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Serum Albumin

What Is It, Regulation, and More

Author: Nikol Armata

Editors: Alyssa Haag, Ian Mannarino, MD, MBA, Kelsey LaFayette, DNP, RN

Illustrator: Jessica Reynolds, MS

Copyeditor: David G. Walker

What is serum albumin?

Serum albumin is the most abundant circulating plasma protein. It constitutes about half of the total protein content (3.4 to 5.4 g/dL) of the plasma (i.e., component of blood without blood cells). Albumin is a protein synthesized by hepatocytes in the liver and excreted in very high quantities in the blood. Minimal amounts of albumin are also stored in the liver. 

Once albumin enters the circulation, about 30% to 40% remains in the bloodstream and the rest enters the interstitial space. The serum albumin levels are a very useful laboratory value and are easily measured with a serum albumin test, which is a common blood test.

What is the purpose of albumin in the body?

Serum albumin has multiple homeostatic functions in the body. Most importantly, it maintains the intravascular oncotic pressure, preventing fluid leakage into the extravascular space. In addition, albumin functions as a carrier of several different endogenous (e.g., long chain fatty-acids, steroids) and exogenous (e.g., various medications) compounds in the blood. The binding of those substances to albumin can reduce their toxicity as seen in the cases of unconjugated bilirubin and medications (e.g., methadone, propranolol, furosemide, warfarin, and methotrexate). 

Albumin binds at least 40% of the circulating calcium and is a transporter of hormones, such as thyroxine, cortisol, and testosterone. It is also the main carrier of fatty acids, has significant antioxidant properties, and is involved in maintaining acid-base balance, acting as a blood plasma buffer. Serum albumin can also be used as a highly sensitive marker for an individual's nutritional status and severity of illness, particularly in chronically and critically ill individuals.

What do serum albumin levels indicate?

The serum albumin levels mainly reflect the liver’s biosynthetic capacity and, more specifically, its ability to produce proteins. Albumin levels combined with a prothrombin time (PT) provide a better assessment of the liver’s ability to function properly. However, serum albumin values may remain unaffected in individuals with chronic liver disease and be abnormal in those who do not have liver problems. 

What causes low serum albumin?

Hypoalbuminemia, or low serum albumin levels, may be a result of increased loss of albumin via the kidneys, gastrointestinal (GI) tract, skin, or extravascular space; intravascular volume expansion; increased catabolism of albumin; decreased production of albumin; or a combination of the above.

Increased Loss of Albumin

Renal Loss

Albumin loss from the kidneys is usually minimal (i.e., less than 30 mg per day), as albumin's large size prevents it from passing through the glomerulus. However, albuminuria, or the increased loss of albumin through urine output, may occur due to high fever, intense exercise, or from certain postures. Typically, increased renal loss of albumin results from damage to the glomerulus that can be caused in many different conditions. For example, nephrotic syndrome is characterized by renal loss of proteins and especially albumin (3.5 g or more of protein per day). Due to the significant proteinuria, nephrotic syndrome results in low serum albumin levels that lead to edema and ascites (i.e., accumulation of fluids within the abdomen). In addition, chronic kidney disease (CKD) often results in a loss of 30 to 300 mg of albumin per 24 hours for three or more months. Finally, end-stage renal disease also causes significant proteinuria and consequent hypoalbuminemia. 

Gut Loss

Protein-losing enteropathies are characterized by the considerable loss of proteins, including albumin, via the gastrointestinal tract. This loss exceeds the rate of protein synthesis, thereby leading to hypoalbuminemia. The protein loss in such cases is usually due to three main causes: conditions associated with increased lymphatic pressure (e.g., compression of the lymphatics due to lymphadenopathy, lymphangiectasis), conditions with erosions of the intestinal mucosa (e.g., Crohn disease), and certain conditions without mucosal erosions (e.g., celiac disease, scleroderma).

Intravascular Volume Expansion

Hypervolemia, an increase in blood volume, can also cause hypoalbuminemia due to dilution of the albumin in the intravascular space. For example, in pregnancy, and especially during the second and third trimester, hypoalbuminemia is a common finding as a result of fluid retention, plasma volume expansion, and decreased vascular resistance. 

Increased Catabolism of Albumin

Sepsis and Critical Illness

Critically ill and septic individuals are characterized by an increase in vascular permeability and capillary leakage resulting in albumin loss. Additionally, such critical conditions often lead to reduced synthesis and increased catabolism of albumin.

Decreased Production of Albumin

Decreased albumin production is a rare cause of hypoalbuminemia. Severe chronic liver impairment, like advanced hepatic cirrhosis, is required before a noticeable decrease in blood plasma albumin is evident.

Heart Failure

Hypoalbuminemia is very common in individuals with heart failure. Hypoalbuminemia in heart failure is a combination of various factors including malnutrition, inflammation, liver dysfunction, protein-losing enteropathies, and increased extravasation. The risk of hypoalbuminemia with heart failure increases as the disease progresses. 

Burns

Individuals with severe burns have an increased vascular permeability resulting in the extravasation of albumin from the intravascular to the extravascular compartments. There is also an acute phase response that affects liver protein synthesis and causes a further decrease in serum albumin levels. Serum albumin levels are also used to evaluate the severity of burn wounds and to predict the morbidity and mortality of affected individuals.

Nutritional Deficiency

Hypoalbuminemia is a common finding in malnourished individuals. The effects of fasting can cause a rapid decrease in albumin production, leading to a one-third decrease in albumin within the first 24 to 48 hours of fasting. Since malnourishment has been associated with adverse events in the postsurgical period, serum albumin is commonly used as a clinical indicator for nutritional optimization and readiness for surgery.  

Kwashiorkor is an example of severe malnutrition, which is present in starving children. Individuals with Kwashiorkor have low serum albumin levels due to a decreased supply of amino acids and other nutrients (e.g., iron and zinc) to the liver, leading to the accumulation of fluid in the body’s tissues. Additionally, individuals with anorexia nervosa may also have slightly decreased serum albumin levels due to their very low nutritional intake, although hypoalbuminemia is not the main consequence of this eating disorder.

What causes high serum albumin?

The most common cause of hyperalbuminemia, or high serum albumin levels, is dehydration. This is because there is a loss of intravascular fluid due to depletion. The amount of albumin may stay the same; however, because there is loss of fluids, the amount of albumin measured (g/dL) in blood serum is higher. Secondarily, hyperalbuminemia can also be associated with metabolic syndrome and, more specifically, insulin resistance. Although a significant correlation between albumin and diabetes has not been identified yet, studies have shown that insulin affects albumin production. Insulin-resistant conditions that may be identified, especially in individuals with metabolic syndrome, can act as a triggering factor, increasing the production of albumin by the liver.

How is serum albumin regulated?

Serum albumin regulation varies depending on the concentration of albumin in the blood plasma. With a half-life of about 20 days, albumin is constantly degraded by lysosomal enzymes despite a non-fixed catabolic rate (i.e., the time needed to break down complex substances into simpler ones). Its sites of degradation are widespread throughout the body and include the kidneys, capillaries, and liver sinuses. Albumin’s catabolic rate is slowly reduced when serum albumin levels are low, as is the case with protein deficiency, cirrhosis, nephrotic syndrome, and diseases of the gastrointestinal tract. On the other hand, infusion of albumin may slowly increase its catabolic rate. This must be taken into consideration by a clinician when trying to regulate serum albumin levels in chronic diseases. 

As a short-term regulatory mechanism when albumin levels are low, a shift of albumin from the extravascular to the intravascular compartment may occur. The regulation of albumin’s synthesis and degradation is independent of each other; albumin’s synthesis is mostly affected by alterations in the body’s osmotic pressure (i.e., a force determined by the difference in solutes between the two sides of the cell membrane), whereas its degradation is dependent on concentration of albumin. This mechanism effectively regulates the serum albumin level.

What are the most important facts to know about serum albumin?

Serum albumin is a plasma protein with multiple homeostatic functions in the body; it maintains the intravascular oncotic pressure and carries many compounds of the blood, like hormones, ions, and various medications. Albumin’s regulation varies, depending on its concentration in the blood plasma. Hypoalbuminemia may be a result of increased loss of albumin via the kidneys, gastrointestinal (GI) tract, skin, or extravascular space; intravascular volume expansion; increased catabolism of albumin; decreased albumin production; or a combination of the above. Hyperalbuminemia, on the other hand, is usually associated with dehydration, and less frequently with metabolic syndrome. 

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