Protein losing enteropathy
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Synonyms and keywords: Protein loss, protein deficiency, GI protein loss, gastrointestinal protein loss, protein-losing gastroenteropathy, protein-losing gastroenteropathy, gastroenteropathy, gastric protein loss, helicobacter pylori, H pylori, giant hypertrophic gastropathy, menetrier disease, ménétrier, disease, loss of plasma proteins from the gastrointestinal tract, excessive leakage of plasma proteins into the lumen of the gastrointestinal tract, lymphatic obstruction, mucosal disease with erosions, ulcerations, swelling of the legs, peripheral edema, decreased plasma oncotic pressure
Protein losing enteropathy is the loss of plasma proteins from the gastrointestinal tract caused by an array of abnormalities, such as primary gastrointestinal diseases and lymphatic obstruction. Protein losing enteropathy is not a separate disease entity but a complication of different pathological conditions leading to hypoproteinemia. Treatment is tailored towards the underlying etiology leading to protein losing enteropathy as a complication.
- There is no historical significance associated with protein losing enteropathy.
- There is no classification for protein losing enteropathy according to recent updates.
Normally there is a balance between the synthesis and degradation of proteins maintained by a series of interconnected processes in the body. Any condition which disrupts the normal protein stasis where the loss of protein through the gastrointestinal tract exceeds the body’s ability to synthesize proteins failing to compensate for the loss leads to the development of a state of low serum protein called hypoproteinemia. 
- Primary gastrointestinal diseases such as inflammatory bowel disease and malignancies initiates a series of abnormal changes leading to the disruption of the protective mucosal layer of the gut resulting in inflammation, erosions and ulcerations of the normal mucosa leading to:
- Alteration in the mucosal lining of the gut.
- An increase in the permeability for the previously semi-permeable and non-permeable proteins, leading to excessive protein leakage through gastrointestinal tract.
- Decrease surface area for protein reabsorption leading to poor reabsorption.
- Non-erosive gastrointestinal conditions such as connective tissue disorders and infectious diseases affecting the mucosa of the gastrointestinal tract causes the leakage of proteins into the lumen of gastrointestinal tract in a similar manner as erosive gastrointestinal diseases.
- Conditions leading to lymphatic obstruction such as lymphomas and other benign or malignant masses causes an increase in the pressure inside the lymphatic system which forces the lymph to leak out of the lymphatic vessels into the lumen of gastrointestinal tract leading to protein loss. 
Most cases of protein losing enteropathy are caused as a result of:
- Primary gastrointestinal diseases
- Lymphatic obstruction
Primary Gastrointestinal Diseases
Primary gastrointestinal diseases causing erosion or ulceration of the mucosa of the gut leading to fecal loss of proteins such as:
- Inflammatory bowel diseases (Crohn disease, Ulcerative colitis)
- Malignancies involving the gut mucosa
- Graft vs. host disease
- Esophageal and gastric erosions or ulcerations
- Carcinoid syndrome
- Bacterial infection with Clostridium difficile causing pseudomembranous colitis
- Parasitic infection with Giardia
Non-Erosive/Ulcerative Mucosal involvement
- Celiac disease
- Eosinophilic gastritis
- Hypertrophic gastritis
- Connective tissue disorders: Systemic lupus erythematosus
- Cutaneous burns
Conditions responsible for causing lymphatic obstruction leading to the leakage of lymph into the lumen of gut such as:
- Congenital or acquired lymphatic diseases
- Lymphatic filariasis
- Cardiovascular diseases: Congestive heart failure, Restrictive pericarditis
- Intestinal Tuberculosis
- Fontan surgical procedure
- Cirrhosis with portal hypertension
- Retroperitoneal fibrosis  
Complete Differential Diagnosis Of Underlying Causes
Protein losing enteropathy must be differentiated from any condition causing hypoproteinemia. Some common condition are listed below:    
- Acute gastroenteritis
- Bacterial overgrowth
- Carcinoid Syndrome
- Clostridium Difficile
- Heart Failure
- Connective tissue disorders
- Chronic liver diseases
- Nephrotic syndrome
- Severe protein calorie malnutrition
- Malabsorption syndromes
- Graft vs. Host Disease
- Intestinal parasites
- Menetrier's Disease
- Pseudomembranous colitis
- Retroperitoneal fibrosis
As hypoproteinemia is the key factor in evaluating a patient for protein losing enteropathy, other common causes of hypoproteinemia such as nephrotic syndrome, impaired protein synthesis due to chronic liver disease and malnutrition must be excluded first.
As the most prominent laboratory finding is a decrease in serum concentration of albumin and globulin, the diagnostic work up protein losing enteropathy consist of quantitative measurements of Alpha-1 antitrypsin or 51Cr-albumin.
- Alpha-1 antitrypsin (A1AT) used as an endogenous marker is a sensitive and inexpensive laboratory test performed to diagnose protein losing enteropathy and has become the current standard for quantitating protein losing enteropathy. Measurement of fecal volume and fecal loss of alpha-1 antitrypsin depicts the plasma concentration of alpha-1 antitrypsin as;
- Alpha 1-AT plasma concentration = ((stool volume) x (stool alpha 1-AT)) / (serum alpha-1 AT)
- Gastrointestinal loss of alpha-1 antitrypsin is measured in feces and a clearance greater than 27mL/day is considered diagnostic for protein losing enteropathy.
- 51Cr-labeled albumin can also be measured followed by stool collection to determine the amount of protein loss into the gastrointestinal tract.
Following the detection of abnormal amounts of alpha-1 antitrypsin in the stool, the following tests can be performed to detect the specific etiology for the protein loss into the gastrointestinal lumen.
- Administration of technetium-99 labeled macromolecules such as albumin. Imaging is required to localize the primary site of protein leakage with no requirement for fecal collection. Scintigraphy is becoming popular in the diagnosis and localization of the site of protein leakage.
- For the diagnosis of lymphatic obstruction, computed tomography, lymphangiography or magnetic resonance imaging can be used.
- Radiographic contrast studies and endoscopy can be performed to evaluate the ulcerative or erosive gastrointestinal causes of the protein loss.
- For detecting cardiac diseases causing loss of protein, echocardiography or radionuclide scanning of the heart can be performed.
- All patients should undergo basic laboratory tests such as complete blood test, liver and renal function tests.
- Work up for autoimmune diseases such as systemic lupus erythematosus should be ordered if there is a suspicion of connective tissue disorder causing protein loss in the gastrointestinal tract.
- Biopsy samples of the mucosa and stool cultures for ova and parasites should be performed if there is a suspicion of ulcerative or erosive gastrointestinal disease and parasitic infection, respectively.
- Symptomatic relief can be achieved with dietary modifications and medications.
- Supplementation with proteins with 2 to 3 g/kg a day as well as micronutrients, electrolytes and vitamins to compensate for the loss of proteins plays a critical role.
- Treatment with steroids or heparin to stop protein leak via the intestines could also provide symptomatic relief.
- However, protein losing enteropathy is not a separate disease entity but a complication of different pathological conditions and hence the mainstay of treatment depends upon the underlying etiology of the disease causing protein losing enteropathy.
- Effectual treatment depends on a better understanding of the pathophysiology of the disease, for instance, if the underlying pathology involves inflammation or autoimmune condition such as; inflammatory bowel disease or connective tissue disorder, treatment strategy is tailored towards treating the underlying pathology with immunosuppressive medications.
- Similarly, if cardiovascular disease is the underlying pathology of protein losing enteropathy, the mainstay of treatment would be optimization of the medications for heart failure. Diuretics can be used for symptomatic relief.
- Lymphatic obstruction can be relieved according to the underlying etiologies such as; treatment of the parasitic or bacterial infection causing protein losing enteropathy, increased lymphatic pressure can be relieved with octreotide and surgical resection should be considered in case of refractory inflammatory bowel disease.  
- ↑ 1.0 1.1 Craven, Melanie D.; Washabau, Robert J. (2019). "Comparative pathophysiology and management of protein‐losing enteropathy". Journal of Veterinary Internal Medicine. 33 (2): 383–402. doi:10.1111/jvim.15406. ISSN 0891-6640.
- ↑ 2.0 2.1 "StatPearls". 2020. PMID https://www.ncbi.nlm.nih.gov/pubmed/31194423 Check
- ↑ Waldmann, T.A.; Wochner, R.D.; Strober, W. (1969). "The role of the gastrointestinal tract in plasma protein metabolism". The American Journal of Medicine. 46 (2): 275–285. doi:10.1016/0002-9343(69)90011-4. ISSN 0002-9343.
- ↑ Craven MD, Washabau RJ (2019). "Comparative pathophysiology and management of protein-losing enteropathy". J Vet Intern Med. 33 (2): 383–402. doi:10.1111/jvim.15406. PMC 6430879. PMID 30762910.
- ↑ Akkelle BS, Tutar E, Sengul OK, Celikel CA, Ertem D (2018). "A Rare Complication of Giardiasis in Children: Protein-losing Enteropathy". Pediatr Infect Dis J. 37 (12): e345–e347. doi:10.1097/INF.0000000000002025. PMID 30408010.
- ↑ Zubiaga Toro L, Ruiz-Tovar J, Castro MJ, Ortiz de Solórzano FJ, Luque de León E, Jiménez JM; et al. (2019). "Whipple disease after bariatric surgery: from malabsorption to malnutrition status". Nutr Hosp. 36 (1): 238–241. doi:10.20960/nh.02258. PMID 30834767.
- ↑ Venkatesh, Balasubramanian; Gough, Jenny; Ralston, David R.; Muller, Michael; Pegg, Stuart (2004). "Protein losing enteropathy in critically ill adult patients with burns: a preliminary report". Intensive Care Medicine. 30 (1): 162–166. doi:10.1007/s00134-003-2050-2. ISSN 0342-4642.
- ↑ Furfaro F, Bezzio C, Maconi G (2015). "Protein-losing enteropathy in inflammatory bowel diseases". Minerva Gastroenterol Dietol. 61 (4): 261–5. PMID 26446687.
- ↑ Amiot A (2015). "[Protein-losing enteropathy]". Rev Med Interne. 36 (7): 467–73. doi:10.1016/j.revmed.2014.12.001. PMID 25618488.
- ↑ "StatPearls". 2020. PMID 31194423.
- ↑ Tsochatzis, Emmanuel A; Bosch, Jaime; Burroughs, Andrew K (2014). "Liver cirrhosis". The Lancet. 383 (9930): 1749–1761. doi:10.1016/S0140-6736(14)60121-5. ISSN 0140-6736.
- ↑ Rieder, Simone C.; Huber, Lars C.; Trachsler, Johannes; Herberger, Elisabeth (2019). "CME: Das nephrotische Syndrom beim Erwachsenen: Präsentation, Abklärung, Therapie". Praxis. 108 (5): 347–355. doi:10.1024/1661-8157/a003223. ISSN 1661-8157.
- ↑ Grover, Zubin; Ee, Looi C. (2009). "Protein Energy Malnutrition". Pediatric Clinics of North America. 56 (5): 1055–1068. doi:10.1016/j.pcl.2009.07.001. ISSN 0031-3955.
- ↑ Clark, Ricketta; Johnson, Ragan (2018). "Malabsorption Syndromes". Nursing Clinics of North America. 53 (3): 361–374. doi:10.1016/j.cnur.2018.05.001. ISSN 0029-6465.
- ↑ Hazenberg, Bouke P.C. (2013). "Amyloidosis". Rheumatic Disease Clinics of North America. 39 (2): 323–345. doi:10.1016/j.rdc.2013.02.012. ISSN 0889-857X.
- ↑ Umar, Sarah B; DiBaise, John K (2010). "Protein-Losing Enteropathy: Case Illustrations and Clinical Review". American Journal of Gastroenterology. 105 (1): 43–49. doi:10.1038/ajg.2009.561. ISSN 0002-9270.
- ↑ 17.0 17.1 Levitt, David; Levitt, Michael (2017). "Protein losing enteropathy: comprehensive review of the mechanistic association with clinical and subclinical disease states". Clinical and Experimental Gastroenterology. Volume 10: 147–168. doi:10.2147/CEG.S136803. ISSN 1178-7023.
- ↑ Karbach U, Ewe K (1989). "Enteric protein loss in various gastrointestinal diseases determined by intestinal alpha 1-antitrypsin clearance". Z Gastroenterol. 27 (7): 362–5. PMID 2475983.
- ↑ Florent C, L'Hirondel C, Desmazures C, Aymes C, Bernier JJ (1981). "Intestinal clearance of alpha 1-antitrypsin. A sensitive method for the detection of protein-losing enteropathy". Gastroenterology. 81 (4): 777–80. PMID 6973500.
- ↑ Rychik, Jack; Spray, Thomas L. (2002). "Strategies to treat protein-losing enteropathy". Seminars in Thoracic and Cardiovascular Surgery: Pediatric Cardiac Surgery Annual. 5 (1): 3–11. doi:10.1053/pcsu.2002.31498. ISSN 1092-9126.