Difference between revisions of "Protein Losing Enteropathy"

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== Introduction ==
 
'''Protein-losing enteropathy (PLE)''' refers to the loss of plasma proteins into the gastro-intestinal (GI) tract, exceeding the absorptive capacity of the intestines. PLE can be caused by disruption to the intestinal wall due to [[Inflammation - Pathology|inflammation]] or infiltrative disease or by venous congestion of the GI tract and GI [[Haemorrhage|haemorrhage]].
 
  
Hence, there are numerous causes of PLE in cats and dogs, including:
+
{{dog}}
*'''Inflammation'''
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{{cat}}
*:[[Inflammatory Bowel Disease]] (including lymphocytic-plasmacytic enteritis, eosinophilic enteritis, granulomatous enteritis and histiocytic-ulcerative colitis)
 
*[[Lymphoma]]
 
*Infectious disease
 
*:[[Giardiasis|''Giardia duodenalis'']]
 
*:[[Uncinaria stenocephala|Hookworm]]
 
*:[[Histoplasmosis]]
 
*Chronic [[Intussusception|intussusception]] in juvenile animals
 
*'''[[Lymphangiectasia]]'''
 
*'''Infiltrative disease'''
 
*:Alimentary lymphoma
 
*'''Venous congestion'''
 
*:Portal hypertension
 
*:Posterior caval syndrome
 
*[[Heart Failure - Pathophysiology|Right-sided congestive heart failure]]
 
*'''GI haemorrhage'''
 
*:This may occur with [[hypoadrenocorticism]] or with other causes of GI ulceration
 
  
Rare causes of PLE include [[Antibiotic Responsive Diarrhoea|Small intestinal bacterial overgrowth (SIBO)]], [[hypoalbuminaemia]] causing intestinal mural oedema, increased activation of tissue plasminogen activator, [[Systemic Lupus Erythematosus|systemic lupus erythematosis (SLE)]] and chemotherapy or radiotherapy.
 
  
Normally, dietary protein and protein from shed enterocytes is almost completely absorbed. In PLE there is excess loss of protein into the gut lumen of particularly non-selective albumin and globulin. This causes panhypoproteinaemia and hypocholesterolaemia. If this is severe, oedema and weight loss may result.
 
  
== Signalment ==
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==Signalment==
Inflammatory bowel disease and lymphoma are the most common causes of PLE in both cats and dogs but lymphangiectasia occurs much more commonly in dogs than in cats. Chronic intussusception (usually occurring secondary to acute enteritis) and endoparasite infection are the most common causes of PLE in juvenile cats and dogs.
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Breed predisposition:
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*[[Canine Breeds - WikiNormals #Hound Group|Basenji]]
'''Basenjis''', '''Norwegian Lundehunds''', '''Soft-coated Wheaten terriers''' (SCWT), '''Yorkshire terriers''' and '''Shar peis''' all show breed predispositions for PLE. related to secretory enteropathy. Basenjis develop PLE as a result of secretory enteropathy, a type of inflammatory bowel disease.  Soft-coated Wheaten Terriers often suffer from concurrent protein-losing nephropathy and most affected animals of this breed have a common ancestor who is thought to have lived in the USA.  Females of this breed are more commonly affected than males.
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*Lundehund
 +
*[[Canine Breeds - WikiNormals #Terrier Group|Soft-Coated Wheaten Terrier]]
 +
*[[Canine Breeds - WikiNormals #Toy Group|Yorkshire Terrier]]
 +
*[[Canine Breeds - WikiNormals #Utility Group|Shar Pei]]
  
== Clinical Signs ==
 
'''Weight loss''' is the most evident sign, with '''diarrhoea''' occurring due to the loss of protein into the GI tract and subsequent osmotic movement of fluid.  Melaena may occur with GI haemorrhage. [[Oedema|'''Oedema''']], '''ascites''' and '''pleural effusion''' due to reduced plasma oncotic pressure are notable clinical signs. The animal will also usually have [[vomiting]] and anorexia and will be depressed and lethargic. '''Thickened intestines''' may be detectable on abdominal palpation and this finding may be related to the primary pathological process. [[Thromboembolism|'''Thromboembolic]] disease''' due to the loss of plasma anticoagulants such as antithrombin III may also occur. '''Hypocalcaemic tetany''' due to a reduced ability to absorb calcium and the fat soluble vitamin D may also be a sign of the condition. Apparent hypocalcaemia may also develop as the protein-bound portion of the blood total calcium concentration is reduced.
 
  
== Diagnosis ==
+
==Description==
 +
'''Protein-losing enteropathy (PLE)''' can result from any intestinal disease which produces sufficient [[Inflammation - Pathology|inflammation]], congestion or bleeding.  This causes protein to leak into the intestines, which exceeds capacity of the gut lumen protein synthesis.  Hence, there are numerous causes of PLE, including [[Lymphangiectasia - WikiClinical|lymphangiectasia]], infectious causes, structural causes, neoplasia, [[Inflammation - Pathology|inflammation]], endoparasites and gastrointestinal [[Haemorrhage - Pathology|haemorrhage]]. 
 +
 
 +
The major causes of PLE in adult dogs are [[Inflammatory Bowel Disease - WikiClinical|inflammatory bowel disease (IBD)]], alimentary tract lymphoma, fungal infections (e.g. [[Systemic Mycoses #Histoplasmosis|histoplasmosis]]).  Other causes include ulcerations or erosions, severe disease of intestinal crypts and parasites.  The most common causes in very young dogs are [[Small Animals #Nematodes of Dogs - the HOOKWORMS|hookworms]] and chronic intussusception.  Chronic intussusception results from acute enteritis which has not resolved completely.  The animal shows some clinical improvement but diarrhoea still continues.  PLE is less common in cats than dogs, and most often caused by alimentary tract lymphoma and IBD.  Cats almost never suffer from [[Lymphangiectasia - WikiClinical|lymphangiectasia]], and rarely have severe parasitic infection severe enough to cause PLE.  Non-intestinal diseases can be associated with PLE include ][[Pathophysiology of Heart Failure - Pathology|congestive heart failure]], caval obstruction and portal hypertension.  However, these animals usually present with ascites rather than [[Intestine Diarrhoea - Pathology|diarrhoea]].
 +
 
 +
==Diagnosis==
 +
===Clinical Signs===
 +
*Weight loss (predominant feature)
 +
*Vomiting and diarrhoea ± melena
 +
*[[Oedema - Pathology|Oedema]], ascites and pleural effusion
 +
*Thickened intestines
 +
*[[Thrombosis - Pathology #Thromboembolism|Thromboembolic]] disease if procoagulants predominant due to loss of anticoagulant
 +
 
 
===Laboratory Tests===
 
===Laboratory Tests===
Changes consistent with possible differential diagnoses, such as hepatic and renal disease, should also be ruled out.
 
 
 
====Haematology====
 
====Haematology====
[[Lymphopenia|'''Lymphopaenia]]''' occurs with lymphangiectasia due to the loss of lymph.
+
*Panhypoproteinaemia
 +
**Hepatic insufficiency and protein-losing nephropathy should also be pursued with hypoalbuminaemia.
 +
*[[Changes in Inflammatory Cells Circulating in Blood - Pathology #Lymphopenia|Lymphopaenia]]
  
 
====Biochemistry====
 
====Biochemistry====
'''Panhypoproteinaemia''' is a pattern more suggestive of PLE since albumin is usually lost in excess of globulin in protein losing nephropathy. Hypoproteinaemia may also develop with haemorrhage, dermal protein loss (after severe burns of degloving injury) or if the rate of synthesis of albumin is reduced by a severe hepatic insult. Oedema and ascites typically develop when serum albumin concentration drops below 15 g/l.
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*Hypocholesterolaemia
 +
*[[Hypocalcaemia - Small Animal|Hypocalcaemia]]
  
'''Hypocholesterolaemia''' may be present, especially in lymphangiectasia.
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====Other Tests====
 +
*Measurement of faecal loss alpha1-protease inhibitor
  
'''Hypocalcaemia''' also may be present, but ionised calcium concentration should be measured to determine the significance of this finding as serum calcium concentration is closely related to total protein level.
 
<br>
 
====Other Tests====
 
'''Measurement of faecal alpha1-protease inhibitor''' - This marker has a similar molecular weight to albumin and it is lost into the GI tract in PLE.  Its concentration can therefore be measured in faeces as it is not degraded by GI enzymes. (Faecal samples must be frozen on collection before submission to a laboratory in the USA.)
 
<br>
 
'''Administration of 51-Chromium labelled albumin''' - A radioactive marker (51-Chromium) is attached to recombinant albumin molecules before injection into animal. Faecal samples are collected to determine whether the labelled albumin is being lost into the GI tract.  Although this test represents the 'gold standard' test, it is available only at a limited number of referral institutes.
 
<br>
 
 
===Diagnostic Imaging===
 
===Diagnostic Imaging===
 
====Radiography====
 
====Radiography====
The results of '''abdominal radiographs''' are usually unremarkable but discrete mass lesions or ascites may be evident. '''Thoracic radiographs''' may show the presence of [[Effusions|pleural effusion]], metastatic neoplasia or evidence of [[Histoplasmosis|histoplasmosis]]).
+
*Abdominal radiographs are usually unremarkable.
<br>
+
*Thoracic radiographs may show [[Peritoneal Cavity Effusions - Pathology|pleural effusion]], metastatic neoplasia or eveidence of [[Systemic Mycoses #Histoplasmosis|histoplasmosis]]).
 +
 
 
====Ultrasonography====
 
====Ultrasonography====
This may reveal changes to intestinal wall structure, including thickening without loss of normal layers (as with inflammatory bowel disease), thickening with loss of layers (as with infiltrative intestinal neoplasia) and 'tiger stripes', an unreliable indicator of lymphangiectasia. It may also show ascites or pleural effusion and mesenteric lymphadenopathy.
+
*This may reveal thickening of intestines, mesenteric lymphadenopathy or abdominal effusion.
<br>
+
 
 +
 
 
===Histopathology===
 
===Histopathology===
'''Endoscopy''' can be used to visualise the proximal intestinal luminal surface and to obtain grab biopsies.  Surgical biopsies may be obtained for definitive diagnosis of lymphoma and [[Lymphangiectasia#Description|secondary lymphangiectasia]].  A small fatty meal could be given the night before biopsy to increase the chance of diagnosing [[Lymphangiectasia|lymphangiectasia]].
+
*Endoscopically-guided multiple biopsies are useful.  Surgical biopsy may be required for a definitive diagnosis of lymphoma and [[Lymphangiectasia - WikiClinical #Description|secondary lymphangiectasia]].  A small fatty meal could be given the night before biopsy to increase the chance of diagnosing [[Lymphangiectasia - WikiClinical|lymphangiectasia]].
Care should be taken with this procedure as animals with PLE have a greater risk of surgical wound dehiscence with the subsequent development of [[Peritonitis - Cats and Dogs|peritonitis]].
 
<br>
 
Lesions that may be observed on histopathological analysis of biopsy samples include: signs of inflammatory bowel disease, dilated lymphatics and lipogranulomatous lymphangitis (especially in Soft-coated Wheaten terriers).
 
 
 
PLE may also be associated with protein losing nephropathy (PLN). PLN may be a chronic sequelae to the PLE. It follows immune complex deposition in the glomerulus, causing [[glomerulonephritis]] or glomerulosclerosis. PLN causes hypoalbuminaemia and hypercholesterolaemia.
 
Similar PLN and PLE lesions are seen in young Basenjis with immunoproliferative enteropathy and glomerulosclerosis.
 
  
 
==Treatment==
 
==Treatment==
Treatment of the underlying cause of disease should be initiated, if possible.  In the case of severe respiratory embarrassment, treatment should be directed at draining any pleural effusion and providing support in case of a pulmonary [[Thromboembolism|thromboembolus]]. 
 
 
 
===Plasma transfusion===
 
===Plasma transfusion===
This may be used to increase plasma volume but, as much of the albumin is lost into the gut, there may be a disappointing increase in serum albumin concentration after transfusion. Large [[Colloids|colloids]] (such as hetastarch) may also be administered to try to maintain plasma oncotic pressure.
+
*This may be used to increase plasma volume.  However, much of the albumin is lost in the gut and a substantial amount fails to remain in the intravascular compartment.  Therefore, the extent of increase in serum albumin level is not great.
 +
*Administration of [[Colloids|colloid]] may be more suitable if it is essential to increase the plasma oncotic pressure.
  
===[[Diuretics Effects on Kidneys - Anatomy & Physiology|Diuretics]]===
+
===Diuretics===
These may be used to reduce any ascites or pleural effusion and it has been suggested that [[Heart Failure, Treatment#C. Pharmacological |spironolactone]] may be more effective than [[Heart Failure, Treatment#C. Pharmacological|frusemide]] for this purpose.
+
*This can be used to reduce ascites.
 
+
*[[Treatment of Heart Failure - WikiClinical #C. Pharmacological |Spironolactone]] 1-2 mg/kg PO BID may be more effective than [[Treatment of Heart Failure - WikiClinical #C. Pharmacological|frusemide]].
===Antithrombotic therapy===
 
Treatment may be initiated with low dose aspirin to prevent the development of thrombo-embolism.
 
 
 
===Dietary Supplementation with Calcium===
 
Calcium carbonate may be added to the diet if a low serum concentration of ionised calcium is documented.
 
  
 
==Prognosis==
 
==Prognosis==
This depends on the underlying cause but Soft-coated Wheaten terriers are known to have a median survival time of five months after diagnosis of PLE and of two months if they suffer from concurrent protein-losing nephropathy.
+
This depends on the underlying cause.
  
{{Learning
 
|Vetstream = [https://www.vetstream.com/canis/Content/Disease/dis02613.asp, Protein-losing enteropathy]
 
|flashcards = [[Small Animal Abdominal and Metabolic Disorders Q&A 01]]
 
|literature search = [http://www.cabdirect.org/search.html?q=%28%28title%3A%28PLE%29+AND+sc%3A%22ve%22%29%29+OR+%28%28title%3A%28%22Protein+Losing+Enteropathy%22%29%29%29 Protein Losing Enteropathy publications]
 
}}
 
  
 
==References==
 
==References==
Littman MP, Dambach DM, Vaden SL, Giger U (2000) '''Familial protein-losing enteropathy and protein-losing nephropathy in Soft Coated Wheaten Terriers: 222 cases (1983-1997)''' ''Journal of Veterinary Internal Medicine. 2000 Jan-Feb;14(1):68-80.''
+
*Ettinger, S.J. and Feldman, E. C. (2000) '''Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2''' (Fifth Edition) ''W.B. Saunders Company''.
<br>
+
*Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) '''BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition)''' ''BSAVA''.
Ettinger, S.J. and Feldman, E. C. (2000) '''Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2''' (Fifth Edition), ''W.B. Saunders Company''.
+
*Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''' ''Mosby Elsevier''.
<br>
+
*Willard, M. (2005) '''Protein-Losing Enteropathy in Dogs and Cats''' ''30th World Congress of the WSAVA''.
Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) '''BSAVA Manual of Canine and Feline Gastroenterology '''(2nd Edition), ''British Small Animal Veterinary Association.''
 
<br>
 
Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''', ''Mosby Elsevier''.
 
<br>
 
Willard, M. (2005) '''Protein-Losing Enteropathy in Dogs and Cats''', ''30th World Congress of the WSAVA''.
 
 
 
 
 
{{review}}
 
 
 
{{OpenPages}}
 
 
 
[[Category:Intestine_-_Inflammatory_Pathology]]
 
[[Category:Intestinal Diseases - Cat]]
 
[[Category:Intestinal Diseases - Dog]][[Category:Alimentary_Disorders]]
 
[[Category:Expert Review - Small Animal]]
 

Revision as of 16:27, 19 August 2009


Category:WikiClinical CanineCow
Category:WikiClinical FelineCow


Signalment

Breed predisposition:


Description

Protein-losing enteropathy (PLE) can result from any intestinal disease which produces sufficient inflammation, congestion or bleeding. This causes protein to leak into the intestines, which exceeds capacity of the gut lumen protein synthesis. Hence, there are numerous causes of PLE, including lymphangiectasia, infectious causes, structural causes, neoplasia, inflammation, endoparasites and gastrointestinal haemorrhage.

The major causes of PLE in adult dogs are inflammatory bowel disease (IBD), alimentary tract lymphoma, fungal infections (e.g. histoplasmosis). Other causes include ulcerations or erosions, severe disease of intestinal crypts and parasites. The most common causes in very young dogs are hookworms and chronic intussusception. Chronic intussusception results from acute enteritis which has not resolved completely. The animal shows some clinical improvement but diarrhoea still continues. PLE is less common in cats than dogs, and most often caused by alimentary tract lymphoma and IBD. Cats almost never suffer from lymphangiectasia, and rarely have severe parasitic infection severe enough to cause PLE. Non-intestinal diseases can be associated with PLE include ]congestive heart failure, caval obstruction and portal hypertension. However, these animals usually present with ascites rather than diarrhoea.

Diagnosis

Clinical Signs

  • Weight loss (predominant feature)
  • Vomiting and diarrhoea ± melena
  • Oedema, ascites and pleural effusion
  • Thickened intestines
  • Thromboembolic disease if procoagulants predominant due to loss of anticoagulant

Laboratory Tests

Haematology

  • Panhypoproteinaemia
    • Hepatic insufficiency and protein-losing nephropathy should also be pursued with hypoalbuminaemia.
  • Lymphopaenia

Biochemistry

Other Tests

  • Measurement of faecal loss alpha1-protease inhibitor

Diagnostic Imaging

Radiography

Ultrasonography

  • This may reveal thickening of intestines, mesenteric lymphadenopathy or abdominal effusion.


Histopathology

  • Endoscopically-guided multiple biopsies are useful. Surgical biopsy may be required for a definitive diagnosis of lymphoma and secondary lymphangiectasia. A small fatty meal could be given the night before biopsy to increase the chance of diagnosing lymphangiectasia.

Treatment

Plasma transfusion

  • This may be used to increase plasma volume. However, much of the albumin is lost in the gut and a substantial amount fails to remain in the intravascular compartment. Therefore, the extent of increase in serum albumin level is not great.
  • Administration of colloid may be more suitable if it is essential to increase the plasma oncotic pressure.

Diuretics

Prognosis

This depends on the underlying cause.


References

  • Ettinger, S.J. and Feldman, E. C. (2000) Textbook of Veterinary Internal Medicine Diseases of the Dog and Cat Volume 2 (Fifth Edition) W.B. Saunders Company.
  • Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition) BSAVA.
  • Nelson, R.W. and Couto, C.G. (2009) Small Animal Internal Medicine (Fourth Edition) Mosby Elsevier.
  • Willard, M. (2005) Protein-Losing Enteropathy in Dogs and Cats 30th World Congress of the WSAVA.