I. Introduction
I. Basic concepts
II. Stepwise approach to diagnosing acid-base disorders.

IV. Specific Acid-Base Disorders and Diagnoses


I. Introduction

This document is designed to provide a practical approach to arterial blood gas analysis and will provide basic principles for understanding acid-base disturbances commonly encountered in medical practice. Although physiologic equations will appear throughout, the derivation and physiologic basis will not be discussed. Prior background in the physiology of respiratory system and acid-base disturbances is strongly recommended, but not required to complete this section.

II. Basic concepts

The anatomy of an arterial blood gas (ABG) as seen most often in the medical record:

7.40/40/98/24 or

pH/PaCO2/PaO2/HCO3-

pH: arterial blood pH
PaCO2: arterial CO2 pressure, mm Hg (often written more simply as PCO2)
PaO2: arterial O2 pressure, mm Hg (often written more simply as PO2)
HCO3-: serum bicarbonate concentration, mEq/liter

Hypoxia refers to reduced oxygen pressure in the alveolus. Hypoxemia refers to low arterial PaO2. At or near sea level (in Iowa), the following equation will estimate the average value for arterial PaO2:

PaO2 = 104.2 - (0.27 x age)

In the alveolus a reciprocal relationship exists between oxygen and carbon dioxide. Carbon dioxide accumulation as a result of inadequate ventilation displaces oxygen. Also, a normal gradient of about 10 mmHg exists between alveolar oxygen pressure (PAO2) and the arterial oxygen pressure (PaO2). Generally, there is no gradient between the alveolar carbon dioxide pressure (PACO2) and the arterial PaCO2. The ABG PaCO2 and PaO2 values will reflect these relationships. The reciprocal relationship between the PAO2 and PACO2, is illustrated by the Alveolar Gas Equation shown below. The second of the two following equations is simplified for Iowa atmospheric conditions and breathing ambient air (FiO2 = fraction of inspired oxygen which is .21 for ambient air, the correction factor for PCO2 is derived by dividing by R (respiratory quotient) which is estimated to be 0.8; see your physiology book for more details):

PAO2 = FiO2(700) - (PACO2 x 1.25), or

PAO2 = 147 - (PACO2 x 1.25) (for Iowa)

The PACO2 is equivalent to PaCO2 because there is no gradient. The PAO2 to PaO2 gradient is normally close to 10 (up to 21 in older individuals) and is written as follows:

P(A-a)O2 = 10 mmHg

These relationships are most pertinent in cases of hypercarbia or elevated PaCO2, due to impaired ventilation. Impaired ventilation results in respiratory acidosis which is discussed in greater detail in the next section. The following table illustrates the effect of increased PACO2 in a patient with a normal P(A-a)O2 gradient of 10.

Table 1. Effect of PACO2 on PaO2

PACO2 & PaCO2 PAO2 PaO2
40 97 87
64 67 57
80 47 37

Acidemia and alkalemia refer to the alterations in the blood pH. Both respiratory and metabolic disorders can contribute to alterations in pH and are referred to as a respiratory acidosis or respiratory alkalosis, and a metabolic acidosis or metabolic alkalosis. A single disorder may account for the observed acidemia or alkalemia, but often more than one disorder occurs concurrently. These are referred to as mixed or complex acid-base disorders. For example an alkalemic ABG may exhibit a mixed respiratory acidosis and a metabolic alkalosis. Identifying the simple as well as the complex acid-base disorders will be possible by applying the stepwise approach outlined in the next section.

III. Stepwise approach to diagnosing acid-base disorders

The following is a six-step logical approach to analyzing acid-base disorders utilizing the ABG and serum electrolyte data. It was originally proposed by Narins and Emmett (3) and further refined by Morganroth (1,2). These steps are based on sound physiologic principles, yet require an elementary understanding of those principles on the part of the student.

The pH of the arterial blood gas measurement identifies the disorder as alkalemic or acidemic.

Normal arterial blood pH = 7.40 Ī 0.02

Acidemic: pH < 7.38
Alkalemic: pH > 7.42

This step requires one to determine whether the disturbance effects primarily the arterial PaCO2 or the serum HCO3-

A respiratory disturbance alters the arterial PaCO2 (normal value 40, range 38-42). Go to step 3.

A metabolic disturbance alters the serum HCO3- (normal value 24, range 22-26).

  • If HCO3- < 22, metabolic acidosis is present. Go to step 4.
  • If HCO3- > 26, metabolic alkalosis is present, is respiratory compensation adequate? Go to step 6.

The Henderson-Hasselbalch equation provides the basis for the relationship between the blood pH and PaCO2, HCO3-, and it is shown below. The calculation, however, has no practical value.

pH = pK + log [HCO3-/PaCO2] x K, or

[H+] = 24 x PaCO2/HCO3-

A respiratory acidosis results from accumulation of PaCO2 and a respiratory alkalosis results from hyperventilation or a low PaCO2 (specific causes of respiratory acidosis and alkalosis are listed in section IV). For acute disturbances a PaCO2 variation from normal by 10 mm Hg is accompanied by a pH shift of approx. 0.08 units. A chronic disturbance reflects renal mediated HCO3- shifts. Renal compensation requires several hours to develop and is maximal after 4 days. Therefore during chronic disturbances, a PaCO2 variation from normal of 10 is accompanied by a smaller pH shift of only 0.03 units. Also, the renal correction brings the pH back towards normal, but not completely. These relationships are spelled out in the following equations:

Acute respiratory acidosis: pH decrease = 0.08 x (PaCO2 - 40)/10
Chronic respiratory acidosis: pH decrease = 0.03 x (PaCO2 - 40)/10

Acute respiratory alkalosis: pH increase = 0.08 x (40 - PaCO2)/10
Chronic respiratory alkalosis pH increase = 0.03 x (40 - PaCO2)/10

The anion gap calculation simplifies the diagnosis of the cause for a metabolic acidosis.

What is the anion gap? The normal anion gap is 12 mEq/L. The anion gap is the calculated difference between negatively charged (anion) and positively charged (cation) electrolytes, which are measured in routine serum assays. The total of measured cations represented by sodium (Na+), is greater than the total measured anions, HCO3- and chloride (Cl-). Turned around, that difference or gap also can be viewed as the unmeasured anion concentration. The unmeasured anion concentration dominates the balance between the unmeasured serum anions and cations as illustrated in Table 2.

Table2. Anion Gap reflects the unmeasured anion and cations.

Unmeasured Anions

vs

Unmeasured Cations

Proteins, mostly albumin 15 mEq/L

 

Calcium 5 mEq/L

Organic acids 5 mEq/L

 

Potassium 4.5 mEq/L

Phosphates 2 mEq/L

 

Magnesium 1.5 mEq/L

Sulfates 1 mEq/L

   
Totals: 23 mEq/L  

11 mEq/L

Thus the balance favors the unmeasured anions by 12 mEq/L, which is the normal anion gap. The unmeasured anions rarely change enough to effect anion gap interpretation. Knowledge of the unmeasured anions is not essential to the calculation of the anion gap. However, one needs to understand the concept in order to recognize the rare instances when the anion gap is not 12 for reasons other than a metabolic acidosis. These exceptions are listed at the end of this section.

The causes of an anion gap acidosis differ from those of a normal or non-anion gap acidosis (see causes of metabolic acidosis in section IV). The anion gap determination is an excellent tool for narrowing the list of potential causes of a metabolic acidosis. The simple calculation is shown below. The anion gap calculation requires values for the serum Na+, Cl-, and HCO3-:

Anion gap = Na+ - (Cl- + HCO3-),
Anion gap metabolic acidosis, anion gap > 12
Normal or non-anion gap acidosis, anion gap £ 12

The calculation of the anion gap provides reliable data with the following rare exceptions (One should come back to these later after one has a solid grasp of the six-step system for acid-base analysis):

Patients with a low serum albumin (e.g. cirrhosis, nephrotic syndrome, malnutrition) have an anion gap acidosis, but the measured anion gap is normal or < 12. The reason is that albumin has many negative charges on its surface and accounts for a significant proportion of the unmeasured anions. Severe hypoalbuminemia may exhibit a normal anion gap as low as 4. Therefore in severe hypoalbuminemia if the anion gap increases and approaches 12, one must suspect an additional metabolic cause for the increased anion gap (see causes of anion gap acidosis in section IV)

Alkalemic patients with pH > 7.5, the anion gap may be elevated due to metabolic alkalosis and not because of additional metabolic acidosis. This is probably due to unmeasured anion accumulation. Specifically, the negative charges on the surface of albumin become more negative in alkalemic conditions which would increase the unmeasured anions (Table 2) and the anion gap. The distinction between whether an anion gap is due to alkalemia or an underlying acidosis in an alkalemic patient needs to be considered in some clinical situations.

A non-anion gap acidosis or a metabolic alkalosis (section IV for specific causes) may exist concurrently with an anion gap acidosis. This determination requires one to account for the increase in the anion gap and determine whether additional variation in HCO3- exists. If no other metabolic disturbance exists, then the following calculation would result in 24:

Corrected HCO3- = measured HCO3- + (anion gap - 12)

If the corrected HCO3- varies significantly above or below 24, then a mixed or more complex metabolic disturbance exists. To be more specific, if the corrected HCO3- is greater than 24, a metabolic alkalosis co-exists. If the corrected HCO3- is less than 24 then a non-gap acidosis co-exists.

The following examples help one understand how this step works. A patient with a anion gap metabolic acidosis has a HCO3- of 10 mEq/L and an anion gap of 26. By calculating the corrected HCO3- one finds the result to be 24 and can conclude that no other metabolic disturbance co-exists. If this patient had a HCO3- of 15 and an anion gap of 26, then the corrected HCO3- would calculated to 29, a value significantly greater than 24. One would then conclude that metabolic alkalosis co-exists with the gap acidosis.

The respiratory system responds quickly to a metabolic disturbance and most predictably to a metabolic acidosis. The change in PaCO2 exhibits a linear correlation with the change in HCO3-. The equation that predicts the respiratory response to a metabolic acidosis is called Winterís formula:

Expected PaCO2 = (1.5 x HCO3-) + (8 Ī 2)

In the setting of a simple metabolic acidosis, the measured PaCO2 will fall within the range predicted by Winterís formula. If a respiratory disturbance is occurring concurrently with the metabolic acidosis, it would be defined by the direction the PaCO2 varies outside the range predicted by Winterís formula, not by the PaCO2 variation from the normal value of 40.

Working through the following example illustrates how to utilize Winterís formula to assess the respiratory response to metabolic acidosis. If the serum HCO3- is 10 mEq/L, the PaCO2 should be between 21 and 25 according to Winterís formula. If the measured PaCO2 falls outside of this range, then an additional respiratory disturbance must be occurring concurrently. If the measured PaCO2 is less than 21, then the additional disturbance is a respiratory alkalosis. If the measured PaCO2 is greater than 25, then the additional disturbance is a respiratory acidosis.

Winterís formula does not predict the respiratory response to a metabolic alkalosis. The magnitude of respiratory response to metabolic alkalosis is not easily predictable. When present, the respiratory response to metabolic alkalosis is hypoventilation, but the degree of PaCO2 increase does not exhibit a linear relationship with the HCO3-. Two general rules hold up for the respiratory response to a metabolic alkalosis:

IV. Specific Acid-Base Disorders and Diagnoses

1. Respiratory Acidosis:

Respiratory acidosis results from hypoventilation which is manifested by the accumulation of CO2 in the blood and a drop in blood pH. Examples of specific causes can be categorized as follows:

2. Respiratory Alkalosis:

Respiratory alkalosis results from hyperventilation which is manifested by excess elimination of CO2 from the blood and a rise in the blood pH. Examples of specific causes are listed below:

3. Anion Gap Acidosis

Anion gap acidosis results from accumulation of acidic metabolites and is manifested by a low HCO3- and an anion gap > 12 (anion gap calculation discussed in step 3). Examples of specific causes:

One may use a mnemonic device to remember these items. MULEPAK is a mnemonic commonly used (Methanol, Uremia, Lactic acidosis, Ethylene glycol intoxication, Paraldehyde intoxication, Aspirin, Ketoacidosis).

4. Non-Anion Gap Acidosis

Non-anion gap acidosis results from loss of bicarbonate or external acid infusion and is manifested by a low HCO3-, but the anion gap is <12 (anion gap calculation is discussed in step 3). Examples of specific causes:

A mnemonic device may be used to remember this list of causes. The commonly used mnemonic is ACCRUED (Acid infusion, Compensation for respiratory alkalosis, Carbonic anhydrase inhibitor, Renal tubular acidosis, Ureteral diversion, Extra alimentation or hyperalimentation, Diarrhea).

5. Metabolic Alkalosis

Metabolic alkalosis results from elevation of serum bicarbonate. Examples of specific causes:

References:

  1. Morganroth, ML. An analytic approach to diagnosing acid-base disorders. J Crit Ill 5(2):138-150, 1990
  2. Morganroth, ML. Six steps to acid-base analysis: clinical applications. J Crit Ill 5(5) 460-469, 1990.
  3. Narins, RG. Simple and mixed acid-base disorders: a practical approach. Medicine 59:161-187, 1980.
 
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