Skip to Content

Acid-Base Disorders


James L. Lewis III

, MD, Brookwood Baptist Health and Saint Vincent’s Ascension Health, Birmingham

Last full review/revision Jan 2020| Content last modified Jan 2020

Acid-base disorders are pathologic changes in carbon dioxide partial pressure (Pco2) or serum bicarbonate (HCO3) that typically produce abnormal arterial pH values.

  • Acidemia is serum pH < 7.35.
  • Alkalemia is serum pH > 7.45.
  • Acidosis refers to physiologic processes that cause acid accumulation or alkali loss.
  • Alkalosis refers to physiologic processes that cause alkali accumulation or acid loss.

Actual changes in pH depend on the degree of physiologic compensation and whether multiple processes are present.

(See also Acid-Base Regulation.)

Classification of Acid-Base Disorders

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 HCO3 or in Pco2.

Metabolic acidosis is serum HCO3< 24 mEq/L (< 24 mmol/L). Causes are

  • Increased acid production
  • Acid ingestion
  • Decreased renal acid excretion
  • Gastrointestinal or renal HCO3 loss

Metabolic alkalosis is serum HCO3> 28 mEq/L (> 28 mmol/L). Causes are

  • Acid loss
  • HCO3 retention

Respiratory acidosis is Pco2> 40 mm Hg (hypercapnia). Cause is

  • Decrease in minute ventilation (hypoventilation)

Respiratory alkalosis is Pco2< 38 mm Hg (hypocapnia). Cause is

  • Increase in minute ventilation (hyperventilation)

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.

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.

Pearls & Pitfalls

  • Compensatory mechanisms for acid-base disturbances cannot return pH completely to normal and never overshoot.

Primary Changes and Compensations in Simple Acid-Base Disorders

Primary Disturbance


Bicarbonate (HCO3)


Expected Compensation

Metabolic acidosis

< 7.35

Primary decrease

Compensatory decrease

1.2 mm Hg decrease in Pco2 for every 1 mEq/L (1 mmol/L) decrease in HCO3


Pco2= (1.5 × HCO3) + 8 (± 2)


Pco2= HCO3+ 15


Pco2= last 2 digits of pH ×100

Metabolic alkalosis

> 7.45

Primary increase

Compensatory increase

0.6–0.75 mm Hg increase in Pco2 for every 1 mEq/L (1 mmol/L) increase in HCO3 (Pco2 should not rise above 55 mm Hg in compensation)

Respiratory acidosis

< 7.35

Compensatory increase

Primary increase

Acute: 1–2 mEq/L (1–2 mmol/L) increase in HCO3 for every 10-mm Hg increase in Pco2

Chronic: 3–4 mEq/L (3–4 mmol/L) increase in HCO3 for every 10-mm Hg increase in Pco2

Respiratory alkalosis

> 7.45

Compensatory decrease

Primary decrease

Acute: 1–2 mEq/L (1–2 mmol/L) decrease in HCO3 for every 10-mm Hg decrease in Pco2

Chronic: 4–5 mEq/L (4–5 mmol/L) decrease in HCO3 for every 10-mm Hg decrease in Pco2

* Imprecise but convenient rules of thumb.

HCO3- = bicarbonate; Pco2 = carbon dioxide partial pressure.

Symptoms and Signs of Acid-Base Disorders

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 Disorders





Impaired cardiac contractility

Arteriolar dilation


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

Arteriolar constriction

Reduced coronary blood flow

Reduced anginal threshold

Decreased threshold for cardiac arrhythmias


Insulin resistance

Inhibition of anaerobic glycolysis

Reduction in ATP ( adenosine triphosphate) synthesis


Protein degradation

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

Diagnosis of Acid-Base Disorders

  • Arterial blood gases (ABG)
  • Serum electrolytes
  • Anion gap calculated
  • If metabolic acidosis is present, delta gap calculated and Winters formula applied
  • Search for compensatory changes

Evaluation is with ABG and serum electrolytes. The ABG directly measures arterial pH and Pco2. HCO3 level reported on the arterial blood gas panel is calculated using the Henderson-Hasselbalch equation. The HCO3 level on serum chemistry panel is directly measured. Directly measured HCO3 levels are considered more accurate in cases of discrepancy.

Acid-base balance is most accurately assessed with measurement of pH and Pco2 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 Pco2 reflect the respiratory component, and changes in HCO3 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, it is important when evaluating acid-base disorders to determine whether changes in Pco2 and HCO3 show the expected compensation (see table Primary Changes and Compensation in Simple Acid-Base Disorders). If not, then a second primary process causing the abnormal compensation should be suspected. Interpretation must also consider clinical conditions (eg, chronic lung disease, renal failure, drug overdose).

The anion gap should always be calculated; elevation almost always indicates a metabolic acidosis. A normal anion gap with a low HCO3 (eg, < 24 mEq/L [< 24 mmol/L]) and high serum chloride (Cl) indicates a non-anion gap (hyperchloremic) metabolic acidosis. If metabolic acidosis is present, a delta gap is calculated to identify concomitant metabolic alkalosis, and Winters formula is applied to determine whether respiratory compensation is appropriate or reflects a second acid-base disorder (predicted Pco2 = 1.5 [HCO3] + 8 ± 2; if Pco2 is higher, there is also a primary respiratory acidosis—if lower, respiratory alkalosis).

Respiratory acidosis is suggested by Pco2> 40 mm Hg; HCO3 should compensate acutely by increasing 3 to 4 mEq/L ( 3 to 4 mmol/L) for each 10-mm Hg rise in Pco2 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 HCO3 implies a primary metabolic alkalosis; lesser increase suggests no time for compensation or coexisting primary metabolic acidosis.

Metabolic alkalosis is suggested by HCO3> 28 mEq/L (> 28 mmol/L). The Pco2 should compensate by increasing about 0.6 to 0.75 mm Hg for each 1 mEq/L (1 mmol/L) increase in HCO3 (up to about 55 mm Hg). Greater increase implies concomitant respiratory acidosis; lesser increase, respiratory alkalosis.

Respiratory alkalosis is suggested by Pco2< 38 mm Hg. The HCO3 should compensate over 4 to 12 h by decreasing 4 to 5 mEq/L (4 to 5 mmol/L) for every 10 mm Hg decrease in Pco2. 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, HCO3, and Pco2.

Calculation of the anion gap

The anion gap is defined as serum sodium (Na) concentration minus the sum of chloride (Cl) and bicarbonate (HCO3) concentrations.

Na+− (Cl+ HCO3)

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 + HCO3+ unmeasured anions (UA)


the anion gap,

Na+ − (Cl+ HCO3) = UA − UC

The predominant "unmeasured" anions are phosphate (PO43), sulfate (SO4), 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) HCO3. 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 HCO3 equivalent, because for every unit rise in the anion gap, the HCO3 should lower by 1 (by buffering). Thus, if the delta gap is added to the measured HCO3, the result should be in the normal range for HCO3; elevation indicates the additional presence of a metabolic alkalosis.

Example: A vomiting, ill-appearing alcoholic patient has laboratory results showing

  • Na: 137
  • K: 3.8
  • Cl: 90
  • HCO3: 22
  • pH: 7.40
  • Pco2: 41
  • Po2: 85

At first glance, 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 Pco2= 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 HCO3:

25 − 10 = 15

15 + 22 = 37

The resulting corrected HCO3 is above the normal range for HCO3, 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.

Key Points about Acid-Base Disorders

  • Acidosis and alkalosis refer to physiologic processes that cause accumulation or loss of acid and/or alkali; blood pH may or may not be abnormal.
  • Acidemia and alkalemia refer to an abnormally acidic (pH < 7.35) or alkalotic (pH > 7.45) serum pH.
  • Acid-base disorders are classified as metabolic if the change in pH is primarily due to an alteration in serum bicarbonate (HCO3) and respiratory if the change is primarily due to a change in Pco2 (increase or decrease in ventilation).
  • The pH establishes the primary process (acidosis or alkalosis), changes in Pco2 reflect the respiratory component, and changes in HCO3 reflect the metabolic component.
  • All acid-base disturbances result in compensation that tends to normalize the pH. Metabolic acid-base disorders result in respiratory compensation (change in Pco2); respiratory acid-base disorders result in metabolic compensation (change in HCO3 ).
  • More than one primary acid-base disorder may be present simultaneously. It is important to identify and address each primary acid-base disorder.
  • Initial laboratory evaluation of acid-base disorders includes measurement of arterial blood gases and serum electrolytes and calculation of the anion gap.
  • Use one of several formulas, rules-of-thumb, or an acid-base nomogram to determine if laboratory values are consistent with a single acid-base disorder (and compensation) or if a second primary acid-base disorder is also present.
  • Treat each primary acid-base disorder.

Drugs Mentioned In This Article

Drug Name Select Trade
lithium LITHOBID

Copyright © 2021 Merck & Co., Inc., known as MSD outside of the US, Kenilworth, New Jersey, USA. All rights reserved. Merck Manual Disclaimer