Mixed Acid-Base Disorders - Clinical Chemistry

157 downloads 87 Views 1MB Size Report
Keyphrases: acidemia alkalemia metabolic and respiratory acidosis and alkalosis blood gases. The simple, or primary, acid-base disorders (respiratory.
CLIN. CHEM.

31/2, 321-325

(1985)

Mixed Acid-Base Disorders R. N. Walmsley and G. H. White Mixed acid-base disorders, the occurrence of two or more primary acid-base disturbances in the same patient, are common in the hospital population, but are usually misdiagnosed because of lack of knowledge of the consequences of the primary disturbances. This paper describes seven examples of these disorders recently seen in the authors’ hospital, and provides a logical approach to their diagnosis. AddItIonal Keyphrases: acidemia and respiratory acidosis and alkalosis

alkalemia blood gases

metabolic

The simple, or primary, acid-base disorders (respiratory and metabolic acidosis and alkalosis) evoke a compensatory response that produces a secondary acid-base disturbance and reversion of the blood pH towards (rarely to) normal; e.g., a simple metabolic acidosis will result in a secondary respiratory alkalosis, both of which will ordinarily be reflected in the patients’ acid-base-related analytes in blood. When two primary acid-base disturbances arise simultaneously in the same patient, the complex is called a mixed acid-base disorder. If three primary disturbances occur together, the patient is described as having “triple acid-base disorder.” Available information on the incidence of mixed acidbase disorders is meager; however, in one survey of hospitalized patients, Hodgkin et al. (1) found that 26% of patients with respiratory alkalosis and 41% of patients with respiratory acidosis had mixed disorders. In our institution a survey of 41 cases of chronic obstructive airway disease disclosed 13 (32%) with an underlying diuretic-induced primary metabolic alkalosis. ifthese figures are typical of other hospitals, then the incidence of mixed acid-base disorders is fairly high. The importance of being able to identify these disorders lies in their diagnostic and therapeutic implications. For example, the development of a primary metabolic alkalosis in a patient with chronic obstructive airway disease who is being treated with diuretics should alert the clinician to the possibility of potassium depletion, and a patient presenting with a mixed respiratory alkalosis and metabolic acidosis should be evaluated for possible salicylate intoxication. The diagnosis of these mixed disorders can usually be made simply by inspecting the test results for blood gases and plasma electrolytes. For a more confident evaluation, however, both the clinical picture and the blood analyte values should be considered; i.e., suspect the disturbance from the clinical story, and confirm or reject the diagnosis by examining the blood analyte values. The ability to make a laboratory diagnosis of the mixed acid-base disorders requires a thorough understanding of the compensatory responses of the four simple disturbances-metabolic acidosis and alkalosis, and respiratory acidosis and alkalosis-and a knowledge of the limits of these processes. Department of Clinical Biochemistry, Flinders Medical Centre, Bedford Park, South Australia 5042. Received September 17, 1984; accepted November 29, 1984.

Evaluation of Blood Gasses The Henderson-Hasselbalch equation for the bicarbonate buffer system in blood can be simplified to an uncomplicated proportional relationship: pH

[HC0I Pco2

The numerator

([HC0])

indicates

the metabolic

aspect of

acid-base status:an increase signifies metabolic alkalosis, and a decrease denotes a metabolic acidosis, either of which

can be a primary or a secondary (compensatory) process. The denominator (pco2) indicates any respiratory process: i.e., an increase denotes a respiratory acidosis, etc.-again, either primary or secondary. The simplest approach to interpretation of blood gas values is to consider the pH (acidemia or alkalemia), [HC0fl (metabolic acidosis or alkalosis), and the Pco2 (respiratory acidosis or alkalosis) separately, then amalgamate the information to arrive at a diagnosis. For example, a patient with a low pH (acidemia), a high [HCOfl (metabolic alkalosis), and a high Pco2 (respiratory acidosis) has a simple respiratory acidosis; i.e., the patient is acidemic and therefore the primary disorder is likely to be an acidosis (respiratory in this case) and the metabolic alkalosis is a compensatory process. Because simple acid-base disorders do not overcompensate (change an acidemia to an alkalemia and vice versa), the metabolic alkalosis is unlikely to be the primary disorder. Metabolic Acidosis The compensatory response to metabolic acidosis is hyperventilation and a decrease in the blood Pco2 (respiratory alkalosis). This response reaches a maximum within 12 to 24 h. The Pco, values attained, for a given concentration of bicarbonate in plasma, can be estimated from the following formula (2): Pco, (mmHg)

=

1.54 x [HC01

The limit of compensation,

(mmolIL) i.e., the lowest

+

8.36 (± 1.1) (1) value

to which

the Pco2 will fall, is approximately 10 minHg. Patients with a metabolic acidosis (acidemia plus a low plasma [HC0]), whose calculated Pco, is less than the measured value, have, in addition, an underlying respiratory alkalosis. Conversely, patients with a calculated value greater than the measured value have a primary respiratory acidosis in addition to the metabolic acidosis (provided the disorder has been present longer than 12 h). Metabolic Alkalosis In metabolic alkalosis (alkalemia plus a high plasma [HC0I) the compensatory response is hypoventilation and an increase in the blood Pco, (respiratory acidosis). Unlike metabolic acidosis, the pco2 response in this condition is irregular, but the limit of compensation for pco2 is about 60 mmHg (3). This value possibly reflects the respiratory drive CLINICAL

CHEMISTRY,

Vol. 31, No. 2, 1985

321

of hypoxia that will eventually occur if hypoventilation is prolonged. Despite the unpredictable response of Pco, to metabolic alkalosis, we have found the equation derived by Fulop (4) helpful in calculating the Pco, for a given concentration of bicarbonate in plasma: Pco, (mmHg)

=

0.9 x [HCO1

(mmollL)

+

9

(2)

Thus the patient with metabolic alkalosis and a measured Pco2 greater than 60 mmHg, or significantly greater than the value calculated from equation 2, is deemed to have an additional underlying primary respiratory acidosis, whereas the patient with a Pco, less than the calculated value (provided the condition has been present for more than 12 h) has an additional respiratory alkalosis. Respiratory

Acidosis

The compensatory increase in the plasma EHCO] in to hypercapnia can be divided into two phases. In an early, or acute, phase a mild increase in bicarbonate of 2 to 4 mmol/L occurs within 10 mm; the chronic phase is characterized by a further, fairly rapid, increase over the next 24 h, followed by a slower increase that plateaus over the next two to four days. Acute respiratory acidosis: The early increase in the plasma [HCOI related to respiratory acidosis comes from the production of carbonic acid from the retained C02, i.e., (3 CO2 + H20 H2C03 H + HCO response

-*

-

ions produced are buffered by the nonbicar(e.g., protein, hemoglobin) and the bicarbonate ions remain behind. The carbon dioxide also enters the erythrocytes where, under the influence of carbonate dehydratase (EC 4.2.1.1), it is converted to hydrogen and bicarbonate ions; the hydrogen ions are buffered by hemoglobin, and the bicarbonate diffuses into the plasma. The amount of HCO generated, even at Pco2 values of 100 to 130 mmHg, is minimal and has been shown experimentally to be about 2 to 4 mmol/L; the total concentration does not exceed 32 mmol/L (5). Thus, a patient with an acute respiratory The hydrogen

bonate systems

acidosis who has a plasma [HCO1 in excess of 32 mmol/L should be suspected of having a superimposed metabolic aJ.kalosis; conversely, if the [HCO] is below the lower reference limit (-23 mmol/L), an underlying metabolic acidosis is present. Chronic respiratory acidosis: The compensatory increase in the plasma [HCO1 during chronic hypercapnia is due to generation of this ion by the kidney. The concentration attained at a given Pco2 has been determined in dogs and humans with varying results. Engle et al. (6) studied the problem in a group of patients with simple chronic respiratory acidosis and found the following relationship: [HCO1 (mmollL)

=

0.43 x Pco, (mmHg)

+ 7.6 (±2)

(4)

The maximum level of compensation is a plasma [HCO1 of around 45 mmol/L (7, 8). Thus a patient with chronic respiratory acidosis (present for at least four days) whose measured plasma [HCO] exceeds 45 mmolJL, or that calculated from equation 4, should be suspected of having an additional underlying primary metabolic alkalosis. If the concentration is below the lower reference interval (-23 mmolJL), or significantly less than the calculated value from equation 4, then a primary metabolic acidosis should be suspected.

In mild chronic respiratory acidosis, where Pco2 is less complete compensation (return of the pH to normal) may occur (9). This situation should always be considered before a diagnosis of mixed respiratory acidosis than 60 mmHg,

322

CLINICAL CHEMISTRY, Vol. 31, No. 2, 1985

and metabolic Respiratory

alkalosis

is made.

Alkalosis

As in hypoventilation, the plasma bicarbonate response to hyperventilation can be divided into two phases: an acute phase, occurring during the first 10 mm, in which the concentration decreases 2 to 4 mmolJL, and a chronic phase, where a sustained decrease levels out over the following two to four days. Acute respiratory alkalosis: During hypocapnia, as the Pco2 decreases, equation 3 is driven to the left and the reverse of hypercapnia occurs; i.e., the plasma [HCOI falls, usually to not less than 18 mmolJL (5, 10). Thus acute respiratory alkalosis associated with a plasma [HCO1 of less than 18 mmol/L suggests an underlying primary metabolic acidosis. If the bicarbonate is greater than the lower reference limit (-23 mmol/L), a primary metabolic alkalosis should be suspected. Chronic respiratory alkalosis: The compensatory response to chronic respiratory alkalosis, like that of respiratory acidosis, involves the renal system in that there is mild bicarbonaturia resulting in hypobicarbonatemia. The lowest plasma [HCO} that can be reached is 12 to 16 mmol/L (11). The decrease in the plasma [HCO1 is on the order of 0.5 mniol of HCO per liter for each 1.0 mmHg decrease in the Pco2. For example, assuming a “normal” pco2 of 40 mmHg and a “normal” [HCO1 of 25 mmol/L, then a Pco2 of 20 mmHg will be associated with a [HCO1 of 15 mmol/L. Chronic respiratory alkalosis is, with the possible exception of mild chronic respiratory acidosis (see above), the only simple acid-base disorder that can fully compensate, i.e., return the pH value to normal. However, this will usually occur only if the condition has been present for roughly seven to 14 days (12). From this we can appreciate that “chronic respiratory alkalosis” with a plasma [HCO1 less than 12 rnr.nolJL suggests an underlying metabolic acidosis; and if the bicarbonate is greater than the lower reference limit (-23 mmollL), there is an associated metabolic alkalosis. When applying the above principles to the evaluation of blood gas values, remember that compensation of simple acid-base disorders returns the pH towards, but rarely to, normal. Thus, except in chronic respiratory alkalosis and occasionally in mild chronic respiratory acidosis, a patient who has a normal pH associated with abnormal values for both blood pco2 and plasma [HCO] will usually have a mixed acid-base disturbance.

Case Presentations Case 1 A 68-year-old woman had a cardiopulmonary arrest immediately on returning to the ward after a surgical procedure. The biochemical parameters shown in Table 1 are those of an arterial blood sample taken approximately five minutes after the catastrophe. Diagnosis: Combined respiratory and metabolic acidosis. Comment: This acid-base disturbance is easily recognized: the high pco2 indicates a respiratory acidosis and the low blood [HCOI signifies a metabolic acidosis. The respiratory acidosis is due to respiratory arrest and circulatory collapse (decreased pulmonary ventilation and perfusion), and the metabolic acidosis is a consequence of the associated tissue anoxia, i.e., anaerobic glycolysis, with excessive production of peripheral lactic acid.

Case 2 The blood and plasma analyte values shown in the second column of Table 1 are those of a 60-year-old woman admit-

Table 1. Values for Plasma and Blood Analytes In Seven Cases Caeea 1 Blood gases pH H, nmol/L

Ao2’ mmHg Po2 mmHg HCO3,

mmol/L

6.85 141 82 21 14

2

3

4

5

6

7.64

7.42 38 87 63 55

7.43 37 20

7.41 40 32 88 19

7.58 26

23 32 72 33

105 13

7

Reference range 7.35-7.45 35-45 35-45

21 154 19

80-110 22-32

Plasma analytes, mmol/L

Na 2.1

2.6

2.7

C1 12

HCO

Urea Creatinine

Anion gap Glucose Lactate

24

23

34 88

127 5.2 79 20 50.5 0.38 33

144 5.0 114 10 55.0 0.76 25

132-144 3.2-4.8 93-108 23-33 3.0-8.0 0.06-0.12 7-17 3.0-5.5 >2

12 + Ketones absent Diagnoses:(1) mixedrespiratory and metabolicacidosis;(2) mixedrespiratoryand metabolic alkalosis; (3) mixed respiratory acidosis and metabolic alkalosis; (4) mixed respiratory alkalosis and metabolic acidosis; (5) mixed metabolic alkalosis and metabolicacidosis;(6) triple disorder: respiratory alkalosis, metabolic

acidosis, and metabolic alkalosis; (7) mixed hyperchioremic and high anion-gap acidosis.

ted to hospital with lobar pneumonia. She had been taking thiazide diuretics over the previous six months for congestive cardiac failure. Diagnosis: Mixed respiratory and metabolic alkalosis. Comment: In this patient the respiratory alkalosis is due to hyperventilation consequent to lobar pneumonia; the metabolic alkalosis can be attributed to the thiazide-induced hypokalemia. Although her blood [HCO] is only slightly above the upper reference interval, before the onset of the metabolic alkalosis it would have been several millimoles per liter lower, given that respiratory alkalosis (chronic and acute) is associated with a compensatory decrease in the plasma bicarbonate.

Case 3 The third column of Table 1 details the blood analyte values for a 55-year-old man with chronic emphysema. He also had right-heart failure, for which he had been treated with thiazide diuretics. Diagnosis: Mixed respiratory acidosis and metabolic alkalosis. Comment: The high pco2 in this patient indicates a respiratory acidosis; the high bicarbonate, metabolic alkalosis. The pH suggests complete compensation of either a primary respiratory acidosis or a primary metabolic alkalosis, but either is unlikely for the following reasons: #{149} Of the simple acid-base disorders, only chronic respiratory alkalosis and mild respiratory acidosis (Pco2