JPPT REVIEW ARTICLE The ABC’s of Acid-Base Balance Gordon S. Sacks, PharmD The University of Wisconsin—Madison, Madison, Wisconsin A step-wise systematic approach can be used to determine the etiology and proper management of acid-base disorders. The objectives of this article are to: (1) discuss the physiologic processes in- volved in acid-base disturbances, (2) identify primary and secondary acid-base disturbances based upon arterial blood gas and laboratory measurements, (3) utilize the anion gap for diagnostic pur- poses, and (4) outline a stepwise approach for interpretation and treatment of acid-base disorders. Case studies are used to illustrate the application of the discussed systematic approach. KEYWORDS: acid-base J Pediatr Pharmacol Ther 2004;9:235-42 Although acid-base disorders are frequently terms of H+, but due to confusing terminology it encountered in hospital and ambulatory care set- was proposed to convert H+ terminology to pH.1 tings, they are often considered the most difficult When taking the negative logarithm of the H+ areas to understand in medicine. Misdiagnosis due to common misconceptions of acid-base ho- ABBREVIATIONS: AG, Anion gap; HCO3, Bicarbonate; CNS, meostasis often delays identification of the pri- Central nervous system; ECF, Extracellular fluid; Hgb, Hemoglobin; ICU, Intensive care unit; THAM, Tromethamine mary disorder, causing a disruption in the deliv- ery of appropriate therapy. By understanding the concentration, pH represents a measure of H+ basic principles of acid-base physiology, the inter- activity. Optimal function for tissues and organs pretation of acid-base data, and the mechanisms within the human body depends on maintaining responsible for acid-base perturbations, the clini- blood pH between 7.10 and 7.60. For purposes of cian should be able to recognize all acid-base dis- diagnosis, the generally accepted range of normal- orders and develop a systematic approach for the ity is pH 7.36 to 7.44. Any pH less than 7.36 is called management of such disorders. acidemia and any pH greater than 7.44 is called alkalemia. Acidemia refers to the acid condition of BACKGROUND the blood (pH < 7.36), whereas acidosis is the pro- cess by which a patient develops acidemia. The same In order to identify acid-base abnormalities and is true for alkalemia and alkalosis.2 develop a treatment plan, it is necessary to first When an acid-base disorder occurs, the body comprehend the mechanisms responsible for attenuates this physiologic change by making ad- acid-base equilibrium. An acid is defined as a sub- justments through a compensatory mechanism. + stance that can donate a hydrogen ion (H ), Compensation refers to a change of the pH to- whereas a base is a substance that can accept an ward normal. When there is a shift in H+, the body + H . The acidity of body fluids can be expressed in may respond by three different mechanisms: chemical buffering, respiratory compensation, or Address correspondence to: Gordon S. Sacks, 2 PharmD, The University of Wisconsin, 777 Highland renal compensation. The most immediate re- + Avenue, Room 1037 Madison, WI 53705-2222, e-mail: sponse to rapid changes in body H is by chemi- [email protected] cal buffering with intracellular and extracellular © 2004 Pediatric Pharmacy Advocacy Group buffers. Buffers are agents that minimize the abil- J Pediatr Pharmacol Ther 2004 Vol. 9 No. 4 • www.ppag.org 235 JPPT Sacks GS ity of acids and bases to alter pH when added to a Table 1. Normal Blood Gas Values system. Major extracellular buffers in the human Arterial Blood Venous Blood body include bicarbonate (HCO ), hemoglobin 3 pH* 7.40 (7.35–7.45) 7.36 (7.33–7.43) (Hgb) and certain proteins, and phosphates. In- PO † 80–100 mm Hg 35–40 mm Hg tracellular buffering involves H+ entering the cell 2 PCO ‡ 35–45 mm Hg 41–51 mm Hg in exchange for potassium and sodium. Respira- 2 HCO § 22–26 mEq/L 24–28 mEq/L tion is a second line of defense that acts to re- 3 || O saturation 95% 70% - 75% store the ratio of acid to base by altering the 2 > Base excess¶ –2 to +20 to +4 amount of CO2 gas in the body. The amount of CO CO2 gas in the body is typically referred to as P 2, *pH = identifies the presence of acidemia or alkalemia. †PO pressure exerted by oxygen dissolved in the plasma. which represents the pressure exerted by dissolved 2 = ‡PCO = pressure of dissolved CO gas in the blood. CO gas in the blood. Although CO is produced 2 2 2 2 §HCO3 = bicrobanate. in cells, it diffuses into the plasma to combine with ||O2 saturation = percentage of oxygen that hemoglobin is carrying water to form carbonic acid (H CO ). Thus, it is related to the total amount the hemoglobin could carry. 2 3 ¶Base excess = primarily reflects the concentration of bicarbonate CO helpful to consider P 2 as an acidic substance that and is affected only by metabolic processes; positive values reflect is only controlled by the respiratory system. metabolic alkalosis and negative values reflect metabolic acidosis. Changes in the rate and depth of breathing can Table 1 lists the parameters and normal values be used to adjust the pH of body fluids. For ex- commonly reported in an arterial blood gas ample, in the presence of acidemia the body may (ABG). Acid-base disturbances are typically clas- respond by increasing ventilation and thereby sified according to the cause, resulting in an aci- removing excess CO . Ventilation rate can change 2 dosis (pH < 7.35) or an alkalosis (pH > 7.45). The PCO and pH of blood in a matter of minutes, with 2 causes are either respiratory in nature due to maximal compensation being achieved within 12 changes in breathing rate and pattern or meta- to 24 hours. The kidneys are the final buffering bolic as a result of an accumulation of fixed acids system and can affect blood pH by reabsorbing (e.g., ketones) or excessive loss of bicarbonate HCO , by allowing excess H+ to be excreted in the 3 (e.g., pancreatic fluid). The best method to accu- urine, and by generating new HCO via acid se- 3 rately and consistently identify the etiology for cretion. Bicarbonate is considered a base, and it acid-base disturbances is to employ a systematic, reflects a metabolic process (versus a respiratory stepwise approach. Five simple steps can be used process) that is only affected by the kidneys. The to identify the primary acid-base disorder and the time required for the kidneys to compensate is body’s attempt to compensate.3 This approach is slow, requiring several hours to change the extra- summarized in Table 2. cellular fluid volume compartment and 5-7 days to achieve maximal compensation. 1. Evaluate the pH First evaluate the ABG to determine the pres- Interpretation of Arterial Blood Gases ence of acidemia or alkalemia. A normal pH is any value between 7.35 and 7.45. Any value < 7.35 In order to most precisely evaluate acid-base indicates acidemia, while a value > 7.45 represents status, an arterial (instead of venous) blood gas is alkalemia. A normal pH may reflect a normal usually preferred. Arterial blood represents a mix- blood gas, or, alternatively, the presence of full ture of blood from various parts of the body com- CO compensation in which the P 2 and HCO3 will pared to venous blood obtained from an extrem- be outside the normal ranges. ity which reveals information primarily about that extremity. Arterial blood also identifies the abil- 2. Identify the primary process: respiratory or ity of the lungs to oxygenate the blood. Mixed metabolic venous blood samples can yield information about CO Normal P 2 is any value between 35 and 45 mm tissue oxygenation, but cannot determine the con- CO Hg. It is important not to confuse P 2 (mm Hg) in tribution of the heart versus lungs. Thus, normal the ABG report with CO2 (mEq/L) in the serum arterial oxygenation confirms normal lung func- electrolyte report. “CO2” is reported on the serum tion, but low oxygen concentration in mixed electrolyte report in mEq/L and represents total venous blood could indicate that the heart, lungs, CO2, which is a combination of HCO3 and dissolved or both are failing. CO2/H2CO3 in the blood. Since CO2/H2CO3 are 236 J Pediatr Pharmacol Ther 2004 Vol. 9 No. 4 • www.ppag.org The ABC’s of Acid-Base Balance JPPT Table 2. Systematic Approach to Arterial Blood Gas crease in HCO . When the AG is > 14 mEq/L, 3 3 Interpretation this indicates that the presence of a metabolic 1. Evaluate the pH to determine the presence of acidemia or acidosis should be investigated. The AG does have alkalemia. limitations, though, and a normal AG does not 2. Determine whether the primary process is respiratory or metabolic. exclude the possibility of the accumulation of 3. Calculate the “gaps.” unmeasured anions. Yet, when the AG exceeds 4. Check for the degree of compensation. 25 mEq/L, a metabolic acidosis is always present. 5. Determine whether there is a 1:1 relationship between anions in the blood. 4. Always check for the degree of compensation The human body has compensatory mecha- only a small fraction of the total CO2 in a serum nisms for returning the abnormal pH toward nor- sample, total CO2 is considered equal to HCO3. mal. During compensation, the component NOT CO If alkalemia is present and the P 2 is less than involved in the primary disorder is adjusted in an 35 mm Hg, then the primary disorder is respira- effort to correct the pH.