Application of Traditional versus Strong Ion Acid-base Analysis to Clinical Cases
Acid base disturbances are common in critically ill patients. The ability to accurately interpret and treat a wide range of acid-base disorders is of paramount importance to the practicing veterinarian. Severe derangements of blood pH may life threatening and require immediate intervention. Less severe alterations may be better tolerated by the patient, but are important because they facilitate detection of underlying disorders. Using a case based approach; this presentation will review the interpretation of complex acid base abnormalities contrasting the use of traditional versus a strong ion approach.
Evaluation of Blood Gases
The following systematic approach to blood gas interpretation is recommended.
1. Evaluate the pH and the severity of the disturbance
2. Evaluate the respiratory component
3. Evaluate the metabolic component
4. Determine the primary and compensatory responses. Is it a simple or mixed disturbance?
5. What underlying disease process is responsible for the disturbance?
A pathophysiologic process that results in a net accumulation of acid or alkali in the body is referred to as an acidosis or an alkalosis. Acidosis and alkalosis can each be of either respiratory or metabolic origin resulting in four primary disturbances, respiratory acidosis, respiratory alkalosis, metabolic acidosis and metabolic alkalosis. The terms acidemia and alkalemia refer specifically to the pH of the extracellular fluid. A mild, compensated acidosis or alkalosis will change the patient's blood pH but it may remain in the normal range. In patients with mixed acid-base disturbances, the two counterbalancing acid-base disturbances can result in a normal blood pH. Normal values are listed below.
Respiratory Acid-Base Disorders
The partial pressure of carbon dioxide in arterial and/or venous blood can be used to evaluate the respiratory component in a patient with an acid base disturbance. When the blood pH and the PCO2 change in opposite directions a primary respiratory disorder should be suspected. Because PCO2 is an independent variable in the determination of pH, there is no difference in evaluation of respiratory disorders using traditional versus the strong ion difference approach.
Respiratory alkalosis is characterized by an increased pH and a PaCO2 < 35 mmHg. Respiratory alkalosis results from an increase in ventilatory rate, resulting in elimination of more CO2 than is produced by normal metabolic function. Hypocapnea develops, and alkalemia is generated. Causes of respiratory alkalosis include hypoxemia caused by pulmonary or circulatory abnormalities, primary pulmonary diseases that stimulate ventilation independent of hypercarbia, central nervous system disorders, and iatrogenic tachypnea with assisted ventilation. Treatment for respiratory alkalosis should be directed at normalizing the underlying disorder. Clinical signs are minimal, and no other therapy should be needed if the first treatment goal can be achieved. Respiratory alkalosis is the normal compensatory response to a primary metabolic acidosis.
Respiratory acidosis is characterized by a decreased pH and an increase in PaCO2. Respiratory acidosis or hypercapnea is caused by hypoventilation secondary to respiratory center depression, neuromuscular disease, pleural space disease and pulmonary failure. Disorders in which respiratory acidosis occur include circulatory failure from cardiopulmonary arrest, central nervous system disease, respiratory muscle failure, physical impairment to ventilation (pleural space disease, pain, thoracic wall disease or external constriction), or primary pulmonary disease (alveolar flooding, interstitial disease, pulmonary thromboembolism). Iatrogenic respiratory acidosis results from inadequate ventilatory monitoring and assistance under general anesthesia. Clinical signs of hypercapnea are consistent with the underlying disorder. Situations that might cause respiratory acidosis must be anticipated and diagnosed with appropriate monitoring. Respiratory acidosis is the normal compensatory response to a primary metabolic alkalosis. Treatment for respiratory acidosis involves correcting the underlying disorder by increasing alveolar ventilation. Chronic respiratory acidosis should be corrected slowly. Sodium bicarbonate should not be administered since this drug will exacerbate hypercapnea. Increasing inspired oxygen concentration may be lifesaving; however with severe hypercapnea, stimulation for respiration becomes driven by hypoxia. Resolving hypoxia may result in decreased voluntary respiration.
Metabolic Acid-Base Disorders
The concentration of bicarbonate (traditional) or the SID, Atot, and/or strong ion gap (strong ion approach) can be used to evaluate the metabolic component in a patient with an acid base disturbance. When the blood pH and the HCO3- change in the same directions a primary metabolic disorder should be suspected. The strong ion approach may be preferred in patients with abnormalities in albumin, phosphate and/or globulin concentration because it provides additional insight into the cause of the disturbance.
Metabolic Alkalosis is characterized by an increase in pH and an increased concentration of bicarbonate. Metabolic alkalosis may be caused by a decrease in Atot (hypoalbuminemia) or an increase in SID. Common causes of SID alkalosis are listed in Table 1.1 Metabolic alkalosis is generated by loss of chloride in excess of extracellular fluid volume, either due to upper GI fluid loss or sequestration, or by administration of a diuretic causing chloride wasting. Rarely, metabolic alkalosis may be caused by overzealous administration of sodium bicarbonate or another organic anion, or by hyperaldosteronism causing sodium retention in excess of chloride. The most commonly associated clinical disease in small animal practice is gastric obstruction, with loss of chloride-containing gastric fluid. Renal compensation prevents an acid base disorder until hypovolemia causes aldosterone release. Aldosterone increases renal uptake of sodium. During normal renal function, sodium is reabsorbed with bicarbonate or chloride, or exchanged for potassium. Since gastric fluid has high chloride and potassium concentrations, when these are depleted, sodium can only be reabsorbed with bicarbonate.
Clinical signs associated with metabolic alkalosis depend upon the predisposing disorder. Muscle twitching and seizures have been reported. Signs associated with concurrent potassium depletion may include weakness, cardiac arrhythmias, renal dysfunction, and gastrointestinal motility disturbances. Treatment for metabolic alkalosis is directed at resolving the predisposing disorder. Intravenous fluids (0.9% NaCl) should be initiated to restore intravenous volume. If vomiting is the underlying cause, use of drug therapy to minimize gastric HCl excretion may be warranted. Intravenous potassium therapy should be utilized to treat the hypokalemia frequently encountered with metabolic alkalosis.
Metabolic acidosis is the most common acid-base abnormality found in small animal medicine and results from gain of H+ from addition of an acid into the body, increase of production of an endogenous acid, or failure of elimination of an acid load at the renal tubular cells. Metabolic acidosis can also be caused by a loss of HCO3- buffering ability. When acid accumulates in circulation, H+ combines with HCO3- to buffer the acid load. When the acid dissociates, the anion remains in solution. Since electroneutrality must be maintained, another anion in circulation must decrease correspondingly. Metabolic acidosis is characterized by a decrease in bicarbonate and a decrease in blood pH. In the traditional approach, metabolic acidosis is further classified by anion gap.
Anion gap (AG) is a formula created to classify disorders causing metabolic acidosis. Anion gap is calculated from four common cations and anions from a serum chemistry profile, and states: AG = [Na+ + K+] - [Cl- + HCO3-]. In normal animals, AG is 16 +/- 4. Elevated anion gap metabolic acidosis is caused by a gain of acid, while normal anion gap metabolic acidosis (hyperchloremic metabolic acidosis) is caused by loss of bicarbonate buffers and corresponding increase of chloride to maintain electroneutrality. Causes of high anion gap metabolic acidosis include ethylene glycol intoxication, uremia, tissue hypoxia, diabetic ketoacidosis, salicylate intoxication, and other unusual intoxications (drugs, alcohol). Hyperchloremic metabolic acidosis is less common, and is caused by renal tubular acidosis (failure of the renal bicarbonate buffer system), severe diarrhea and loss of intestinal bicarbonate, or iatrogenically following administration of an alkali-free chloride containing solution for intravenous volume replacement.
In the strong ion approach SID and Atot can be evaluated to determine the cause of the underlying abnormality. Hyperphosphatemia can cause a significant increase in Atot resulting in metabolic acidosis. A decrease in SID is associated with metabolic acidosis. Causes of SID acidosis are listed in Table 2.1 The simplified strong ion gap (SIG simplified) has been suggested as a more sensitive than anion gap in detecting the presence of unmeasured strong ions in patients with hyperphosphatemia and/or hypoalbuminemia.2
Clinical signs associated with metabolic acidosis include lethargy, decreased cardiac output, decreased blood pressure, and decreased hepatic and renal blood flow. These signs may be referable to the acidemia, or to the underlying cause of the acid-base disorder. Compensatory mechanisms would cause an increase in respiratory rate to eliminate CO2 generated by carbonic acid formation. Treatment should be aimed at correcting the underlying disorder by improving tissue perfusion with intravenous fluid therapy, eliminating ingested toxin, and correcting metabolic, renal, or gastrointestinal disease. With severe metabolic acidosis (pH, 7.1, HCO3- < 12mEq/l), sodium bicarbonate may be administered judiciously. Chronic metabolic acidosis should be corrected slowly to avoid undesired side effects including hyperosmolality, hypernatremia, hypokalemia, hypocalcemic tetany from shift of calcium from the ionized to the protein-bound form, and iatrogenic metabolic alkalosis.
Each primary disturbance will be accompanied by a compensatory or adaptive change in the opposing component of the system. The compensatory response returns the pH towards, but not completely to normal. Overcompensation does not occur. Expected compensatory changes are listed in Table 3.
Simple Versus Mixed Disturbances
An acid-base disorder is considered simple if it is limited to the primary disorder and the expected compensatory response. A patient has a mixed disorder if two or more primary abnormalities are occurring. A mixed disorder should be suspected whenever the compensatory response is less than or greater then expected. Mixed metabolic disturbances can be identified using the relationship between the change in anion gap and the change in serum bicarbonate. This relationship is sometimes called the gap-gap. It is calculated by the following formula:
AG excess/HCO3 deficit = (AG-12)/ (24- HCO3)
If there is a high anion gap acidosis, the change in AG should equal the change in bicarbonate and the ration should equal one. In the presence of a normal anion gap acidosis, the ratio should equal zero. When a mixed acidosis is present (High AG + normal AG), the ratio will fall between zero and one depending on the relative contribution of the two processes. A ratio greater than one is seen with mixed high anion gap acidosis and a metabolic alkalosis.
Table 1. Causes of SID alkalosis.
Contraction alkalosis: (Decreased free water, Increase in strong cations [sodium])
Pure water loss
Hypotonic fluid loss
Nonoliguric renal failure
Hypochloremic alkalosis: (Decreased chloride, Decrease in strong anions)
Excessive gain of sodium relative to chloride
Sodium bicarbonate administration
Excessive loss of chloride relative to sodium
Vomiting of stomach contents
Therapy with thiazide or loop diuretics
Table 2. Causes of SID acidosis.
Dilutional acidosis: (Increased free water, decrease in strong cations [sodium])
Gain of hypotonic fluid
Severe liver disease
Congestive heart failure
Gain of free water
Hypotonic fluid infusion
Loss of hypertonic fluid
Third space loss
Hyperchloremic acidosis: (Increased chloride, Increase in strong anions)
Excessive loss of sodium relative to chloride
Excessive gain of chloride relative to sodium
Fluid therapy (0.9% NaCl, 7.2% NaCl, KCL supplemented fluids)
Total parenteral nutrition
Organic acidosis: (Increased unmeasured strong anions, Increase in strong anions)
Table 3. Expected compensatory responses.
Metabolic acidosis: 0.7 mmHg decrease in pC02 for each 1 meq/L decrease in [HCO3-]
Metabolic alkalosis: 0.7 mmHg increase in pC02 for each 1 meq/L increase in [HCO3-]
Acute: 1.5 mEq/L increase in [HCO3-] for each 10 mmHg increase in pC02
Chronic: 3.5 mEq/L increase in [HCO3-] for each 10 mmHg increase in pC02
Acute: 2.5 mEq/L decrease in [HCO3-] for each 10 mmHg decrease in pC02
Chronic: 5.0 mEq/L decrease in [HCO3-] for each 10 mmHg decrease in pC02
1. Autran deMorais, Constable PD. Strong Ion Approach to Acid-Base Disorders. In Fluid, Electrolyte, and Acid-Base Disorders 3 ed. St. Louis: Saunders, 2006;310.
2. Story DA. Bench-to bedside review: A brief history of clinical acid-base Crit Care 2004, 8::253-258.