Protein-Losing Enteropathy

Protein-Losing Enteropathy

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Protein-losing enteropathy is characterized by the severe loss of serum proteins into the intestine. [1] Normal protein loss in the gastrointestinal tract mainly consists of sloughed enterocytes and pancreatic and biliary secretions. Albumin loss through the gastrointestinal tract normally accounts for 2-15% of the total body degradation of albumin, but, in patients with severe protein-losing gastrointestinal disorders, the enteric protein loss may reach up to 60% of the total albumin pool.

The serum protein level reflects the balance between protein synthesis, metabolism, and protein loss. Protein-losing enteropathy is characterized by more loss of proteins via the gastrointestinal tract than synthesis leading to hypoalbuminemia. It is not a single disease, but an atypical manifestation of other diseases. [2]

The pathophysiology of this disorder is directly related to the excessive leakage of plasma proteins into the lumen of the gastrointestinal tract. Mechanisms for gastrointestinal protein loss include lymphatic obstruction, mucosal disease with erosions, ulcerations, or increased mucosal permeability to proteins as a result of cell damage or death. Proteins entering the gastrointestinal tract are metabolized into constituent amino acids by gastric, pancreatic, and small intestinal enzymes and are reabsorbed. When the rate of gastrointestinal protein loss exceeds the body’s capacity to synthesize new proteins, hypoproteinemia develops. [3]

Primary gastrointestinal mucosal diseases (typically ulcerative/erosive) include the following:

Erosions or ulcerations of the esophagus, stomach, or duodenum

Regional enteritis

Graft versus host disease

Pseudomembranous colitis (Clostridium difficile) [4]

Mucosal-based neoplasia

Carcinoid syndrome

Idiopathic ulcerative jejunoileitis

Amyloidosis [5]

Kaposi sarcoma

Protein dyscrasia

Ulcerative colitis


Cytomegalovirus infection [6]

Increased interstitial pressure or lymphatic obstruction leading to protein loss can be caused by the following:



Retroperitoneal fibrosis


Intestinal endometriosis

Lymphoenteric fistula

Whipple disease

Cardiac disease (constrictive pericarditis or congestive heart failure)

Intestinal lymphangiectasia [7]

Nonerosive upper gastrointestinal diseases include the following:

Cutaneous burns [8]

Whipple disease

Connective tissue disorders

Acquired immunodeficiency syndrome (AIDS) [2]

Enteropathy, such as angioedema (idiopathic or hereditary) and Henoch-Schönlein purpura

Celiac sprue

Tropical sprue

Allergic gastroenteritis

Eosinophilic gastroenteritis

Giant hypertrophic gastritis (Ménétrier disease) [9, 10, 11]

Bacterial overgrowth

Intestinal parasites

Microscopic colitis

Dientamoeba fragilis [12]

Cases in which protein-losing enteropathy was the initial manifestation of systemic lupus erythematosus have been reported. [13, 14]

Protein-losing enteropathy can also occur as a complication of the Fontan procedure, an operation for several congenital heart abnormalities; the surgery allows systemic venous blood to reach the lungs without circulating through a ventricle. [15, 16, 17]  In children, protein-losing enteropathy may occur before or after the procedure, especially in the setting of hemodynamic disturbances. [18]

The prevalence rate is not known.

The prevalence rate is not known.

No racial, sexual, or age predilection exists.

A retrospective study by John et al indicated that the survival rate has increased for patients who develop protein-losing enteropathy as a complication of the Fontan procedure, an operation for the treatment of several types of congenital heart abnormalities. Although the 5-year mortality rate has been reported to be 50% for patients who develop protein-losing enteropathy following the surgery, the investigators found that in 42 such patients identified from Mayo Clinic clinical databases, the survival rate at 5 years after the diagnosis of enteropathy was 88%. [16]

The survival rate tended to be lower, however, in patients with a high Fontan pressure, reduced ventricular function (ejection fraction < 55%), and a New York Heart Association functional classification of greater than 2. Treatments associated with a higher survival rate included spironolactone, octreotide, and sildenafil, as well as the creation of fenestrae and Fontan obstruction relief. [16]

Morbidity and mortality of this condition directly relate to its cause, either primary gastrointestinal disease or a multisystem disorder.

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Naeem Aslam, MD Fellow, Department of Medicine, Division of Gastroenterology/Hepatology, University of Louisville School of Medicine

Naeem Aslam, MD is a member of the following medical societies: American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Richard Wright, MD Professor and Chief, Department of Medicine, Division of Gastroenterology/Hepatology, University of Louisville School of Medicine

Richard Wright, MD is a member of the following medical societies: American Association for Physician Leadership, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Noel Williams, MD, FRCPC FACP, MACG, Professor Emeritus, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada; Professor, Department of Internal Medicine, Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada

Noel Williams, MD, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

Burt Cagir, MD, FACS Clinical Professor of Surgery, The Commonwealth Medical College; Director, General Surgery Residency Program, Robert Packer Hospital; Attending Surgeon, Robert Packer Hospital and Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Terence David Lewis, MBBS, MBBS 

Terence David Lewis, MBBS, MBBS is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, California Medical Association, Royal College of Physicians and Surgeons of Canada, Sigma Xi

Disclosure: Nothing to disclose.

Protein-Losing Enteropathy

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