Albumin, the body's predominant serum-binding protein, transports a variety of substances, including bilirubin, fatty acids, metals, ions, hormones, and exogenous drugs. Albumin comprises 75-80% of normal plasma colloid oncotic pressure and 50% of protein content. 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 per day in a healthy person, but the rate can vary significantly with various types of physiologic stress. The half-life of albumin is approximately 20 days, with degradation of about 4% per day. Little is known about the site of degradation.

Albumin is one of the best indices of nutritional status as it relates to outcome. The level of serum albumin correlates directly with outcome; however, it is important to note that the underlying condition is of greater prognostic significance than the absolute albumin level. Because of the numerous possible diseases that produce hypoalbuminemia, the presentation, physical examination, and lab studies vary and are heavily dependent upon the underlying disease process.

The use of intravenous albumin therapy to increase intravascular osmotic pressure remains controversial, particularly when compared to nonprotein colloids (ie, dextran, hetastarch) and crystalloid solutions.

Pathophysiology: Serum albumin levels are dependent upon the rate of synthesis, secretion from the liver cell, distribution in body fluids, and degradation. Hypoalbuminemia results from a derangement in one or more of these processes.


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.


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.

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

After 2 hours, 90% of 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. 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 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 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. How many round trips that molecule makes while carrying on its functions before being degraded in approximately 20 days is unknown. Tagged albumin studies suggest that albumin may be degraded within the endothelium of the capillaries, bone marrow, and liver sinuses. Albumin molecules apparently are degraded randomly with no differentiation between old and new molecules.


Mortality/Morbidity: Mortality and morbidity depend upon the severity of the underlying disease; however, generally in patients who are critically ill, the risk of death is inversely related to serum albumin concentration.

Race: No race predilection exists.

Sex: No sex predilection exists.

Age: Hypoalbuminemia affects all age groups, depending on the underlying cause.

History: The potential underlying causes of hypoalbuminemia are numerous. Patients’ histories vary significantly depending upon the underlying disease state.

Physical: Abnormal physical findings may be found in multiple organ systems depending upon the underlying disease.

Causes: Hypoalbuminemia can result from decreased albumin production, defective synthesis because of hepatocyte damage, deficient intake of amino acids, increased losses of albumin via disease, and stress-induced catabolism of body protein. Some of the many causes are as follows:


Lab Studies:

Imaging Studies:


Histologic Findings: When hypoalbuminemia is due to cirrhosis, liver biopsy shows 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 (IgA nephropathy), or no changes (minimal change disease). Electron microscopy may show subepithelial immunoglobulin (IgG) deposits (membranous glomerulonephritis). A very large differential exists for secondary causes of nephrotic syndrome.


Medical Care: Treatment should focus on the underlying cause of hypoalbuminemia. Simply replacing albumin intravenously generally has been found to be ineffective and may be harmful.

Surgical Care: Only when indicated for underlying cause

Consultations: Depending upon the clinical situation, multiple consultations may be necessary.

Diet: Support the underlying cause with adequate nutrition (sufficient high biological value protein and caloric intake for anabolism).

Activity: Depends on severity of underlying disease


Hypoalbuminemia is a common phenomenon in patients with serious illness. Treatment should focus on the underlying cause rather than simply replacing albumin. In general, albumin supplementation transiently increases serum albumin, but it does not influence the clinical course. In fact, albumin administration can be harmful. Limited indications for albumin do exist, and considerable clinical judgment is required when administering albumin. However, in general, albumin is not given specifically to treat hypoalbuminemia, which is a marker for serious disease.


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