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Protein-Losing Enteropathy - Causes, Symptoms, Diagnosis, and Treatment

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Protein-losing enteropathy occurs when too much protein is leaked into the gastrointestinal tract. To learn in detail, read the following article.

Medically reviewed by

Dr. Ghulam Fareed

Published At June 8, 2023
Reviewed AtApril 9, 2024


Protein-losing enteropathy is a syndrome characterized by the loss of serum proteins in the intestine. In most cases, this loss of protein is because of abnormalities in lymphatic flow. The lymphatic system plays an important role in the immune system and in the delivery of nutrients to the body. The lymphatic system absorbs the excess watery fluid (lymph) containing the proteins, cells, electrolytes, and other substances from the organs and returns it to the bloodstream. In a normal healthy body, the lymphatic channels from the liver and mesentery (which attach the intestines to the abdominal wall) drain towards the thoracic duct, which is the main lymphatic vessel draining the lymph. In the case of protein-losing enteropathy, the channels originating in the liver and connecting to the intestine or originating in the intestine flow in the opposite direction, causing leaks in the intestinal wall. There is no way the body can absorb the spilled lymphatic fluid.

What Is Protein-Losing Enteropathy?

Protein-losing enteropathy is a condition in which excess loss of proteins occurs through the gastrointestinal tract due to different etiologies. In the bloodstream, albumin is the protein that exists in the highest concentration. Albumin is made by the liver and a large amount of it is lost due to protein-losing enteropathy. The functions of albumin include transporting hormones and water retention in the bloodstream.

What Are the Signs and Symptoms of Protein-Losing Enteropathy?

  • Diarrhea.
  • Edema (swelling of tissues).
  • Bloating.
  • Pain in the abdomen.
  • Shortness of breath.
  • Feeding intolerance refers to the inability to consume or digest food without experiencing discomfort or illness.
  • Problems with tissue healing.
  • Ascites (excess fluid trapped in the abdomen).
  • Pericardial and pleural effusions (excess fluid around the heart).
  • Hypoproteinemia (lower than normal levels of protein in the body).
  • Severe malnutrition.
  • Hypocalcemia (low calcium in the body).
  • Lymphocyte deficiency indicates a shortage of lymphocytes, which are a specific type of white blood cell.
  • Susceptibility to infection.

What Is the Pathophysiology of Protein-Losing Enteropathy?

Protein-losing enteropathy occurs when the loss of proteins through the digestive tract is more than the synthesis of proteins by the body. Generally, the proteins entering the gut are degraded into amino acids and reabsorbed. The mucosal permeability increases in conditions causing erosions and inflammation of the gastrointestinal tract, resulting in excessive leakage of proteins into the intestine and poor reabsorption, leading to hypoproteinemia. There is an increased leak of lymph fluid into the gastrointestinal tract in conditions causing increased lymphatic pressure and lymphatic obstruction, leading to a deficiency of fat-soluble vitamins and protein loss.

What Is the Etiology of Protein-Losing Enteropathy?

There are three main groups of disorders that can cause excess protein loss in stools. They are:

Primary Erosive or Ulcerative Gastrointestinal Disorders - This includes gastrointestinal malignancies, inflammatory bowel diseases (Crohn's disease and ulcerative colitis), Clostridium difficile colitis, carcinoid syndrome, any erosions or ulcers of the stomach or duodenum and graft versus host disease.

Non-Erosive or Non-Ulcerative Gastrointestinal Disorders - This includes celiac disease, tropical sprue, amyloidosis, cutaneous burns, bacterial overgrowth, Whipple disease, collagenous colitis, mixed connective tissue disease, Meniere's disease, eosinophilic gastroenteritis, rheumatoid arthritis, systemic lupus erythematosus (SLE), parasitic intestinal infections, and acquired immunodeficiency syndrome (AIDS).

Disorders Causing Increased Interstitial Pressure or Lymphatic Obstruction - This includes right-sided heart failure, congenital heart disease, cirrhosis with portal hypertension gastropathy, hepatic venous outflow obstruction, primary intestinal lymphangiectasia, constrictive pericarditis, Fontan procedure for single ventricle, mesenteric tuberculosis or sarcoidosis, lymph enteric fistula, retroperitoneal fibrosis, thoracic duct obstruction, and lymphoma.

How to Diagnose Protein-Losing Enteropathy?

The diagnosis of protein-losing enteropathy is suspected in patients with hypoproteinemia once the other alternative causes such as chronic liver disease, severe malnutrition, or nephrotic syndrome have been ruled out. The diagnostic tests recommended include:

Blood Tests - The blood tests are done to check for levels of the specific protein, albumin. If the level of albumin is found low, then the stool test is done.

Stool Tests - This test is done to check for levels of protein alpha 1 antitrypsin (A1AT) in the stool. The presence of A1AT in the stool is a primary and important clue for the diagnosis of protein-losing enteropathy as it is not normally absorbed or secreted into the intestine. If the results show high levels of A1AT in the stool, then it is more likely that the loss of proteins is more.

Radioactive Albumin Test - In this test, radioactively labeled albumin is given to the patient, and the way it is cleared from the body is monitored. This test is done if the stool test is inconclusive.

Imaging Tests - This includes tests such as X-rays, CT (computed tomography) scans, and MRI (magnetic resonance imaging) scans. These tests are done to find out the underlying disease causing protein-losing enteropathy.

Endoscopy and Biopsy - Endoscopy involves the utilization of an endoscope, which is a slender and flexible tube equipped with a light and camera, to examine the gastrointestinal tract for potential diseases and, if necessary, obtain a tissue sample from the affected region. The extracted tissue sample is forwarded to a laboratory for the purpose of pathological testing, commonly referred to as a biopsy.

What Are the Treatment Options for Protein-Losing Enteropathy?

The primary objective in treating protein-losing enteropathy is to restore protein levels in the body and address the root cause of the condition. The treatment option includes:

1) Diet -

  • Adding dietary supplements to the routine.
  • Modifying diet so as to eat more food that is high in protein and low in fat.
  • Intravenous infusion of protein is done under medical supervision.

2) Medical Care - This focuses on treating the underlying cause of protein-losing enteropathy. Medications like steroids and diuretics are the first line of treatment as they can reduce the inflammation associated with the condition. For example, the patient with intestinal parasites is treated with appropriate medication for the infestation, and the patient with congestive heart failure is treated with diuretics and digitalis.

3) Surgical Care - Surgery is suggested for menetrier disease (giant hypertrophic gastropathy) and localized lymphatic obstruction. In these cases, lymphovenous anastomosis (affected lymph vessels are connected to a nearby vein to bypass the damaged area) proves to be beneficial. Embolization surgery to plug holes in the duodenum is used in case the cause involves lymph fluid entering the intestine.


Protein-losing enteropathy is characterized by a significant depletion of serum protein within the intestine. The complications of this condition depend on the underlying cause. The treatment focuses on increasing the level of protein in the body and treating the underlying cause. If there is successful management of the underlying cause, it can lead to the complete resolution of protein-losing enteropathy.

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Dr. Ghulam Fareed
Dr. Ghulam Fareed

Medical Gastroenterology


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