Hypoalbuminemia Clinical Presentation

  • Author: Ruben Peralta, MD, FACS; Chief Editor: Michael R Pinsky, MD, CM, FCCP, FCCM   more...
 
Updated: Apr 15, 2010
 

History

The potential underlying causes of hypoalbuminemia are numerous. Patients' histories vary significantly depending on the underlying disease state.

  • Gather past medical history for a history of liver or renal failure, hypothyroidism, malignancy, and malabsorption.
  • Evaluate the patient for appropriate dietary intake.
  • Seek potential causes of acute or chronic inflammation that could explain the low albumin levels.
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Physical

Abnormal physical examination findings may be found in multiple organ systems depending on the underlying disease. The findings listed below suggest the potential underlying disease processes rather than the underlying hypoalbuminemia per se.

  • Head, eyes, ears, nose, and throat - Facial edema, macroglossia, parotid swelling, conjunctival icterus, temporal wasting
  • Integumentary - Loss of subcutaneous fat, delayed wound healing, dry coarse skin, painful dermatoses, peripheral edema, thin hair, spider angiomas, palmar erythema, changes due to surgery and burns, jaundice
  • Cardiovascular - Bradycardia, hypotension, cardiomegaly
  • Respiratory - Decreased respiratory expansion due to pleural effusion and weakened intercostal muscles
  • Gastrointestinal - Hepatosplenomegaly, ascites
  • Musculoskeletal - Muscle wasting, growth retardation in children, atrophy of the interosseus hand muscles
  • Neurological - Encephalopathy, asterixis
  • Genitourinary - Testicular atrophy
  • Endocrine - Gynecomastia, hypothermia, thyromegaly
  • Other - Various other signs related to associated specific nutrient deficiencies
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Causes

Hypoalbuminemia can result from decreased albumin production, defective synthesis because of hepatocyte damage, deficient intake of amino acids, increased losses of albumin via GI or renal processes, and, most commonly, acute or chronic inflammation. Some of the many causes are as follows:

  • Protein malnutrition: Deficient protein intake results in the rapid loss of cellular ribonucleic acid and disaggregation of the endoplasmic reticulum–bound polysomes and, therefore, decreased albumin synthesis. Albumin synthesis can decrease by more than one third during a 24-hour fast. Albumin synthesis may be stimulated by amino acids produced in the urea cycle, such as ornithine.
  • Defective synthesis: In patients with cirrhosis, synthesis is decreased because of the loss of hepatic cell mass. Also, portal blood flow is often decreased and poorly distributed, leading to maldistribution of nutrients and oxygen. The flow of substrate may affect certain functions of the liver, including protein synthesis, which is decreased in patients with cirrhosis who lack ascites. Albumin synthesis may actually increase in patients with cirrhosis who have ascites, possibly because of a change in hepatic interstitial colloid levels, which may act as an overriding stimulus for albumin production. Although synthesis is increased, the concentration of albumin is decreased because of dilution.
  • Extravascular protein loss
    • Nephrotic syndrome: This can produce hypoalbuminemia by massive proteinuria, with 3.5 g or more of protein lost within 24 hours. Albumin is filtered by the glomerulus and catabolized by the renal tubules into amino acids that are recycled. In patients with chronic renal disease, in whom both glomerular and tubular diseases are present, excessive protein filtration may lead to both increased protein loss and increased degradation. Only at higher rates of albuminuria (>100 mg/kg/d) and only when the diet is adequate is albumin synthesis increased.
    • Protein-losing enteropathy: Under normal conditions, less than 10% of the total albumin is lost through the intestine. This fact has been confirmed by comparing albumin labeled with chromium-51, which helps measure intestinal losses, to albumin labeled with iodine-125, which helps measure overall degradation. In cases of protein-losing enteropathy related to bacterial overgrowth, hypoalbuminemia is exacerbated by peripheral factors that inhibit albumin synthesis by mechanisms similar to those observed with burns, trauma, infection, and carcinoma.
    • Extensive burns: The skin is the major site for extravascular albumin storage and is the major exchangeable albumin pool needed to maintain plasma levels. Hypoalbuminemia results from direct losses of albumin from tissue damage, from compromised hepatic blood flow due to volume loss, and from inhibitory tissue factors (eg, tumor necrosis factor, interleukin-1, interleukin-6) released at the burn sites.
    • Lymphatic blockage or mucosal disease: Diseases that result in protein loss from the intestine are divided into 2 main types. The first is lymphatic blockage, which can be caused by constrictive pericarditis, ataxia telangiectasia, and mesenteric blockage due to tumor. The second is mucosal disease with direct loss into the bowel, which is observed with (1) inflammatory bowel disease and sprue and (2) bacterial overgrowth, as in blind loop syndrome after intestinal bypass surgery.
  • Hemodilution: In the presence of ascites from any cause, the serum albumin level is not a good index of the residual synthetic capacity of the liver unless actual radioisotopic measurements of production are used. With ascites, synthesis may be normal or even increased, but serum levels are low because of the larger volume of distribution. This is true even for ascites due to cirrhosis.
  • Congestive heart failure: The synthesis of albumin is normal in patients with congestive heart failure. Hypoalbuminemia results from an increased volume of distribution.
    • Oncotic pressure increase: The serum oncotic pressure partially regulates albumin synthesis. The regulation site may be the oncotic content in the hepatic interstitial volume because albumin synthesis is inversely related to the content of this volume. Conditions that increase other osmotically active substances in the serum tend to decrease the serum albumin concentration by decreasing synthesis. Examples include elevated serum globulin levels in hepatitis and hypergammaglobulinemia.
  • Acute and chronic inflammation: Albumin levels that are low because of acute inflammation should normalize within weeks of resolution of the inflammation. Persistent hypoalbuminemia beyond this point should prompt an investigation for an ongoing inflammatory process. The cytokines (TNF, IL-6) released as part of the inflammatory response to physiologic stress (infection, surgery, trauma) can decrease serum albumin by the following mechanisms:
    • Increased vascular permeability (allowing albumin to diffuse into the extravascular space)
    • Increased degradation
    • Decreased synthesis (among other mechanisms, by activating TNF-a, which decreases transcription of the albumin gene)
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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 Association of Blood Banks, American College of Healthcare Executives, 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.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

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.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St 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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