Physiological Approach to Assessment of Acid-Base Disturbances
2014年10月09日
In certain cases, normal values for concentrations of bicarbonate, PaCO2, and pH do not ensure the absence of an acid-base disturbance. An increase in the anion gap of more than 5 mmol per liter may then be the only clue to an underlying mixed acid-base disorder.9,71 Because the individual anion gap and concentration of bicarbonate before the acid-base disorder are usually not the concentration of bicarbonate are wide, the △AG - △[HCO3-] remains an approximation.70,71
CONSIDERATION OF THE SERUM ( OR PLASMA ) OSMOLAL GAP
The fifth step in the evaluation of an acid-base disturbance is to note the serum osmolal gap in any patient with an unexplained high anion-gap acidosis, coma, or suspicion of ingestion of a (toxic ) alcohol and in hospitalized patients with an increased risk of iatrogenic propylene glycol intoxication (e.g., because of high-dose lorazepam administration in sedated patients in an intensive care unit ).72-76 Laboratory confirmation of toxic alcohol ingestion is generally not rapidly available, and physicians must infer such a diagnosis by considering disorders that may necessitate immediate treatment. The osmolal gap is the difference between measured serum osmolality and calculated serum osmolality. The serum osmolality is calculated as 2 ( [Na+][ in millimoles per liter ]) + ( glucose [ in milligrams per deciliter ]) /18 + (BUN [ in milligrams per deciliter ])/2.8.
If ethanol is involved, the result of this calculation would be added to the amount of ethanol ( in milligrams per deciliter ) divided by 3.7. An osmolal gap below 10 mOsm per kilogram is considered to be normal, but the normal range in the general population is large ( -10 to 10 mOsm per liter ).73,74 In ethylene glycol and methanol intoxication, the osmolal gap will be high shortly after ingestion, but substantial amounts of acids will not be generated for several hours.72-76 Symptoms are considerably delayed by simultaneous ethanol ingestion because of competition for the enzyme alcohol dehydrogenase.74-76
The use of the osmolal gap has some pitfalls. The wide normal range of the osmolal gap in the general population renders the test rather insensitive to small but potentially toxic concentration of ethylene glycol and methanol.74 In addition, the osmolal gap lacks specificity, given that it may also be moderately elevated in other clinical situations such as lactic acidosis, alcoholic ketoacidosis, and diabetic ketoacidosis.74
EVALUATION OF THE RESPIRATORY COMPONENT OF AN ACID-BASE DISORDER
The respiratory component of an acid-base disorder can be determined by differentiating between acute and chronic respiratory acid-base disorders with the use of clinical information and calculations ( Table 1 ) and the oxygenation level. Hypoxemia, a major cause of lactic acidosis, may induce respiratory alkalosis. Evalution of the partial pressure of arterial oxygen ( PaO2 ) relative to ventilation, with the alveolar-arterial oxygen-tension diference ( hereafter called the alveolar-arterial difference ) taken into account, may distinguish pulmonary from extrapulmonary diseases. Tha difference in the partial oxygen pressures between the alveolar and arterial side of the alveolar-capillary membrane will be high if the patient has associated lung disease ( Table 3 ).77,78 The PaO2 in the alveolus is not equal to that in the pulmonary circulation because physiological hypoventilation occurs in various portions of the lung; therefore, the
alveolar-arterial difference will be about 5 to 10 mmHg in helthy young persons and 15 to 20
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Physiological Approach to Assessment of Acid-Base Disturbances
2014年10月09日
mmHg not healthy elderly persons. The alveolar-arterial difference is calculated as FiO2 × ( barometric pressure – water – vapor pressure ) – PaO2 – ( PaCO2 ÷ gas – exchange ratio ). The fraction of inspired oxygen ( FiO2 ) is 0.21 in ambient air, the barometric pressure is 760 mmHg at sea level, and the water-vapor pressure is 47 mmHg at 37℃, the alveolar-arterial
difference can be estimated77,78 as FiO2 × ( 760 – 47 ) – PaO2 – (PaCO2 ÷ 0.8) or 150 – PaO2 – 1.25 PaCO2.
INTERPRETATION OF ACID-BASE DISORDERS IN THE CLINICAL CONTEXT
The final step in evaluating acid-base disorders is to determine the cause of the identified processes. The evaluation of the laboratory data must fit with the clinical presentation of the patient ( see Three Case Examples ). The stepwise approach described here can be helpful in assessing acid-base disorders, but one should always check for other information to support the diagnosis, such as a lactate gap in ethylene glycol intoxication79 (see the Supplementary Appendix, available with the full text of this article at NEJM.org ) or an oxygen-saturation gap in carbon monoxide, methemoglobinemia, or cyanide intoxication,80
CONCLUSIONS
Currently , there is no ideal method of assessing acid-base disturbances. The two other widely practiced methods also have limitations. The physicochemical ( strong ion or Stewart22,57,81) approach is complex and often requires cumbersome calculations that cannot be per formed at the beside. Many clinicians think that it does not provide a diagnostic or prognostic
advantage33,42,81 and that the large number of parameters used in calculations will increase the magnitude of variability and error.26 The standard base-excess method accurately quantifies the change in metabolic acid-base ststus in vivo and is conveniently provided by the blood-gas machine.82 However, “mixed” acid-base disorders will not be detected42 by that method without the use of elaborate base-excess partitioning.34,52,53 Therefore, in our view, the physiological approach, considered here, remains the simplest, most rigorous, and most serviceable approach to the assessment of acid-base disorders.42
THREE CASE EXAMPLES
Patient 1, a 22-year-old woman WHO had been injured in an accident, received 6 liters of isotonic saline, after which the level of sodium was 135 mmol per liter, potassium 3.8 mmol per liter, chloride 115 mmol per liter, and bicarbonate 18 mmol per liter. The arterial blood pH was 7.28, and the PaCO2 was 39 mmHg. The urinary sodium level was 65 mmol per liter, potassium 15 mmol per liter, and chloride 110 mmol per liter.
This patient had a low anion-gap metabolic acidosis ( 2 mmol per liter ), but she also had
respiratory acidosis, because the expected PaCO2 is lower ( 1.5 × bicarbonate＋8 ± 2 mmHg ＝ 35 ± 2 mmHg ). If these findings are the alveolar-arterial O2 difference could be normal, assuming no underlying lung pathology. The majority of patients with a normal anion-gap metabolic
acidosis have diarrhea and renal tubular acidosis. The high chloride content of saline normalizes the anion gap because of the concomitant decrease in the level of bicarbonate. The low anion gap is probably the result of a low albumin level because of bleeding and dilution. The urinary
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Physiological Approach to Assessment of Acid-Base Disturbances
2014年10月09日
anion gap ( [Na]＋[K] – [Cl– ] ) was negative ( – 30 mmol per liter ) because of the use of saline. It would have been positive in a patient with renal tubular acidosis type 1 or 4.
Patient 2, a 50-year-old woman with a recent onset of hypertension, the level of sodium was 150 mmol per liter, potassium 2.2 mmol per liter, chloride 103 mmol per liter, and bicarbonate 32 mmol per liter. The arterial blood pH was 7.50, and the PaCO2 was 43 mmHg.
This patient was found to have an aldosterone-secreting adrenal adenoma. In a patient with
metabolic alkalosis and hypokalemia, the clinician should always rule out vomiting and the use of diuretics before considering a renin-aldosterone problem. Vomiting should lead to a chloride level below 10 mmol per liter in the urine, whereas an aldosterone-secreting tumor should lead to a urinary choride level greater than 40 mmol per liter. 63 The expected PaCO2 would be 40＋0.7×△bicarbonate ions = 40＋0.7×(32-24)=45.7 mmHg, which is only marginally higher than the value in the patient.
Patient 3, a previously healthy 22-year-old man, developed large volumes of watery diarrhea from infectious gastroenteritis. Laboratory tests revealed a plasma sodium concentration of 140 mmol per liter, potassium 3.0 mmol per liter, chloride 86 mmol per liter, and bicarbonate 38 mmol per liter. The arterial blood pH was 7.60, and the PaCO2 was 40 mmHg.
The patient had metabolic alkalosis. The levels of pH and bicarbonate increases, but because the PaCO2 did not increase, the patient also had respiratory alkalosis, perhaps because of stress or fever. The albumin-uncorrected alkalosis, perhaps because of stress or fever. The
albumin-uncorrected anion gap was 16 mmol per liter; a much higher value might be indicative of additional metabolic acidosis. Also, metabolic alkalosis, particularly that which is caused by vomiting or diuretic use, can be associated with an increment in the serum anion gap of
approximately 4 to 6 mmol per liter because of an increase of the albumin concentration and is release of protons.33 The metabolic alkalosis was the result of gastrointestinal losses.
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Disclosure forms provided by the author are available with the full text of this artile at NEJM.org. No potential conflict of interest relevant to this article was reported.
SOURCE INFORMATION
From the Department of Internal Medicine, St.Elisabeth Hospital , Willemstad, Curacao ( K.B.); and the Division of Nephrology, Department of Medicine, Leiden University Medical Cental, and Leiden University, Leiden (A.P.J.V.), and the Department of Internal Medicine, University of
Groningen, University Medical Center Groningen,Groningen (R.O.B.G.) – both in the Netherlands. Address reprint requests to Dr.Berand at the Department of Internal Medicine,St.Elisabeth Hospital, Breedestraat 193, Willernstad, Curacao, or at kenber2@me.com.
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