Abstract
Acid-base disorders are manifestations of underlying pathology and also very helpful clues regarding a patient’s likely differential diagnoses. When severe, acid-base derangements can themselves have deleterious effects. These disorders fall into four broad categories: metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis. The metabolic acidoses can be subdivided into high anion gap and normal anion gap (or hyperchloremic) forms. The metabolic alkaloses can be subdivided into types that respond, or do not respond, to the administration of sodium chloride (or volume expansion). The respiratory acidoses and respiratory alkaloses are subdivided into acute and chronic forms of these disorders. All acid-base disorders generate compensatory responses that ameliorate the pH derangement. Mixed acid-base disorders exist when two or more primary disturbances occur sequentially or simultaneously.
Keywords
Acid-base, Anion gap, Acidosis, Alkalosis
Acid-base disorders can have major clinical and diagnostic implications. If they generate extreme acidemia or alkalemia, the abnormal pH itself may result in pathophysiologic consequences. For example, the tertiary structure of proteins is altered by extreme pH conditions, potentially affecting the activity of enzymes and ion transport systems. Consequently, every metabolic pathway may be impacted by acidemia or alkalemia. In addition, extreme acidemia can depress cardiac function, impair the vascular response to catecholamines, and cause arteriolar vasodilation and venoconstriction, with resultant systemic hypotension and pulmonary edema. Insulin resistance, reduced hepatic lactate uptake, and accelerated protein catabolism are other effects of acidemia. Alkalemia can generate cardiac arrhythmias, produce neuromuscular irritability, and contribute to tissue hypoxemia. In alkalemic patients, cerebral and myocardial blood flow falls, and respiratory depression occurs. Potassium disorders, a common accompaniment of acid-base perturbations, also contribute to the morbidity.
Although mild and moderate acid-base disorders may not directly affect physiologic function, the identification of such disorders may be an important diagnostic clue to the existence of serious medical conditions. Whenever an acid-base disorder is identified, the underlying cause should be sought. This diagnostic imperative often overrides the importance of any therapeutic intervention directed at the pH itself. The situation is analogous to the discovery of fever or hypothermia. Although very high or very low temperatures can themselves be dangerous and require aggressive therapy directed at restoration of a more normal temperature, often more important is the effort to identify and treat the underlying cause of the abnormal temperature. Similarly, the recognition of an acid-base disorder must generate a search for its clinical cause or causes, and recognition of a mixed acid-base disorder should trigger an investigation to determine the etiology of each component.
The acid-base status of the extracellular fluid (ECF) is carefully regulated to maintain the arterial pH in a narrow range between 7.36 and 7.44 (hydrogen ion concentration [H + ] 44 to 36 nEq/L). The pH is stabilized by multiple buffer systems in the ECF, cells, and bone. The CO 2 tension (pCO 2 ), primarily under neurorespiratory control, and the serum bicarbonate concentration ([ 
]), primarily under renal/metabolic regulation, are the most important variables in this complex system of buffers.
Currently three different methodologic approaches are widely used to describe normal acid-base status and simple and mixed acid-base disorders.
- 1.
The physiologic method uses measurements of arterial pH, pCO 2 , and [
], together with an analysis of the anion gap (AG) and a set of compensation rules.
- 2.
The base excess (BE) method uses measurements of arterial pH and pCO 2 , and calculation of the BE and the AG.
- 3.
The physicochemical method uses measurements of arterial pH and pCO 2 together with the calculated apparent (SIDa) and effective (SIDe) “Strong Ion Difference,” the “Strong Ion Gap” (SIG = SIDa − SIDe), and the total concentration of plasma weak acids (Atot).
Each of these approaches can be effectively used to characterize acid-base disorders, each has its vocal proponents and detractors, and each has certain unique characteristics that may be particularly helpful under certain conditions. We believe the physiologic method is the most straightforward and the easiest model to understand and use. It is generally acceptable in most clinical circumstances and will be the method we use in this chapter.
The physiologic method to the elucidation of acid-base disorders uses the following information:
- 1.
Recognition of diagnostic clues provided by the patient’s history and physical examination
- 2.
Analysis of the serum [
], arterial pH, and pCO 2 (Although a blood gas analysis is not always necessary to make a diagnosis, it is generally required for complicated cases.)
- 3.
Knowledge of the predicted compensatory response to simple acid-base disorders
- 4.
Calculation of the AG, with consideration of the expected “baseline” AG for each patient
- 5.
Analysis of the degree of change (Δ) in AG and the degree of Δ in [
] to see if the magnitude of these respective changes is reciprocal. This has been dubbed the Delta/Delta or 
.
Acidemia, Alkalemia, Acidosis, and Alkalosis
The normal arterial blood pH range is between 7.36 and 7.44 ([H + ] between 44 and 36 nEq/L). Acidemia is defined as an arterial pH <7.36 ([H + ] >44 nEq/L) and may result from a primary elevation in pCO 2 , a fall in [ 
], or both. Alkalemia is defined as an arterial pH >7.44 ([H + ] <36 nEq/L). Alkalemia may result from a primary increase in [ 
], a fall in pCO 2 , or both.
The relationship among pH, pCO 2 , and 
concentrations is described by the familiar Henderson-Hasselbalch equation:
pH = 6.1 + log ( [ HCO 3 − − ] / ( 0.03 × pCO 2 ) ) .
Acidosis and alkalosis are pathophysiologic processes that, if unopposed by therapy or complicating disorders, would cause acidemia or alkalemia, respectively.
Simple (Single) Acid-Base Disturbances and Compensation
The simple acid-base disorders are divided into primary metabolic and primary respiratory disturbances. Each of these simple, or single, acid-base disorders generates a compensatory response that acts to return the blood pH back toward the normal range. By convention, the physiologic approach to acid-base analysis considers the compensatory response to a simple acid-base disorder to be an integral component of that disorder. Hence there are four primary simple acid-base disturbances (six if each respiratory disorder is divided into an acute and chronic phase):
- •
Metabolic acidosis: The underlying pathophysiology tends to reduce the serum bicarbonate concentration [
]. Although we refer to serum bicarbonate here, it is often directly measured as total CO 2 , which includes bicarbonate ( 
), carbonic acid (H 2 CO 3 ), and dissolved CO 2 . The latter two components account for a very small fraction of the total (roughly 1.2 mEq/L at normal pCO 2 ). Therefore, for clinical purposes, total CO 2 is equated to serum bicarbonate concentration. Causes include excess generation of metabolic acids, excessive exogenous acid intake, reduced kidney excretion of acid, or excessive exogenous loss of 
(usually in stool or urine). Metabolic acidosis reduces the arterial plasma pH and generates a hyperventilatory compensatory response, which reduces the arterial pCO 2 and blunts the degree of acidemia.
- •
Metabolic alkalosis: The underlying pathophysiology tends to increase the [
]. Causes include exogenous intake of 
salts (or salts that can be converted to 
) and/or endogenous generation of 
. Regardless of the origin of the 
, the pathology must also include reduced or impaired renal 
excretion. Metabolic alkalosis increases the arterial plasma pH and generates a hypoventilatory compensatory response, which increases the arterial pCO 2 and blunts the degree of alkalemia.
- •
Respiratory acidosis: The underlying pathophysiology tends to increase the arterial pCO 2 . The compensatory response is an increase of the plasma [
] due to rapid generation from buffers and, over a period of days, renal 
generation and retention.
- •
Respiratory alkalosis: The underlying pathophysiology tends to decrease the arterial pCO 2 . The compensatory response reduces the plasma [
]. This occurs acutely as H + is released from buffers and chronically, over a period of days, as the kidneys excrete 
and/or retain acid.
The magnitude of each compensatory response is proportional to the severity of the primary disturbance. Generally, respiratory responses to primary metabolic acid-base disorders occur rapidly (within an hour) and are fully developed within 12 to 36 hours. In contrast, the compensatory metabolic alterations triggered by the primary respiratory disorders are divided into two phases. A chemical buffering response occurs within minutes (acute), whereas the quantitatively more significant kidney response takes several days (chronic) to develop fully. Hence each primary respiratory disorder is subdivided into an acute and a chronic disorder to differentiate the expected compensatory response.
The expected degree of compensation for each simple disorder has been determined by studying patients with isolated simple disorders and normal subjects with experimentally induced acid-base disorders. These data have been used to create various graphic acid-base nomograms, simple mathematical relationships, and a number of mnemonic methods for predicting expected compensation ranges. Fig. 12.1 and Table 12.1 provide some of these “compensation rules.” Appropriate compensation should generally be present in all patients with an acid-base disorder, and when it is not identified, a complex, or mixed, acid-base disorder must be considered.
