Protein losing enteropathy

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Protein losing enteropathy
Upper and lower human gastrointestinal tract Digestive system diagram edit.svgpharynxoral cavity
Upper and lower human gastrointestinal tract
Protein losing enteropathy affects the GI tract [1]
Specialty Gastroenterology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Swelling of the legs [2]
Causes Inflammatory bowel disease, idiopathic ulcerative jejunoileitis [1]
Diagnostic method Scintigraphy, viral serologies [1]
Treatment Octreotide, surgery [1]

Protein losing enteropathy (PLE) is a syndrome in which blood proteins are lost excessively via the gastrointestinal (GI) tract. It may be caused by many different underlying diseases that damage the lining of the GI tract (mucosa) or cause blockage of its lymphatic drainage. [3]

Contents

Signs and symptoms

The signs and symptoms of protein losing enteropathy include diarrhea, fever, and general abdominal discomfort. [4] Swelling of the legs due to peripheral edema can also occur; however, if the PLE is related to a systemic disease such as congestive heart failure or constrictive pericarditis, then these symptoms could be due directly to the underlying illness. [2] In severe cases, anasarca, a generalized form of edema, may develop. [5]

Causes

The causes of protein-losing enteropathy can include GI conditions (among other causes), like the following: [1]

Mechanism

Proteoglycan Protein ACAN PDB 1tdq.png
Proteoglycan

The pathophysiology of protein losing enteropathy is a result of plasma protein loss to the GI tract lumen. [2] PLE is a complication of a disorder, be it lymphatic obstruction or mucosal injury. [7]

Protein losing enteropathy is a syndrome, characterized by a collection of signs and symptoms that are due to an underlying primary medical condition. Thus, there are many different pathophysiologic mechanisms of intestinal protein loss. Erosive disease, is characterized by mucosal damage or erosions of the colon intestinal epithelium and capillary bed underlying the epithelium, leading to a leakage of proteins from the capillaries into the interstitial space and then into the intestinal lumen where they are lost from the body. [8] This type of inflammation may be seen in inflammatory bowel diseases, peptic ulcers and infections. [8] A second pathological mechanism, the non-erosive type, is characterized by increased intestinal permeability causing protein to be lost from the interstitium into the intestinal lumen. [8] This increased intestinal permeability may be seen in eosinophilic gastroenteritis and other conditions causing increased inflammation in the gut, or certain genetic disorders affecting the cell adhesions between gut enterocytes. [8] And a third type is due to intestinal lymphangiectasia in which the lymphatic vessels that drain interstitial fluid from the gut are damaged, leading to a blockage of lymphatic drainage and a buildup of interstitial fluid near the gut, thus causing leakage of proteins into the gut. [8] This may be due to primary or congenital disease states of the lymphatic system or secondary (acquired) damage to the lymphatic system. [8] Possible secondary causes of lymphangiectasis include congestive heart failure or constrictive pericarditis. These conditions cause an increase in the central venous pressure. The lymphatic system drains into the central venous system following a negative pressure gradient to the subclavian vein via the thoracic duct or right lymphatic duct. However, any pathological mechanism that leads to increased central venous pressure may also cause increased lymphatic pressure, thus impairing lymphatic drainage at the gut and lead to protein losing enteropathy. [8] Certain infections such as Whipple disease can also lead to impaired lymphatic drainage by destroying the lymphatic lacteals, which are lymphatic capillaries underlying intestinal villi and facilitating the drainage of lymph from the gut. [8] Congenital disorders of the lymphatic system such as Primary Intestinal Lymphangiectasia are due to congenitally dilated or malformed lacteals that lead to lymph leakage into the small bowel, causing protein loss and protein losing enteropathy. [9]

The widespread hypoproteinemia seen in protein losing enteropathy may present with complications related to the specific proteins lost, especially in severe disease. A decrease in antibodies (also known as immune globulins) may lead to an increased susceptibility to infections. [8] And the loss of inhibitory coagulation factors may lead to a hypercoagulable state. [8]

In pediatric protein losing enteropathy, changes in epithelial cells contribute to the pathogenesis of PLE by augmenting the rate of efflux of serum proteins. Congenital molecular mutations, poor lymphatic drainage and/or inflammation may cause epithelial matrix changes. [10] The absence of proteoglycans, which are glycosaminoglycan chains attached to protein, may contribute to PLE and augment inflammatory cytokines. Children who have certain congenital glycosylation defects may have protein losing enteropathy. [10] [11]

Diagnosis

The diagnosis of protein losing enteropathy is made by excluding other causes of protein loss. Endoscopy can be used to localize the cause of the protein loss in the bowel. Different methods of quantifying protein loss in the bowel include faecal excretion of alpha 1-antitrypsin, a marker of protein losing enteropathy, as well as viral serologies, which may be useful to determine the cause of the PLE. [1] Alpha 1-antitrypsin is a blood protein that is lost in the gut, however, it is not actively secreted or absorbed by the gut, and it resists proteolysis in the gut lumen, thus making it a preferred protein for quantification of gut protein loss in protein losing enteropathy. [8] Fecal alpha 1-antitrypsin may be quantified in a random stool sample, or more accurately, in a 24-hour stool sampling to quantify the amount of protein loss in PLE. [8] In suspected cases of local disease, or when PLE is suspected to be due to lymph drainage abnormalities, lymphangiography may be used to localize the areas of lymphatic leakage. [8] Imaging of the thoracic or abdominopelvic cavities may also aid in the diagnosis, possibly by identifying masses impairing lymphatic and venous drainage from the intestines and thus contributing to PLE. [8]

Treatment

Treatment for protein losing enteropathy depends upon the underlying condition; according to Rychik and Spray (2002) this could mean treatment of hypoproteinemia or of the intestinal mucosa. [12]

For causes related to the heart, treatment for PLE after the Fontan operation treatment must be equal to the level of hypoproteinemia present. Therefore, it is useful to categorize patients based on their serum albumin levels, if less than normal (typically less than 3.5 g/dL) but greater than 2.5 g/dL, this can be seen as a mild form of protein losing enteropathy. Symptomatic management of edema with furosemide (and aldactone) can provide relief for the individual with mild hypoproteinemia. [13] [14]

In animals

Dogs can also suffer from PLE. Because the proteins are lost from the intestine, these dogs have low levels of albumin in the blood. Chronic enteropathy is one of the possible reasons for PLE and it has been shown in a study that hypoalbuminaemia is a risk factor for negative outcome and the prognosis is guarded for these dogs. [15] Gastrointestinal lymphoma and intestinal lymphangiectasia are other diseases that can cause protein losing enteropathy in dogs. [16] The Breed Lundehunds seem to be predisposed for PLE. [17]

Related Research Articles

<span class="mw-page-title-main">Edema</span> Accumulation of excess fluid in tissue

Edema, also spelled oedema, and also known as fluid retention, dropsy and hydropsy, is the build-up of fluid in the body's tissue, a type of swelling. Most commonly, the legs or arms are affected. Symptoms may include skin that feels tight, the area feeling heavy, and joint stiffness. Other symptoms depend on the underlying cause.

<span class="mw-page-title-main">Small intestine</span> Organ in the gastrointestinal tract

The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through the pancreatic duct to aid in digestion. The small intestine is about 5.5 metres long and folds many times to fit in the abdomen. Although it is longer than the large intestine, it is called the small intestine because it is narrower in diameter.

<span class="mw-page-title-main">Inflammatory bowel disease</span> Medical condition

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine, as well as the mouth, esophagus, stomach and the anus, whereas UC primarily affects the colon and the rectum.

<span class="mw-page-title-main">Malabsorption</span> Abnormality in absorption of food nutrients across the gastrointestinal tract

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Tropical sprue is a malabsorption disease commonly found in tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine. It differs significantly from coeliac sprue. It appears to be a more severe form of environmental enteropathy.

<span class="mw-page-title-main">Chylothorax</span> Accumulation of chyle in the pleural space around the lungs

A chylothorax is an abnormal accumulation of chyle, a type of lipid-rich lymph, in the pleural space surrounding the lung. The lymphatic vessels of the digestive system normally return lipids absorbed from the small bowel via the thoracic duct, which ascends behind the esophagus to drain into the left brachiocephalic vein. If normal thoracic duct drainage is disrupted, either due to obstruction or rupture, chyle can leak and accumulate within the negative-pressured pleural space. In people on a normal diet, this fluid collection can sometimes be identified by its turbid, milky white appearance, since chyle contains emulsified triglycerides.

<span class="mw-page-title-main">Hypoalbuminemia</span> Abnormally low levels of albumin in the blood

Hypoalbuminemia is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or abnormal distribution between body compartments. Patients often present with hypoalbuminemia as a result of another disease process such as malnutrition as a result of severe anorexia nervosa, sepsis, cirrhosis in the liver, nephrotic syndrome in the kidneys, or protein-losing enteropathy in the gastrointestinal tract. One of the roles of albumin is being the major driver of oncotic pressure in the bloodstream and the body. Thus, hypoalbuminemia leads to abnormal distributions of fluids within the body and its compartments. As a result, associated symptoms include edema in the lower legs, ascites in the abdomen, and effusions around internal organs. Laboratory tests aimed at assessing liver function diagnose hypoalbuminemia. Once identified, it is a poor prognostic indicator for patients with a variety of different diseases. Yet, it is only treated in very specific indications in patients with cirrhosis and nephrotic syndrome. Treatment instead focuses on the underlying cause of the hypoalbuminemia. Albumin is an acute negative phase respondent and not a reliable indicator of nutrition status.

<span class="mw-page-title-main">Lymphangiectasia</span> Medical condition

Lymphangiectasia, also known as "lymphangiectasis", is a pathologic dilation of lymph vessels. When it occurs in the intestines it is known as intestinal lymphangiectasia, colloquially recognized as Waldmann's disease in cases where there is no secondary cause. The primary defect lies in the inability of the lymphatic system to adequately drain lymph, resulting in its subsequent accumulation and leakage into the intestinal lumen. This condition, first described by Waldmann in 1961, is typically diagnosed in infancy or early childhood. However, it can also manifest in adults, exhibiting a broad spectrum of clinical symptoms.

<span class="mw-page-title-main">Intestinal pseudo-obstruction</span> Medical condition

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<span class="mw-page-title-main">Microvillous inclusion disease</span> Medical condition

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<span class="mw-page-title-main">Intestinal epithelium</span> Single-cell layer lining the intestines

The intestinal epithelium is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract. Composed of simple columnar epithelium its main functions are absorption, and secretion. Useful substances are absorbed into the body, and the entry of harmful substances is restricted. Secretions include mucins, and peptides.

<span class="mw-page-title-main">Milroy's disease</span> Lymphedema commonly located in legs, caused by congenital abnormalities in the lymphatic system

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Waldmann disease, also known as Primary Intestinal Lymphangiectasia (PIL), is a rare disease characterized by enlargement of the lymph vessels supplying the lamina propria of the small intestine. Although its prevalence is unknown, it being classified as a "rare disease" means that less than 200,000 of the population of the United States are affected by this condition and its subtypes and there have been approximately 50 reported cases of adult-onset PIL since 1961.

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<span class="mw-page-title-main">CD55 deficiency</span> Medical condition

CD55deficiency, also called DAF deficiency or CHAPLE syndrome, is a rare genetic disorder of the immune system. CHAPLE stands for "CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and severe protein-losing enteropathy (PLE)." The disorder usually manifests in childhood and can be life-threatening. This condition was described by Özen, et al. in 2017.

<span class="mw-page-title-main">Aleixo Muise</span> Canadian scientist and physician

Aleixo M. Muise is a Canadian scientist, pediatrician and gastroenterologist known for contributions to the understanding of very early onset inflammatory bowel disease. He is a professor of pediatrics at the University of Toronto, a Tier 1 Canada Research Chair in pediatric inflammatory bowel disease, and a pediatric gastroenterologist at the Hospital for Sick Children.

References

  1. 1 2 3 4 5 6 Knott, Laurence (2021-11-09). "Protein-losing Enteropathy: Causes, Symptoms and Treatment". Patient. Archived from the original on 2021-01-23. Retrieved 2024-01-30.
  2. 1 2 3 Protein-Losing Enteropathy at eMedicine
  3. ↑ Ozen, Ahmet; Lenardo, Michael J. (24 August 2023). "Protein-Losing Enteropathy". New England Journal of Medicine. 389 (8): 733–748. doi:10.1056/NEJMra2301594. PMID   37611123.
  4. ↑ MedlinePlus Encyclopedia : Protein-losing enteropathy
  5. ↑ Kattula, Sri Rama Surya Tez; Avula, Akshay; Baradhi, Krishna M. (2024). "Anasarca". StatPearls. StatPearls Publishing. PMID   30085555.
  6. ↑ Johnson, JN; Driscoll, DJ; O'Leary, PW (June 2012). "Protein-losing enteropathy and the Fontan operation". Nutrition in Clinical Practice. 27 (3): 375–84. doi:10.1177/0884533612444532. PMID   22516942.
  7. ↑ Wyllie, Robert; Hyams, Jeffrey S.; Kay, Marsha (2015). Pediatric Gastrointestinal and Liver Disease. Elsevier Health Sciences. p. 389. ISBN   978-0-323-24099-4.
  8. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Ozen, Ahmet; Lenardo, Michael J. (24 August 2023). "Protein-Losing Enteropathy". New England Journal of Medicine. 389 (8): 733–748. doi:10.1056/NEJMra2301594. PMID   37611123.
  9. ↑ Vignes, Stéphane; Bellanger, Jérôme (December 2008). "Primary intestinal lymphangiectasia (Waldmann's disease)". Orphanet Journal of Rare Diseases. 3 (1): 5. doi: 10.1186/1750-1172-3-5 . PMC   2288596 . PMID   18294365.
  10. 1 2 Pediatric Protein-Losing Enteropathy at eMedicine
  11. ↑ Iozzo, Renato V.; Schaefer, Liliana (March 2015). "Proteoglycan form and function: A comprehensive nomenclature of proteoglycans". Matrix Biology. 42: 11–55. doi:10.1016/j.matbio.2015.02.003. PMC   4859157 . PMID   25701227.
  12. ↑ Rychik, Jack; Spray, Thomas L. (January 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. PMID   11994860.
  13. ↑ Rychik, Jack (September 2007). "Protein-Losing Enteropathy after Fontan Operation". Congenital Heart Disease. 2 (5): 288–300. doi:10.1111/j.1747-0803.2007.00116.x. PMID   18377444.
  14. ↑ Topol, Eric J.; Califf, Robert M. (2007). Textbook of Cardiovascular Medicine. Lippincott Williams & Wilkins. p. 519. ISBN   978-0-7817-7012-5.
  15. ↑ Allenspach, K.; Wieland, B.; Gröne, A.; Gaschen, F. (2007). "Chronic Enteropathies in Dogs: Evaluation of Risk Factors for Negative Outcome". Journal of Veterinary Internal Medicine. 21 (4): 700–708. doi: 10.1892/0891-6640(2007)21[700:ceideo]2.0.co;2 . PMID   17708389.
  16. ↑ Nakashima, K.; Hiyoshi, S.; Ohno, K.; Uchida, K.; Goto-Koshino, Y.; Maeda, S.; Mizutani, N.; Takeuchi, A.; Tsujimoto, H. (July 2015). "Prognostic factors in dogs with protein-losing enteropathy". The Veterinary Journal. 205 (1): 28–32. doi:10.1016/j.tvjl.2015.05.001. PMID   26025135.
  17. ↑ Flesjå, Kjell; Yri, Torstein (January 1977). "Protein-losing enteropathy in the Lundehund". Journal of Small Animal Practice. 18 (1): 11–23. doi:10.1111/j.1748-5827.1977.tb05819.x. PMID   853728.

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