Hypoalbuminemia 

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

Background

Albumin, the body's predominant serum-binding protein, has several important functions, as follows:

  • Albumin comprises 75-80% of normal plasma colloid oncotic pressure and 50% of protein content. When plasma proteins, especially albumin, no longer sustain sufficient colloid osmotic pressure to counterbalance hydrostatic pressure, edema develops.
  • Albumin transports various substances, including bilirubin, fatty acids, metals, ions, hormones, and exogenous drugs. One consequence of hypoalbuminemia is that drugs that are usually protein bound are free in the plasma, allowing for higher drug levels, more rapid hepatic metabolism, or both.
  • Alterations in albumin level affect platelet function.Albumin. Albumin.

Reference serum values range from 3.5-4.5 g/dL, with a total body content of 300-500 g. Synthesis occurs only in hepatic cells at a rate of approximately 15 g/d in a healthy person, but the rate can vary significantly with various types of physiologic stress. The half-life of albumin is approximately 21 days, with a degradation rate of approximately 4% per day.

Hypoalbuminemia is a common problem among persons with acute and chronic medical conditions. At the time of hospital admission, 20% of patients have hypoalbuminemia. Hypoalbuminemia can be caused by various conditions, including nephrotic syndrome, hepatic cirrhosis, heart failure, and malnutrition; however, most cases of hypoalbuminemia are caused by acute and chronic inflammatory responses.

Serum albumin level is an important prognostic indicator. Among hospitalized patients, lower serum albumin levels correlate with an increased risk of morbidity and mortality.

The presentation, physical examination findings, and laboratory results associated with hypoalbuminemia depending on the underlying disease process.

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Pathophysiology

Serum albumin levels are dependent on the rate of synthesis, the amount secreted from the liver cell, the distribution in body fluids, and the level of degradation. Hypoalbuminemia results from a derangement in one or more of these processes.

Synthesis

Albumin synthesis begins in the nucleus, where genes are transcribed into messenger ribonucleic acid (mRNA). The mRNA is secreted into the cytoplasm, where it is bound to ribosomes, forming polysomes that synthesize preproalbumin. Preproalbumin is an albumin molecule with a 24 amino acid extension at the N terminus. The amino acid extension signals insertion of preproalbumin into the membrane of the endoplasmic reticulum. Once inside the lumen of the endoplasmic reticulum, the leading 18 amino acids of this extension are cleaved, leaving proalbumin (albumin with the remaining extension of 6 amino acids). Proalbumin is the principal intracellular form of albumin. Proalbumin is exported to the Golgi apparatus, where the extension of 6 amino acids is removed prior to secretion of albumin by the hepatocyte. Once synthesized, albumin is secreted immediately; it is not stored in the liver.

Distribution

Tracer studies with iodinated albumin show that intravascular albumin is distributed into the extravascular spaces of all tissues, with the majority being distributed in the skin. Approximately 30-40% (210 g) of albumin in the body is found within the vascular compartments of the muscle, skin, liver, gut, and other tissues.

Albumin enters the intravascular space via 2 pathways. First, albumin enters this space by entering the hepatic lymphatic system and moving into the thoracic duct. Second, albumin passes directly from hepatocytes into the sinusoids after traversing the Space of Disse.

After 2 hours, 90% of secreted albumin remains within the intravascular space. The half-life of intravascular albumin is 16 hours. Daily losses of albumin from the intravascular space are approximately 10%. Certain pathological conditions, such as nephrosis, ascites, lymphedema, intestinal lymphangiectasia, and edema, can increase the daily loss of albumin from the plasma.

Albumin distributes into the hepatic interstitial volume, and the concentration of colloids in this small volume is believed to be an osmotic regulator for albumin synthesis. This is the principal regulator of albumin synthesis during normal periods without stress.

Degradation

Degradation of albumin is poorly understood. After secretion into the plasma, the albumin molecule passes into tissue spaces and returns to the plasma via the thoracic duct. Tagged albumin studies suggest that albumin may be degraded within the endothelium of the capillaries, bone marrow, and liver sinuses. Albumin molecules apparently degrade randomly, with no differentiation between old and new molecules.

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Epidemiology

Frequency

United States

Hypoalbuminemia is more frequent in older patients who are institutionalized, patients who are hospitalized with advanced stages of disease (eg, terminal cancer), and malnourished children.

Mortality/Morbidity

Low serum albumin levels are an important predictor of morbidity and mortality. A meta-analysis of cohort studies found that, with every 10 g/L decrease in serum albumin, mortality was increased by 137% and morbidity increased by 89%. Patients with serum albumin levels of less than 35 at 3 months following discharge from the hospital have a 2.6 times greater 5-year mortality than those with a serum albumin levels greater than 40.

Hypoalbuminemia has also been studied as an important prognostic factor among subsets of patients, such as patients with severe sepsis, burns, and regional enteritis (Crohn disease).

Whether or not hypoalbuminemia is merely a marker of severe protein malnutrition, which itself is a cause of increased morbidity and mortality or an independent risk factor for death, is unclear.

Race

No race predilection exists.

Sex

No sex predilection exists.

Age

Hypoalbuminemia affects persons of all age groups, depending on the underlying cause.

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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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