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The lack of a clear understanding and precise use of the terminology of acid–base disorders often leads to confusion and error. The following definitions provide the appropriate frame of reference for the remainder of the chapter and this textbook.
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Whereas the terms acidosis and alkalosis refer to processes that tend to change pH in a given direction, acidemia and alkalemia only refer to the actual pH. By definition, a patient is said to have:
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A metabolic acidosis if the arterial pH is less than 7.40 and serum bicarbonate concentration ([HCO3−]) is less than 24 mEq/L. Because acidemia stimulates ventilation (respiratory compensation), metabolic acidosis is usually accompanied by a PCO2 less than 40 mm Hg.
A metabolic alkalosis if the arterial pH is greater than 7.40 and serum [HCO3−] is greater than 24 mEq/L. Because alkalemia inhibits ventilation (respiratory compensation), metabolic alkalosis is usually accompanied by a PCO2 greater than 40 mm Hg.
A respiratory acidosis if the arterial pH is less than 7.40 and partial pressure of carbon dioxide (PCO2) is greater than 40 mm Hg. Because an elevated PCO2 stimulates renal acid excretion and the generation of HCO3− (renal compensation), respiratory acidosis is usually accompanied by a serum [HCO3−] greater than 24 mEq/L.
A respiratory alkalosis if the arterial pH is greater than 7.40 and PCO2 is less than 40 mm Hg. Because a decreased PCO2 decreases renal net acid excretion and increases the excretion of HCO3− (renal compensation), respiratory alkalosis is usually accompanied by a serum [HCO3−] less than 24 mEq/L.
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It is important to note that under most circumstances, a venous pH permits an approximation of arterial pH (see Chap. 29 for a further discussion of the relationship between arterial and venous pH). Any combination of acidoses and alkaloses can be present in any one patient at any given time. The terms acidemia and alkalemia refer only to the resultant arterial pH of blood (acidemia referring to a pH <7.40 and alkalemia referring to a pH >7.40). These terms do not describe the processes that led to the alteration in pH. Thus, a patient with acidemia must have a primary metabolic or respiratory acidosis but may have an alkalosis present at the same time. Clues to the presence of more than one acid–base abnormality include the clinical presentation, an apparent excess or insufficient “compensation” for the primary acid–base abnormality, a delta (Δ) anion gap-to-Δ [HCO3−] ratio that significantly deviates from one, or an electrolyte abnormality that is uncharacteristic of the primary acid–base disorder.
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Determining the Primary Acid–Base Abnormality
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It is helpful to begin by determining whether the patient has an acidosis or an alkalosis. This is followed by an assessment of the pH, PCO2, and [HCO3−]. With these three parameters defined, the patient’s primary acid–base disorder can be classified using the aforementioned definitions. Next it is important to determine whether the compensation of the primary acid–base disorder is appropriate. It is generally assumed that overcompensation cannot occur.97 That is, if the primary process is metabolic acidosis, respiratory compensation tends to raise the pH toward normal but never to greater than 7.40. If the primary process is respiratory alkalosis, compensatory renal excretion of HCO3− tends to lower the pH toward normal but not to less than 7.40. The same is true for primary metabolic alkalosis and primary respiratory acidosis. As a rule, compensation for a primary acid–base disorder that is inadequate or excessive is indicative of the presence of a second primary acid–base disorder.
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Based on patient data, the Winters equation (Equation 19–1)7 predicts the degree of the respiratory compensation (the decrease in PCO2) in metabolic acidosis as follows:
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(Eq. 19–1)PCO2 = (1.5 × [HCO3–]) + 8 ± 2
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Thus, in a patient with an arterial [HCO3−] of 12 mEq/L, the predicted PCO2 may be calculated as
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If the actual PCO2 is substantially lower than is predicted by the Winters equation, it can be concluded that both a primary metabolic acidosis and a primary respiratory alkalosis are present. If the PCO2 is substantially higher than the predicted value, then both a primary metabolic acidosis and a primary respiratory acidosis are present.
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An alternative to the Winters equation is the observation by Narins and Emmett that in compensated metabolic acidosis, the arterial PCO2 is usually the same as the last two digits of the arterial pH.97 For example, a pH of 7.26 predicts a PCO2 of 26 mm Hg.
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Guidelines are also available to predict the compensation for metabolic alkalosis,56 respiratory acidosis, and respiratory alkalosis.74 Patients with a metabolic alkalosis compensate by hypoventilating, resulting in an increase of their PCO2 above 40 mm Hg. However, the concomitant development of hypoxemia limits this compensation so that respiratory compensation in the presence of a metabolic alkalosis usually results in a PCO2 of 55 mm Hg or less. It is difficult to be more accurate about the expected respiratory compensation for a metabolic alkalosis, although the compensation, as in the case of metabolic acidosis, is nearly complete within hours of onset.
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By contrast, the degree of compensation in primary respiratory disorders depends on the length of time the disorder has been present. In a matter of minutes, primary respiratory acidosis results in an increase in the serum [HCO3−] of 0.1 times the increase (Δ) in the PCO2. This increase is a result of the production and dissociation of H2CO3. Over a period of days, respiratory acidosis causes the compensatory renal excretion of acid. This compensation increases the serum [HCO3−] by 0.3 times the ΔPCO2. Primary respiratory alkalosis acutely decreases the serum [HCO3−] by 0.2 times the ΔPCO2. If a respiratory alkalosis persists for several days, renal compensation, by the urinary excretion of HCO3−, decreases the serum [HCO3−] by 0.4 times the ΔPCO2.
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Calculating the Anion Gap
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The concept of the anion gap is said to have arisen from the “Gamblegram” originally described in 1939;44 however, its use was not popularized until the determination of serum electrolytes became routinely available. The law of electroneutrality states that the net positive and negative charges of all fluids must be equal. Thus, all of the negative charges present in the serum must equal all of the positive charges, and the sum of the positive charges minus the sum of the negative charges must equal zero. The problem that immediately arose (and produced an “anion gap”) was that all charged species in the serum were not routinely measured.
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Normally present but not routinely measured cations include calcium and magnesium; normally present but not routinely measured anions include phosphate, sulfate, albumin, and organic anions (eg, lactate and pyruvate).36 Whereas Na+ and K+ normally account for 95% of extracellular cations, Cl− and HCO3− account for 85% of extracellular anions. Thus, because more cations than anions are among the electrolytes usually measured, subtracting the anions from the cations normally yields a positive number, known as the anion gap. The anion gap is therefore derived as shown in Equation 19–2:
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(Eq. 19–2)[Na+] + [K+] + [Unmeasured Cations (Uc)] = [Cl−] + [HCO3−] + [Unmeasured Anions (Ua)] Anion Gap = [Ua] − [Uc] or Anion Gap = ([Na+] + [K+]) − ([Cl−] + [HCO3−])
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Because the serum [K+] varies over a limited range of perhaps 1–2 mEq/L above and below normal and therefore rarely significantly alters the anion gap, it is often deleted from the equation for simplicity. Most prefer this approach, yielding Equation 19–3:
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(Eq. 19–3)Anion Gap = ([Na+]) − ([Cl−] + [HCO3−])
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Using Equation 19–3, the normal anion gap was initially determined to be 12 ± 4 mEq/L.36 However, because the normal serum [Cl−] is higher on modern laboratory instrumentation, the current range for a normal anion gap is 7 ± 4 mEq/L.138
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A variety of pathologic conditions may result in a rise or fall of the anion gap. High anion gaps result from increased presence of unmeasured anions or decreased presence of unmeasured cations (Table 19–1).36,80 Conversely, a low anion gap results from an increase in unmeasured cations or a decrease in unmeasured anions (Table 19–2).36,42,52,119
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Anion Gap Reliability
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Several authors have considered the usefulness of the anion gap determination.19,43,64 When 57 hospitalized patients were studied to determine the cause of elevated anion gaps in patients whose anion gap was greater than 30 mEq/L, the cause was always a metabolic acidosis with elevated lactate or ketoacidosis.43 In patients with smaller elevations of the anion gap, the ability to define the cause of the elevation diminished; in only 14% of patients with anion gaps of 17 to 19 mEq/L could the cause be determined. Another study determined that although the anion gap is often used as a screening test for hyperlactatemia (as a sign of poor perfusion), only patients with the highest serum lactate concentrations had elevated anion gaps.64 Finally, in a sample of 571 patients, those with greater elevations in anion gaps tended to have more severe illness. This logically correlated with higher admission rates, a greater percentage of admissions to intensive care units, and a higher mortality rate.19 Thus, although the absence of an increased anion gap does not exclude significant illness, a very elevated anion gap can generally be attributed to a specific cause (typically lactate or ketones) and usually indicates a relatively severe illness.
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After the diagnosis of metabolic acidosis is established by finding an arterial pH less than 7.40, [HCO3−] <24 mEq/L, and PCO2 < 40 mm Hg, the serum anion gap should be analyzed. Indeed, the popularity of the anion gap is primarily based on its usefulness in categorizing metabolic acidosis as being of the high anion gap or normal anion gap type. This determination should be made after correcting the anion gap for the effect of hypoalbuminemia, a common and important confounding factor in sick patients. The anion gap decreases approximately 3 mEq/L per 1-g/dL decrease in the serum [albumin].41 In general, the electrolyte abnormalities that frequently accompany metabolic acidosis usually have only small and insignificant effects on the anion gap.
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It should be noted that although many clinicians rely on the mnemonics MUDPILES (M, methanol; U, uremia; D, diabetic ketoacidosis; P, paraldehyde; I, iron; L, lactic acidosis; E, ethylene glycol; and S, salicylates) or KULT (K, ketones; U, uremia; L, lactate; T, toxins), to help remember this differential diagnosis, these mnemonics include rarely used drugs (phenformin, paraldehyde) and omit important others (eg, metformin, cyanide).
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A high anion gap metabolic acidosis results from the absorption or generation of an acid that dissociates into an anion other than Cl− that is neither excreted nor metabolized. The retention of this “unmeasured” anion (eg, glycolate in ethylene glycol poisoning) increases the anion gap. A normal anion gap metabolic acidosis results from the absorption or generation of an acid that dissociates into H+ and Cl−. In this case, the “measured” Cl− is retained as HCO3− is titrated and its concentration reduced during the acidosis, and no increased anion gap is produced. Normal anion gap acidosis, also referred to as hyperchloremic metabolic acidosis, may be caused by intestinal or renal bicarbonate losses as in diarrhea or renal tubular acidosis, respectively. Other causes of high and normal anion gap metabolic acidoses are described elsewhere1,2 and shown in Tables 19–3 and 19–4.
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Narrowing the Differential Diagnosis of a High Anion Gap Metabolic Acidosis
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The ability to diagnose the etiology of a high anion gap metabolic acidosis is an essential skill in clinical medicine. The following discussion provides a rapid and cost-effective approach to the problem. As always, the clinical history and physical examination may provide essential clues to the diagnosis. For example, iron poisoning is virtually always associated with significant GI symptoms, the absence of which essentially excludes the diagnosis (Chap. 46). Furthermore, when iron overdose is suspected, an abdominal radiograph may show the presence of tablets. The acidosis associated with isoniazid (INH) toxicity results from seizures, the absence of which excludes INH as the cause of a metabolic acidosis (Chap. 58). Methanol poisoning may be associated with visual complaints or abnormal funduscopic examination findings (Chap. 109). Methyl salicylate has a characteristic wintergreen odor (Chap. 26). When these findings are absent, the laboratory analysis must be relied on, as follows:
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Begin with the serum electrolytes, BUN, creatinine, and glucose. A rapid blood glucose reagent test should be performed to help confirm or exclude hyperglycemia. Although hyperglycemia should raise the possibility of diabetic ketoacidosis, the absence of an elevated serum glucose does not exclude the possibility of euglycemic diabetic ketoacidosis,66 or alcoholic or starvation ketoacidosis, which are often associated with normal or even low serum glucose concentrations. An elevated BUN and creatinine are essential to diagnose acute or chronic kidney failure.
Proceed to the urinalysis. Do not wait for the laboratory results because all of these urinary studies are easily performed. In addition, if there is a suspicion of a high anion gap metabolic acidosis and only the arterial or venous blood gas analysis is completed, the evaluation may begin here while the electrolyte determination is pending. A urine dipstick for glucose and ketones helps with the diagnosis of diabetic ketoacidosis and other ketoacidoses. However, the absence of urinary ketones does not exclude a diagnosis of alcoholic ketoacidosis (Chap. 80), and ketones are often present in severe salicylism (Chap. 39) and biguanide-associated metabolic acidosis (Chap. 53). The urine of a patient who has ingested fluorescein-containing antifreeze (ethylene glycol) may fluoresce when exposed to a Wood lamp. Also, because ethylene glycol is metabolized to oxalate, calcium oxalate crystals may be present in the urine of a poisoned patient. Although the presence of a fluorescent urine and calcium oxalate crystals are useful findings, their absence does not exclude ethylene glycol poisoning (Chap. 109). When clinically available, a urine ferric chloride test should be performed. Although highly sensitive and specific for the presence of salicylates, this test is not specific for the diagnosis of salicylism because small amounts of salicylate will be detected in the urine even days after its last use (Chap. 39). Thus, a serum salicylate concentration must be obtained to quantify the findings of a positive urine ferric chloride test result. A negative urine ferric chloride test result essentially excludes a diagnosis of salicylism.
A blood lactate concentration can be helpful. In theory, if the lactate (measured in mEq/L) can entirely account for the fall in serum [HCO3−], then the cause of the high anion gap can be attributed to lactic acidosis. However, it is important to remember that glycolate (a metabolite of ethylene glycol) can produce a false-positive elevation of the lactate concentration with many current laboratory techniques.91,139
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When the above analysis of a high anion gap metabolic acidosis is nondiagnostic, the diagnosis is usually toxic alcohol ingestion, starvation, alcoholic ketoacidosis (with minimal urine ketones), or a multifactorial process involving small amounts of lactate and other anions. One approach is to provide the patient with 1 to 2 hours of intravenous (IV) hydration, dextrose, and thiamine. If the acidosis improves, the etiology is either ketoacidosis or metabolic acidosis with hyperlacatemia. In the absence of improvement, a more detailed search for the toxic alcohols, involving measurement of either the osmol gap or actual methanol and ethylene glycol concentrations, should be initiated (discussed later).
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The Δ Anion Gap-to-Δ[HCO3–] Ratio
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Many patients have mixed acid–base disorders such as metabolic acidosis and respiratory alkalosis. Depending on the relative effects of the acid–base disorders, the patient may have significant acidemia or alkalemia, minor alterations in pH, or even a normal pH. Although the clinical presentation, degree of compensation for the primary acid–base disorder, or the presence of unexpected electrolyte abnormalities may suggest whether more than one primary acid–base disorder is present, comparing the Δ anion gap (ΔAG) with the Δ[HCO3−] gap may be useful.
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In a patient with a simple high anion gap metabolic acidosis, each 1 mEq/L decrease in the serum [HCO3−] should (at least initially) be associated with a 1 mEq/L rise in the anion gap.97 This occurs because the unmeasured anion is paired with the acid that is titrating the HCO3−. Any deviation from this direct relationship may be an indication of a mixed acid–base disorder.53,97,102 Thus, the ratio of the change in the anion gap (ΔAG) to the deviation of the serum [HCO3−] from normal (Equation 19–4) evolved:
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(Eq. 19–4)Anion Gap Ratio = ΔAG/Δ[HCO3−]
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A ratio close to one would suggest a pure high anion gap metabolic acidosis. When the ratio is greater than one, there is a relative increase in [HCO3−] that can result only from a concomitant metabolic alkalosis or renal compensation such as renal generation of HCO3− for a respiratory acidosis. Alternatively, when the ratio is less than one, the additional presence of either hyperchloremic (normal anion gap) metabolic acidosis or compensated respiratory alkalosis is suggested. Although the usefulness of this relationship has been supported strongly by some authors,100,102 others suggest that it is often flawed and frequently misleading.30,115
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After reviewing the arguments, the statements of one author30 appear to be correct in concluding that “the exact relationship between the ΔAG and Δ[HCO3−] in a high anion gap metabolic acidosis is not readily predictable and deviation of the ΔAG/Δ[HCO3−] ratio from unity does not necessarily imply the diagnosis of a second acid–base disorder.” Regardless, very large deviations from a value of one usually are associated with the presence of a second primary acid–base disorder.
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The osmol gap, which is sometimes used to screen for toxic alcohol ingestion, is defined as the difference between the values for the measured serum osmolality and the calculated serum osmolarity. Osmolarity is a measure of the total number of particles in 1 liter of solution. Osmolality differs from osmolarity in that the number of particles is expressed per kilogram of solution. Thus, osmolarity and osmolality represent molar and molal concentrations of solutes, respectively. In clinical medicine, whereas osmolarity is usually calculated, osmolality is usually measured.
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Calculating osmolarity requires a summing of the known particles in solution. Because molarity and milliequivalents are particle-based measurements, unlike weight or concentration, the known constituents of serum have to be converted to molar values. Assumptions are required based on the extent of dissociation of polar compounds (eg, NaCl), the water content of serum, and the contributions of various other solutes such as Ca2+ and Mg2+. The nature and limitations of these assumptions are beyond the scope of this chapter. Readers are referred to several reviews for more details.59,101 Many equations have been used and evaluated for calculating serum osmolarity. One investigation that used 13 different methods to evaluate sera from 715 hospitalized patients32 concluded that Equation 19–5 provided the most accurate calculation:
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(Eq. 19–5)1.86([Na+] in mEq/L) + ([Glucose] in mg/dL/18 + ([BUN] in mg/dL/2.8)
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Obvious sources of potential error in this calculation include laboratory error in determining the measured parameters and the failure to account for a number of osmotically active particles.
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The measurement of serum osmolality has the potential for error stemming from the use of different laboratory techniques.35 It is essential to assure that the freezing point depression technique or osmometry is used because when the boiling point elevation method is used, xenobiotics with low boiling points (ethanol, isopropanol, methanol) will not be detected.
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Conceptual errors may also result. In methanol poisoning, the methanol molecule has osmotic activity that is measured but not calculated, and no increase in the anion gap is present until it is metabolized to formate. Although the metabolite also has osmotic activity, its activity is accounted for by Na+ in the osmolarity calculation because it is largely dissociated, existing as Na+ formate. Thus, shortly after a ethylene glycol ingestion, there will be an elevated osmol gap and a normal anion gap; later, the anion gap will increase, and the osmol gap will decrease. This effect is highlighted by several case reports.9,26
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Using Equation 19–5 to calculate osmolarity, it is often stated that the “normal” osmol gap is 10 ± 6 mOsm/L.32 However, when more than 300 adult samples were studied with a more commonly used equation (Eq. 19–6),
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(Eq. 19–6)2([Na+] in mEq/L) + ([Glucose] in mg/dL/18) + ([BUN] in mg/dL/2.8)
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normal values were −2 ± 6 mOsm/L.59 Almost identical results are reported in children.87
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The largest limitation of the osmol gap calculation is due to the documented large standard deviation around a small “normal” number.32,59 An error of 1 mEq/L (<1.0%) in the determination of the serum [Na+] may result in an error of 2 mOsm/L in the calculation of the osmol gap. Considering this variability, the molecular weights (MWs) and relatively modest serum concentrations of the xenobiotics in question (eg, ethylene glycol; MW, 62 Da; at a concentration of 50 mg/dL theoretically contributes only 8.1 mOsm/L) and the predicted fall in the osmol gap as metabolism occurs, small or even negative osmol gaps can never be used to exclude toxic alcohol ingestion.59 This overall concept is illustrated by an actual patient with an osmol gap of 7.2 mOsm (well within the normal range) who ultimately required hemodialysis for severe poisoning.127 An additional error may result when including ethanol in the determination of the osmol gap. When present, ethanol is osmotically active and should be included in the calculated osmolarity. In theory, because the MW of ethanol is 46 g/mol, dividing the serum ethanol concentration (in mg/dL) by 4.6 will yield the osmolar contribution in mmol/L. However, because the physical interaction of ethanol with water is complex, it may be more scientifically accurate to divide by lower numbers as the ethanol concentration increases.106 However, because the osmol gap is a screening tool, we suggest continuing to use the 4.6 divisor in an attempt to reduce clinical false-negative test results.
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Finally, although exceedingly large serum osmol gaps may be suggestive of toxic alcohol ingestions, common conditions such as alcoholic ketoacidosis, metabolic acidosis with elevated lactate, kidney failure, and shock are all associated with elevated osmol gaps.65,118,123 This may be surprising because lactate, acetoacetate, and β-hydroxybutyrate should not account for any increase in the osmol gap because they are charged (and accounted for in the osmolarity calculation). Apparently, these conditions are associated with the accumulation of small uncharged molecules in the serum.
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Thus, although the negative and positive predictive values of the osmol gap are too poor to recommend this test to routinely screen for xenobiotic ingestion, the presence of very high osmol gaps (>50–70 mOsm/L) usually indicates a diagnosis of toxic alcohol ingestion (Chap. 109).
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Differential Diagnosis of a Normal Anion Gap Metabolic Acidosis
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Although the differential diagnosis of a normal anion gap metabolic acidosis is extensive (Table 19–4), most cases result from either urinary or GI HCO3− losses: renal tubular acidosis (RTA) or diarrhea, respectively. A number of xenobiotics also can cause this disorder, including toluene,23 which also may cause a high anion gap metabolic acidosis. When the findings of the history and physical examination cannot be used to narrow the differential diagnosis, the use of a urinary anion gap is suggested.13,110
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The urinary anion gap can be calculated as shown in Equation 19–7:
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(Eq. 19–7)([Na+] + [K+]) – [Cl−]
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The size of this gap is inversely related to the urinary ammonium (NH4+) excretion.51 As NH4+ elimination increases, the urinary anion gap narrows and may become negative because NH4+ serves as an unmeasured urinary cation and is accompanied predominantly by Cl−.
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The normal anion gap metabolic acidosis associated with diarrhea results from HCO3− loss. During this process, the kidney’s ability to eliminate NH4+ is undisturbed; in fact, it increases as a normal response to the acidemia. Thus, with GI HCO3− losses the urinary anion gap should decrease and may become negative. By contrast, a patient with RTA has lost the ability to either reabsorb HCO3− (type 2 RTA) or increase NH4+ excretion in response to metabolic acidosis (types 1 and 4 RTA) and the urinary anion gap should become more positive. Indeed, when the urinary anion gap was calculated in patients with diarrhea or RTA, it was found that patients with diarrhea had a mean negative gap (−20 ± 5.7 mEq/L) compared with a positive gap (23 ± 4.1 mEq/L) in those with RTA.51 Therefore, when evaluating the patient with a normal anion gap metabolic acidosis, the determination of a urinary anion gap may help to determine the source of the disorder.
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Adverse Effects of Metabolic Acidosis
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The acuity of onset and severity of metabolic acidosis determine the consequences of this disorder. Acute metabolic acidosis is usually characterized by obvious hyperventilation (caused by respiratory compensation). At arterial pH values less than 7.20, cardiac and central nervous system abnormalities may become evident. These may include decreases in blood pressure and cardiac output, cardiac dysrhythmias, and progressive obtundation.1,2 Chronic metabolic acidosis may not manifest clinical symptoms. The symptoms of anorexia and fatigue may be the only manifestations of chronic acidosis, and compensatory hyperventilation may be undetectable. Because the consequences of even severe metabolic acidosis are not specific, the presence of metabolic acidosis is most often suggested by the history and physical examination.
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Management Principles in Patients with Metabolic Acidosis
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The treatment of metabolic acidosis depends on its severity and cause. Most cases of severe poisoning, with a serum [HCO3−] concentration less than 8 mEq/L and an arterial pH value less than 7.20 should probably be treated with HCO3− to increase the pH to greater than 7.20, as described in detail elsewhere.1,2 As an example, to raise the serum [HCO3−] by 4 mEq/L in a 70-kg person with an estimated HCO3− distribution space of 50% of body weight, approximately 140 mEq must be administered. When ECFV overload (caused by heart failure, kidney failure, or the sodium bicarbonate therapy itself) cannot be prevented or managed by administering loop diuretics, hemofiltration or hemodialysis may be necessary.
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In patients with arterial pH values greater than 7.20, the cause of the acidosis should guide therapy. Metabolic acidosis primarily caused by the overproduction of acid, as in the case of ketoacidosis and toxic alcohol poisoning, requires very large quantities of HCO3− and may not respond well to sodium bicarbonate therapy. Treatment in these patients should be directed at the cause of acidosis (eg, insulin and IV fluids in diabetic ketoacidosis; fomepizole in methanol, ethylene glycol and DEG poisonings {Antidotes in Depth: A30} fluids, glucose, and thiamine in alcoholic ketoacidosis; fluid resuscitation, antibiotics, and vasopressors in sepsis-induced hyperlactatemia). Patients with metabolic acidosis primarily caused by underexcretion of acid (eg, acute or chronic kidney failure, RTA) should be treated with a low-protein diet (if feasible) and oral sodium bicarbonate or substances that generate HCO3− during metabolism. Such patients can usually be managed with an oral sodium citrate solution such as Shohl solution, which yields 1 mEq base/mL. The goal of therapy is to increase the serum [HCO3−] to 20 to 22 mEq/L and the pH to 7.30.