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Hypoalbuminemia: Differential Diagnoses & Workup

Author: Ruben Peralta, MD, FACS, Professor of Surgery, Anesthesia and Emergency Medicine, Senior Medical Advisor, Board of Directors, Program Chief of Trauma, Emergency and Critical Care, Consulting Staff, Professor Juan Bosch Trauma Hospital, Dominican Republic
Coauthor(s): Brad A Rubery, MD, Consulting Staff, Department of Internal Medicine, Division of Emergency Medicine, Gastroenterology Associates; Sarah C Langenfeld, MD, Assistant Professor of Psychiatry, Department of Psychiatry, University of Massachusetts Medical School; Attending Psychiatrist, Community HealthLink
Contributor Information and Disclosures

Updated: Nov 3, 2009

Workup

Laboratory Studies

  • Clinical suspicion of the underlying disease process should guide appropriate laboratory studies, some of which are outlined below.
    • Malnutrition: Lymphocyte count and blood urea nitrogen levels are decreased. Transferrin, prealbumin, and retinol-binding protein have shorter half-lives compared with albumin and better reflect short-term changes in nutritional status than albumin, which has a long half-life.
    • Inflammation: C-reactive protein levels and increased erythrocyte sedimentation rate are elevated.
    • Nephrotic syndrome: The 24-hour urine collection contains more than 3 g of protein in 24 hours.
    • Cirrhosis: Liver function test findings (transaminase levels) may be elevated or normal in patients who are cirrhotic. Coagulation studies may be abnormal. Cirrhosis has numerous potential etiologies, and more specific studies, such as hepatitis screening, may be needed.
    • Malabsorption: Fecal fat studies including Sudan qualitative stain for fat, 72-hour quantitative fecal fat collection, and fecal a-1-antitrypsin clearance are needed.
    • Serum protein electrophoresis results help to determine if hypergammaglobulinemia is present.
    • None of the various correction factors for determining the effects of hypoalbuminemia on the plasma calcium concentration has proven reliable. Corrected calcium (mg/dL) is equal to measured total calcium (mg/dL) plus 0.8 (average normal albumin level of 4.4 minus serum albumin [g/dL]). The only method of identifying true (ionized) hypocalcemia in the presence of hypoalbuminemia is to measure the ionized fraction directly.
    • Elderly patients living in nursing homes or other institutionalized settings who have hypoalbuminemia should be evaluated for treatable co-morbid conditions contributing to the malnutrition (eg, medications causing decreased appetite, thyroid dysfunction, diabetes, malabsorption, depression, cognitive impairment).

Imaging Studies

  • Liver ultrasound for evidence of cirrhosis
  • Small bowel barium series for mucosal abnormalities typical of malabsorption syndromes
  • Imaging studies as appropriate to seek infectious causes of inflammation and hypoalbuminemia (eg, chest radiography)
  • Echocardiogram for congestive heart failure

Procedures

  • Liver biopsy to confirm cirrhosis
  • Kidney biopsy to help evaluate etiology of nephrosis

Histologic Findings

When hypoalbuminemia is due to cirrhosis, liver biopsy findings show a loss of hepatic architecture, fibrosis, and nodular regeneration. The pattern of injury and special stains can help determine the etiology of cirrhosis.

When hypoalbuminemia is due to nephrotic syndrome secondary to a primary renal disorder, light microscopy may show sclerosis (focal glomerulosclerosis), mesangial immunoglobulin A (immunoglobulin A nephropathy), or no changes (minimal change disease). Electron microscopy may show subepithelial immunoglobulin G deposits (membranous glomerulonephritis).

More on Hypoalbuminemia

Overview: Hypoalbuminemia
Differential Diagnoses & Workup: Hypoalbuminemia
Treatment & Medication: Hypoalbuminemia
Follow-up: Hypoalbuminemia
Multimedia: Hypoalbuminemia
References
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References

  1. Vincent JL. Relevance of albumin in modern critical care medicine. Best Pract Res Clin Anaesthesiol. Jun 2009;23(2):183-91. [Medline].

  2. Finfer S, Bellomo R, McEvoy S, Lo SK, Myburgh J, Neal B, et al. Effect of baseline serum albumin concentration on outcome of resuscitation with albumin or saline in patients in intensive care units: analysis of data from the saline versus albumin fluid evaluation (SAFE) study. BMJ. Nov 18 2006;333(7577):1044. [Medline].

  3. [Best Evidence] Dubois MJ, Orellana-Jimenez C, Melot C, De Backer D, Berre J, Leeman M, et al. Albumin administration improves organ function in critically ill hypoalbuminemic patients: A prospective, randomized, controlled, pilot study. Crit Care Med. Oct 2006;34(10):2536-40. [Medline].

  4. Chojkier M. Inhibition of albumin synthesis in chronic diseases: molecular mechanisms. J Clin Gastroenterol. Apr 2005;39(4 Suppl 2):S143-6. [Medline].

  5. Cochrane Injuries Group Albumin Reviewers. Human albumin administration in critically ill patients: systematic review of randomised controlled trials. Cochrane Injuries Group Albumin Reviewers. ALYSIS. Jul 25 1998;317(7153):235-40. [Medline].

  6. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008. Intensive Care Med. Jan 2008;34(1):17-60. [Medline].

  7. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. Jan 2008;36(1):296-327. [Medline].

  8. Don BR, Kaysen G. Serum albumin: relationship to inflammation and nutrition. Semin Dial. Nov-Dec 2004;17(6):432-7. [Medline].

  9. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. May 27 2004;350(22):2247-56. [Medline].

  10. Gibbs J, Cull W, Henderson W, Daley J, Hur K, Khuri SF. Preoperative serum albumin level as a predictor of operative mortality and morbidity: results from the National VA Surgical Risk Study. Arch Surg. Jan 1999;134(1):36-42. [Medline].

  11. Haller C. Hypoalbuminemia in renal failure: pathogenesis and therapeutic considerations. Kidney Blood Press Res. 2005;28(5-6):307-10. [Medline].

  12. Haynes GR, Navickis RJ, Wilkes MM. Albumin administration--what is the evidence of clinical benefit? A systematic review of randomized controlled trials. Eur J Anaesthesiol. Oct 2003;20(10):771-93. [Medline].

  13. Herrmann FR, Safran C, Levkoff SE, Minaker KL. Serum albumin level on admission as a predictor of death, length of stay, and readmission. Arch Intern Med. Jan 1992;152(1):125-30. [Medline].

  14. Johnson AM. Low levels of plasma proteins: malnutrition or inflammation?. Clin Chem Lab Med. Feb 1999;37(2):91-6. [Medline].

  15. Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr. Aug 2004;80(2):299-307. [Medline].

  16. Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, McAllister CJ, Alcorn H Jr, Kopple JD. Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction. Nephrol Dial Transplant. Sep 2005;20(9):1880-8. [Medline].

  17. Kalantar-Zadeh K, Kopple JD, Humphreys MH, Block G. Comparing outcome predictability of markers of malnutrition-inflammation complex syndrome in haemodialysis patients. Nephrol Dial Transplant. Jun 2004;19(6):1507-19. [Medline].

  18. Kaysen GA, Chertow GM, Adhikarla R, et al. Inflammation and dietary protein intake exert competing effects on serum albumin and creatinine in hemodialysis patients. Kidney Int. Jul 2001;60(1):333-40. [Medline].

  19. Kaysen GA, Dubin JA, Muller HG, et al. Relationships among inflammation nutrition and physiologic mechanisms establishing albumin levels in hemodialysis patients. Kidney Int. Jun 2002;61(6):2240-9. [Medline].

  20. Kaysen GA, Dubin JA, Müller HG, Rosales L, Levin NW, Mitch WE. Inflammation and reduced albumin synthesis associated with stable decline in serum albumin in hemodialysis patients. Kidney Int. Apr 2004;65(4):1408-15. [Medline].

  21. Kerr RM, Du Bois JJ, Holt PR. Use of 125-I- and 51-Cr-labeled albumin for the measurement of gastrointestinal and total albumin catabolism. J Clin Invest. Dec 1967;46(12):2064-82. [Medline].

  22. McIntyre LA, Fergusson D, Cook DJ, Nair RC, Bell D, Dhingra V, et al. Resuscitating patients with early severe sepsis: a Canadian multicentre observational study. Can J Anaesth. Oct 2007;54(10):790-8. [Medline].

  23. McIntyre LA, Hébert PC, Fergusson D, Cook DJ, Aziz A. A survey of Canadian intensivists' resuscitation practices in early septic shock. Crit Care. 2007;11(4):R74. [Medline].

  24. Myburgh J, Cooper DJ, Finfer S, Bellomo R, Norton R, Bishop N, et al. Saline or albumin for fluid resuscitation in patients with traumatic brain injury. N Engl J Med. Aug 30 2007;357(9):874-84. [Medline].

  25. Offringa M. Excess mortality after human albumin administration in critically ill patients. Clinical and pathophysiological evidence suggests albumin is harmful. BMJ. Jul 25 1998;317(7153):223-4. [Medline].

  26. Pulimood TB, Park GR. Debate: Albumin administration should be avoided in the critically ill. Crit Care. 2000;4(3):151-5. [Medline].

  27. Puskarich-May CL, Sullivan DH, Nelson CL, et al. The change in serum protein concentration in response to the stress of total joint surgery: a comparison of older versus younger patients. J Am Geriatr Soc. May 1996;44(5):555-8. [Medline].

  28. Reuben DB. Quality indicators for the care of undernutrition in vulnerable elders. J Am Geriatr Soc. Oct 2007;55 Suppl 2:S438-42. [Medline].

  29. Rothschild MA, Oratz M, Schreiber SS. Albumin synthesis (second of two parts). N Engl J Med. Apr 13 1972;286(15):816-21. [Medline].

  30. Rothschild MA, Oratz M, Schreiber SS. Albumin synthesis. 1. N Engl J Med. Apr 6 1972;286(14):748-57. [Medline].

  31. Rothschild MA, Oratz M, Schreiber SS. Alcohol, amino acids, and albumin synthesis. Gastroenterology. Dec 1974;67(6):1200-13. [Medline].

  32. Rothschild MA, Oratz M, Schreiber SS. Serum albumin. Hepatology. Mar-Apr 1988;8(2):385-401. [Medline].

  33. Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. BMJ. Mar 28 1998;316(7136):961-4. [Medline].

  34. Schortgen F, Lacherade JC, Bruneel F, Cattaneo I, Hemery F, Lemaire F, et al. Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study. Lancet. Mar 24 2001;357(9260):911-6. [Medline].

  35. Sullivan DH, Roberson PK, Bopp MM. Hypoalbuminemia 3 months after hospital discharge: significance for long-term survival. J Am Geriatr Soc. Jul 2005;53(7):1222-6. [Medline].

  36. Sung J, Bochicchio GV, Joshi M. Admission serum albumin is predicitve of outcome in critically ill trauma patients. Am Surg. Dec 2004;70(12):1099-102. [Medline].

  37. Vermeulen LC, Ratko TA, Erstad BL, et al. A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. Arch Intern Med. Feb 27 1995;155(4):373-9. [Medline].

  38. Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM. Hypoalbuminemia in acute illness: is there a rationale for intervention? A meta-analysis of cohort studies and controlled trials. Ann Surg. Mar 2003;237(3):319-34. [Medline].

  39. Vincent JL, Navickis RJ, Wilkes MM. Morbidity in hospitalized patients receiving human albumin: a meta-analysis of randomized, controlled trials. Crit Care Med. Oct 2004;32(10):2029-38. [Medline].

  40. Wilkes MM, Navickis RJ. Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials. Ann Intern Med. Aug 7 2001;135(3):149-64. [Medline].

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Further Reading

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Keywords

hypoalbuminemia, albumin, decreased albumin production, defective albumin synthesis, deficient intake of amino acids, increased albumin loss, stress-induced catabolism of body protein, protein malnutrition, protein-losing enteropathy

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Contributor Information and Disclosures

Author

Ruben Peralta, MD, FACS, Professor of Surgery, Anesthesia and Emergency Medicine, Senior Medical Advisor, Board of Directors, Program Chief of Trauma, Emergency and Critical Care, Consulting Staff, Professor Juan Bosch Trauma Hospital, Dominican Republic
Ruben Peralta, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Association for Academic Surgery, Eastern Association for the Surgery of Trauma, Massachusetts Medical Society, Society of Critical Care Medicine, and Society of Laparoendoscopic Surgeons
Disclosure: Nothing to disclose.

Coauthor(s)

Brad A Rubery, MD, Consulting Staff, Department of Internal Medicine, Division of Emergency Medicine, Gastroenterology Associates
Brad A Rubery, MD is a member of the following medical societies: American College of Physicians and American Medical Association
Disclosure: Nothing to disclose.

Sarah C Langenfeld, MD, Assistant Professor of Psychiatry, Department of Psychiatry, University of Massachusetts Medical School; Attending Psychiatrist, Community HealthLink
Sarah C Langenfeld, MD is a member of the following medical societies: American Medical Association, American Psychiatric Association, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Sat Sharma, MD, FRCPC, Professor and Head, Division of Pulmonary Medicine, Department of Internal Medicine, University of Manitoba; Site Director, Respiratory Medicine, St Boniface General Hospital
Sat Sharma, MD, FRCPC is a member of the following medical societies: American Academy of Sleep Medicine, American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, American Thoracic Society, Canadian Medical Association, Royal College of Physicians and Surgeons of Canada, Royal Society of Medicine, Society of Critical Care Medicine, and World Medical Association
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Harold L Manning, MD, Associate Professor, Departments of Medicine, Anesthesiology and Physiology, Section of Pulmonary and Critical Care Medicine, Dartmouth Medical School
Harold L Manning, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michael R Pinsky, MD, CM, FCCP, FCCM, Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology, Vice-Chair, Academic Affairs, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center
Michael R Pinsky, MD, CM, FCCP, FCCM is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American Heart Association, American Thoracic Society, Association of University Anesthetists, Shock Society, and Society of Critical Care Medicine
Disclosure: LiDCO Ltd Honoraria Consulting; iNTELOMED Intellectual property rights Board membership; Edwards Lifesciences Honoraria Consulting; Applied Physiology, Ltd Honoraria Consulting; Cheetah Medical Consulting fee Consulting

 
 
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