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**[[Histoplasmosis]]
 
**[[Histoplasmosis]]
 
*Chronic [[Intussusception|intussusception]] in juvenile animals
 
*Chronic [[Intussusception|intussusception]] in juvenile animals
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'''[[Lymphangiectasia]]'''
 
'''[[Lymphangiectasia]]'''
 
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== 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.  
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'''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.
*'''Hypocalcaemic tetany''' due to a reduced ability to absorb calcium and the fat soluble vitamin D.  Apparent hypocalcaemia may also develop as the protein-bound portion of the blood total calcium concentration is reduced.
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* Lesions include:
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** Inflammatory bowel disease
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** Dilated lymphatics
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** Lipogranulomatous lymphangitis.
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* Intestinal crypts become dilated with mucus, sloughed epithelial cells with or without inflammatory cells.
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* PLE is also associated with protein losing nephropathy (PLN).
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** PLN may be a chronic sequelae to the PLE.
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** Follows immune complex deposition in the glomerulus, causing glomerulonephritis or glomerulosclerosis.
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** PLN causes hypoalbunaemian and hypercholesterolaemia.
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** Similar PLN and PLE lesions seen in young Besenjis with immunoproliferative enteropathy and glomerulosclerosis.
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== 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.
 
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====Haematology====
 
====Haematology====
 
[[Lymphopenia|'''Lymphopaenia]]''' occurs with lymphangiectasia due to the loss of lymph.
 
[[Lymphopenia|'''Lymphopaenia]]''' occurs with lymphangiectasia due to the loss of lymph.
 
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====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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'''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''', especially in lymphangiectasia.
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*'''Hypocalcaemia''' 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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'''Hypocholesterolaemia''' may be present, especially in lymphangiectasia.
 
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'''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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====Other Tests====
 
====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.)
 
'''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.)
 
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'''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.
 
'''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.
 
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===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]]).
 
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]]).
 
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====Ultrasonography====
 
====Ultrasonography====
 
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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:
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#Changes to intestinal wall structure, including:
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**Thickening without loss of normal layers (as with inflammatory bowel disease)
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**Thickening with loss of layers (as with infiltrative intestinal neoplasia)
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**'Tiger stripes', an unreliable indicator of lymphangiectasia
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#Ascites or pleural effusion
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*Mesenteric lymphadenopathy
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===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]].
 
'''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]].
 
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]].
 
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]].
 
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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).
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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 Besenjis with immunoproliferative enteropathy and glomerulosclerosis.
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==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]].   
 
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===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.
 
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===[[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.
 
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===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.
 
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===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.
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==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.
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==Literature Search==
 
==Literature Search==
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<br><br><br>
 
[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]
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==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)''' ''J Vet Intern Med. 2000 Jan-Feb;14(1):68-80.''
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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''.
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*Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) '''BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition)''' ''BSAVA''.
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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''.
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<br>
*Willard, M. (2005) '''Protein-Losing Enteropathy in Dogs and Cats''' ''30th World Congress of the WSAVA''.
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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.
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Nelson, R.W. and Couto, C.G. (2009) '''Small Animal Internal Medicine (Fourth Edition)''', ''Mosby Elsevier''.
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<br>
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Willard, M. (2005) '''Protein-Losing Enteropathy in Dogs and Cats''', ''30th World Congress of the WSAVA''.
       
[[Category:Intestine_-_Inflammatory_Pathology]]
 
[[Category:Intestine_-_Inflammatory_Pathology]]
 
[[Category:Intestinal Diseases - Cat]][[Category:Intestinal Diseases - Dog]][[Category:Alimentary_Disorders]]
 
[[Category:Intestinal Diseases - Cat]][[Category:Intestinal Diseases - Dog]][[Category:Alimentary_Disorders]]
[[Category:To Do - Clinical]]
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[[Category:To Do - Review]]
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