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== Introduction ==

== 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]].

'''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:

Hence, there are numerous causes of PLE in cats and dogs, including:

*'''Inflammation'''

 

*:[[Inflammatory Bowel Disease]] (including lymphocytic-plasmacytic enteritis, eosinophilic enteritis, granulomatous enteritis and histiocytic-ulcerative colitis)

'''Inflammation'''

*[[Inflammatory Bowel Disease]] (including lymphocytic-plasmacytic enteritis, eosinophilic enteritis, granulomatous enteritis and histiocytic-ulcerative colitis)

*Infectious disease

*Infectious disease

**''Giardia duodenalis''

*:[[Giardiasis|''Giardia duodenalis'']]

**[[Uncinaria stenocephala|Hookworm]]

*:[[Uncinaria stenocephala|Hookworm]]

**[[Histoplasmosis]]

*:[[Histoplasmosis]]

*Chronic [[Intussusception|intussusception]] in juvenile animals

*Chronic [[Intussusception|intussusception]] in juvenile animals

*'''[[Lymphangiectasia]]'''

 

*'''Infiltrative disease'''

'''[[Lymphangiectasia]]'''

*:Alimentary lymphoma

 

'''Infiltrative disease'''

*Alimentary lymphoma

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.

**[[Heart Failure - Pathophysiology|Right-sided congestive heart failure]]

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.

 

 

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 i.e. albumin and globulin. This causes panhypoproteinaemia and hypocholesterolaemia. If this is severe, oedema and weight loss may result.

 

== Signalment ==

== 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 intussuscepta (usually occurring secondary to acute enteritis) and endoparasite infection are the most common causes of PLE in juvenile cats and dogs.  

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.  

   

   

'''Basenjis''', '''Norwegian Lundehunds''', '''Soft-coated Wheaten terriers''' (SCWT), '''Yorkshire terriers''' and '''Shar peis''' all show breed predispositions for PLE. related to secretory enteropathy

'''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.

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

 

== Clinical Signs ==

== Clinical Signs ==

'''Weight loss''' is the most evident sign, with '''Diarrhoea''' occuring 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 Dmay 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.

'''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 ==

== Diagnosis ==

===Laboratory Tests===

===Laboratory Tests===

Changes consistent with possible differential diagnoses, such as hepatic and renal disease, should also be ruled out.

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.

[[Lymphopenia|'''Lymphopaenia]]''' occurs with lymphangiectasia due to the loss of lymph.

 

====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.

'''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.

 

'''Hypocholesterolaemia''' may be present, especially in lymphangiectasia.

'''Hypocholesterolaemia''' may be present, especially in lymphangiectasia.

 

'''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.

'''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.

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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).

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.

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 Besenjis with immunoproliferative enteropathy and glomerulosclerosis.

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]].   

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 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.

 

===[[Diuretics Effects on Kidneys - Anatomy & Physiology|Diuretics]]===

===[[Diuretics Effects on Kidneys - Anatomy & Physiology|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.

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.

 

===Antithrombotic therapy===

===Antithrombotic therapy===

Treatment may be initiated with low dose aspirin to prevent the development of thrombo-embolism.

Treatment may be initiated with low dose aspirin to prevent the development of thrombo-embolism.

 

===Dietary Supplementation with Calcium===

===Dietary Supplementation with Calcium===

Calcium carbonate may be added to the diet if a low serum concentration of ionised calcium is documented.

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 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.

==Literature Search==

==Literature Search==

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[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]

[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==

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''.

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''.

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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.

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.''

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Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''', ''Mosby Elsevier''.

Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''', ''Mosby Elsevier''.

[[Category:Intestine_-_Inflammatory_Pathology]]

[[Category:Intestine_-_Inflammatory_Pathology]]

[[Category:Intestinal Diseases - Cat]][[Category:Intestinal Diseases - Dog]][[Category:Alimentary_Disorders]]

[[Category:Intestinal Diseases - Cat]]

[[Category:To Do - Review]]

[[Category:Intestinal Diseases - Dog]][[Category:Alimentary_Disorders]]

[[Category:Expert Review Small Animal]]