13:36:57 – Acid-Base Disorders

Key Concepts

  • •

    Metabolic acidoses are classified into wide anion gap and normal anion gap acidoses, based on basic metabolic panel (BMP) values. A wide anion gap metabolic acidosis is present when the gap exceeds 15 mmol/L.

  • •

    Common causes of a wide anion gap metabolic acidosis are summarized with the mnemonic MUDPILES (Methanol, Uremia, DKA, Paraldehyde, Polyethylene glycol, or Paracetamol (Acetaminophen), Iron, Lactate, Ethylene Glycol, Salicylates).

  • •

    When a wide anion gap metabolic acidosis is identified on the BMP, the potential underlying causes can be determined through analysis of the delta gap and the osmolar gap.

  • •

    Common causes of a normal anion gap acidosis are summarized with the mnemonic HARDUP (Hyperalimentation/Hospital-acquired administration of saline, Acid infusion, Addison’s disease, Carbonic Anhydrase Inhibitors, Renal Tubular Acidosis, Diarrhea, Ureterosigmoidostomy, and Pancreatic drainage/fistula.)

  • •

    The optimal use of sodium bicarbonate therapy for metabolic acidosis is not clear and is the subject of ongoing research. A common strategy is to use sodium bicarbonate to increase pH above 7.10 in severe metabolic acidosis or above 7.20 for patients with severe metabolic acidosis and acute kidney injury.

  • •

    Metabolic alkalosis is associated with decreased circulating volume. GI-based chloride losses can be corrected with the administration of sodium chloride–containing intravenous fluids.

  • •

    Metabolic alkalosis caused by impaired renal excretion of sodium chloride that does not respond to intravenous fluids.

  • •

    Respiratory acidosis or alkalosis relates to carbon dioxide (CO 2 ) clearance, and thus is dependent on minute ventilation. Respiratory acidoses are caused by etiologies that decrease the ability of the body to rid itself of CO 2 , such as primary lung disease, chest wall disorders, and entities that decrease respiratory drive.

  • •

    Respiratory alkalosis results from disorders that increase CO 2 clearance such as hyperventilation and salicylate toxicity. Values from the blood gas are used primarily to identify the presence of respiratory acid-base disorders.

Acknowledgements

We would like to recognize Corey M. Slovis, MD for helping develop many of the concepts presented in this chapter.

Foundations

The body’s homeostatic mechanisms must keep acid-base balance under tight control. Acid-base disturbances can be life-threatening, with severe acid-base disorders leading to cellular compromise and death within hours due to alterations in hydrogen bonds, protein structures, and enzyme function.

The pH of the blood summarizes the systemic acid-base balance. pH is the negative logarithm of hydrogen-ion concentration (H + ) and has a normal range of 7.35 to 7.45. This normal pH is maintained by the kidneys’ regulation of plasma bicarbonate ( HCO 3 − ) and the lungs’ regulation of the partial pressure of arterial carbon dioxide (Pa co 2 ). The relationship of [ HCO 3 − ] and Pa co 2 to pH is described by the Henderson-Hasselbach equation: pH = pK + log 10 ([ HCO 3 − ]/[0.03 × Pa co 2 ]), where pK denotes the acid dissociation constant, [ HCO 3 − ] is measured in millimoles per liter (mmol/L), and Pa co 2 is measured in millimeters of mercury (mm Hg).

The terms acidemia and alkalemia describe the summary acid-base state, or the pH of the blood, while the terms acidosis and alkalosis describe discrete conditions. Blood pH less than 7.35 defines acidemia, while a pH greater than 7.45 defines alkalemia. An acidosis is an acid-base disturbance that increases [H + ] and lowers the pH. An alkalosis is an acid-base disturbance that decreases [H + ] and increases the pH. Multiple acidoses and alkaloses may be present at the same time; in these situations, pH describes the balance among all the acid-base disturbances.

The “metabolic system” includes cellular production and renal excretion of acids and bases. The respiratory system ventilates acid, in the form of carbon dioxide, out of the body through the lungs. The metabolic system and respiratory system are tightly coordinated to maintain acid-base hemostasis. Metabolic acid-base disorders are caused by abnormalities of cellular function, altered renal excretion of acids and bases, and exogenous gain or loss of acids and bases through the gastrointestinal tract. In clinical medicine, the principal test to evaluate for metabolic acid-base disturbances is plasma bicarbonate concentration ([ HCO 3 − ]). When a primary metabolic acid-base disturbance develops, the respiratory system compensates through increased or decreased ventilation of carbon dioxide to maintain acid-base hemostasis. Respiratory compensation typically takes 12 to 24 hours for a metabolic acidosis and 24 to 36 hours for a metabolic alkalosis.

Respiratory acid-base disorders are caused by abnormalities in ventilating carbon dioxide out of the body through the lungs. In clinical medicine, a common method of evaluating ventilation is by measuring the partial pressure of carbon dioxide in arterial blood (Pa co 2 ). After a primary respiratory acid-base disturbance develops, the metabolic system compensates by altering the excretion of acid in the kidneys to maintain acid-base hemostasis. Metabolic compensation typically takes between 2 and 5 days after a respiratory acidosis or alkalosis develops.

Acid-base disorders are categorized by their pathophysiologic mechanism (metabolic or respiratory) and effect on pH (acidosis or alkalosis). Hence, the four broad categories of acid-base disorders are metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis ( Fig. 113.1 ). A simple acid-base disturbance describes a physiologic state with a single acid-base disorder with or without compensation. A mixed-acid base disturbance describes a state with more than one primary acid-disorder, each with or without compensation.

Fig. 113.1

Classification of the four major categories of acid-base disorders.

This chapter provides an overview of the identification and classification of acid-base disorders in emergency medicine. Specific acid-base disorders are discussed in detail in other disease-focused chapters.

Clinical Features

A variety of patient presentations may prompt a clinician to search for acid-base disorders. This typically occurs in one of the three following scenarios in the emergency department:

  • 1.

    The patient presents with undifferentiated signs and symptoms and is ill-appearing with vital sign abnormalities, respiratory distress, or altered mental status.

  • 2.

    The patient presents with signs, symptoms or chronic medical conditions known to potentially cause acid-base abnormalities, such as toxic ingestions, vomiting, diarrhea, pregnancy, diabetes mellitus, chronic kidney disease, chronic liver disease, chronic lung disease, or neuromuscular disease.

  • 3.

    The patient is well-appearing and does not have an overt clinical presentation consistent with an acid-base disorder, but laboratory studies demonstrate an acid-base abnormality.

Once an acid-base abnormality is suspected, the clinician should initiate targeted diagnostic testing to identify the type of acid-base disorder present and its underlying cause.

Differential Diagnosis and Diagnostic Testing

The initial phase of evaluating most patients with acid-base disorders is interpretation of laboratory data. These data can assist the clinician in classifying the type of acid-base disorder(s) present: metabolic acidosis, metabolic alkalosis, respiratory acidosis, or respiratory alkalosis. Once the class of acid-base disorder is identified, the clinician can develop a differential diagnosis for the cause of the disorder.

Diagnostic Testing

Acid-base disorders can be characterized by the pH, Pa co 2 , and HCO 3 − concentration. Hence, interpretation of the basic metabolic panel (BMP) and blood gas is essential. Blood gas measurements can be obtained from either an arterial sample (arterial blood gas, ABG) or a venous sample (venous blood gas, VBG). Respiratory and acid-base physiology were classically described using ABG values, and ABG measurements provide a direct evaluation of oxygenation status as opposed to VBGs. However, obtaining an ABG requires arterial puncture, which is painful for patients, time-consuming for clinicians, and higher risk than venous blood sampling.

A VBG can be obtained from a routine venous blood draw with other laboratory studies and is a reasonable screening test in many settings. In the following sections, we provide a detailed discussion using ABG values; many of these concepts also apply to VBG values with the following considerations. On average, pH on a VBG is about 0.03 less than a concurrent ABG pH. The relationship between venous P co 2 (Pv co 2 ) and Pa co 2 is more variable, with Pv co 2 about 5 to 9 mm Hg higher than concurrent Pa co 2 for many patients. Pv co 2 less than 45 mm Hg has nearly 100% negative predictive value for ruling out hypercapnia (defined as Pa co 2 > 50 mm Hg). Pv o 2 does not correlate with Pa o 2 and cannot be used to guide management decisions about oxygen supplementation. However, oxygenation can be adequately measured noninvasively in most patients with pulse oximetry providing saturation of peripheral oxygen (Sp o 2 ) values. Hence, the combination of a VBG and Sp o 2 is a useful screen for acid-base disturbances and hypoxemia in most patients. Patients with a complex acid-base disorder or severe respiratory illness often benefit from an ABG in addition to the initial screen with a VBG and Sp o 2 .

Goals for the clinician include identifying whether an acid-base disorder is present, and if so, determining the primary disturbance. Once the primary disturbance has been identified, simple formulas can be used to understand if an appropriate compensatory response has occurred and if another primary acid-base order is also present. Compensatory processes adjust the pH toward normal, but usually not completely to normal and never beyond normal.

Several methods for identifying, classifying, and understanding acid-base disorders have been described, including the physiologic, physiochemical (also known as the Stewart method), and base-excess approaches. A simplified method for acid-base classification that incorporates concepts from each approach can be rapidly applied by clinicians at the bedside and is described in detail below. This method involves a five-step approach that primarily focuses on the interpretation of the BMP to evaluate for metabolic acid-base disturbances and a three-step approach that primarily focuses on the interpretation of the ABG to evaluate for respiratory acid-base disturbances.

Basic Metabolic Panel Interpretation

The BMP is the primary test to evaluate for metabolic acid-base disturbances and includes plasma concentrations for the following: sodium (Na), chloride (Cl), potassium (K), bicarbonate (HCO 3 ), blood urea nitrogen (BUN), creatinine (Cr), and glucose. Normal ranges for laboratory tests vary, and clinicians should be familiar with the normal ranges in their institutions. Specific thresholds are shown below for illustrative purposes.

Five-Step Acid-Base Approach to the BMP

BMP Step 1. Check for Abnormal Values

Evaluate the BMP for any abnormalities. A low HCO 3 concentration (for example, <22 mmol/L) identifies a metabolic acidosis, whereas a high HCO 3 concentration (for example, >29 mmol/L) identifies a metabolic alkalosis.

BMP Step 2. Check the Anion Gap

The anion gap (AG) is calculated with the formula: AG = [Na + ] − ([Cl − ] + [ HCO 3 − ]). The anion gap is used to evaluate for the presence of a wide anion gap metabolic acidosis. A wide anion gap metabolic acidosis is present if the anion gap is elevated, regardless of values for HCO 3 and pH. The anion gap is normally between 9.0 and 15.0 mmol/L, and thresholds to signify a wide anion gap vary between 10 and 15 mmol/L due to differences in laboratory technique. For illustrative purposes, a threshold of 15 mmol/L is used to define a wide anion gap in this chapter.

Plasma is electrically neutral. Hence, the sum of positive ion charges is equal to the sum of negative ion charges, as detailed in the equation: [Na + ] + [K + ] + [Ca 2+ ] + [Mg 2+ ] + [H + ] + unmeasured cations = [Cl – ] + [ HCO 3 − ] + [CO 3 2− ] + [OH − ] + albumin + phosphate + sulfate + lactate + unmeasured anions. Clinical laboratories only routinely measure plasma concentrations of the major ions, resulting in some cations and anions being “unmeasured.” A greater proportion of cation charge is typically measured than the anion charge, resulting in the concept of an “anion gap”—that is, the difference between measured cations and anions ( Fig. 113.2 ). The calculation for the anion gap accounts for the most plentiful measured cation (Na + ) and the two most plentiful measured anions (Cl − and HCO3 − ).

Fig. 113.2

Schematic representation of the anion gap (AG) and strong ion difference (SID). Human plasma is maintained at electroneutrality (no net charge). Thus, the sum of cations in plasma is equivalent to the sum of the anions. Calculation of the anion gap and strong ion difference can help identify the relative contribution of different cations and anions to plasma composition. An increase in anion gap indicates an increase in the contribution of “other anions,” such as lactate in lactic acidosis or ketone bodies in diabetic ketoacidosis. A relative increase in chloride concentration compared to the strong cations (Na + , K + , Ca ++ , Mg ++ ), such as occurs during saline infusion, leads to an increase in “other cations,” including H + , and a decrease in the SID.

Accumulation of “unmeasured anions”—that is, any anion other than chloride and bicarbonate—results in a wide anion gap metabolic acidosis. An acidosis in which the decrease in [HCO3 − ] is accompanied by an increase in [Cl − ] of approximately the same magnitude results in a normal anion gap acidosis, also known as hyperchloremic metabolic acidosis.

BMP Step 3. If a Metabolic Acidosis is Present, Apply the Rule of 15

The rule of 15 is used to evaluate for concomitant respiratory acid-base disturbances in addition to a metabolic acidosis. According to the rule of 15, in an isolated metabolic acidosis, HCO 3 + 15 should equal the Pa co 2 (±2 mm Hg) and the two digits of the pH following the decimal (±0.02). If measured Pa co 2 equals the predicted value, simple respiratory compensation for a primary metabolic acidosis exists. If measured Pa co 2 is less than the predicted value, there is a superimposed primary respiratory alkalosis on top of metabolic acidosis. If the Pa co 2 is higher than the predicted value, a superimposed primary respiratory acidosis is present.

The rule of 15 has an important caveat. When HCO 3 − falls below 10 mmol/L, the rule of 15 loses validity because HCO 3 − and Pa co 2 have a nonlinear relationship. In cases with HCO 3 between 5 mmol/L and 10 mmol/L, the expected Pa co 2 is about 15 mm Hg and the expected pH is about 7.15 (this is known as the corollary to the rule of 15). Alternatively, in these cases with HCO 3 − less than 10 mmol/L, Winters equation can be used to calculate a more precise expected Pa co 2 : expected Pa co 2 = [ HCO 3 − ] ∗ 1.5 + 8 ± 2. There are examples of the interpretation of the BMP using anion gap calculations and the rule of 15 available at the end of this chapter on ExpertConsult.com

BMP Step 4. If a Wide Anion Gap Metabolic Acidosis Is Present (Anion Gap ≥15), Check the Delta Gap

Calculation of the delta gap is used to identify additional metabolic acid-base disturbances superimposed on a wide anion gap metabolic acidosis. The delta gap explores the difference between the calculated anion gap and 15 mmol/L, which is the upper limit of normal for the anion gap, as well as the change in measured bicarbonate level from 24 mmol/L, which is the upper limit of normal for the bicarbonate level. In an isolated wide anion gap metabolic acidosis, each incremental increase in the anion gap is matched by an incremental decrease in HCO 3 of approximately the same magnitude. For example, each 1 mmol/L increase in the anion gap above 15 mmol/L is expected to be accompanied by a 1 mmol/L drop in HCO 3 below 24 mmol/L. A measured bicarbonate concentration higher than predicted by the delta gap calculation indicates a concomitant metabolic alkalosis. A measured bicarbonate concentration lower than predicted by the delta gap calculation indicates a concomitant normal anion gap metabolic acidosis. There are examples of delta gap calculations available at the end of this chapter on ExpertConsult.com

BMP Step 5. If a Wide Anion Gap Metabolic Acidosis Is Present (Anion Gap ≥15), But the Cause Is Not Evident, Check the Osmolar Gap

The osmolar gap is used to screen for the presence of abnormal particles dissolved in the blood. In the evaluation of acid-base disorders, calculation of the osmolar gap is commonly used to screen for the possibility of toxic alcohol ingestion as a cause for an unexplained wide anion gap metabolic acidosis.

Osmolality is a direct measure of the number of separate particles (solute) dissolved in a unit of water (solvent) within the blood. Calculated osmolarity is a calculated value of the expected number of osmotically active solutes in blood based on measured concentrations of the most common solutes. In normal physiologic states, the major solutes are sodium, the counter anions to sodium (e.g., chloride, bicarbonate, others), glucose, and urea. In patients who have been drinking ethanol, ethanol concentration (ETOH) is easily measured and is also a major contributor. Thus, the calculated osmolarity is calculated with the equation:

calculated osmolarity = ( 2 ∗ Na ) + ( glucose / 18 ) + ( BUN / 2.8 ) + ( ETOH / 3.7 )

In this equation, Na is measured in mmol/L, and glucose, BUN, and ETOH are measured in mg/dL. Units for osmolarity are mOsm/kg of water; the equation above has built-in constants that convert mg/dL to mmol/L.

Osmolality can be measured in clinical laboratories. The measured osmolality includes the solutes in the calculated osmolarity equation and other solutes in the blood not included in the equation. The difference between measured osmolality and calculated osmolarity is the osmolar gap:

Osmolar gap = ( measured osmoality ) − ( calculated osmolarity )
= ( Measured osmolality ) − [ ( 2 ∗ Na ) + ( glucose / 18 ) + ( BUN / 2.8 ) + ( ETOH / 3.7 ) ]

A normal osmolar gap is 10 mOsm/kg or less. A wide osmolar gap (>10 mOsm/kg) indicates accumulation of a significant volume of solute not included in the osmolarity equation (that is, a significant volume of “unanticipated” osmotically active solutes). In the setting of a wide anion gap metabolic acidosis, a wide osmolar gap may indicate the presence of toxic alcohols, such as methanol or ethylene glycol. However, it is important to note that a normal osmolar gap does not eliminate the possibility of a toxic alcohol poisoning, because the osmolar gap decreases as toxic alcohols are metabolized. Additionally, the calculation assumes a normal baseline osmolality, which is not always true. When an elevated osmolar gap is caused exclusively by a toxic alcohol, the plasma concentration of methanol or ethylene glycol can be estimated from the osmolar gap. To estimate the concentration of methanol in mg/dL, multiply the osmolar gap by 3. To estimate the concentration of ethylene glycol in mg/dL, multiply the osmolar gap by 6. There is an example of the osmolar gap calculation in Box 113.1 .

BOX 113.1

Identifying Acid-Base Disturbances With the Five-Step Focused Algorithm for Interpreting a Basic Metabolic Panel (BMP)

Clinical Concern: Acute Antifreeze (Ethylene Glycol) Ingestion

Laboratory Data

Na = 140 mmol/L

Cl = 100 mmol/L

HCO 3 = 8 mmol/L

BUN = 30 mg/dL

Cr = 2.5 mg/dL

Glucose = 80 mg/dL

ETOH = 240 mg/dL

Pa co 2 = 17 mmHg

pH = 7.13

Measured Osmolality: 425 mOsm/kg

  • 1.

    Check the numbers : Na = 140 mmol/L; Cl = 100 mmol/L; HCO 3 = 8 mmol/L; BUN = 30 mg/dL; Cr = 2.5 mg/dL; Glucose = 80 mg/dL. A low bicarbonate indicates a metabolic acidosis.

  • 2.

    Calculate the anion gap : AG = 140 − (100 + 8) = 32. A high anion gap indicates wide anion gap metabolic acidosis.

  • 3.

    Apply the rule of 15 : HCO 3 is below 10 mmol/L. According to the corollary to the rule of 15, simple respiratory compensation would lead to a Pa co 2 of approximately 15 mm Hg (±2), which is consistent with the patient’s measured Pa co 2 of 17 mm Hg. The patient’s acid-base status is consistent with a primary metabolic acidosis with respiratory compensation without an additional primary respiratory acid-base disturbance.

  • 4.

    Calculate the delta gap : Change in AG = measured AG − 15 = 32 − 15 = 17. Change in HCO 3 = 24 − measured HCO 3 = 24 − 8 = 16. The predicted change in bicarbonate concentration is 17 mmol/L, and the measured change is very similar at 16 mmol/L; this indicates the metabolic acid-base state is fully accounted for by a wide anion gap metabolic acidosis.

  • 5.

    Calculate the osmolar gap : Calculated osmolarity = (2∗Na) + (Glucose/18) + (BUN/2.8) + (ETOH/ 3.7) = (2∗140) + (80/18) + (30/2.8) + (240/3.7) = 360 mOsm/kg. Osmol gap = (measured osmolality) − (calculated osmolarity) = 425 mOsm/kg − 360 mOsm/kg = 65 mOsm/kg. An osmolar gap >10 mOsm/kg indicates accumulation of a significant volume of abnormal solute in the blood. In the setting of suspected ethylene glycol ingestion, the wide osmolar gap is presumed to be due to ethylene glycol until plasma ethylene glycol concentration results are available. The estimated ethylene glycol concentration = (osmolar gap) ∗ 6 = 65 ∗ 6 = 390 mg/dL.

Blood Gas Interpretation

Blood gases are the primary tests to evaluate for respiratory acid-base disturbances and include measurements for pH, the partial pressure of carbon dioxide (P co 2 ) and the partial pressure of oxygen (PO 2 ).

Three-Step Acid-Base Approach to the ABG

ABG Step 1. Determine if the Patient Is Acidemic or Alkalemic

Evaluate the pH. A pH less than 7.35 indicates acidemia; pH greater than 7.45 indicates alkalemia. pH is a summary measure that describes the overall balance of acid-base status. A pH in the normal range (7.35 to 7.45) may indicate no acid-base disturbance is present, a disturbance is present with compensation resulting in pH within the normal range, or multiple disturbances are present that, when combined, result in a pH in the normal range.

ABG Step 2. Determine if a Predominant Respiratory or Metabolic Acid-Base Disturbance Is Present

Evaluate Pa co 2 and place it into context with the pH. In predominant respiratory acid-base disturbances, the change in Pa co 2 is in the opposite direction of the change in pH. Using Pa co 2 of 40 mm Hg and pH of 7.40 as idealized normal values, a Pa co 2 greater than 40 with a pH less than 7.40 indicates a predominant respiratory acidosis. In predominant metabolic acid-base disturbances, the change in Pa co 2 and pH are in the same direction. For example, a Pa co 2 less than 40 mm Hg with a pH less than 7.40 indicates a predominant metabolic acidosis. There are two examples illustrating the use of ABG to determine the predominant respiratory or metabolic acid-base disturbance available at the end of this chapter on ExpertConsult.com.

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Apr 6, 2026 | Posted by in EMERGENCY MEDICINE | Comments Off on 13:36:57 – Acid-Base Disorders

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