Metabolic Acidosis Workup

Updated: Oct 10, 2018
  • Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Workup

Approach Considerations

Often the first clue to metabolic acidosis is a decreased serum HCO3- concentration observed when serum electrolytes are measured. Remember, however, that a decreased serum [HCO3-] level can be observed as a compensatory response to respiratory alkalosis. An [HCO3-] level of less than 15 mEq/L, however, almost always is due, at least in part, to metabolic acidosis.

The only definitive way to diagnose metabolic acidosis is by simultaneous measurement of serum electrolytes and arterial blood gases (ABGs), which shows pH and PaCO2 to be low; calculated HCO3- also is low. (For more information, see Metabolic Alkalosis.)

A low serum HCO3- and a pH of less than 7.40 upon ABG analysis confirm metabolic acidosis.

Go to Pediatric Metabolic Acidosis and Emergent Management of Metabolic Acidosis for complete information on these topics.

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Laboratory Evaluation

The diagnosis is made by evaluating serum electrolytes and ABGs. A low serum HCO3- and a pH of less than 7.40 upon ABG analysis confirm metabolic acidosis. The anion gap (AG) should be calculated to help with the differential diagnosis of the metabolic acidosis and to diagnose mixed disorders. In general, a high-AG acidosis is present if the AG is greater than 10-12 mEq/L, and a non-AG acidosis is present if the AG is less than or equal to 10-12 mEq/L. It is important to note that the AG decreases by 2.5 mEq for every 1 g/dL decrease in serum albumin.

If the AG is elevated, the osmolar gap should be calculated by subtracting the calculated serum osmolality from the measured serum osmolality. Ethylene glycol and methanol poisoning increase the AG and the osmolar gap. Acetone, produced by decarboxylation of acetoacetate, can also raise serum osmolality. Other tests can be performed, including a screen for toxins (eg, ethylene glycol, salicylate) and tests for metabolic disorders (eg, ketoacidosis, lactic acidosis), that are known to elevate the AG.

If the AG is not elevated, then a urinalysis should be performed and a urine pH obtained with a pH electrode on a fresh sample of urine collected under oil or in a capped syringe. A urine AG is calculated from the measurement of urine Na+, K+, and Cl-. This helps to differentiate between GI and renal losses of HCO3- in non-AG metabolic acidosis.

The change in AG (delta AG) helps in detecting the presence of a second acid-base disorder in patients with an elevated AG. It is calculated by the following equation:

(AG - 10)/(24 - HCO3-)

A value less than 1 indicates that the drop in serum HCO3- is not accompanied by a corresponding increase in the AG. This suggests that a portion of the H+ load is not accompanied by an unmeasured anion and indicates the presence of a mixed metabolic acidosis (eg, a non-AG acidosis and a high-AG acidosis).

A value greater than 1.6 indicates that the drop in serum HCO3- is associated with a larger-than-expected increase in the AG. This would occur if the serum HCO3- level was higher than normal prior to the onset of the metabolic acidosis and then dropped below normal with the addition of H+ coupled to an unmeasured anion. This indicates the presence of a mixed metabolic acidosis and metabolic alkalosis.

Special tests

Measuring the transtubular potassium gradient (TTKG) is useful in determining the etiology of hyperkalemia or hypokalemia associated with metabolic acidosis.

Plasma renin activity and plasma aldosterone levels are useful in determining the etiology of the hyperkalemia and hypokalemia that accompany metabolic acidosis.

FEHCO3- is useful in the diagnosis of proximal renal tubular acidosis (RTA).

The NH4 Cl loading test is useful in patients with nephrocalcinosis and/or nephrolithiasis, who may have an incomplete form of distal RTA. These patients may not have a pH less than 7.35 or a drop in serum HCO3-; metabolic acidosis can be induced by administration of NH4 Cl (0.1 g/kg for 3 d). Under these circumstances of induced acidemia, a urine pH greater than 5.3 indicates distal RTA.

A recently described alternative to the NH4 Cl loading test involves the simultaneous oral administration of furosemide to increase distal Na+ delivery and fludrocortisone to increase collecting duct Na+ absorption and proton secretion. [9] Under these circumstances, a urine pH greater than 5.3 indicates distal RTA.

Measuring the urine-blood PaCO2 gradient following an HCO3- load is useful in some patients with classic distal RTA to differentiate a permeability defect from other defects. This test is useful in patients with nephrocalcinosis in whom distal RTA is suspected but urine is acidified appropriately in the face of metabolic acidosis. Some of these patients have a rate-dependent defect in proton secretion, revealed by a low urine-blood PaCO2 gradient following HCO3- loading.

Abdominal radiographs (eg, kidneys, ureters, bladder), CT scans, and/or renal ultrasound images may show renal stones or nephrocalcinosis in patients with distal RTA.

Base excess/base deficit

ABGs also measure base excess/base deficit (BE/BD), which is the best indicator of the degree of acidosis/alkalosis. BE/BD is measured by gauging the amount of acid or base that is required to titrate the patient's blood sample to a pH of 7.40, given a PCO2 level of 40 mm Hg at 37°C.

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Complete Blood Count

An elevation of the white blood cell (WBC) count is a nonspecific finding, but it should prompt consideration of septicemia, which causes lactic acidosis.

Severe anemia with compromised oxygen delivery may cause lactic acidosis.

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Urinalysis

A urine pH is normally acidic at less than 5.0. In acidemia, the urine normally becomes more acidic. If the urine pH is above 5.5 in the face of acidemia, this finding is consistent with a type I RTA. Alkaline urine is typical in salicylate poisoning.

Patients with ethylene glycol toxicity may present with calcium oxalate crystals, which appear needle shaped, in the urine.

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Urine Anion Gap

Calculating the urine AG is helpful in evaluating some cases of non-AG metabolic acidosis. The major measured urinary cations are Na+ and K+, and the major measured urinary anion is Cl-:

Urine AG = ([Na+] + [K+]) - [Cl-]

In the face of metabolic acidosis, the kidneys increase the amount of NH3 synthesized to buffer the excess H+ and NH4 Cl excretion increases. The increased unmeasured NH4+ thus increases the measured anion Cl- in the urine, and the net effect is a negative AG, representing a normal response to systemic acidification. The finding of a positive urine AG in the face of non-AG metabolic acidosis points toward a renal acidification defect (eg, RTA [10] ). See earlier section on urine anion gap.

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Ketone Level

Elevations of ketones indicate diabetic, alcoholic, and starvation ketoacidosis.

The nitroprusside test is used to detect the presence of ketoacids in the blood and the urine. This test measures only acetoacetate and acetone; therefore, it may underestimate the degree of ketonemia and ketonuria, because it will not detect the presence of beta-hydroxybutyrate (BOH). This limitation of the test can be especially problematic in patients with ketoacidosis who cannot convert BOH to acetoacetate because of severe shock or liver failure.

An assay for BOH is unavailable in some hospitals. An indirect method to circumvent this problem is to add a few drops of hydrogen peroxide to a urine specimen. This enzymatically will convert BOH into acetoacetate, which will be detected by the nitroprusside test.

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Serum Lactate level

The normal plasma lactate concentration is 0.5-1.5 mEq/L. Lactic acidosis is considered present if the plasma lactate level exceeds 4-5 mEq/L in an acidemic patient.

Most cases of lactic acidosis are due to tissue hypoxia (eg, from shock). Less commonly, underlying disease (eg, diabetic ketoacidosis), drugs, or toxins may be the cause. [19]

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Salicylate levels and Iron levels

Therapeutic salicylate levels range up to 20-35 mg/dL. Plasma levels exceeding 40-50 mg/dL are in the toxic range.

Plasma levels provide some information as to the severity of intoxication: 40-60 mg/dL is considered mild; 60-100 mg/dL is moderate; and greater than 100 mg/dL is considered severe.

Iron toxicity is associated with lactic acidosis. Iron levels greater than 300 mg/dL are considered toxic.

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Transtubular Potassium Gradient

Measuring the transtubular potassium gradient (TTKG; see the calculation below) is useful in determining the etiology of hyperkalemia or hypokalemia associated with metabolic acidosis.

TTKG = urine K+ × serum osmolality/serum K+ × urine osmolality

A TTKG of greater than 8 indicates that aldosterone is present and that the collecting duct is responsive to it. A TTKG of less than 5 in the presence of hyperkalemia indicates aldosterone deficiency or resistance. For the test to be interpretable, the urine Na+ level should be greater than 10 mEq/L and the urine osmolality should be greater than or equal to serum osmolality.

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Plasma Renin Activity, Plasma Aldosterone levels, and FEHCO3-

Plasma renin activity and plasma aldosterone levels are useful in determining the etiology of the hyperkalemia and hypokalemia that accompany metabolic acidosis.

Measurement of the fractional excretion of bicarbonate (FEHCO3-) is useful in the diagnosis of proximal RTA.

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Ammonium Chloride Loading Test

The ammonium chloride (NH4 Cl) loading test is useful in patients with nephrocalcinosis and/or nephrolithiasis, who may have an incomplete form of distal RTA. These patients may not have a pH of less than 7.35 or a drop in serum HCO3-; metabolic acidosis can be induced by administration of NH4 Cl (0.1 g/kg for 3 d). Under these circumstances of induced acidemia, a urine pH of greater than 5.3 indicates distal RTA.

An alternative to the NH4 Cl loading test involves the simultaneous oral administration of furosemide to increase distal Na+ delivery and fludrocortisone to increase collecting duct Na+ absorption and proton secretion. [9] Under these circumstances, a urine pH greater than 5.3 indicates distal RTA.

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Urine-Blood PaCO2 Gradient Following HCO3- Loading

Measuring the urine-blood PaCO2 gradient following an HCO3- load is useful in some patients with classic distal RTA to differentiate a permeability defect from other defects. This test is useful in patients with nephrocalcinosis in whom distal RTA is suspected but urine is acidified appropriately in the face of metabolic acidosis. Some of these patients have a rate-dependent defect in proton secretion, revealed by a low urine-blood PaCO2 gradient following HCO3- loading.

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Imaging Studies and Electrocardiography

Abdominal radiographs (eg, kidneys, ureters, bladder), computed tomography (CT) scans, and/or renal ultrasonographic images may show renal stones or nephrocalcinosis in patients with distal RTA.

If iron ingestion is suspected, perform imaging studies on the abdominal area, including the kidneys, ureters, and bladder.

An electrocardiogram (ECG) may be used to detect abnormalities that result from the effects of electrolyte imbalances (eg, hyperkalemia).

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