Acid-base disorders are pathologic changes in carbon dioxide partial pressure (P co 2 ) or serum bicarbonate (HCO 3 − ) that typically produce abnormal arterial pH values.
Actual changes in pH depend on the degree of physiologic compensation and whether multiple processes are present.
Primary acid-base disturbances are defined as metabolic or respiratory based on clinical context and whether the primary change in pH is due to an alteration in serum HCO 3 − or in P co 2 .
Metabolic alkalosis is serum HCO 3 − > 28 mEq/L (> 28 mmol/L). Causes are
Respiratory acidosis is P co 2 > 40 mm Hg (hypercapnia). Cause is
Compensatory mechanisms begin to correct the pH (see table Primary Changes and Compensations in Simple Acid-Base Disorders ) whenever an acid-base disorder is present. Compensation cannot return pH completely to normal and never overshoots.
Overview of Acid-Base Maps and.A simple acid-base disorder is a single acid-base disturbance with its accompanying compensatory response.
Mixed (sometimes called complex) acid-base disorders comprise ≥ 2 primary disturbances.
Primary Changes and Compensations in Simple Acid-Base Disorders
1.2 mm Hg decrease in P co 2 for every 1 mEq/L (1 mmol/L) decrease in HCO 3 −
P co 2 = (1.5 × HCO 3 − ) + 8 ( ± 2)
P co 2 = last 2 digits of pH × 100
0.6–0.75 mm Hg increase in P co 2 for every 1 mEq/L (1 mmol/L) increase in HCO 3 − (P co 2 should not rise above 55 mm Hg in compensation)
Acute: 1–2 mEq/L (1–2 mmol/L) increase in HCO 3 − for every 10-mm Hg increase in P co 2
Chronic: 3–4 mEq/L (3–4 mmol/L) increase in HCO 3 − for every 10-mm Hg increase in P co 2
Acute: 1–2 mEq/L (1–2 mmol/L) decrease in HCO 3 − for every 10-mm Hg decrease in P co 2
Chronic: 4–5 mEq/L (4–5 mmol/L) decrease in HCO 3 − for every 10-mm Hg decrease in P co 2
* Imprecise but convenient rules of thumb.
HCO 3 - = bicarbonate; P co 2 = carbon dioxide partial pressure.
Compensated or mild acid-base disorders cause few symptoms or signs.
Severe, uncompensated disorders have multiple cardiovascular, respiratory, neurologic, and metabolic consequences (see table Clinical Consequences of Acid-Base Disorders and figure Oxyhemoglobin dissociation curve ).
Clinical Consequences of Acid-Base DisordersClinical Consequences of Acid-Base Disorders
Impaired cardiac contractility
Centralization of blood volume
Increased pulmonary vascular resistance
Decreased cardiac output
Decreased systemic blood pressure
Decreased hepatorenal blood flow
Decreased threshold for cardiac arrhythmias
Attenuation of responsiveness to catecholamines
Reduced coronary blood flow
Reduced anginal threshold
Decreased threshold for cardiac arrhythmias
Inhibition of anaerobic glycolysis
Reduction in ATP ( adenosine triphosphate) synthesis
Bone demineralization (chronic)
Stimulation of anaerobic glycolysis
Formation of organic acids
Decreased oxyhemoglobin dissociation
Decreased ionized calcium
Inhibition of metabolism and cell-volume regulation
Obtundation and coma
Compensatory hyperventilation with possible respiratory muscle fatigue
Compensatory hypoventilation with hypercapnia and hypoxemia
Evaluation is with ABG and serum electrolytes. The ABG directly measures arterial pH and P co 2 . HCO 3 − level reported on the arterial blood gas panel is calculated using the Henderson-Hasselbalch equation. The HCO 3 − level on serum chemistry panel is directly measured. Directly measured HCO 3 − levels are considered more accurate in cases of discrepancy.
Acid-base balance is most accurately assessed with measurement of pH and P co 2 in an arterial blood sample. In cases of circulatory failure or during cardiopulmonary resuscitation, measurements from a sample of venous blood may more accurately reflect conditions at the tissue level and may be a more useful guide to bicarbonate administration and adequacy of ventilation.
The pH establishes the primary process (acidosis or alkalosis), although pH moves toward the normal range with compensation. Changes in P co 2 reflect the respiratory component, and changes in HCO 3 − reflect the metabolic component.
Complex or mixed acid-base disturbances involve more than one primary process. In these mixed disorders, values may be deceptively normal. Thus, when evaluating acid-base disorders, it is important to determine whether changes in P co 2 and HCO 3 − show the expected compensation (see table Primary Changes and Compensation in Simple Acid-Base Disorders ). If not, then a second primary process should be suspected of causing the abnormal compensation. Interpretation must also consider clinical conditions (eg, chronic lung disease, renal failure, drug overdose).
Overview of Plasma Anion GapRespiratory acidosis is suggested by P co 2 > 40 mm Hg; HCO 3 − should compensate by increasing 3 to 4 mEq/L ( 3 to 4 mmol/L) for each 10-mm Hg rise in P co 2 sustained for 4 to 12 hours (there may be no increase or only an increase of 1 to 2 mEq/L [1 to 2 mmol/L], which slowly increases to 3 to 4 mEq/L [3 to 4 mmol/L] over days). Greater increase in HCO 3 − implies a primary metabolic alkalosis; lesser increase suggests no time for compensation or coexisting primary metabolic acidosis.
Metabolic alkalosis is suggested by HCO 3 − > 28 mEq/L (> 28 mmol/L). The P co 2 should compensate by increasing about 0.6 to 0.75 mm Hg for each 1 mEq/L (1 mmol/L) increase in HCO 3 − (up to about 55 mm Hg). Greater increase implies concomitant respiratory acidosis; lesser increase, respiratory alkalosis.
Respiratory alkalosis is suggested by P co 2 < 38 mm Hg. The HCO 3 − should compensate over 4 to 12 hours by decreasing 4 to 5 mEq/L (4 to 5 mmol/L) for every 10 mm Hg decrease in P co 2 . Lesser decrease means there has been no time for compensation or a primary metabolic alkalosis coexists. Greater decrease implies a primary metabolic acidosis.
Nomograms (acid-base maps) are an alternative way to diagnose mixed disorders, allowing for simultaneous plotting of pH, HCO 3 − , and P co 2 .
Equations for Calculating Acid-Base Balance Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical Calculators Clinical CalculatorsThe anion gap is defined as serum sodium (Na) concentration minus the sum of serum chloride (Cl − ) and serum bicarbonate (HCO 3 − ) concentrations.
The term “gap” is misleading, because the law of electroneutrality requires the same number of positive and negative charges in an open system; the gap appears on laboratory testing because certain cations (+) and anions (−) are not measured on routine laboratory chemistry panels. Thus,
Na + + unmeasured cations (UC) = Cl − + HCO 3 − + unmeasured anions (UA)
and the anion gap,
Na + − (Cl − + HCO 3 − ) = UA − UC
The predominant "unmeasured" anions are phosphate (PO 4 3 − ), sulfate (SO 4 − ), various negatively charged proteins, and some organic acids, accounting for 20 to 24 mEq/L (20 to 24 mmol/L).
The predominant "unmeasured" extracellular cations are potassium (K + ), calcium (Ca ++ ), and magnesium (Mg ++ ) and account for about 11 mEq/L (5.5 mmol/L).
Thus, the typical anion gap is 23 − 11 = 12 mEq/L (12 mmol/L). The anion gap can be affected by increases or decreases in the UC or UA.
Increased anion gap is most commonly caused by metabolic acidosis in which negatively charged acids—mostly ketones, lactate, sulfates, or metabolites of methanol, ethylene glycol,or salicylate—consume (are buffered by) HCO 3 − . Other causes of increased anion gap include hyperalbuminemia or uremia (increased anions) and hypocalcemia or hypomagnesemia (decreased cations).
Decreased anion gap is unrelated to metabolic acidosis but is caused by hypoalbuminemia (decreased anions); hypercalcemia , hypermagnesemia , lithium intoxication, and hypergammaglobulinemia as occurs in myeloma (increased cations); or hyperviscosity or halide (bromide or iodide) intoxication. The effect of low albumin can be accounted for by adjusting the normal range for the anion gap 2.5 mEq/L (2.5 mmol/L) downward for every 1g/dL (10 g/L) fall in albumin .
Negative anion gap occurs rarely as a laboratory artifact in severe cases of hypernatremia, hyperlipidemia , and bromide intoxication.
The delta gap: The difference between the patient’s anion gap and the normal anion gap is termed the delta gap. This amount is considered an HCO 3 − equivalent, because for every unit rise in the anion gap, the HCO 3 − should lower by 1 (by buffering). Thus, if the delta gap is added to the measured HCO 3 − , the result should be in the normal range for HCO 3 − ; elevation indicates the additional presence of a metabolic alkalosis .
Example: A vomiting, ill-appearing patient with alcohol use disorder has laboratory results showing
At first glance, the results appear unremarkable. However, calculations show elevation of the anion gap:
137 − (90 + 22) = 25 (normal, 10 to 12)
indicating a metabolic acidosis. Respiratory compensation is evaluated by Winters formula:
Predicted P co 2 = 1.5 (22) + 8 ± 2 = 41 ± 2
Predicted = measured, so respiratory compensation is appropriate.
Because there is metabolic acidosis, the delta gap is calculated, and the result is added to measured HCO 3 − :
The resulting corrected HCO 3 − is above the normal range for HCO 3 − , indicating a primary metabolic alkalosis is also present. Thus, the patient has a mixed acid-base disorder.
Using clinical information, one could theorize a metabolic acidosis arising from alcoholic ketoacidosis combined with a metabolic alkalosis from recurrent vomiting with loss of acid (HCl) and volume. The management of this patient should include treatments to address each primary acid-base disorder.