The Practitioner’s Acid–Base Primer: Differential Diagnoses & Treatment

Lori S. Waddell, DVM, Diplomate ACVECC

The first article of this 2-part series, Obtaining & Interpreting Blood Gases (May/June 2013), addressed techniques for obtaining blood gases and interpretation; this article further investigates metabolic and respiratory disturbances, including therapeutic measures for both.

This 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:

• Altered cardiovascular, neurologic, and respiratory function
• Altered response to various drug therapies.

Blood gases, either arterial or venous, evaluate acid–base status, and also test respiratory function (with arterial samples superior to venous), more specifically:

• Oxygenation
• Ventilation.

METABOLIC ACIDOSIS

Clinical Signs & Consequences
Severe acidosis can lead to:

• Cardiovascular: Vasodilation, hypotension, arrhythmias, decreased cardiac contractility
• Metabolic: Insulin resistance
• Neurologic: Mental dullness
• Respiratory: Increased respiratory effort.

Differential Diagnoses
Increased Anion Gap Metabolic Acidosis
(Normochloremic)

• Lactate
• Ketones (eg, diabetic ketoacidosis)
• Uremic acids (eg, elevated sulfates and phosphates in marked azotemia)
• Toxins (eg, metabolites of ethylene glycol, salicylates).

Normal Anion Gap Metabolic Acidosis (Hyperchloremic)

• Renal tubular acidosis
• HCO3- loss through diarrhea

Therapeutic Measures
Treatment of metabolic acidosis should be aimed at correcting the underlying problem.

Increased Anion Gap Metabolic Acidosis
In patients with increased anion gap (AG) metabolic acidosis, unmeasured organic anions, such as ketones or lactate, can be metabolized to HCO3- during recovery.

• If metabolic acidosis is due to lactate from hypovolemia, take appropriate measures—intravascular volume resuscitation using IV fluids—to restore adequate oxygen delivery to tissues.
• If lactic acidosis is due to decreased arterial oxygen content (see Decreased Oxygen Delivery), administer red blood cells via transfusion and/or provide supplemental oxygen.
• If severe, persistent metabolic acidosis (pH < 7.1) is due to a cause other than lactate, consider sodium bicarbonate administration (see Sodium Bicarbonate Administration). However, only consider sodium bicarbonate administration in:
  • Cases of increased AG metabolic acidosis refractory to fluid therapy
  • Cases with evidence of cardiovascular compromise secondary to metabolic acidosis.

Normal Anion Gap Metabolic Acidosis

Patients with a normal AG metabolic acidosis have experienced a loss of bicarbonate, either through gastrointestinal (GI) tract from diarrhea or via the kidneys from renal tubular acidosis. These patients often need sodium bicarbonate therapy to correct metabolic acidosis.

METABOLIC ALKALOSIS

Clinical Signs & Consequences

Consequences of metabolic alkalosis include:

• Cardiovascular: Cardiac arrhythmias, decreased oxygen delivery to tissues (via shifting of oxygen hemoglobin curve to the left)
• Neurologic: Neuromuscular dysfunction
• Metabolic (in acute, severe alkalosis only): Muscle twitching due to decreased serum ionized calcium concentration caused by increased binding of calcium ions to albumin, hypokalemia as H+ ions shift out of cells and K+ moves into them.

In humans, these signs are described as malaise, lethargy, and weakness, and can progress to confusion, stupor, muscle twitching, tetany, seizures, and coma.

Differential Diagnoses

• GI obstruction in the upper GI tract (stomach or proximal duodenum), that results in loss of H+, K+, and, most important, Cl- in the vomitus
• Furosemide administration
• Administration of alkali (sodium bicarbonate)
• Post chronic hypercarbia (rare)
• Primary hyperaldosteronism (rare)
• Hyperadrenocorticism (rare)

Therapeutic Measures
As with metabolic acidosis, treatment of metabolic alkalosis should be aimed at correcting the underlying problem. Metabolic alkalosis is typically associated with hypokalemia, and the most common causes of metabolic alkalosis are GI obstruction with loss of H+, K+, and Cl- in the vomitus, and furosemide administration.

In patients with upper GI losses of Cl-:

• Treatment should be aimed at:
  • Correcting intravascular volume depletion and Cl- concentrations
  • Eliminating GI obstruction
  • Addressing hypokalemia, if present.
• Initial IV boluses, if indicated, should be 0.9% sodium chloride, but without potassium due to risk for bradycardia.
• Once any boluses have been completed, fluid therapy of choice is:
  • 0.9% sodium chloride due to its high Cl- concentration
  • Potassium chloride supplementation.

If metabolic alkalosis is due to diuretic administration:

• It will usually correct itself once:
  • Diuretic therapy has been discontinued or
  • Diuretic dose is reduced and patient is eating again.
• Administration of oral potassium chloride improves alkalosis by correcting chloride deficits and hypokalemia.
• Including potassium-sparing diuretics can also reduce or eliminate metabolic alkalosis in these patients.

RESPIRATORY ACIDOSIS (Hypoventilation)

Clinical Signs & Consequences

Respiratory acidosis is associated with:

• 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, hypoxia, and electrolyte derangements, can result in tachyarrhythmias, including ventricular fibrillation.
• Metabolic: Acidosis causes a shift of H+ ions into the cells, resulting in extracellular movement of K+.
• Neurologic: Complications include cerebral vasodilation 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 (narcotics, barbiturates), neurologic disease (brainstem or high cervical cord)
• Airway obstruction: Foreign body, mass, tracheal collapse, laryngeal paralysis, brachycephalic airway disease, asthma, obstructed endotracheal tube
• Neuromuscular disease: Myasthenia gravis, botulism, tick paralysis, polyradiculoneuritis, severe hypokalemia, drugs (neuromuscular blockers, organophosphates)
• Restrictive disorders preventing lung expansion: Pleural space disease
• Severe primary pulmonary disease: Pneumonia, pulmonary edema
• Increased CO2 production with decreased alveolar ventilation: Cardiopulmonary arrest, heat stroke, malignant hyperthermia.

Therapeutic Measures
Respiratory acidosis can rapidly become life-threatening and requires immediate recognition and treatment. Treatment is aimed at correcting the:

• Underlying problem, particularly airway obstruction or restrictive disease
• Concurrent hypoxia.

If anesthetic or sedative agents have been administered and are causing hypercarbia due to depression of brain respiratory centers:

• Anesthetic plane should be lightened or
• Reversal agents administered.

If the cause of hypoventilation cannot be rapidly corrected, the following are indicated:

• Intubation (Figure)
• Support with positive pressure ventilation.

Figure. Tracheostomy tubes can be used to treat hypoventilation and respiratory acidosis in dogs with upper airway obstruction.

RESPIRATORY ALKALOSIS (Hyperventilation)

Clinical Signs & Consequences

• Hypocapnia can result in cerebral vasoconstriction and, therefore, decreased perfusion; however, this degree of hyperventilation rarely occurs except in patients with significant intracranial disease.
• In humans with acute respiratory alkalosis due to hyperventilation, lightheadedness and confusion are often reported.
• Extremely high pHs (> 7.6) may be associated with metabolic, cardiac, and neurologic consequences as listed under Metabolic Alkalosis.

Differential Diagnoses

• Hypoxemia
• Pulmonary disease: Stimulation of nociceptors, independent of hypoxia
• Central nervous system disease: Trauma, neoplasia, infection, inflammation
• Sepsis/systemic inflammatory response syndrome (SIRS)
• Drugs: Corticosteroids, progesterone (pregnancy), methylxanthines (aminophylline)
• Liver disease
• Hyperadrenocorticism
• Exercise
• Stress and/or pain (common in patients arriving at the hospital)
• Excessive mechanical ventilation.

Therapeutic Measures
Treatment is aimed at correcting the underlying process that is driving the hyperventilation.

• In hypoxic patients: Oxygen supplementation
• In stressed or painful patients: Sedation/analgesia corrects the majority of cases of respiratory alkalosis.
• In exceptional cases of documented hypocapnia: Rebreathing CO2 using a paper bag may be required, analogous to first-aid therapy applied to humans for hyperventilation.

SUMMARY

Interpretation of venous and arterial blood gases can be essential to treatment of many patients. Blood gas analysis has important implications with regard to:

• When fluid therapy is indicated
• What fluid types are the best choices
• When oxygen and mechanical ventilation are needed, including when the patient can be weaned off this support.

AG = anion gap; BE = base excess/deficit; BUN = blood urea nitrogen; Cl- = chloride; CO2 = carbon dioxide; GI = gastrointestinal; H+ = hydrogen; HCO3- = bicarbonate; K+ = potassium; Na+ = sodium; O2 = oxygen; pCO2 = partial pressure of carbon dioxide; pO2 = partial pressure of oxygen; SIRS = systemic inflammatory response syndrome; UA = unmeasured anions; UC = unmeasured cations

References 

1. DiBartola SP. Introduction to acid–base disorders. In DiBartola SP(ed): Fluid, Electrolyte, and Acid–Base Disorders in Small Animal Practice, 4th ed. St. Louis: Elsevier Saunders, 2012, pp 231-252.

Suggested Reading

• De Morais HA, Leisewitz AL. Mixed acid–base disorders. In DiBartola SP (ed): Fluid, Electrolyte, and Acid–Base Disorders in Small Animal Practice, 4th ed. St. Louis: Elsevier Saunders, 2012, pp 302-315.
• DiBartola SP. Metabolic acid–base disorders. In DiBartola SP (ed): Fluid, Electrolyte, and Acid–Base Disorders in Small Animal Practice, 4th ed. St. Louis: Elsevier Saunders, 2012, pp 253-286.
• Johnson RA, De Morais HA. Respiratory acid–base disorders. In DiBartola SP (ed): Fluid, Electrolyte, and Acid–Base Disorders in Small Animal Practice, 4th ed. St. Louis: Elsevier Saunders, 2012, pp 287-301.

Lori S. Waddell, DVM, Diplomate ACVECC, is an adjunct associate professor in critical care at the University of Pennsylvania School of Veterinary Medicine, working in the Intensive Care Unit. Her areas of interest include colloid osmotic pressure, acid–base disturbances, and coagulation in critically ill patients. Dr. Waddell received her DVM from Cornell University; then completed an internship at Angell Memorial Animal Hospital in Boston, Massachusetts. After her internship, she worked as an emergency clinician in private practice until pursuing a residency in emergency medicine and critical care at University of Pennsylvania.