Protein-losing enteropathy (Proceedings)
Protein-losing enteropathy (PLE) denotes a clinical condition characterized by excessive loss of plasma proteins into the gastrointestinal tract. Protein-losing enteropathy occurs with a variety of gastrointestinal disorders including inflammatory bowel disease, neoplasia, fungal enteropathy, and intestinal lymphangiectasia. Simplistically, it is characterized by significant malabsorption of fat, fat soluble vitamins and other nutrients. Most animals with mucosal inflammation will have watery small bowel diarrhea; however, PLE associated with intestinal lymphangiectasia may cause no diarrhea but may cause abdominal effusion. Animals with PLE are important to recognize since (1) they usually present with overt gastrointestinal signs, (2) mucosal biopsy is generally required for definitive diagnosis, and (3) the prognosis in many cases is guarded to poor.
Pathophysiology of PLEThe mechanism for protein-loss in PLE patients may be due to inflammation, erosion affecting the normal barrier function of the gut, or to acquired or congenital abnormalities of the intestinal lymphatics promoting lymphatic hypertension. The source of the enteric protein loss in PLE patients is either the mucosal vasculature or the mucosal interstitial space. Alteration of the mucosal epithelial barrier by disease results in plasma protein loss into the intestinal lumen. The resultant hypoalbuminemia and hypoglobulinemia (e.g., panhypoproteinemia) is characteristic of PLE, and helps differentiate it from the hypoalbuminemia of glomerular disorders and hepatic disease.
Intestinal lymphangiectasia is associated with the loss of protein-rich chylomicrons into the gastrointestinal tract. Primary intestinal lymphangiectasia, characterized by congenital abnormalities to the intestinal lymphatic drainage, is uncommon in both dogs and cats. Secondary intestinal lymphangiectasia may develop in adult animals due to obstructive lesions involving ant part of the lymphatic system. Disorders of the hemolymphatic system contributing to secondary lymphagectasia may include neoplastic mucosal infiltration, granulomatous infiltration of the mucosa, pericardial disease, and right-sided heart failure.
Clinical Signs of Protein-losing Enteropathy
Animals with PLE usually exhibit clinical signs of caloric malnutrition and weight loss (severe cachexia and reduced BCS scores). There may be vomiting and diarrhea present, but these signs are not always seen. It is important to note that failure to exhibit diarrhea or other overt signs of gastrointestinal disease does not eliminate the possibility of PLE. Furthermore, PLE is exceedingly uncommon in the cat in comparison to the dog. Findings on the physical examination related to the underlying disease process responsible for PLE may be present and include palpably thickened bowel loops - suggestive of primary mucosal disease), abdominal effusion (suggestive of intestinal lymphangiectasia) and/or cardiac abnormalities. Edema and ascites are often present when serum albumin concentrations decrease to 1.0 g/dl and may occur at higher albumin values if there is concomitant papillary hypertension as seen with congestive heart disease or vasculitis.
Breed Predispositions for PLE
Breed predilections for intestinal PLE are not well documented but Yorkshire terriers, Basenjis, and soft-coated Wheaten Terriers apparently are at risk. Basenji dogs may develop a particularly severe form of PLE characterized by severe ulcerative gastroenterocolitis and hypergastrinemia. Wheaten terriers may also have a high incidence of concurrent protein-losing nephropathy which contributes to body protein depletion.
Diagnosis of PLE
Admission laboratory work consisting of a complete blood count, serum biochemistry profile, urinalysis, fecal examinations, and survey abdominal radiographs should be performed in suspect patients. Diagnosis is most commonly made by eliminating hepatobiliary disease (due to absence of hepatic enzyme elevations and normal serum bile acids and protein-losing nephropathy (based on normal urinalysis and a normal urine protein-to-creatinine ratio) as causes for hypoalbuminemia. Lymphopenia is commonly observed but may be inconsistently seen from one patient to the next. It should be noted that not all patients with PLE will have hypoglobulinemia. In my regional practice, gastrointestinal histoplasmosis may lead to significant increases in globulin concentration as part of the host inflammatory response. Note that the PLE seen with Basenji dogs is unusual in that it is characterized by hyperglobulinemia and hypoalbuminemia. Other biochemical changes occurring in PLE patients may include hypocalcemia and hypocholesterolemia. Hypocalcemia is primarily a reflection of decreased serum albumin as well as vitamin D malabsorption. Hypocholesterolemia presumably results from fat malabsorption associated with failure of chylomicron transport.
Although mucosal biopsy is indicated for definitive diagnosis in most instances, gastrointestinal function tests may provide important clues regarding the presence and magnitude of gastrointestinal protein loss. Estimation of fecal α1- proteinase inhibitor clearance has been shown to be a reliable method to detect PLE in humans and dogs. This plasma proteinase inhibitor has a molecular weight similar to that of albumin, and is present in the vascular space, in the intercellular space, and in lymph fluid. Thus, α1-PI is lost into the gastrointestinal tract whenever albumin leaks into the gastrointestinal lumen and may be measured. Unlike albumin, α1-PI is not degraded by proteolytic enzymes in the GI lumen and is readily passed in feces essentially intact where it can be detected using immunoassays.
If gastrointestinal mucosal disease is suspected, then intestinal biopsy is warranted. Enteroscopic examination may reveal a variety of mucosal abnormalities including increased granularity, multifocal erosions, and/or mucosal friability. With lymphangiectasia, the mucosal appearance may be milky-white or appear granular due to the presence of lipid-filled dilated villi which are readily observed. As with all small intestinal endoscopic biopsy procedures, 10-15 high quality, diagnostically-significant biopsies should be procured. Endoscopic exfoliative cytology is also extremely useful in confirming the presence of mucosal infiltrative disease such as lymphocytic-plasmacytic enteritis, alimentary lymphoma, and gastrointestinal histoplasmosis. In endoscopy cannot be performed, and then full-thickness mucosal biopsies may be obtained for histopathology. Alternatively, laparoscopy and procurement of full-thickness mucosal biopsies may also yield a final diagnosis.