Protein-losing enteropathy describes a wide range of gastrointestinal disorders that are associated with an excessive loss of plasma protein into the gut lumen. Normal daily enteric loss of plasma protein corresponds to less than 1-2% of the plasma pool. The route of plasma protein loss across the normal mucosa is not well defined. It is likely that rapid shedding of epithelial cells from the mucosal surface is accompanied by loss of plasma proteins from the lamina propria at the site of cell extrusion.

In virtually any small intestinal disease, excessive transmural loss of plasma proteins may result from several mechanisms: in mucosal disease without ulceration but with increased permeability; in mucosal disease with erosion or ulceration (loss of inflammatory exudate that contains protein occurs); and in lymphatic obstruction with direct leakage of intestinal lymph from obstructed lacteals. Protein-losing enteropathy may also occur as a result of colonic inflammation, ischemia or tumor. Adaptive changes in endogenous synthesis of individual plasma proteins may compensate partially for excessive enteric loss.

Clinically, albumin loss may be manifested by dependent edema. A depression of the levels of thyroid and cortisol binding proteins will lower the total plasma level of these hormones, although normal levels of free hormone will maintain normal hormone function. Excessive enteric loss of plasma proteins other than albumin rarely leads to clinical problems; secondary hypogammaglobulinemia in these patients does not predispose them to infection, and the loss of blood clotting factors is rarely sufficient to impair hemostasis.

Patients with protein-losing enteropathy due to lymphatic obstruction, however, lose not only albumin and other plasma proteins but also intestinal lymph, with loss of long-chain triglycerides, fat-soluble vitamins and small lymphocytes.

Protein-losing enteropathy is considered in patients who exhibit hypoproteinemia and in whom other causes for hypoproteinemia (e.g., proteinuria, protein malnutrition and liver disease) are excluded. Fecal protein loss can then be quantitated using ⁵¹Cr-labeled albumin or a₁-antitrypsin clearance into stool.

Management of protein-losing enteropathy involves the appropriate treatment of the disease(s) causing the protein loss. Enteral or parenteral feeding can be used to improve nutrition while the underlying disease is being treated. Enteric protein loss in patients with intestinal lymphangiectasia usually decreases with a low-fat diet. The normal absorption of long-chain triglycerides stimulates intestinal lymph flow; in their absence there is a decrease in the pressure within intestinal lymphatic vessels and hence a diminished loss of lymph into the lumen. Medium-chain triglycerides, which do not require intestinal lymphatic transport, can be substituted for the long-chain triglycerides and further decrease intestinal lymphatic pressure, with subsequent reduction in enteric lymph and protein loss.