Hypoalbuminemia Clinical Presentation

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.

Abnormal physical examination findings may be found in multiple organ systems depending on the underlying disease. The following findings 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

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 discussed below.

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)