maintain acid-base
an elevated blood pH is considered an alkalemia. An individual balance: regulation of PCO2 by alveolar ventilation, buffering of acids
process in the system that tends to decrease or increase pH is referred by bicarbonate and nonbicarbonate buffer systems, and changes in
to as an acidosis or an alkalosis, respectively. renal excretion of acid or base. As mentioned previously, PCO2
Clinical assessment of acid-base balance first evaluates the pH:
normal, acidemia or alkalemia. The system is then partitioned into
the respiratory and metabolic components and each is evaluated BOX 54-1  Henderson-Hasselbalch Equation
separately. PCO2 represents the respiratory component universally,
but there are numerous measures available for assessment of the pH = 6.1 + log ([ HCO3 − ] ÷ [0.03 × PCO2 ])
metabolic component. These include the Henderson-Hasselbalch, or where 6.1 is the pKa in body fluids; HCO3− is the concentration of
traditional, approach; the Stewart approach; and a semi-quantitative bicarbonate measured in mEq/L or mmol/L; 0.03 is the solubility
approach that combines aspects of both the traditional and Stewart coefficient for carbon dioxide in plasma; and PCO2 is the partial
approaches. This chapter will review traditional acid-base analysis pressure of carbon dioxide in mm Hg.
and Chapter 55 will discuss the nontraditional approaches.

289
290 PART V  •  ELECTROLYTE AND ACID-BASE DISTURBANCES

represents the respiratory component, and in the traditional approach have the same acid-base balance as humans. Herbivores tend to have
changes in bicarbonate concentration (or BE) represent the metabolic a more positive “normal” BE than people, whereas carnivores tend to
component (influenced by both buffering systems and renal handling have a more negative “normal” BE than people. See Appendix 1 for
of acid). As the HH equation describes, pH is not dependent on a reported normal range of acid-base values for dogs and cats.
having a specific PCO2 and bicarbonate concentration. Rather, pH is The major advantage of using BE over bicarbonate concentration
the consequence of the ratio of bicarbonate to PCO2. For example, a is that it is independent of changes in the respiratory system. When
patient can have a high bicarbonate concentration, but as long as the there are minimal changes in PCO2 present, the BE and bicarbonate
PCO2 has increased by a similar magnitude, the HCO3− : PCO2 ratio should correlate well. The BE can be estimated by the measured
will remain normal and hence pH will remain in the normal range. bicarbonate concentration minus the normal bicarbonate concentra-
Because maintenance of an acceptable pH is optimal to maintain tion. In the face of substantial abnormalities in PCO2, the BE is a
physiologic processes, it is no surprise that when an abnormality in more reliable measure of the metabolic component.14,15,18
one system (respiratory or metabolic) occurs, changes are made in
the opposing system in an attempt to return the ratio of bicarbonate Total Carbon Dioxide
to PCO2 toward normal; hence pH is driven back toward a more Many blood gas machines and most diagnostic laboratories will
normal value. This process is known as compensation and tends to provide a parameter called total carbon dioxide (TCO2). This is a
return pH toward normal, but it is generally accepted that compensa- misleading name because this represents the metabolic acid-base
tion will not be complete. This means compensation will rarely result component, not the respiratory system component. The TCO2 is a
in a pH within the normal range and will not overcompensate. See measure of all the carbon dioxide in a blood sample, and the majority
later in this chapter for further discussion of compensation. of carbon dioxide is carried as bicarbonate in the blood. In general,
TCO2 will be 1 to 2 mmol/L higher than the true bicarbonate
PCO2 concentration.6

Carbon dioxide acts as an acid in the body because of its ability to Anion Gap
react with water to produce carbonic acid. With increases in PCO2, The anion gap (AG) was developed to better define the cause of a
the ratio of bicarbonate to PCO2 is decreased, hence pH falls. Another metabolic acidosis. Electroneutrality requires there to be an equal
way to consider this process is that with an increase in PCO2 the number of anions and cations in physiologic systems. In reality there
carbonic acid equation (shown below) will be driven to the right, is no actual AG; the apparent AG exists because more cations in the
increasing the hydrogen ion concentration. system are readily measured than anions. The AG is a reflection of
unmeasured cations and unmeasured anions and is calculated
CO2 + H2O ←→ H2CO3 ←→ H + + HCO3 −
according to the equation in Box 54-2. The AG of a normal individual
Because carbon dioxide is a gas and its concentration in the blood is is primarily composed of negatively charged plasma proteins, mostly
controlled by pulmonary ventilation, the lung plays an important albumin.19
role in controlling acid-base status. Changes in alveolar ventilation There are two common mechanisms of metabolic acidosis. The
occur rapidly and can alter blood pH within minutes. An increased first is the loss of bicarbonate from the body via the gastrointestinal
PCO2 has an acidotic influence (a respiratory acidosis) and a tract or kidneys; this bicarbonate is produced by cells and involves
decreased PCO2 represents a respiratory alkalosis. the exchange of bicarbonate and chloride. The result is a rise in serum
chloride as bicarbonate is lost, a hyperchloremic metabolic acidosis.
Bicarbonate No change in AG would be expected. The other common clinical
Bicarbonate is a parameter calculated by blood gas machines, cause of metabolic acidosis is the gain of acid. When there is excess
although some clinical laboratories do measure it directly. Elevations acid in the system, hydrogen ions will titrate (combine) with bicar-
in bicarbonate are consistent with a metabolic alkalosis, whereas bonate, leading to a fall in bicarbonate concentration; the anion that
decreases in bicarbonate concentration represent a metabolic acido- accompanied the hydrogen ion (the conjugate base) will accumulate,
sis. One of the major criticisms of using bicarbonate as the measure maintaining electroneutrality and increasing the AG. Common acids
of the metabolic component is that it is not independent of changes associated with an increased AG include lactate, ketone bodies,
in PCO2.14-16 As discussed earlier, changes in PCO2 will alter the sulfate, phosphate, and toxins such as ethylene glycol.20 A useful
equilibration of the carbonic acid equation. Elevations of PCO2 will mnemonic for increased AG metabolic acidosis in small animals is
lead to elevations of bicarbonate, whereas decreases in PCO2 will lead DUEL, standing for diabetic ketoacidosis, uremic acids (sulfates,
to a decrease in bicarbonate. As such it is important that changes in phosphates), ethylene glycol, and lactic acidosis (Box 54-3).
bicarbonate concentration are always evaluated in terms of the pH It is important to note that hypoalbuminemia can mask the pres-
and PCO2. ence of unmeasured anions. Albumin and phosphorus are the major
contributors to the AG in the normal animal. In states of hypoalbu-
Base Excess minemia, abnormal unmeasured anions (e.g., lactate or ketones) may
Base excess (BE) is the titratable acidity (or base) of the blood sample. be present but the calculated anion gap may still remain within the
It is defined as the amount of acid or base that must be added to a reported reference range. As a result the AG is not reliable in hypo-
sample of oxygenated whole blood to restore the pH to 7.4 at 37° C albuminemic patients.21,22
and at a PCO2 of 40 mm Hg.17 Theoretically a normal individual
should not have an excess or deficit of acid or base and hence BE
would equal 0. An increased BE (more positive value) is consistent BOX 54-2  Anion Gap Equation
with an alkalotic process (either gain of bicarbonate or loss of acid).
A decreased BE (more negative value), also known as a base deficit, Anion gap* = ([ Na + ] + [ K + ]) − ([ HCO3 − ] + [Cl − ])
represents an acidotic process. The BE is a parameter calculated by
*Physiologically there is no actual anion gap; rather, this is a measure of
an algorithm programmed into blood gas machines. These machines unmeasured anions and cations in the system. An increase in the anion gap
use human algorithms with normal human blood having a BE of usually reflects an increase in unmeasured anions.
approximately 0 mmol/L. Unfortunately veterinary species do not
 CHAPTER 54  •  Traditional Acid-Base Analysis 291

BOX 54-3  Possible Causes for Metabolic Acidosis Table 54-2  Expected Compensatory Changes to
Primary Acid-Base Disorders
Increased Anion Gap Normal (or Low) Anion
Metabolic Acidosis Gap Metabolic Acidosis Primary Disorder Expected Compensation
DUEL • Renal bicarbonate loss Metabolic acidosis ↓ PCO2 of 0.7 mm Hg per 1 mEq/L
• Diabetic ketoacidosis • Gastrointestinal decrease in [HCO3−] ±3
bicarbonate loss
• Uremia Metabolic alkalosis ↑ PCO2 of 0.7 mm Hg per 1 mEq/L
• Ethylene glycol intoxication • Dilutional acidosis
• Hypoadrenocorticism decrease in [HCO3−] ±3
• L-Lactic acidosis
• Hypoalbuminemia Respiratory ↑ [HCO3−] of 0.15 mEq/L per 1 mm Hg
Other Less Common Causes acidosis—acute ↑ PCO2 ±2
• D-Lactic acidosis Respiratory ↑ [HCO−3] of 0.35 mEq/L per 1 mm Hg
• Salicylate ingestion acidosis—chronic ↑ PCO2 ±2
• Methanol intoxication
Respiratory ↓ [HCO−3] of 0.25 mEq/L per 1 mm Hg
alkalosis—acute ↓ PCO2 ±2
Respiratory ↓ [HCO−3] of 0.55 mEq/L per 1 mm Hg
Table 54-1  Simple Acid-Base Disturbances Identified alkalosis—chronic ↓ PCO2 ±2
with the Traditional Acid-Base Approach [HCO3−], Bicarbonate concentration measured in mEq/L or mmol/L;
PCO2, partial pressure of carbon dioxide measured in mm Hg,
Acid-base ↑ increased; ↓, decreased.
Disturbance pH Primary Disorder Compensation

Respiratory Decreased Increased PCO2 Increased HCO3−

acidosis in anesthetized cats.26-28 There is a single study in the literature
Respiratory Increased Decreased PCO2 Decreased HCO3 − reporting that cats do not develop respiratory compensation in
alkalosis response to a metabolic acidosis and there are no studies evaluating
the respiratory response of adult cats to a metabolic alkalosis.29 Con-
Metabolic Decreased Decreased HCO3− Decreased PCO2
acidosis sequently extrapolation of the canine calculations of expected meta-
bolic compensation to respiratory disorders should be performed
Metabolic Increased Increased HCO3− Increased PCO2
alkalosis
with caution in cats. Extrapolation of the canine calculations of
expected respiratory compensation to metabolic disorders cannot be
HCO3−, Bicarbonate concentration measured in mEq/L or mmol/L; recommended in cats.
PCO2, partial pressure of carbon dioxide measured in mm Hg.
Acid-Base Analysis
Compensation Traditional acid-base analysis can identify four simple disorders,
Traditional acid-base analysis can identify primary (or simple) acid- defined as a single acid-base abnormality, where any changes in the
base disorders in which there is an abnormality of one system (respi- opposing system are attributed solely to compensation (see Table
ratory or metabolic) and any changes evident in the opposing system 54-1). In addition, mixed disorders can be diagnosed; these are any
are considered consistent with normal compensation (Table 54-1). situation where there is an abnormality in both the metabolic and
For example, a primary metabolic acidosis should have respiratory respiratory components. Mixed disorders are evident when both the
compensation. The respiratory response to a primary metabolic respiratory and metabolic components have the same influence on
abnormality is rapid in onset and complete within hours (assuming acid-base balance (i.e., metabolic acidosis and respiratory acidosis or
a stable level of the metabolic abnormality).23,24 In comparison, the metabolic alkalosis and respiratory alkalosis). A mixed disorder is
metabolic compensatory response to a primary respiratory disorder also present when there are abnormalities evident in both the meta-
takes hours to begin and 2 to 5 days to complete.24,25 The degree of bolic and respiratory components but the pH is in the normal range.
expected compensation in dogs is commonly estimated from guide- In this situation it is important to recall the rule that compensation
lines derived from healthy experimental animals (Table 54-2).24 If the does not return pH all the way back to normal. Lastly a mixed dis-
change observed in the secondary system is similar in magnitude to order may be identified when the change in the opposing system is
the calculated, expected response, it is consistent with compensation not consistent with expected compensation.
and the assessment is a simple acid-base disorder. In other words, the There are numerous possible approaches to diagnosing an acid-
change in the secondary system is completely attributed to compen- base disturbance using the traditional approach. One such approach
sation and no other acid-base abnormality is suspected. A mixed is provided in Box 54-4. In this method the pH is assessed as repre-
acid-base disorder is diagnosed when the changes in the secondary senting acidemia or alkalemia for that species. Then the respiratory
system are not within a range compatible with expected compensa- component and the metabolic component are both assessed for their
tion for the primary disorder. The assumption is that there is some influence on the acid-base balance as acidosis, alkalosis, or normal.
disturbance of the secondary system preventing appropriate com- The process that is influencing acid-base in the same direction as the
pensation from occurring or causing the appearance of “overcom- pH abnormality is the primary disorder. For example:
pensation” (which does not occur).
pH   7.26 (7.35 to 7.42) = Acidemia
Some caution is necessary when interpreting the appropriateness PvCO2 30 (38 to 42 mm Hg) = Respiratory alkalosis
of metabolic compensation to a primary respiratory disorder because HCO3 12 (18 to 22 mmol/L) = Metabolic acidosis
it will depend on the chronicity of the respiratory abnormality, which
may or may not be accurately determined. There are no published In this example, the only process that can be considered respon-
guidelines for the compensatory responses of cats. Cats may demon- sible for the change in pH is the metabolic system; the primary
strate similar metabolic compensation for respiratory disorders as disturbance is therefore a metabolic acidosis. The next step is to
dogs, although two of the three studies on this topic were performed determine if the opposing system (in this example the respiratory
292 PART V  •  ELECTROLYTE AND ACID-BASE DISTURBANCES

A respiratory acidosis is the consequence of increased CO2 pro-

BOX 54-4  Approach to Blood Gas Analysis duction or decreased V A . Clinically the most common causes of
1. Confirm the sample collection and handling was appropriate changes in PCO2 are a result of changes in V A . When primary meta-
2. Evaluate the pH (select one): bolic acid-base abnormalities alter pH, it is sensed by both central
In the normal range and peripheral chemoreceptors and there is a resultant alteration in
Acidemia V A to change PCO2 in a manner to reduce the magnitude of pH
Alkalemia change (respiratory compensation).
3. Evaluate the respiratory component, PCO2 (select one): Because minute ventilation is the product of respiratory rate and
In the normal range tidal volume, common causes of a respiratory acidosis are diseases
Process (increased CO2)
that reduce respiratory rate, tidal volume, or both. Airway obstruc-
Alkalotic process (decreased CO2)
4. Evaluate the metabolic component, HCO3 or SBE (select one): tion can impair tidal volume. Depression of the respiratory center of
In the normal range the brainstem as a consequence of drugs (e.g., many anesthetics and
Acidotic process (decreased HCO3, negative SBE) sedatives), brain injury, mass lesion, and other conditions can lead
Alkalotic process (increased HCO3, positive SBE) to lack of stimulus for V A . Diseases that prevent transmission of
5. Define the primary process, either respiratory or metabolic— impulses from the respiratory center to the respiratory muscles, such
that is, which process is causing a change in the same direction as cervical spinal cord disease, peripheral neuropathies, and diseases
as the pH change? of the neuromuscular junction, can all cause respiratory paralysis and
6. Evaluate if compensation is as expected respiratory acidosis. Myopathies or muscular fatigue can also occur,
7. Determine the overall acid-base analysis impairing respiratory muscle function. Increases in CO2 production
8. Is a primary metabolic acidosis present?
can occur in patients with hyperthermia, seizures, fever, and malig-
If yes, calculate the anion gap.
nant hyperthermia. However, the awake, neurologically intact animal
should increase V A to compensate for an increase in VCO
 2 , so gener-
ally these abnormalities cause respiratory acidosis in the compro-
system) is consistent with expected compensation. First the direction mised or anesthetized animal. See Chapter 16 further discussion of
of the change in the opposing system needs to be evaluated to see if this topic.
it is appropriate for compensation (see Table 54-1), keeping in mind The ideal treatment for respiratory acidosis is resolution of the
the time required for metabolic compensation to occur. In many underlying disease when possible. In severe cases of hypoventilation
cases the presence of a change in the opposing system in the direction that persists despite therapy, mechanical ventilation is indicated (see
expected for compensation is sufficient to diagnose a simple disorder. Chapter 30). Elevated levels of CO2 can cause hypoxemia in patients
In dogs the expected compensatory change can be calculated using breathing room air, and all animals with significant hypercapnia
Table 54-2 and, if the change in the opposing system is similar to that (>60 mm Hg) should receive oxygen therapy. It is important to note
calculated, a simple disorder is then diagnosed. If the change in the that bicarbonate therapy is contraindicated in patients with a respira-
opposing system is not similar to that expected (calculated), a mixed tory acidosis.
disorder is diagnosed. In this example the predicted respiratory com-
pensation for a bicarbonate concentration of 12 mmol/L would be a Respiratory Alkalosis
PCO2 in the range of ~31 ± 3 mm Hg. The patient has a PCO2 of From the previous discussion it is evident that a decreased PCO2 is
30 mm Hg, consistent with compensation and a simple metabolic the result of an increase in V A (decreased CO2 production is not a
acidosis is the diagnosis. Lastly, if a metabolic acidosis has been clinically relevant issue). A low PCO2 may occur as an appropriate
identified, the AG can be calculated in an effort to help determine compensatory response to a metabolic acidosis. Primary disease pro-
the underlying cause of the abnormality, assuming the patient is not cesses that may stimulate an increased respiratory rate or tidal
hypoalbuminemic. volume include significant hypoxemia, pulmonary parenchymal
The advantage of the traditional approach to acid-base analysis is disease (causing stimulation of stretch receptors or nociceptors), and
its relative simplicity and adherence to sound chemical principles. It airway inflammation.31 In addition, central stimulation of respiratory
has been tried and tested for the best part of a century in both the rate and effort by the respiratory center can occur. This can be a
experimental and clinical environment and has been proven to be pathologic process resulting from brain injury or it could be behav-
reliable and accurate. The major criticism of the traditional approach ioral as a result of pain or anxiety. An animal’s respiratory rate cannot
to metabolic acid-base disorders is its failure to identify individual be used to determine if it is hyper- or hypoventilating. Dead space
disease processes that are contributing to the acid-base abnormality. ventilation, as occurs with panting, can allow a very rapid rate
Although the AG may help to determine causes of a metabolic aci- without change to PCO2 while slow respiratory rates can be associ-
dosis, it is prone to error and only narrows the possible diagnoses ated with hyperventilation if larger tidal volumes are generated.
but does not provide a definitive diagnosis. Ventilatory status can only be accurately determined by measure-
ment of PCO2.
CAUSES OF ACID-BASE ABNORMALITIES Treatment of respiratory alkalosis is focused on therapy for the
underlying disease; specific therapy for the respiratory alkalosis itself
Respiratory Acidosis is rarely attempted.
Elevations in PCO2 can represent a primary respiratory acidosis or
can occur in an attempt to compensate for a primary metabolic Metabolic Acidosis
alkalosis. Respiratory acidosis results from an imbalance in CO2 pro- Metabolic acidosis occurs relatively commonly in small animal
duction via metabolism and alveolar minute ventilation in the lung. patients, identified in 43% of dogs and cats that had blood gas analy-
This is best described by the equation sis at a university teaching hospital.32 As described previously, meta-
  bolic acidosis can result from the loss of bicarbonate or the gain of
PaCO2 ~ VCO 2 VA
acid, and the calculation of the AG may aid in determining which of

where VCO 
2 is the production of CO2 by the tissues and VA is alveo- these processes is present. Metabolic acidosis caused by bicarbonate
lar minute ventilation.30 loss, typified by hyperchloremia and a normal anion gap, can occur
 CHAPTER 54  •  Traditional Acid-Base Analysis 293

through the intestinal tract via diarrhea or can be due to renal losses. Increases in bicarbonate concentration can occur as an appropri-
Hyperchloremic metabolic acidosis in association with small bowel ate renal compensation to a respiratory acidosis. Pathologic increases
diarrhea has been well reported in human patients and large animal in bicarbonate concentration can also occur with contraction alka-
species but is an infrequent occurrence in dogs and cats. Renal loss loses, iatrogenic administration of an alkalinizing therapy (e.g.,
of bicarbonate can be an appropriate response to a persistent respira- sodium bicarbonate), or metabolism of organic anions such as
tory alkalosis (metabolic compensation). When it occurs as a primary lactate, ketones, acetate, and citrate. Hypokalemia can play a signifi-
disease process, it is known as renal tubular acidosis (RTA). It can be cant role in the generation and maintenance of metabolic alkalosis.
broadly categorized as proximal or distal tubular dysfunction. In Intracellular shifts of hydrogen ions in exchange for potassium ions
animals with proximal RTA there is inadequate reabsorption of leaving the cells will increase the pH of the extracellular fluid. Further,
bicarbonate in the proximal nephron. Reported causes in dogs and hypokalemia promotes renal acid loss.35,36
cats include congenital abnormalities (e.g., Fanconi syndrome), as The kidney has the ability to excrete large quantities of bicarbon-
well as acquired abnormalities secondary to toxins, drugs, and ate, such that metabolic alkalosis should be rectified rapidly. When
various diseases (e.g., hypoparathyroidism and multiple myeloma). metabolic alkalosis is persistent, there must be factors limiting renal
Distal RTA is a disorder involving inadequate hydrogen ion secretion bicarbonate excretion. Decreased effective circulating volume and
in the distal tubule that prevents maximal acidification of the urine; hypochloremia can both limit renal bicarbonate excretion. Hypoka-
it is often accompanied by hypokalemia and is more rarely reported lemia and aldosterone excess further impair renal bicarbonate
in the veterinary literature than proximal RTA. Potential causes excretion.
include pyelonephritis and immune mediated hemolytic anemia. There are three important aspects to treatment of metabolic
The interested reader is directed to reference 33 for further reading alkalosis: (1) Ensure there is adequate effective circulating volume,
on RTA. Hypoadrenocorticism not only leads to hypovolemia and a (2) normalize electrolytes, and, (3) when possible, correct the primary
lactic acidosis but also impairs urine acidification, leading to meta- disease.36
bolic acidosis.
Treatment of metabolic acidoses caused by bicarbonate loss is BICARBONATE THERAPY
primarily based on therapy of underlying diseases. In addition,
intravenous (IV) fluid therapy may speed the resolution of this There are many potential adverse effects of metabolic acidosis,
disorder. Fluids containing a “buffer” such as lactated Ringer’s solu- including decreased myocardial contractility, arterial vasodilation,
tion will aid in the metabolism of hydrogen ions. When treating impaired coagulation, decreased renal and hepatic blood flow, insulin
patients with a hyperchloremic metabolic acidosis, use of lower resistance, and altered central nervous function.37-39 It is no surprise
chloride containing fluids (i.e., avoiding 0.9% NaCl) will also be of that clinicians are eager to resolve a metabolic acidosis by treatment
benefit. When the acidosis is severe or the compensatory respiratory of the primary disease, IV fluid administration, and, in some
alkalosis is considered detrimental to the patient, bicarbonate instances, alkalinizing therapy.
administration is indicated (see Bicarbonate Therapy later in the Sodium bicarbonate is the most common alkali therapy used
chapter). in veterinary medicine. Alternative alkalinizing therapies include
Metabolic acidosis caused by a gain in acid is typified by normo- tris-hydoxymethyl aminomethane (also known as tromethamine
chloremia and an elevated AG. The common causes in dogs and cats [THAM]) and Carbicarb, an equimolar mixture of sodium bicarbon-
were mentioned previously—diabetic ketoacidosis (DKA), uremia, ate and sodium carbonate. These alternative buffer therapies may
lactic acidosis, and ethylene glycol intoxication. Less common causes have the advantage of having no (THAM) or less (Carbicarb) associ-
include D-lactic acidosis and various additional intoxications, includ- ated CO2 production than sodium bicarbonate. The interested reader
ing salicylates and methanol.20 is directed to reference 38 for further reading on this topic.38
Treatment of metabolic acidosis caused by an acid gain is primar- The indications for sodium bicarbonate administration have been
ily focused on resolution of the underlying cause and appropriate somewhat controversial over the years, although some consensus has
selection of IV fluid therapy, as described earlier. Bicarbonate admin- been reached in recent time. There are several concerns with bicar-
istration may be beneficial in some uremic patients, but is not typi- bonate therapy (Box 54-5). The first is that its use is based on the
cally indicated for treatment of other acidoses (see Bicarbonate premise that acidemia has substantial negative consequences to the
Therapy later in this chapter). patient. Numerous human studies have demonstrated that a low pH
It is interesting to note that in a retrospective study of metabolic is well tolerated; this includes patients subjected to permissive hyper-
acidosis in dogs and cats, 25% of dogs and 34% of cats had neither capnia and patients with DKA.40,41 One of the most commonly cited
an elevated AG nor hyperchloremia, suggesting there are limitations
to this categorization of metabolic acidosis.32

Metabolic Alkalosis BOX 54-5  Potential Adverse Effects Associated

Metabolic alkalosis appears to be less common in small animal with Sodium Bicarbonate
patients, evident in 15% of a population of dogs and cats compared Administration48
with the occurrence of metabolic acidosis in 43% of these animals.33
Metabolic alkalosis broadly can be considered to occur because of • Increased hemoglobin affinity for oxygen
either acid loss or bicarbonate gain. Causes of acid loss include selec- • Increased blood lactate concentration
tive gastric acid loss such as can occur with gastrointestinal obstruc- • Paradoxical intracellular acidosis
tive processes (leading to sequestration or vomiting) and nasogastric • Hypercapnia
tube suctioning. Renal acid loss can occur as a result of loop diuretic • Hypervolemia
administration, mineralocorticoid excess, and the presence of non-
• Hyperosmolality
• Hypernatremia
reabsorbable anions such as carbenicillins.34,35 Acid loss invariably • Hypocalcemia (ionized)
occurs along with chloride in the gastrointestinal tract and renal • Hypokalemia
system and as a result many animals with metabolic alkalosis will also • Phlebitis
be hypochloremic.
294 PART V  •  ELECTROLYTE AND ACID-BASE DISTURBANCES

adverse effects of acidemia is decreased myocardial contractility and causing an iatrogenic metabolic alkalosis. This is of particular
vascular tone. Investigations have not been able to consistently dem- concern when other simultaneous therapies may contribute to reso-
onstrate these negative hemodynamic effects; in addition, studies lution of the metabolic acidosis. Because there is no way to accurately
have failed to demonstrate that bicarbonate administration will determine an appropriate bicarbonate dose, bicarbonate therapy
improve hemodynamic performance in the face of acidemia (in some should be guided by frequent reevaluation of acid-base status.
studies hemodynamic performance actually deteriorates after bicar- Hypertonic sodium bicarbonate should never be administered
bonate administration).42-44 Another concern is that sodium bicar- rapidly (other than in the cardiopulmonary resuscitation setting)
bonate therapy does not reliably increase pH. After administration, because it can cause vasodilation and increases in intracranial pres-
the bicarbonate binds hydrogen ions (hence the alkalinizing effect) sure, which can be fatal.54 The clinician has the choice of giving the
to form carbonic acid; this rapidly dissociates to CO2 and water. dose slowly (over 30 minutes or longer) or diluting it with sterile
If ventilation does not increase appropriately, an elevated PCO2 water to make it an isotonic solution. Dilution usually results in a
will cause a decrease in pH. For this reason, sodium bicarbonate significant volume for administration; the rate of infusion should
therapy is strictly contraindicated in patients with evidence of then be governed by the perceived fluid tolerance of the patient.
hypoventilation. If the hypertonic sodium bicarbonate solution is not diluted to
Of greater concern is the paradoxical intracellular acidosis that an osmolality of less than 600 mOsm/L, it should be given via a
has been shown to occur after sodium bicarbonate administration. central catheter to avoid phlebitis.55 The commercially available
Bicarbonate cannot freely cross cell membranes, but the CO2 pro- 8.4% sodium bicarbonate solution has an osmolality of approxi-
duced as bicarbonate is metabolized can freely enter cells. Once intra- mately 2000 mOsm/L, so a dilution of 1 part sodium bicarbonate to
cellular, the CO2 combines with water, leading to hydrogen ion 3 parts diluent (e.g., sterile water for injection) would be appropriate
release and causing intracellular acidosis. Many animal studies have for peripheral venous administration.
demonstrated decreases in cellular and cerebrospinal fluid pH after Before giving sodium bicarbonate, clinicians should consider
bicarbonate therapy.45-48 Bicarbonate therapy has also been associated their level of concern for the increase in intravascular volume and
with increases in blood lactate concentration in studies of lactic the potential for hypernatremia, hyperosmolality, hypercapnia,
acidosis, hemorrhagic shock, and DKA.43,46,49,50 The exact mechanism hypokalemia, and hypocalcemia (ionized) in the patient. These con-
for this response is not known, but left shifting of the oxygen- cerns may necessitate initiating other therapy before bicarbonate
hemoglobin dissociation curve because of increases in blood pH may administration, a very slow bicarbonate administration rate, or even
play a role. withholding the therapy if the level of concern outweighs the pro-
Sodium bicarbonate therapy can be associated with other adverse posed benefit of the drug.
effects, including hypervolemia, hyperosmolality, hypernatremia,
hypocalcemia (ionized), hypokalemia, and decreases in PaO2 (see
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