Peer reviewed

The Practitioner’s Acid–Base Primer

Differential Diagnoses & Treatment
Lori S. Waddell, DVM, Diplomate ACVECC

T
his article is the second in the 2-part series: The Practitioner’s
Acid–Base Primer. The first article, Obtaining & Interpreting
Blood Gases (May/June 2013) addressed techniques for
obtaining blood gases and interpretation of metabolic and respiratory
disturbances. Read Part 1 at tvpjournal.com. This article will further
investigate metabolic and respiratory disturbances, identifying:
• Clinical signs
• Differential diagnoses
• Treatment options.

Acid–base alterations can lead to: • If metabolic acidosis is due to lactate from hypovole-
• Altered cardiovascular, neurologic, and respiratory function mia, take appropriate measures—intravascular volume
• Altered response to various drug therapies. resuscitation using IV fluids—to restore adequate oxy-
Blood gases, either arterial or venous, evaluate acid– gen delivery to tissues.
base status, and also test respiratory function (with arterial • If lactic acidosis is due to decreased arterial oxygen con-
samples superior to venous), more specifically: tent (see Decreased Oxygen Delivery), administer red
• Oxygenation blood cells via transfusion and/or provide supplemental
• Ventilation. oxygen.
• If severe, persistent metabolic acidosis (pH < 7.1) is due
METABOLIC ACIDOSIS to a cause other than lactate, consider sodium bicarbon-
Clinical Signs & Consequences ate administration (see Sodium Bicarbonate Adminis-
Severe acidosis can lead to: tration, page 26). However, only consider sodium bicar-
• Cardiovascular: Vasodilation, hypotension, bonate administration in:
arrhythmias, decreased cardiac contractility » Cases of increased AG metabolic acidosis refractory to
• Metabolic: Insulin resistance fluid therapy
• Neurologic: Mental dullness » Cases with evidence of cardiovascular compromise sec-
• Respiratory: Increased respiratory effort ondary to metabolic acidosis.
Normal Anion Gap Metabolic Acidosis
Differential Diagnoses Patients with a normal AG metabolic acidosis have experi-
Increased Anion Gap Metabolic Acidosis enced a loss of bicarbonate, either through gastrointesti-
(Normochloremic) nal (GI) tract from diarrhea or via the kidneys from renal
• Lactate tubular acidosis. These patients often need sodium bicar-
• Ketones (eg, diabetic ketoacidosis) bonate therapy to correct metabolic acidosis.
• Uremic acids (eg, elevated sulfates and phosphates in
marked azotemia)
• Toxins (eg, metabolites of ethylene glycol, salicylates)
DECREASED OXYGEN DELIVERY
Normal Anion Gap Metabolic Acidosis Decreased tissue oxygen delivery (causing lactic
(Hyperchloremic) acidosis due to anaerobic metabolism) can occur
• Renal tubular acidosis as a result of:
• HCO3- loss through diarrhea • Decreased stroke volume due to decreased
preload (eg, hypovolemia)—the most common
Therapeutic Measures cause of lactic acidosis in veterinary patients
Treatment of metabolic acidosis should be aimed at cor- • Decreased arterial oxygen content (due to
recting the underlying problem. anemia or hypoxemia) and/or
• Decreased cardiac output (eg, from decreased
Increased Anion Gap Metabolic Acidosis
stroke volume or, much less commonly, patho-
In patients with increased anion gap (AG) metabolic aci-
logic arrhythmias).
dosis, unmeasured organic anions, such as ketones or
lactate, can be metabolized to HCO3- during recovery.

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| The PracTiTioner’s aciD–Base Primer: DifferenTial Diagnoses & TreaTmenT

METABOLIC ALKALOSIS
Clinical Signs & Consequences
DEFINING THE ANION GAP
Consequences of metabolic alkalosis include:
Anions & Cations
calculation of the anion gap (ag) is helpful for • Cardiovascular: Cardiac arrhythmias, decreased oxygen
differentiating causes of metabolic acidosis. delivery to tissues (via shifting of oxygen hemoglobin curve
The ag is the difference in the sum of com- to the left)
monly measured: • Neurologic: Neuromuscular dysfunction
• Anions: negatively charged ions—chloride • Metabolic (in acute, severe alkalosis only): Muscle twitching
(cl-) and bicarbonate (hco3-) due to decreased serum ionized calcium concentration caused
• Cations: Positively charged ions—sodium by increased binding of calcium ions to albumin, hypokalemia
(na+) and potassium (K+) as H+ ions shift out of cells and K+ moves into them.
In humans, these signs are described as malaise, lethargy,
AG = (Na+ + K+) – (Cl- + HCO3-)
and weakness, and can progress to confusion, stupor, muscle
Unmeasured Anions & Cations
twitching, tetany, seizures, and coma.
The ag is an artificial, calculated measure
because the patient always has equimolar Differential Diagnoses
amounts of anions and cations to maintain • GI obstruction in the upper GI tract (stomach or proximal
electroneutrality. The unmeasured anions (Ua) duodenum), that results in loss of H+, K+, and, most impor-
and cations (Uc) maintain the balance of posi- tant, Cl- in the vomitus
tive and negative charges: • Furosemide administration
• Administration of alkali (sodium bicarbonate)
Na+ + K+ + UC = Cl- + HCO3- + UA
Therefore, the anion gap is the difference
between the number of unmeasured anions and
unmeasured cations: SODIUM BICARBONATE ADMINISTRATION
When treating with sodium bicarbonate, calculate the
AG = UA – UC = (Na+ + K+) – (Cl- + HCO3-) amount to administer by using the following equation:
• Unmeasured anions: in healthy (normal) ani- Base excess (Be) x body weight (kg) x 0.3 =
mals, the majority of Uas are plasma pro- Bicarbonate deficit (meq)
teins, with albumin contributing a larger por-
tion than the globulins. Depending on the needs of the patient, usually ¼ to 1/3
• Unmeasured cations: The Ucs are calcium of the calculated dose is given at a time:
and magnesium, which normally do not vary • By slow bolus over 5 to 10 minutes (only to correct
enough to cause appreciable changes in the life-threatening acidosis) or
ag because their serum concentrations are • Through iV fluids over several hours.
tightly regulated. careful monitoring of ph, hco3-, Be, carbon dioxide
(co2), and na+ should occur when sodium bicarbonate is
Differences in Anion Gap administered.
• Decreases in AG are most commonly asso- side effects of sodium bicarbonate therapy should be
ciated with hypoalbuminemia. considered, and include:
• Increases in AG are seen with many causes • Cardiovascular: shifting of oxyhemoglobin curve to
of metabolic acidosis in which additional Ua the left if alkalosis occurs, making it more difficult for
are present in plasma, such as: hemoglobin to unload oxygen to the tissues
» lactic acidosis • Metabolic:
» Ketoacidosis » hypernatremia
» Uremia » hyperosmolality
» ethylene glycol or salicylate intoxication. » Development of alkalosis (after organic anions are
• Normal AG acidosis is often referred to metabolized)
as hyperchloremic acidosis because ag » hypokalemia (K+ ions shift back into intracellular
remains normal due to an increase in cl- spaces as hydrogen [h+] ions move out)
(rather than addition of Ua) when hco3- is » Decreased serum ionized calcium concentration
decreased. caused by increased binding of calcium ions to
» most commonly seen in animals with large albumin
bowel diarrhea and renal tubular acidosis • Neurologic: Paradoxical central nervous system aci-
» also seen with parenteral (or systemic) dosis caused by diffusion of co2 into cerebral spinal
administration of carbonic anhydrase fluid
inhibitors (eg, acetazolamide) and acidify- • Respiratory: secondary respiratory acidosis if patient
ing agents (eg, ammonium chloride, oral is unable to blow off co2 formed from the adminis-
calcium chloride). tered bicarbonate.

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• Post chronic hypercarbia (rare) • Airway obstruction: Foreign body, mass, tracheal
• Primary hyperaldosteronism (rare) collapse, laryngeal paralysis, brachycephalic airway
• Hyperadrenocorticism (rare) disease, asthma, obstructed endotracheal tube
• Neuromuscular disease: Myasthenia gravis, botu-
Therapeutic Measures lism, tick paralysis, polyradiculoneuritis, severe
As with metabolic acidosis, treatment of metabolic alkalosis hypokalemia, drugs (neuromuscular blockers,
should be aimed at correcting the underlying problem. Met- organophosphates)
abolic alkalosis is typically associated with hypokalemia, • Restrictive disorders preventing lung expansion:
and the most common causes of metabolic alkalosis are GI Pleural space disease
obstruction with loss of H+, K+, and Cl- in the vomitus, and • Severe primary pulmonary disease: Pneumonia,
furosemide administration. pulmonary edema
In patients with upper GI losses of Cl-: • Increased CO2 production with decreased alveolar
• Treatment should be aimed at: ventilation: Cardiopulmonary arrest, heat stroke,
» Correcting intravascular volume depletion and Cl- malignant hyperthermia
concentrations
» Eliminating GI obstruction Therapeutic Measures
» Addressing hypokalemia, if present. Respiratory acidosis can rapidly become life-threat-
• Initial IV boluses, if indicated, should be 0.9% sodium chlo- ening and requires immediate recognition and treat-
ride, but without potassium due to risk for bradycardia. ment. Treatment is aimed at correcting the:
• Once any boluses have been completed, fluid therapy of • Underlying problem, particularly airway obstruction
choice is: or restrictive disease
» 0.9% sodium chloride due to its high Cl- concentration • Concurrent hypoxia.
» Potassium chloride supplementation. If anesthetic or sedative agents have been adminis-
If metabolic alkalosis is due to diuretic administration: tered and are causing hypercarbia due to depression
• It will usually correct itself once: of brain respiratory centers:
» Diuretic therapy has been discontinued or • Anesthetic plane should be lightened or
» Diuretic dose is reduced and patient is eating again. • Reversal agents administered.
• Administration of oral potassium chloride improves If the cause of hypoventilation cannot be rapidly
alkalosis by correcting chloride deficits and hypokale- corrected, the following are indicated:
mia. • Intubation (Figure)
• Including potassium-sparing diuretics can also reduce or • Support with positive pressure ventilation.
eliminate metabolic alkalosis in these patients.
RESPIRATORY ALKALOSIS (Hyperventilation)
RESPIRATORY ACIDOSIS (Hypoventilation) Clinical Signs & Consequences
Clinical Signs & Consequences • Hypocapnia can result in cerebral vasoconstriction
Respiratory acidosis is associated with: and, therefore, decreased perfusion; however, this
• Increased pCO2 and bicarbonate levels
• Decreased pH
• Reduced ventilation, which decreases pO2; hypoxemia
makes the condition life-threatening.
Acute hypercarbia can have cardiovascular, metabolic,
and neurologic sequelae.
• Cardiovascular: Hypercarbia causes catecholamine
release, which, along with concurrent acidosis, hypox-
ia, and electrolyte derangements, can result in tachyar-
rhythmias, including ventricular fibrillation.
• Metabolic: Acidosis causes a shift of H+ ions into the
cells, resulting in extracellular movement of K+.
• Neurologic: Complications include cerebral vasodila-
tion from hypercarbia, which can result in increased
intracranial pressure; neurologic signs can range from
agitation and restlessness to depression and coma.

Differential Diagnoses
• Impairment of respiratory center: Drug induced (nar- Figure. Tracheostomy tubes can be used to treat
cotics, barbiturates), neurologic disease (brainstem or hypoventilation and respiratory acidosis in dogs
high cervical cord) with upper airway obstruction.

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CASE STUDY 1
Diagnostic Results & Interpretation
a 2-year-old, castrated male domestic shorthair cat is presented with a few-day history of
lethargy, anorexia, and occasional vomiting. Table 1 provides pertinent laboratory results;
Table 2 provides interpretation of results.

Differential Diagnosis
Differentials for this severe, normochloremic TaBle 1. case sTUDy 1 PerTinenT
(when the slightly low cl- is corrected for the low laBoraTory resUlTs
na+, it is in the normal range), high ag metabolic
REFERENCE
acidosis should include: VALUE RESULT INTERVAL
• Uremia
• Ketoacidosis VENOUS BLOOD GAS ANALYSIS
• lactic acidosis Base excess/deficit (mmol/l) -20.2 -5.7 ± 5
• exogenous toxins, such as metabolites of -)
Bicarbonate (HCO3 (mmol/l) 9.3 19.4 ± 4
ethylene glycol.
Ketosis is unlikely given the normal glucose, Partial pressure of CO2 (mm hg) 28.4 41.8 ± 9
and lactate is normal. however, BUn and Partial pressure of O2 (mm hg) 65 38.6 ± 11
creatinine (248 and 20.6 mg/dl, respectively) pH 7.12 7.3 ± 0.08
indicate that the cat is severely azotemic.
ELECTROLYTE RESULTS
Diagnosis & Treatment Chloride (Cl) (mmol/l) 110.9 116–126
• Diagnosis is lily toxicity as the owners revealed Potassium (K) (mmol/l) 6.43 3.5–4.8
that the cat chewed on a bouquet of flowers
Sodium (Na) (mmol/l) 141.3 146–157
containing lilies a few days before clinical signs
were noted. OTHER
• Treatment should consist of iV fluids: 0.9% Blood urea nitrogen (BUN) (mg/dl) 248 15–32
sodium chloride or balanced electrolyte
Creatinine (mg/dl) 20.6 1–2
replacement solution, such as Plasma-lyte 148
(baxter.com). Glucose (mg/dl) 75 70–168
• if hyperkalemia is persistent, insulin and Lactate (mmol/l) 1.7 <2
dextrose or bicarbonate therapy can be
considered.

TaBle 2. case sTUDy 1 inTerPreTaTion of BlooD gas analysis

STEP-BY-STEP PROCESS INTERPRETATION
Step 1. Determine if venous or arterial sample. Venous
Step 2. assess for acidemia or alkalemia. ph of 7.12 indicates acidemia
Step 3. Perform additional assessments for acidosis. Be of -20.2 mmol/l indicates metabolic acidosis
Step 4. Perform additional assessments for alkalosis. Respiratory alkalosis present (pco2 of 28.4 mm hg)
Step 5. assess oxygenation. oxygenation high for venous sample; causes could include:
• Patient is receiving o2 supplementation
• Decreased o2 extraction by tissues (poor perfusion)
• sample has been exposed to room air.
Step 6. Determine if compensation has occurred.
hco3- is approximately 10 mmol/l lower than normal for a cat. for every 1 mmol/l decrease in hco3-, pco2
should decrease by 0.7 mm hg (Table 5, page 30). Therefore, a decrease of 7 mm hg is expected.
• normal venous pco2 for a cat is approximately 42 mm hg; therefore, pco2 should be 35 mm hg if compensation
was the only process affecting pco2.
• however, this cat’s pco2 of 28 mm hg is lower than expected.
• since overcompensation does not occur, other possible causes of hypocarbia include:
» air contamination of the sample since venous o2 is high (co2 diffused out and o2 diffused in) or
» concurrent primary respiratory alkalosis.

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CASE STUDY 2

Diagnostic Results & Interpretation

a 4-year-old, castrated male boxer is presented with a 4- to 5-day
history of vomiting multiple times daily. Table 3 provides pertinent
laboratory results; Table 4 provides interpretation of results.

Diagnosis & Treatment

• Diagnosis is a mixed acid–base disorder:
» This patient is losing cl- and K+ in
the vomitus and is volume depleted.
» metabolic alkalosis has developed
secondary to the loss of cl- and K+.
TaBle 3. case sTUDy 2 PerTinenT
» The increased lactate indicates laBoraTory resUlTs
concurrent metabolic acidosis—a REFERENCE
VALUE RESULT INTERVAL
second primary metabolic acid–
base disorder, likely caused by VENOUS BLOOD GAS ANALYSIS
hypovolemia due to vomiting.
• Treatment should consist of: Base excess/deficit (mmol/l) +22.9 -4 ± 2
» Volume expansion with 0.9% sodium Bicarbonate (HCO3 -) (mmol/l) 44.8 21–24
chloride Partial pressure of CO2 (mm hg) 50.2 34–41
» supplementation of potassium
chloride in the fluids once any Partial pressure of O2 (mm hg) 48.3 48–56
boluses have been given pH 7.561 7.35–7.44
» Determining the underlying cause for ELECTROLYTE RESULTS
the vomiting.
• abdominal radiographs revealed a Chloride (Cl) (mmol/l) 81 109–120
proximal gi obstruction. Potassium (K) (mmol/l) 2.6 4–5.2
• after stabilization with fluid therapy, Sodium (Na) (mmol/l) 117 140–150
an exploratory laparotomy was per-
formed; a cloth foreign body was OTHER
removed from the proximal duodenum. Lactate (mmol/l) 4.6 <2
• The acid–base and electrolyte abnor-
malities resolved over 24 to 48 hours.

TaBle 4. case sTUDy 2 inTerPreTaTion of BlooD gas analysis

STEP-BY-STEP PROCESS INTERPRETATION
Step 1. Determine if venous or arterial sample. Venous

Step 2. assess for acidemia or alkalemia. ph of 7.561 indicates alkalemia

Step 3. Perform additional assessments for acidosis. Respiratory acidosis present (pco2 of 50.2 mm hg)

Step 4. Perform additional assessments for alkalosis. Be of 22.9 mmol/l indicates metabolic alkalosis

Step 5. assess oxygenation. Adequate

Step 6. Determine if compensation has occurred.

hco3- is 44.8 mmol/l, which is an increase of approximately 25 mmol/l above normal values. for every
1 mmol/l increase in hco3-, pco2 should increase by 0.7 mm hg; therefore, an increase of 17 mm hg is
expected (Table 5, page 30).
• normal pco2 for a dog is 40 mm hg; the dog’s pco2 of 50 mm hg indicates that only partial compensa-
tion is present because the expected pco2 would be 57 mm hg.
other abnormalities:
• lactate is increased, indicating concurrent primary metabolic acidosis.
• significant electrolyte abnormalities are present, including hypochloremia and hypokalemia.

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TaBle 5. exPecTeD comPensaTory changes1

DISORDER CHANGES COMPENSATORY RESPONSE
Metabolic acidosis hco3- 0.7 mm hg decrease in pco2 for each 1 meq/l decrease in hco3-
Metabolic alkalosis hco3- 0.7 mm hg increase in pco2 for each 1 meq/l increase in hco3-
Acute respiratory acidosis pco2 1.5 meq/l increase in hco3- for each 10 mm hg increase in pco2
Chronic respiratory acidosis pco2 3.5 meq/l increase in hco3- for each 10 mm hg increase in pco2
Acute respiratory alkalosis pco2 2.5 meq/l decrease in hco3- for each 10 mm hg decrease in pco2
Chronic respiratory alkalosis pco2 5.5 meq/l decrease in hco3- for each 10 mm hg decrease in pco2

degree of hyperventilation rarely occurs except in ed, including when the patient can be weaned off
patients with significant intracranial disease. this support. n
• In humans with acute respiratory alkalosis due to
hyperventilation, lightheadedness and confusion are ag = anion gap; Be = base excess/deficit; BUn = blood
often reported. urea nitrogen; cl- = chloride; co2 = carbon dioxide; gi
• Extremely high pHs (> 7.6) may be associated with = gastrointestinal; h+ = hydrogen; hco3- = bicarbonate;
metabolic, cardiac, and neurologic consequences as K+ = potassium; na+ = sodium; o2 = oxygen; pco2 =
listed under Metabolic Alkalosis. partial pressure of carbon dioxide; po2 = partial pres-
sure of oxygen; sirs = systemic inflammatory response
Differential Diagnoses syndrome; Ua = unmeasured anions; Uc = unmeasured
cations
• Hypoxemia
• Pulmonary disease: Stimulation of nociceptors, inde- References
pendent of hypoxia 1. diBartola SP. introduction to acid–base disorders. in diBartola SP(ed):
• Central nervous system disease: Trauma, neoplasia, Fluid, Electrolyte, and Acid–Base Disorders in Small Animal Practice,
4th ed. St. Louis: elsevier Saunders, 2012, pp 231-252.
infection, inflammation
• Sepsis/systemic inflammatory response syndrome Suggested Reading
(SIRS) de Morais HA, Leisewitz AL. Mixed acid–base disorders. in diBartola
SP (ed): Fluid, Electrolyte, and Acid–Base Disorders in Small Animal
• Drugs: Corticosteroids, progesterone (pregnancy), Practice, 4th ed. St. Louis: elsevier Saunders, 2012, pp 302-315.
methylxanthines (aminophylline) diBartola SP. Metabolic acid–base disorders. in diBartola SP (ed): Fluid,
• Liver disease Electrolyte, and Acid–Base Disorders in Small Animal Practice, 4th ed.
St. Louis: elsevier Saunders, 2012, pp 253-286.
• Hyperadrenocorticism Johnson rA, de Morais HA. respiratory acid–base disorders. in diBartola
• Exercise SP (ed): Fluid, Electrolyte, and Acid–Base Disorders in Small Animal
Practice, 4th ed. St. Louis: elsevier Saunders, 2012, pp 287-301.
• Stress and/or pain (common in patients arriving at
the hospital)
• Excessive mechanical ventilation
Lori S. Waddell, DVM,
Therapeutic Measures Diplomate ACVECC, is an
Treatment is aimed at correcting the underlying pro- adjunct associate professor
cess that is driving the hyperventilation. in critical care at the Univer-
• In hypoxic patients: Oxygen supplementation sity of Pennsylvania School
• In stressed or painful patients: Sedation/analgesia of Veterinary Medicine,
corrects the majority of cases of respiratory alkalosis. working in the Intensive Care
• In exceptional cases of documented hypocapnia: Unit. Her areas of inter-
Rebreathing CO2 using a paper bag may be required, est include colloid osmotic
analogous to first-aid therapy applied to humans for pressure, acid–base disturbances, and coagula-
hyperventilation. tion in critically ill patients. Dr. Waddell received
her DVM from Cornell University; then completed
SUMMARY an internship at Angell Memorial Animal Hospital
Interpretation of venous and arterial blood gases can in Boston, Massachusetts. After her internship,
be essential to treatment of many patients. Blood gas she worked as an emergency clinician in private
analysis has important implications with regard to: practice until pursuing a residency in emergency
• When fluid therapy is indicated medicine and critical care at University of Penn-
• What fluid types are the best choices sylvania.
• When oxygen and mechanical ventilation are need-

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