eMedicine Specialties > Nephrology > Acid-Base, Fluid, and Electrolyte Disorders

Metabolic Acidosis: Differential Diagnoses & Workup

Author: Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Coauthor(s): Khaled Hamawi, MD, Transplant Nephrology Consultant, King Faisal Specialist Hospital & Research Center
Contributor Information and Disclosures

Updated: Sep 16, 2009

Differential Diagnoses

Acute Renal Failure
Lactic Acidosis
Azotemia
Metabolic Alkalosis
Chronic Renal Failure
Respiratory Alkalosis
Diabetes Mellitus, Type 1
Toxicity, Salicylate
Diabetes Mellitus, Type 2

Other Problems to Be Considered

Hyperosmolar nonketotic acidosis
Mixed acid-base disturbances
Renal tubular acidosis
Toxicity, ethylene glycol
Toxicity, methanol
Toxicity, paraldehyde

Workup

Laboratory Studies

  • 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 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 10-12 mEq/L.
  • 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.
    • 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 (or 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 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 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.5 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.

Imaging Studies

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

More on Metabolic Acidosis

Overview: Metabolic Acidosis
Differential Diagnoses & Workup: Metabolic Acidosis
Treatment & Medication: Metabolic Acidosis
Follow-up: Metabolic Acidosis
References
Further Reading
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References

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  2. Pereira PC, Miranda DM, Oliveira EA, et al. Molecular pathophysiology of renal tubular acidosis. Curr Genomics. Mar 2009;10(1):51-9. [Medline]. [Full Text].

  3. Maciel AT, Park M. Differences in acid-base behavior between intensive care unit survivors and nonsurvivors using both a physicochemical and a standard base excess approach: A prospective, observational study. J Crit Care. Mar 26 2009;[Medline].

  4. Morimatsu H, Toda Y, Egi M, et al. Acid-base variables in patients with acute kidney injury requiring peritoneal dialysis in the pediatric cardiac care unit. J Anesth. 2009;23(3):334-40. [Medline].

  5. Walsh SB, Shirley DG, Wrong OM, et al. Urinary acidification assessed by simultaneous furosemide and fludrocortisone treatment: an alternative to ammonium chloride. Kidney Int. Jun 2007;71(12):1310-6. [Medline].

  6. Adrogue HJ. Metabolic acidosis: pathophysiology, diagnosis and management. J Nephrol. Mar-Apr 2006;19 Suppl 9:S62-9.

  7. Adrogue HJ, Madias NE. Disorders of acid-base balance. In: Schrier R, ed. Atlas of Diseases of the Kidney. ISN Informatics Commission and NKF cyberNephrology.; Available at: http://www.kidneyatlas.org/book1/adk1_06.pdf. [Full Text].

  8. Batlle D, Flores G. Underlying defects in distal renal tubular acidosis: new understandings. Am J Kidney Dis. Jun 1996;27(6):896-915. [Medline].

  9. Batlle DC, Hizon M, Cohen E, et al. The use of the urinary anion gap in the diagnosis of hyperchloremic metabolic acidosis. N Engl J Med. Mar 10 1988;318(10):594-9. [Medline].

  10. Bjerneroth G. Alkaline buffers for correction of metabolic acidosis during cardiopulmonary resuscitation with focus on Tribonat--a review. Resuscitation. Jun 1998;37(3):161-71. [Medline].

  11. Boron WF. Acid-base transport by the renal proximal tubule. J Am Soc Nephrol. Sep 2006;17(9):2368-82. [Medline].

  12. Burton, BD. Metabolic acidosis. In: Burton, BD and Post, T. Clinical Physiology of Acid-Base and Electrolyte Disorders. 5. New York, NY: McGraw-Hill; 1994:; 2001:578-646.

  13. DuBose TD Jr. Hyperkalemic hyperchloremic metabolic acidosis: pathophysiologic insights. Kidney Int. Feb 1997;51(2):591-602. [Medline].

  14. DuBose, TD. Acid Base Disorders. In: Brenner, BM. The Kidney. 1. 7. Philadelphia: Elsevier; 2004:948-971.

  15. Ellison, DH and Thomas, CP. Hereditary Disorders of Distal Nephron Sodium and Potassium Transport. In: Mount, DB and Pollark, MR. Molecular and Genetic Basis of Renal Disease: A companion to Brenner and Rector's The Kidney. 1. Philadelphia: Elsevier Health Sciences; 2007:16: 251-268.

  16. Ethier JH, Kamel KS, Magner PO, et al. The transtubular potassium concentration in patients with hypokalemia and hyperkalemia. Am J Kidney Dis. Apr 1990;15(4):309-15. [Medline].

  17. Forsythe SM, Schmidt GA. Sodium bicarbonate for the treatment of lactic acidosis. Chest. Jan 2000;117(1):260-7. [Medline].

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  21. Kallet RH, Jasmer RM, Luce JM, et al. The treatment of acidosis in acute lung injury with tris-hydroxymethyl aminomethane (THAM). Am J Respir Crit Care Med. Apr 2000;161(4 Pt 1):1149-53. [Medline].

  22. Kamel KS, Halperin ML. An improved approach to the patient with metabolic acidosis: a need for four amendments. J Nephrol. Mar-Apr 2006;19 Suppl 9:S76-85.

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  26. Magner PO, Robinson L, Halperin RM, et al. The plasma potassium concentration in metabolic acidosis: a re-evaluation. Am J Kidney Dis. Mar 1988;11(3):220-4. [Medline].

  27. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). Online Mendelian Inheritance in Man. OMIM. Available at http://www.ncbi.nlm.nih.gov/Omim/. Accessed Mar 29, 2008.

  28. Strife CF, Clardy CW, Varade WS, et al. Urine-to-blood carbon dioxide tension gradient and maximal depression of urinary pH to distinguish rate-dependent from classic distal renal tubular acidosis in children. J Pediatr. Jan 1993;122(1):60-5. [Medline].

  29. Wrenn KD, Slovis CM, Minion GE, et al. The syndrome of alcoholic ketoacidosis. Am J Med. Aug 1991;91(2):119-28. [Medline].

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Further Reading

Related eMedicine topics:
 Acidosis, Metabolic
Alkalosis, Metabolic
Alkalosis, Respiratory
Hypercalcemia [Emergency Medicine]
Hypercalcemia [Nephrology]
Hypercalcemia [Pediatrics: General Medicine]
Hyperkalemia [Emergency Medicine]
Hyperkalemia [Nephrology]
Hyperkalemia [Pediatrics: Cardiac Disease and Critical Care Medicine]
Hypermagnesemia [Emergency Medicine]
Hypermagnesemia [Nephrology]
Hypermagnesemia [Pediatrics: General Medicine]
Hyperphosphatemia [Emergency Medicine]
Hyperphosphatemia [Nephrology]
Hypocalcemia [Emergency Medicine]
Hypocalcemia [Nephrology]
Hypocalcemia [Pediatrics: General Medicine]
Hypochloremic Alkalosis
Hypokalemia [Emergency Medicine]
Hypokalemia [Nephrology]
Hypokalemia [Pediatrics: Cardiac Disease and Critical Care Medicine]
Hypomagnesemia [Emergency Medicine]
Hypomagnesemia [Nephrology]
Hypomagnesemia [Pediatrics: General Medicine]
Hypophosphatemia [Emergency Medicine]
Hypophosphatemia [Nephrology]
Metabolic Alkalosis
Respiratory Acidosis
Respiratory Alkalosis

Clinical guidelines:
Cerebral Edema in Pediatric Diabetic Ketoacidosis

Human Milk Fortifiers and Acid-Base Status

Study of Idebenone in the Treatment of Mitochondrial Encephalopathy Lactic Acidosis & Stroke-like Episodes (MELAS)

Study On the Role of Mitochondrial Dysfunction in the Pathogenesis of Metformin-associated Lactic Acidosis

Uremic Toxins in the Intensive Care Units (ICU): Patients With Lactate Acidosis

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Keywords

metabolic acidosis, acidosis, anion gap, renal tubular acidosis, acidosis renal tubular, renal acidosis, respiratory acidosis, gap acidosis, anion acidosis, acid-base balance, acid-base disorder, acidosis, acidemia, metabolic alkalosis, alkalosis, alkalemia, blood pH, bicarbonate, anion gap acidosis, normal anion gap metabolic acidosis, plasma bicarbonate, plasma bicarbonate level

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Contributor Information and Disclosures

Author

Christie P Thomas, MBBS, FRCP, FASN, FAHA, Professor, Department of Internal Medicine, Division of Nephrology; Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics
Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Federation for Medical Research, American Heart Association, American Society of Nephrology, American Society of Transplantation, American Thoracic Society, International Society of Nephrology, and Royal College of Physicians
Disclosure: Genzyme Grant/research funds Other

Coauthor(s)

Khaled Hamawi, MD, Transplant Nephrology Consultant, King Faisal Specialist Hospital & Research Center
Khaled Hamawi, MD is a member of the following medical societies: American Society of Nephrology and American Society of Transplantation
Disclosure: Nothing to disclose.

Medical Editor

James W Lohr, MD, Fellowship Program Director, Professor, Department of Internal Medicine, Division of Nephrology, State University of New York at Buffalo
James W Lohr, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, and Central Society for Clinical Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eleanor Lederer, MD, Consulting Staff, Louisville VA Hospital; Professor of Medicine; Interim Chief of Nephrology; Director of Nephrology Training Program; Director, Metabolic Stone Clinic; Director of Outpatient Clinics, Kidney Disease Program, University of Louisville School of Medicine
Eleanor Lederer, MD is a member of the following medical societies: American Association for the Advancement of Science, American Federation for Medical Research, American Society for Biochemistry and Molecular Biology, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Rebecca J Schmidt, DO, FACP, FASN, Professor of Medicine, Section Chief, Department of Medicine, Section of Nephrology, West Virginia University School of Medicine
Rebecca J Schmidt, DO, FACP, FASN is a member of the following medical societies: American College of Osteopathic Internists, American College of Physicians, American Medical Association, American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Renal Physicians Association, and West Virginia State Medical Association
Disclosure: Abbott Grant/research funds Speaking and teaching; Genzyme Honoraria Consulting; Amgen Honoraria Speaking and teaching; Ortho Biotech Honoraria Speaking and teaching

Chief Editor

Vecihi Batuman, MD, FACP, FASN, Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System
Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology
Disclosure: Nothing to disclose.

 
 
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