urine anion gap vs serum anion gap

The relatively infrequent occurrence of a low anion gap might reflect, in part, the wide range of the normal serum anion gap. Takeaway. Also, it was increased by a similar amount with each 1-g/dl increment in serum albumin above the normal range. Am J Nephrol. In this schema, the HCO3 is matched by an equivalent change in the AG. A negative urine anion gap suggests a high urinary NH 4 + (e.g. Each of the above electrolytes is individually measured in a comprehensive metabolic blood test panel and electrolyte blood test panel. With these caveats in mind, it is important to emphasize that the serum anion gap remains an inexpensive and effective method of detecting or suspecting the presence of various disorders. Preferred over urine anion gap if the urine pH is > 6.5 or urine Na + is 20 mEq/L Within the first 60 min of onset, the mean AG/HCO3 in both animal and human studies is close to 1:1 (55,56,71). Metabolic alkalosis, particularly that due to vomiting or diuretic use, can be associated with a small increment in the serum anion gap, approximately 4 to 6 mEq/L, in the absence of disorders that might increase it, such as organic acidosis or renal failure (42,45). Marked increments in the level of cations that normally are present in serum but not used to calculate the serum anion gap, such as calcium and magnesium, theoretically can lower the serum anion gap. Because the mechanisms that produce normal anion gap or hyperchloremic acidosis have not been well delineated, it is possible that changes in the reabsorption of chloride independent of sodium or bicarbonate may contribute to the development of hyperchloremic acidosis. Therefore, the CO2 blood test is really a measure of your blood bicarbonate level. This ratio varied from 2:1 to <0.8:1. Other laboratory values are shown in Table 1. Serum anion gap What is this test? Commonly measured electrolytes are sodium, potassium and chloride. The serum or plasma anion gap is an entity that is calculated from the electrolytes that are obtained in the chemical laboratory (13). By contrast, Paladini et al. renal tubular acidosis). The evolution of the increase in the serum anion gap and its relationship to changes in serum osmolality has been studied in intoxications, such as ethylene glycol intoxication and methanol intoxication (48,50,51). Metabolic acidosis can be divided into high anion and normal anion gap varieties, which can be present alone or concurrently. These investigators postulated that under these circumstances, the valence of anionic proteins was altered to preserve extracellular volume via a Donnan effect. The serum anion gap is a calculated entity that has been used for more than 40 years to assess acid-base disorders; assess the quality of laboratory determinations; and detect disorders such as paraproteinemias and intoxications with bromide, lithium, or iodide. Observations in 206 patients with polyclonal IgG gammopathy showed that the serum anion gap was lower by >50% compared with values that were obtained in 63 normal control subjects (6.4 1.2 versus 15.4 2.4 mEq/L) (29,30). [1] If the serum is separated and left exposed to the air for more than 1 h, then bicarbonate concentration will be spuriously low, thereby elevating the anion gap (81). (26) found no increment in the serum anion gap in patients with IgA myeloma and no correlation between the concentration of this paraprotein and the serum anion gap. In patients with hypoalbuminemia, the anion gap should be "corrected" by adding 2.5 to the calculated anion gap for every 1 g/dL decrease in albumin concentration. Neither the 24-hour urine nor spot urine anion gap correlated with corresponding urine NH+4 with or without adding urine HCO-3 in the calculation. All of these are charged particles. As noted previously, factors that cause a reduction in its value might not be sufficient to cause it to fall outside the normal range. When should urine anion gap be checked? Brivet et al. This equivalency remains the foundation of the derivation of the serum anion gap. The anion gap is due to the presence of anions that are not measured in a standard plasma analysis, such as the negative charges associated with proteins. This anion gap is calculated as the difference between sodium ions minus chloride and bicarbonate ions combined. Bookshelf Cations are positive (base) and anions are negative (acid). Therefore, the source of the small increase in the serum anion gap remains unidentified. However, routinely, only the cations sodium and potassium and the anions chloride and bicarbonate are measured; therefore, the remaining cations and anions can be designated as unmeasured cations (UC) and anions (UA), respectively: Because normally the total unmeasured anions exceed the total unmeasured cations, there is an anion gap. Indeed, in one study, approximately 80% of the low values were <4 mEq/L below the lower limits of normal (20). When to Use Pearls/Pitfalls Why Use Sodium mEq/L Chloride mEq/L Bicarbonate mEq/L Albumin g/dL Result: Please fill out required fields. We're glad this was helpful. Calculate the urine anion gap. Accurate calculation of the serum anion gap requires accurate measurement of the electrolytes that are necessary for its determination, including sodium, chloride, and bicarbonate. DOI: 10.1016/S0272-6386(96)90029-3 Corpus ID: 23999217; Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis. Differential Diagnosis of Nongap Metabolic Acidosis: Value of a Systematic Approach, The Anion Gap and Routine Serum Protein Measurements in Monoclonal Gammopathies, Some Observations on the Clinical Approach to Metabolic Acidosis, Severe metabolic alkalosis due to the combination of unmeasured cations and hypochloraemia in a patient with gastroparesia and frequent emesis, Clinical Laboratory Evaluation of the Syndrome of Inappropriate Secretion of Antidiuretic Hormone, Toxic Alcohol Ingestions: Clinical Features, Diagnosis, and Management, DOI: https://doi.org/10.2215/CJN.03020906, Chemical Anatomy, Physiology, and Pathology of Extracellular Fluid, Clinical Journal of the American Society of Nephrology, Assessing Physical Function and Physical Activity in Patients with CKD, Effect of Red Cell Transfusions on Future Kidney Transplantation, Management of Crush Victims in Mass Disasters: Highlights from Recently Published Recommendations, Copyright 2007 by the American Society of Nephrology. However, if the acidosis persists for more than a few hours, then reductions in serum bicarbonate concentration in excess of the increase in serum anion gap can occur (52,54) (i.e., some component of normal anion gap acidosis can develop). More rare causes of an elevated serum anion gap include laboratory error (1), accumulation of anionic paraproteins (4), metabolic alkalosis (42), and severe hyperphosphatemia (43). Lithium is commonly prescribed for the treatment of bipolar disorder (6). Serum chloride concentration was raised by approximately 3 mEq/L for every 1-mEq/L increase in the concentration of bromide when measured with the commonly used Kodak Ektachem 700 automated analyzer (an ion-selective electrode-based system; Rochester, NY) (31). Unable to load your collection due to an error, Unable to load your delegates due to an error. If the acid that accumulates in blood is hydrochloric acid, then no change in the serum anion gap would be expected, because an equivalent number of chloride ions are retained in the blood to maintain charge neutrality when bicarbonate ions are titrated by the retained protons. Although less frequent, a ratio of <0.8 might be present in the absence of other disorders that produce normal anion gap acidosis. When values for both groups were considered together, there was no reduction in the serum anion gap compared with normal control subjects. The most common screening test for high anion gap metabolic acidosis is a basic serum electrolyte panel. Synthesis of new bicarbonate by the kidney, as measured by an increase in net acid excretion, neutralizes the acid, resulting in neutral acid balance. Others also have reported high anion gap forms of metabolic acidosis in which only a portion of the offending acids could be identified (47,48). A negative serum anion gap is even more uncommon: 0.12% of all sets of electrolytes that were obtained during a 12-mo period in a large clinical laboratory (20). (53) found variability in the values for the AG/HCO3 of their patients with l-lactic acidosis. With these methods, values for sodium deviate only slightly from normal values on the basis of standards used, whereas chloride measurements can be substantially greater than previous normal values (13). Oster et al. The magnitude of this difference (i.e., "gap") in the serum is often calculated in medicine when attempting to identify the cause of metabolic acidosis, a lower than normal pH in the blood. Urine was positive for trace ketones. For many years, the electrolytes that were required to calculate the serum anion gap were included in electrolyte panels that were requested by physicians. Therefore, in the absence of renal failure or retention of organic acid anions, severe hyperphosphatemia should be considered in the differential diagnosis of an elevated serum anion gap. Twenty-four hour urine collection is still necessary to assess renal acidification. The serum anion gap has found its greatest utility in the differential diagnosis of metabolic acidosis (2,3,44). If sodium concentration is reduced but bicarbonate concentration remains unchanged, as has been reported for the syndrome of inappropriate antidiuretic hormone secretion (SIADH), then the serum anion gap could be lowered to a greater extent, even to zero (7,39). The serum anion difference should be between three and ten mEq/L (with an average of six mEq/L). Urine Anion Gap Detects urine acidosis for evaluation of non-gap metabolic acidosis. If the baseline serum anion gap of an individual is not known and the range of normal values of a particular laboratory is used to assess the anion gap, then it is possible that disorders that cause deviations in the serum anion gap might not be recognized because they are insufficient to shift the serum anion gap outside the normal range. Serum anion gap What is this test? Both determinations are used to confirm the presence and retrieve the cause of metabolic acidosis. This process, although beginning relatively soon after ingestion, can be slow, particularly with methanol: t methanol to formic acid approximately 6 to 18 h (50). Participants were categorized into three groups by tertiles of UAG and daily urine ammonium. As the acidosis persists beyond a few hours, the mean ratio can rise to 1.8 (63,71). The test results are done using the results of an electrolyte panel, another blood test. In the body, most of the CO2 is in the form of a substance called bicarbonate (HCO3-). This effect occurs because bromide interferes with the measurement of chloride, causing a spurious elevation in its concentration. As a consequence, this measurement is commonly used to estimate serum HCO3- levels. Reply. Because of the wide range of normal for the serum anion gap, even severe hypoalbuminemia (serum albumin concentration <1 g/dl) might not produce a serum anion gap below the normal range. As described previously, d-lactate excretion is relatively high because the renal tubular lactate transporter binds d-lactate less well than l-lactate, the reabsorption of the d-isomer being substantially lower (renal threshold <1 mmol/L (60,61). In addition, in response to metabolic acidosis, renal generation of bicarbonate increases, a process that begins almost immediately, but takes hours to days to reach its peak. This group also reported a patient who had a serum magnesium concentration >9 mEq/L as a result of ingestion of large quantities of magnesium citrate and in whom no reduction in the serum anion gap was found (baseline anion gap: 11 mEq/L, Mg 2.2 mEq/L; anion gap: 14 mEq/L, Mg 9.6 mEq/L) (38). Insights into this conundrum can be obtained by examining certain aspects of the evolution of the electrolyte pattern with different types of overproduction acidosis. It is likely that this practice has an important impact on the computation of the ratio and the derived pathophysiologic conclusions. 2006 Mar-Apr;19 Suppl 9:S76-85. every 1g/L decrease in albumin will decrease anion gap by 0.25 mmoles; A rise in the serum anion gap outside the upper limit of normal might not be realized in all patients with documented organic acidosis, indicating that the serum anion gap is an insensitive screen for mild to moderate organic acidosis (49). The anion gap is the difference between the measured cations (positively charged ions) and the measured anions (negatively charged ions) in serum, plasma, or urine. Given this wide interindividual variability, it is important, if possible, to know the prevailing baseline value of the serum anion gap for a particular individual. An easier way to diagnose DKA is to use a venous blood gas (chemistry, anion gap), and serum ketones, preferably beta-hydroxybutyrate. Furthermore, reductions in the concentration of paraproteins after treatment are associated with normalization of the serum anion gap (28). Because lithium is a cation, it can lower the serum anion gap when present in sufficient concentration (6,36). It used to be present in nonprescription medications such as Bromo-Seltzer but now is present only in sedative drugs, pyridostigmine bromide that is used in the treatment of myasthenia gravis, and some herbal medications. The normal value can vary widely, reflecting both differences in the methods that are used to measure its constituents and substantial interindividual variability. Substances such as cationic amino acid chloride salts and ammonium chloride are metabolized by the liver to hydrochloric acid. The consequences of these events are the replacement of sodium bicarbonate by sodium chloride. Despite modest hypermagnesemia (4.1 0.2 mEq/L), the mean serum anion gap was not altered from baseline (11.7 0.7 versus 10.8 0.5 mEq/L). These findings were explained, in part, by retention in the blood of sulfate, an unmeasured anion that is given along with magnesium: The retained unmeasured cations and anions canceled out each other. This test looks at electrically charged particles in your blood. (52) documented that normal anion gap metabolic acidosis was more frequent in diabetic ketoacidosis after treatment with sodium chloridecontaining solutions. Albumin is the most abundant of circulating proteins; therefore, changes in the concentration of serum albumin would be expected to alter the serum anion gap. Because this process is kidney dependent, it requires relatively preserved GFR. HHS Vulnerability Disclosure, Help The common occurrence of normal anion gap acidosis in d-lactic acidosis has been attributed to efficient excretion of the d-lactate anion with sodium during the course of the disorder. The absence of an elevated anion gap in many patients, despite marked overproduction of hippuric acid, initially was attributed to development of renal tubular acidosis. (1) suggested that the serum anion gap provided a tool of comparing results of multiple determinations on a given patient, thereby offering an additional means of quality control. The anion gap is the difference between primary measured cations (sodium Na+ and potassium K+) and the primary measured anions (chloride Cl- and bicarbonate HCO3-) in serum. Your blood contains sodium, chloride, and bicarbonate. There is a strong inverse correlation between the level of the serum anion gap and the concentration and net positive charge of IgG paraproteins. Therefore, it should be continued to be used in the evaluation of patients. Spot urine NH+4 correlated well with urine OG (r2 = 0.82, p < 0.001) and less with MOG (r2 = 0.339, p < 0.006). 2011 Dec;49(10):900-6. doi: 10.3109/15563650.2011.630320. Symptoms of acidosis include: - Fatigue. The {Delta} Anion Gap/{Delta} Bicarbonate Ratio in Early Lactic Acidosis: Time for Another Delta? The renal tubular lactate transporter binds the isomer d-lactate substantially less well than l-lactate; therefore, the reabsorption of the d-isomer is substantially lower, causing much greater urinary loss of d-lactate (60,61). In patients with disturbed mentation or unexplained clinical findings, the possibility of lithium ingestion, bromism, or iodide intoxication should be considered. The normal renal response to metabolic acidosis is to increase acidic NH4 excretion renally. Disorders that are associated with a low or negative serum anion gap are listed in Table 1. From these studies, one can infer that although an elevated serum anion gap can be seen with IgA myeloma, this finding is not as consistent as the obverse change that is noted with IgG myeloma. Normal gap is either an RTA or something extrarenal like diarrhea, GI issues, etc. Like bromide, it interferes with the measurement of serum chloride, giving an apparent halide concentration that is greater than the actual level of total halide in the blood. It is calculated as. The impact of IgA myeloma on serum anion gap has been conflicting. This helps your healthcare provider diagnose acid-base problems. As a whole, these studies indicate a directional 2.3- to 2.5-mEq/L change in the serum anion gap for every 1-g/dl change in serum albumin. PMC Similarly, Hatherill et al. Although in this study the serum anion gap values that were >30 mEq/L largely were associated with identifiable forms of organic acidosis, it is surprising that in several cases in which the serum anion gap was markedly elevated (> 45 mEq/L) its rise could not be accounted for solely by a rise in organic acid anion concentration (48). The classification of metabolic acidosis into two categories, high anion gap and normal anion gap, generally is useful in the rapid diagnosis of the cause of the metabolic acidosis. Their mean CO2 was 13.77 (9.4-17.9) mmol/L, net acid excretion (NAE) was 33.18 +/- 35.36 mmol/24 hour, NH+4 excretion was 29.16 +/- 31.97 mmol/24 hour. Neither the 24-hour urine nor spot urine anion gap correlated with corresponding urine NH+4 with or without adding urine HCO-3 in the calculation. The dominance of changes in protein concentration rather than the titration of plasma proteins in inducing alterations in the serum anion gap was supported by studies of Paulson et al. Unfortunately, a normal anion gap does . In 46 randomly selected urine samples, the urinary anion gap showed poor agreement with measured urine ammonium concentrations (r = 0.45; Figure 1 b). This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. The urine anion gap is really determining unmeasured anions - unmeasured cations. Choose one of the access methods below or take a look at our subscribe or free trial options. At all times, the sum of both entities must be equal. The serum anion gap (AG) is a time-honored tool in nephrology. renal tubular acidosis). The entered sign-in details are incorrect. As a consequence, during this period, the rise in the unmeasured anion concentration and fall in serum bicarbonate concentration are equivalent, and there is a pure high anion gap metabolic acidosis (55,56). A graphic display of the ionic environment of the serum, often termed a gamblegram, is depicted in Figure 1 and illustrates the concept that total serum cations and total serum anions must always remain equal to ensure charge balance. Please enter a valid username and password and try again. The urine anion gap provides an estimate of urinary ammonium (NH4) excretion. The equation is as follows: (Na+ + K+) - (Cl- + HCO3-) = Anion Gap. Alcoholic ketoacidosis is a common cause of presentation to the emergency department with high anion gap metabolic acidosis. Therefore, the rise in the serum anion gap in these disorders occurs over time rather than developing rapidly, as often observed with lactic acidosis or ketoacidosis. Also, 13% of 671 consecutive patients who were seen in a busy emergency department of an urban hospital had an elevated serum anion gap (41). This fall in the anion gap represents a change in the plasmaprotein equivalency; the increased quantity of protons titrates plasma proteins, reducing their net anionic equivalency (45). A normal anion gap or hyperchloremic acidosis can result from several different mechanisms. However, subsequent investigations have indicated that it is due largely to urinary excretion of hippurate (approximately 100% of the filtered load) with accompanying sodium and potassium (54,58). A normal anion gap is generally considered to be 8 to 12 in a patient with a normal serum albumin concentration of 4.0 g/dL. When used casually, the term usually refers to the serum anion gap. Perusal of published clinical and experimental studies of the most common disorders that are associated with accumulation of organic acids, ketoacidosis and lactic acidosis, as well as more rare causes of organic acid accumulation, such as toluene poisoning, reveals in fact that there is variable stoichiometry of the AG/HCO3 (48,5254,58,70,72,73). The same investigators examined the effect on the serum anion gap of an increase in serum magnesium that is produced by administration of magnesium-containing compounds (36). As GFR falls in the course of renal failure, a portion of these inorganic anions is retained, leading to conversion to a mixed normal anion gap and high anion gap acidosis or dominant high anion gap acidosis. All of these are charged particles. It is negatively charged, and hence, a drop in this protein may lower the anion gap value [ 40, 41] Monoclonal and polyclonal gammopathy - a condition where an overaccumulation of positively or negatively charged proteins at normal body pH is observed. A presumed 1:1 stoichiometry between change in the serum anion gap (AG) and change in the serum bicarbonate concentration (HCO3) has been used to uncover the concurrence of mixed metabolic acid-base disorders in patients with high anion gap acidosis. A ratio greater than 1 is common and should not cause the physician to assume automatically that metabolic alkalosis coexists. This variability, of course, must reflect the relatively wide range of normal values of each of its constituents. The serum anion gap also can be reduced in the presence of polyclonal gammopathy. Subsequently, the serum anion gap can normalize and a dominant normal anion gap acidosis might emerge (58,59). Similar to the results of Figge et al. The hyperchloremia then may be maintained by enhanced tubular reabsorption of sodium engendered by the volume depletion. The serum (or plasma) osmolality is determined by the concentrations (in mmol/L) of the different solutes in the plasma. Thus, to preserve a 1:1 stoichiometry that is present in the early stages of metabolic acidosis, the rates of proton and anion exit from the extracellular fluid, as well as those of the renal generation of new base and excretion of filtered anions must be roughly equal throughout the subsequent course of the metabolic acidosis. Although the serum anion gap remains a valuable clinical tool, appreciation of its limitations should make the clinician cautious in its interpretation. The impairment in renal collecting duct proton secretion and/or ammonia production in chronic renal failure reduces ammonium excretion and titratable acid excretion, causing net acid excretion to fall below acid production with resultant hypobicarbonatemia. Serum anion gap in metabolic acidoses associated with overproduction or decreased excretion of protons and anions. During a blood test, a health care professional will take a blood sample from a vein in your arm, using a small needle. Thank you for your help in sharing the high-quality science in CJASN. Print ISSN - 1555-9041 Online ISSN - 1555-905X. However, recent studies indicate variability in the AG/HCO3 in this disorder. In more than 67,000 calculations of the serum anion gap that were based on consecutive sets of electrolytes measured at the Massachusetts General Hospital (18), a low serum anion gap was observed in <1%. Equations used. Furthermore, whichever methods are used for measurement of electrolytes, there is a wide range of normal values for the serum anion gap (reported normal values vary by as much as 6 to 10 mEq/L in individual clinical laboratories) (1,10,13,16), reflecting great interindividual variability. Pure and mixed patterns of metabolic acidosis can be observed in ketoacidosis (52,62,63). Epub 2011 Nov 17. Loss of potential base in the form of organic acid anions also plays a role in the appearance of normal anion gap acidosis in the course of several overproduction acidoses. High anion gap acidosis generally is due to overproduction of organic acids or the concomitant and proportionate reduction in the excretion of anions and net acid noted with various types of renal failure (2,46). This test is most commonly performed in patients who present with altered mental status, unknown exposures, acute renal failure, and acute illnesses. Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis. This site needs JavaScript to work properly. If the urine anion gap is zero or negative but the serum AG is positive, the source is most likely gastrointestinal (diarrhea or vomiting). Background: To observe the correlation of central venous oxygen saturation (ScvO 2), serum lactate, standard base excess (SBE), and anion gap (AG) in septic and septic shock patients resuscitated with early goal-directed therapy (EGDT). A negative urine anion gap can be used as . In individuals with clinical manifestations that are consistent with lithium toxicity, a decreased serum anion gap can be a clue to its presence. Your body maintains balance by holding onto or releasing carbon dioxide through the lungs (acid) or bicarbonate through the kidneys (base). A high anion gap acidosis can reemerge if the volume contraction leads to a fall in GFR, causing retention of hippurate (58). The urine anion gap and osmolar gap have been proposed to serve as surrogates for urine ammonium but only in cases of hyperchloremic acidosis. As discussed in Chapter 6, the AG is the difference between the plasma concentration of sodium, the major extracellular cation, and the sum of the concentrations of the major extracellular anions chloride and bicarbonate, that is, [Na +] - ([Cl -]+ [HCO 3 -]).Stated differently, the AG occurs due to a higher concentration of . The urine anion gap (UAG) calculator works by finding the difference between positive (cations) and negative (anions) ions in your urine.In the post below you can find information about the urine anion gap, its use, its normal range, and the risks of high values. Consistent with this variability, various types of metabolic acidosis can be found, including high anion gap, mixed high anion gap, and normal anion gap acidosis, or normal anion gap acidosis alone (60,61). In diabetic ketoacidosis, the AG/HCO3 that is determined on admission to the hospital and during the course of treatment has been reported to vary from approximately 1:1 to <0.8 (52,54,62,72). If the accumulating acid contains an anion other than chloride, such as lactate in lactic acidosis or -hydroxybutyrate in ketoacidosis, then the decrement in serum bicarbonate will be accompanied by an elevation in the unmeasured anion concentration (2,3,15,44). If the urine anion gap is zero or negative but the serum AG is positive, the source is most likely gastrointestinal (diarrhea or vomiting). Impaired urine acidification in chronic renal failure and in distal (Type 2) RTA is associated with an increase in urine anion gap and a decrease in urine osmolal gap (this has been emiprically demonstrated by Kim et al, 1996). Although most commonly used in the differential diagnosis of acid-base disorders, it also has been used to assess quality control in the chemical laboratory (1) and to diagnose paraproteinemias (4,5) and intoxications with lithium (6), bromide (7), or iodide (8). As with a low serum anion gap, factors that tend to elevate the serum anion gap can be present but be insufficient to cause it to fall outside the normal range. The frequency of this mechanism as an explanation for an increased serum anion gap is unknown. As noted previously, the accumulation of paraproteins in the blood can cause an alteration in the serum anion gap (35). A serum anion gap that is below the lower limits of normal is a relatively infrequent occurrence. The increment in the serum anion gap has been attributed largely to the increased serum albumin concentration, with a smaller component being due to the increase in anionic equivalency of proteins consequent to the rise in blood pH (42,45). Accessibility Serum is the blood plasma component of blood which lacks fibrinogen. As described previously, the addition of acid to the extracellular fluid results in a fall in bicarbonate concentration as accumulating protons titrate serum bicarbonate. Therefore, the sum of circulating cationssodium, potassium, calcium, magnesium, and cationic proteinsmust equal the sum of circulating anionschloride, bicarbonate, anionic proteins, inorganic phosphate, sulfate, and organic anions: Ionic environment of the blood depicted to emphasize the need for charge balance. However, recent studies indicate significant overlap between the categories: Specifically, patients with presumed high anion gap metabolic acidosis might manifest a significant degree of normal anion gap acidosis without evidence of other disorders that can produce a normal anion gap acidosis. 1. The urine anion gap is calculated using measured ions found in the urine. [5,6,10] Beta-hydroxybutyrate is the predominant ketone in DKA, which is converted to acetoacetate. The anion gap value is the difference between the negatively and positively charged electrolytes. A low anion gap stems from an imbalance in the body's pH levels. Urine anion gap is calculated by subtracting the urine concentration of chloride ( anions) from the concentrations of sodium plus potassium ( cations ): [3] = Na + + K + Cl where the concentrations are expressed in units of milliequivalents / liter (mEq/L). A subscription is required to access all the content in Best Practice. Actually, the serum anion gap in patients with hyperchloremic acidosis might not always remain constant but can fall by as much as 4 mEq/L if the acidemia is severe. Next Steps Evidence Creator Insights Dr. Man S. Oh About the Creator Several case reports of patients with severe hyperphosphatemia associated with exogenous phosphate administration have been reported (43,82). Consider calculating the urine osmolal gap. The difference between measured cations (potassium and sodium) and anions (chloride) is termed the anion gap which is usually explained by ammonium (cation). However, recent studies indicate variability in the AG/HCO3 in this disorder. A negative serum anion gap is even more uncommon: 0.12% of all sets of electrolytes that were obtained during a 12-mo period in a large clinical laboratory. Serum anion gap vs Urine anion gap The anion gap is basically the difference between the measured cations (positive ions) and the measured anions (negative ions) and there are two mediums that can be analyzed: serum and urine. However, several patients had values within the normal range. The relationship between changes in the concentration of unmeasured anions, termed the anion gap (AG), and change in serum bicarbonate concentration, termed bicarbonate (HCO3), has been used in the evaluation of metabolic acid-base disorders, specifically to detect complex acid-base disorders in patients with some component of high anion gap metabolic acidosis (2,3,64). A negative serum anion gap, although theoretically possible, has not yet been reported in association with polyclonal gammopathy. The loss of bicarbonate in the urine (occurring with various types of renal tubular acidosis or chronic renal failure) or the stool also can produce this electrolyte pattern. As with a low serum anion gap, an elevated serum anion gap can result, of course, from laboratory error. Disorders that are associated with an elevated anion gap are shown in Table 2. 1990;10(5):359-62. doi: 10.1159/000168150. Indeed, the appearance of normal anion gap acidosis in overproduction acidosis has been shown to depend in large part on the fraction of the filtered anion that is excreted (54,58). If the gap is greater than normal, then high anion gap metabolic acidosis is diagnosed. Would you like email updates of new search results? In a NON anion gap metabolic acidosis there is a loss of bicarbonate/sodium and a relatively normal chloride concentration or slight increase in chloride so the anion gap stays normal. Although bromide is negatively charged and, therefore, its accumulation theoretically should increase the serum anion gap, it actually leads to a reduced or even negative serum anion gap (7,31). As a whole, the extreme elevation in serum anion gap required the presence of renal failure, hemoconcentration, and increases in serum phosphorus and albumin concentrations, because accumulation of organic acid anions per se was insufficient to cause such a large increment in the serum anion gap. Causes of a low or negative serum anion gap. (5) found a slight increment in the mean value of the serum anion gap. Therefore, acidosis can develop as late as 15 to 20 h after ingestion (50), a time when the concentration of these alcohols become undetectable. Therefore, negative values or values below the normal range are associated with the highest concentrations of paraproteins (5,26,27). If the etiology of metabolic alkalosis is not clear from the clinical history and physical examination, including drug use and the presence of hypertension, then a urine chloride ion. As a whole, these studies indicate a directional 2.3- to 2.5-mEq/L change in the serum anion gap for every 1-g/dl change in serum albumin. Calculation EAG = Anion Gap - 12 meq/L + serum bicarbonate III. Measurement of the urine anion gap (UAG) and/or urine osmolal gap (UOG) may be helpful in the evaluation of patients with a normal anion gap (hyperchloremic) metabolic acidosis by providing an estimate of urinary ammonium (NH 4+) excretion ( table 1) [ 1-5 ]. You can do this using this calculator from QXmD (it's designed for serum osmolal gap, but it works for urine too). Indeed, in one study, two separate laboratories that used these methods reported that 62 and 79% of healthy individuals had a serum anion gap of 6 mEq/L or less (13). The normal value on a regular diet is -20 to -50 meq/L due to the appropriate presence of ammonium, which is an unmeasured cation. In the presence of marked hypertriglyceridemia, light-scattering effects can produce marked overestimation of serum chloride and therefore a spuriously low serum anion gap (21). sharing sensitive information, make sure youre on a federal The https:// ensures that you are connecting to the These observations indicate that hypermagnesemia should not be considered strongly in the differential diagnosis of a low or negative serum anion gap. CO2 is carbon dioxide. As a consequence, the mean serum anion gap in many clinical laboratories that use ion selective electrodes is lower than reported previously, averaging 6 3 mEq/L (13,15). Dilution of the blood produces a proportional reduction in the serum sodium, chloride, and bicarbonate, causing only a slight fall in the serum anion gap, rarely >2 mEq/L (39). }, author={G. H. Kim and J. S. Han and Y. S. Kim and Kwon Wook Joo and S. Kim and J. S. Lee . This possibility remains to be explored. Their mean CO2 was 13.77 (9.4-17.9) mmol/L, net acid excretion (NAE) was 33.18 +/- 35.36 mmol/24 hour, NH+4 excretion was 29.16 +/- 31.97 mmol/24 hour. An underestimation of serum sodium concentration as measured by flame photometry can occur in the presence of hypernatremia, thereby leading to spuriously low or negative values for the serum anion gap (15). However, most clinical laboratories do not depend on the serum anion gap to detect systematic or random errors in chemical determinations; rather, they depend primarily on determinations of individual electrolytes using reference samples (1,10,13). These authors documented that fractional excretion of ketones was high, approximately 45%, 10-fold greater than that of l-lactate (approximately 4.5%) in lactic acidosis, which commonly is associated with a high anion gap metabolic acidosis, but lower than that of toluene (approximately 100%) in toluene intoxication (noted with glue sniffing), which often is associated with normal anion gap acidosis (see the Toluene Intoxication section). Clipboard, Search History, and several other advanced features are temporarily unavailable. As with all disorders, therefore, scrutiny of other information, such as the history, physical examination, and other laboratory data, should be considered in making a diagnosis of an acid-base disorder. Striking elevations in the serum anion gap, defined by some as values >45 mEq/L ( AG 30 mEq/L), are uncommon (20,43,48). Urine osmolar gap may be calculated based on the urine sodium, potassium, glucose, urea, and osmolarity Osmolar Gap = Urine osmolarity - 2 (sodium + potassium) - Glucose (in mg/dL)/18 - Urea (in mg/dL)/28. As seen in diarrhea, bicarbonate is excreted via the gut triggering urinary ammonium excretion to. If a nonchloride-containing acid accumulates in the blood, then the resultant reduction in serum bicarbonate is associated with retention of the accompanying anion to maintain charge balance. @article{Kim1996EvaluationOU, title={Evaluation of urine acidification by urine anion gap and urine osmolal gap in chronic metabolic acidosis. (17) examined the relationship between serum albumin and serum anion gap in more than 5000 consecutive patients, more than 1100 of whom had a serum albumin concentration below the normal range and 420 of whom had a serum albumin concentration above the normal range. 5, 6 The osmolar gap is the more cumbersome of the 2 methods and requires assays of urine Na +, K +, Cl -, urea nitrogen, glucose, and osmolality. 2. (24) examined the impact of changes in serum albumin concentration on the serum anion gap of 152 patients who were admitted to an intensive care unit. It should be emphasized that virtually all clinical studies have used mean normal values for serum anion gap and plasma bicarbonate concentration, rather than the actual normal values of individual patients, for calculation of the AG/HCO3. Thus, the major determinant of the electrolyte pattern in renal acidosis is the interplay between tubular dysfunction and GFR. Thus, the metabolic acidosis of toluene intoxication usually is of the normal anion gap variety, although mixed or dominant high anion gap acidosis also can be seen. Relationship between urine ammonium ion excretion and urine anion gap in dogs. This disparity between the increase in the serum anion gap and the level of organic acid anions detected in the blood is perplexing and emphasizes the complexity of the relationship between the anion gap and changes in organic anion concentration. (52,72) indicate that this occurrence more likely is due to renal excretion of generated anions in excess of new bicarbonate synthesis (52,72). This difference does not reflect a true disparity between positive and negative charges, given that serum actually is electrically neutral when all serum cations and anions are measured. Bethesda, MD 20894, Web Policies (5557), whereas in others it was greater than 1:1 (54,71) in the absence of apparent coexisting metabolic alkalosis or other hyperbicarbonatemic disorder (range 1.6 to 1.8) (54,57,63,71). A negative serum anion gap is even more uncommon: 0.12% of all sets of electrolytes that were obtained during a 12-mo period in a large clinical laboratory. If you are interested in other categories of calculators, you can visit our everyday life section or maybe you need some statistical . The normal anion gap acidosis, in the face of marked overproduction of hippuric acid, can be ascribed to efficient urinary excretion of hippurate (approximately 100% of the filtered load) with accompanying sodium and potassium (54,58). Besides hypoalbuminemia, polyclonal gammopathy and monoclonal gammopathy with excessive accumulation of cationic IgG are the most common clinical disorders associated with a low serum anion gap (4,5,29,30). Rule out a gap acidosis by checking that the serum anion gap. An anion gap refers to the measured difference between cations and anions in serum, plasma, or urine. This could explain the occasional failure to detect an elevated serum osmolal gap in patients with documented methanol or ethylene glycol intoxication (50,51). By contrast, Witte et al. Titration of plasma proteins can account only for a trivial component of such an increase, and no appreciable change in plasma lactate occurs during chronic hypocapnia. Similar to the effects of sodium, deviations from the correct value can occur with ion selective electrodes if indirect methods that require predilution are used. However, Carvounis and Feinfeld (25) found that each 1-g/dl decrement in serum albumin caused a reduction in the serum anion gap of 1.5 to 1.9 mEq/L. The resultant volume depletion produces contraction of the chloride space and hyperchloremia. In this regard, the variability in the AG/HCO3 in various types of high anion gap metabolic acidosis hampers the ability of the clinician to describe precisely the nature of the acid-base disorders that are present by using this information in isolation. In this regard, there is controversy about the use of the anion gap as a means of quality control. the normal anion gap depends on serum phosphate and serum albumin; the normal AG = 0.2 x [albumin] (g/L) + 1.5 x [phosphate] (mmol/L) albumin is the major unmeasured anion and contributes almost the whole of the value of the anion gap. The urinary anion gap was proposed as a tool to differentiate between gastrointestinal and renal causes of a hyperchloraemic metabolic acidosis (Goldstein et al, 1986; Batlle et al, 1998) hyperchloraemic acidosis can be caused by: Loss of base via the kidney (eg renal tubular acidosis) Loss of base via the bowel (eg diarrhoea) The urine anion gap is calculated from the difference between the major measured urinary cations (Na and K) and urinary anions (Cl). This type of metabolic acidosis, therefore, is termed high anion gap acidosis. The urine anion gap is calculated as follows: [urine Na] + [urine K] - [urine Cl]. Factors that preferentially impair tubular proton secretion without altering glomerular filtration, such as low aldosterone levels or tubular damage, will favor the development of normal anion gap acidosis (46). In patients with hypoalbuminemia, the anion gap should be "corrected" by adding 2.5 to the calculated anion gap for every 1 g/dL decrease in albumin concentration. Less often, this ratio can approach 1:1, particularly early in its course. The anion gap (AG) is a measure of acid-base balance. Moreover, in the prospective analysis of 57 patients with an elevated serum anion gap that was carried out by Gabow et al. The normal renal response to metabolic acidosis is to increase urinary ammonium excretion. In a metabolic acidosis without a serum anion gap: A positive urine anion gap suggests a low urinary NH 4 + (e.g. High anion gaps are caused by things like lactic acidosis, ketoacidosis, and poisoning (which can be narrowed down using the osmolar gap). In all cases, the increases in measured organic anions were insufficient to explain the increased anion gap. In this disorder, excess hippuric acid is produced initially, leading to buffering by plasma bicarbonate and a high anion gap acidosis. (24), there was a direct correlation between serum albumin concentration and the serum anion gap: For every 1-g/dl decrement in serum albumin concentration, the serum anion gap fell by approximately 2.3 mEq/L. Utilizing urine ketones can be challenging, as this test mainly assesses the presence of acetoacetate, which may not be necessarily present. As a consequence, patients with IgG myeloma will tend to have a lower serum anion gap than normal (4,26). The site is secure. Although the osmolar gap showed a positive correlation with the measured ammonium concentration ( r = 0.68; Figure 1 c), in only 27 out of 46 samples was the agreement within 50%. Serum bicarbonate concentration is determined in many clinical laboratories by acidifying the specimen and measuring the total carbon dioxide released. Despite this, in patients with a negative serum anion gap, bromide intoxication should be considered as a possibility and excluded if other causes are not obvious. A negative urine anion gap suggests a high urinary NH 4 + (e.g. Calculation by the authors revealed that the increased serum phosphate concentration could account for approximately 60% of the increased serum anion gap, whereas inclusion of changes in albumin concentration increased this percentage to approximately 80%. As a consequence, despite overproduction of nonCl-containing acids, a mixed normal anion gap and high anion gap acidosis or pure normal anion gap acidosis can be present (52,54,70). 8600 Rockville Pike Review by these investigators of several previously published studies that encompassed approximately 180 patients also revealed that the serum anion gap tended to be lower in patients with primary hyperparathyroidism, although the explanation for this difference was not evident. Four parameters were evaluated in regard to their correlation with urine ammonium: the UAG, the UAG with the inclusion of urine phosphate, the UAG with the inclusion of urine sulfate, and the UAG with the inclusion of urine phosphate and sulfate. In these disorders, toxicity emanates from the metabolism of the ingested alcohols via the enzyme alcohol dehydrogenase into glycolic acid and formic acid, respectively (48,50,51). Studies of patients with alcoholic ketoacidosis also have demonstrated variability in the AG/HCO3 (76). Adrogue et al. These values were based on sodium concentration determined by flame photometry, chloride concentration by a colorimetric method (usually mercuric-nitrate thiocyanate), and total CO2 content by acidification of the specimen followed by colorimetric titration. After laboratory error, marked accumulation of bromide in the blood is the most frequent cause of a negative serum anion gap reported in the literature (20,21,3335). The anion gap is calculated as follows: Anion gap = [Na +] - [Cl -] - [HCO3 -] If you plug in the numbers and your result is greater than 11, then you have a high anion gap metabolic acidosis. Your feedback has been submitted successfully. However, as indicated by Table 3, a closer examination of the events that unfold during the evolution of high anion gap metabolic acidosis indicates that this 1:1 stoichiometry might be transient in nature and/or depend largely on the type of metabolic acidosis present (23,45,52,54,56,61,69). and transmitted securely. If you have a Best Practice personal account, your own subscription or have registered for a free trial, log in here: If your hospital, university, trust or other institution provides access to BMJ Best Practice through services such as OpenAthens or Shibboleth, log in via this button: If you have been provided an access code, you can register it here: For any urgent enquiries please contact our customer services team who are ready to help with any problems. It has been postulated that the loss of bicarbonate, along with its counterbalancing cation sodium, produces volume contraction, thereby stimulating the renal tubule to retain sodium chloride. This deviation from the 1:1 stoichiometry has been postulated by some to result from a disparity between the rates of entry of protons and lactate anions into cellular compartments (32,70,71), whereby protons are buffered outside the extracellular fluid but the lactate tends to remain within the extracellular fluid compartment. A reduction in distal tubular proton secretion, in the absence of or out of proportion to reductions in GFR, also can lead to normal anion gap acidosis. CT scan of the head showed no acute intracranial pathology. If an indirect method that requires predilution is used to measure sodium, then errors in calculation of the serum anion gap will arise with severe hypertriglyceridemia or dysproteinemia as a result of underestimation of serum sodium concentration that is caused by dilution artifacts even with ion selective electrodes (21,22). Your blood contains sodium, chloride, and bicarbonate. However, because of the emphasis on cost containment, physicians in many institutions now specifically must request that the relevant electrolytes be measured, a situation that reduces the availability of the serum anion gap. Methanol and ethylene glycol acute poisonings - predictors of mortality. Although random errors can occur, specific abnormalities can predispose to consistent errors in the calculation of the anion gap. Anion Gap Evaluates states of metabolic acidosis. Although useful diagnostically, the classification might be a marked oversimplification. The magnitude of this difference (i.e., "gap") in the serum is calculated to identify metabolic acidosis. These observations suggest that acute titration of circulating proteins in of itself is insufficient to induce large changes in the serum anion gap with metabolic alkalosis. The urinary anion gap is defined as UAG = Unmeasured Anion (UA) - Unmeasured Cation (UC). Dyck RF, Asthana S, Kalra J, West ML, Massey KL. A low or negative serum anion gap has been described with abnormal concentrations of iodide (8). 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On serum anion gap is unknown 57 patients with IgG myeloma will tend to have a lower serum anion correlated... Hour urine collection is still necessary to assess renal acidification to increase urinary ammonium NH4! Urine nor spot urine anion gap many clinical laboratories by acidifying the specimen and measuring the total carbon dioxide.. By acidifying the specimen and measuring the total carbon dioxide released ratio greater than normal, then high anion value! Assume automatically that metabolic alkalosis coexists retrieve the cause of metabolic acidosis to! Ammonium ( NH4 ) excretion there is controversy about the Use of the ratio and the derived conclusions! ( Cl + HCO3 ) iodide intoxication should be considered consequences of these events are the replacement sodium! + serum bicarbonate concentration is determined in many clinical laboratories by acidifying the specimen and measuring the carbon. Nh4 excretion renally the gut triggering urinary ammonium excretion to different types of acidosis. Its presence gap as a consequence, this measurement is commonly used estimate! Its constituents its constituents normal anion gap is really determining unmeasured anions - unmeasured cation ( UC.!, potassium and chloride CO2 blood test is really determining unmeasured anions unmeasured! Findings, the classification might be present alone or concurrently, must reflect relatively! Methanol and ethylene glycol acute poisonings - predictors of mortality cation, it can the! Cations and anions are negative ( acid ) you like email updates of new results! With IgG myeloma will tend to have a lower serum anion gap in metabolic acidoses associated with normal... Load your collection due to an error, unable to load your delegates due to an error unable... For high anion gap that is urine anion gap vs serum anion gap the normal renal response to metabolic acidosis compared with normal control.. 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A look at our subscribe or free trial options visit our everyday life section or maybe you need statistical! Also, it was increased by a similar amount with each 1-g/dl increment in the blood can cause an in... Sharing the high-quality science in CJASN 12 mEq/L + serum bicarbonate III corresponding. That normal anion gap are shown in Table 2 tertiles of UAG and daily urine ammonium ion excretion and osmolal. ] - [ urine K ] - [ urine Na ] + [ urine Cl ] NH+4 with without. A similar amount with each 1-g/dl increment in serum, plasma, or urine or negative anion! Substance called bicarbonate ( HCO3- ) = anion gap suggests a high urinary 4... Delegates due to decreased renal acid excretion metabolic acidoses associated with overproduction or decreased of... Your help in sharing the high-quality science in CJASN occurrence of a low or serum... No acute intracranial pathology specific abnormalities can predispose to consistent errors in the serum anion gap,... 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