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==Introduction==
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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:
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'''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]].
*Disruption to the intestinal wall due to [[Inflammation - Pathology|inflammation]] or infiltrative disease
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<br>
*Venous congestion of the GI tract
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Hence, there are numerous causes of PLE in cats and dogs, including:
*GI [[Haemorrhage|haemorrhage]]
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<br>
 
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Hence, there are numerous <u>causes of PLE in cats and dogs</u>, including:
      
'''Inflammation'''
 
'''Inflammation'''
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*Chronic [[Intussusception|intussusception]] in juvenile animals
 
*Chronic [[Intussusception|intussusception]] in juvenile animals
 
'''[[Lymphangiectasia]]'''
 
'''[[Lymphangiectasia]]'''
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<br>
    
'''Infiltrative disease'''
 
'''Infiltrative disease'''
 
*Alimentary lymphoma
 
*Alimentary lymphoma
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<br>
    
'''Venous congestion'''
 
'''Venous congestion'''
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*Posterior caval syndrome
 
*Posterior caval syndrome
 
**[[Heart Failure - Pathophysiology|Right-sided congestive heart failure]]
 
**[[Heart Failure - Pathophysiology|Right-sided congestive heart failure]]
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<br>
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'''GI haemorrhage'''
 
'''GI haemorrhage'''
 
*This may occur with hypoadrenocorticism or with other causes of GI ulceration
 
*This may occur with hypoadrenocorticism or with other causes of GI ulceration
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<br>
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Rare causes of PLE include:
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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 erythematosis (SLE) and chemotherapy or radiotherapy.
* [[Antibiotic Responsive Diarrhoea|Small intestinal bacterial overgrowth (SIBO)]]
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<br>
* [[Hypoalbuminaemia]] causing intestinal mural oedema
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* Increased activation of tissue plasminogen activator
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* Systemic lupus erythematosis (SLE)
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* Chemotherapy or radiotherapy
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==Signalment==
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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.
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.
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<br>
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== Signalment ==
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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.  
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<br>
 
   
 
   
 
'''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
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==Diagnosis==
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===Clinical Signs===
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*'''Weight loss''' is the most evident sign.
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== Clinical Signs ==
*'''Diarrhoea''' occurs due to the loss of protein into the GI tract and subsequent osmotic movement of fluid.  Melaena may occur with GI haemorrhage.
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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.  
*[[Oedema|'''Oedema''']], '''ascites''' and '''pleural effusion''' due to reduced plasma oncotic pressure.
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*'''Thickened intestines''' may be detectable on abdominal palpation and this finding may be related to the primary pathological process.
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*[[Thromboembolism|'''Thromboembolic]] disease''' due to the loss of plasma anticoagulants such as antithrombin III.
   
*'''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.
 
*'''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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==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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==Protein-Losing Enteropathy (PLE)==
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* Affects soft coated wheaten terriers.
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** Common male ancestor for most of the dogs.
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** Bitches are affected more often than dogs.
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** Also affects Besenji, Lundehund.
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* Normally, dietary protein and protein from shed enterocytes is almost completely absorbed.
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** In PLE there is excess loss of protein into the gut lumen.
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*** The loss is non-selective i.e. albumin and globulin.
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** Causes panhypoproteinaemia and hypocholesterolaemia.
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* If this is severe, oedema and weight loss may result.
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* Enteropathy not due to gluten sensitivity.
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* Can diagnose PLE on basis of finding α1-protease inhibitor in the faeces in dogs.
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===Causes of PLE===
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* Severe inflammatory disease.
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** Protein is lost in exudate.
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* [[Lymphangiectasia|Lymphangiectasia]].
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** Loss of protein-rich lymph due to obstruction of gut lymphatics.
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* Increased mucosal permeability.
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** E.g. erosions, loss of tight junctions, lymphosarcoma.
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* Increased loss of enterocytes (less important).
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* Also:
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** Immunoproliferative enteropathy
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** Lymphocytic plasmacytic enteritis
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** Eosinophilic enteritis
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** GI ulceration/erosion
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** Giardiasis
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** Chronic intussusception
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** Small intestinal bacterial overgrowth
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** Neoplasia
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** Hypoalbunimaemia causing mural oedema
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** Increased activation of tissue plasminogen activator
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** Systemic lupus erythematosis (SLE)
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** Vascular lesion in the GI mucosa
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** Chemotherapy/radiotherapy.
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===Pathology===
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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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