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==Introduction==

 

==Description==

'''Hepatic encephalopathy''' (HE) is characterised by a complex of neurological abnormalities that occur due to congenital or acquired abnormalities in hepatic structure or function.  HE is usually associated with some form of [[Portosystemic Shunt|'''portosystemic shunt''']] (PSS) in dogs and cats, although it may also be caused by a marked reduction in functional hepatic mass.  Other causes of HE, such as [[Hepatic Microvascular Dysplasia|'''microvascular dysplasia''']], '''congenital defects of enzymes of the urea cycle''', '''arginine deficiency''' or '''organic acidaemias''', are very rare or of only experimental interest.  The clinical signs of HE are associated with increases in the blood concentration of several metabolites:

'''Hepatic encephalopathy''' (HE) is characterised by a complex of neurological abnormalities that occur due to congenital or acquired abnormalities in hepatic structure or function.  HE is usually associated with some form of [[Portosystemic Shunt|'''portosystemic shunt''']] (PSS) in dogs and cats, although it may also be caused by a marked reduction in functional hepatic mass.  Other causes of HE, such as [[Hepatic Microvascular Dysplasia|'''microvascular dysplasia''']], '''congenital defects of enzymes of the urea cycle''', '''arginine deficiency''' or '''organic acidaemias''', are very rare or of only experimental interest.  The clinical signs of HE are associated with increases in the blood concentration of several metabolites:

*'''Ammonia''' is a by-product of protein degradation which is transported in the portal vein and metabolised to urea in the liver via the urea cycle.  In animals with PSS, ammonia is not removed from the portal blood as this bypasses the liver, leading to an increase in its blood concentration.  For ammonia generation in normal animals [[Ammonia|see here]].

*'''Ammonia''' is a by-product of protein degradation which is transported in the portal vein and metabolised to urea in the liver via the urea cycle.  In animals with PSS, ammonia is not removed from the portal blood as this bypasses the liver, leading to an increase in its blood concentration.  For ammonia generation in normal animals see [[Ammonia|ammonia]].

*'''Mercaptans''' are products of the bacterial degradation of the amino acid methionine in the colon which are usually removed from the portal blood in the liver.

*'''Mercaptans''' are products of the bacterial degradation of the amino acid methionine in the colon which are usually removed from the portal blood in the liver.

*'''Aromatic amino acids''' may be involved especially when the ratio of aromatic to branched chain amino acids is very high.  This is considered to be a significant component in the pathogenesis of HE in horses.

*'''Aromatic amino acids''' may be involved especially when the ratio of aromatic to branched chain amino acids is very high.  This is considered to be a significant component in the pathogenesis of HE in horses.

==Signalment==

==Signalment==

HE occurs in those breeds that often develop congenital PSS, of which small breeds of dog are most at risk.  Most dogs with PSS present before the end of their first year of life.  Microvascular dysplasia and congenital defects of the urea cycle are very rare.  Acquired PSS may occur in animals with '''[[Hepatitis, Chronic|chronic hepatitis]]''', to which labrador retrievers, West Highland white terriers, English cocker spaniels and Dobermans are predisposed.

HE occurs in those breeds that often develop congenital PSS, of which small breeds of dog are most at risk.  Most dogs with PSS present before the end of their first year of life.  Microvascular dysplasia and congenital defects of the urea cycle are very rare.  Acquired PSS may occur in animals with '''[[Hepatitis, Chronic|chronic hepatitis]]''', to which Labrador retrievers, West Highland white terriers, English cocker spaniels and Dobermans are predisposed.

==Diagnosis==

==Diagnosis==

*'''Central or amaurotic blindness''', where animals retain a menace response but will collide with objects when ambulatory.

*'''Central or amaurotic blindness''', where animals retain a menace response but will collide with objects when ambulatory.

*'''Comas''' and reactive '''seizures''' are uncommon.

*'''Comas''' and reactive '''seizures''' are uncommon.

*'''Gastrointestinal signs''' may be observed, including [[Stomach and Abomasum Consequences of Gastric Disease - Pathology|vomiting]].

*'''Gastrointestinal signs''' may be observed, including [[Vomiting|vomiting]].

Other signs that occur in animals with congenital PSS or microvascular dysplasia include:

Other signs that occur in animals with congenital PSS or microvascular dysplasia include:

*'''Intra-venous fluid therapy''', which can also be used to correct any hypokalaemia or metabolic alkalosis which may be precipitating the HE.  

*'''Intra-venous fluid therapy''', which can also be used to correct any hypokalaemia or metabolic alkalosis which may be precipitating the HE.  

*'''Enemas''' of warm water or lactulose to decrease the population of bacteria in the [[Colon - Anatomy & Physiology|colon]].

*'''Enemas''' of warm water or lactulose to decrease the population of bacteria in the [[Colon - Anatomy & Physiology|colon]].

*'''Antibiotics''' given orally or by per rectum to reduce the number of colonic bacteria.  Suitable products include [[Penicillins|ampicillin]], [[Aminoglycosides|neomycin]] (which, although highly toxic when administered systemically, is also highly polar and therefore restricted to the GI tract) or [[Nitroimidazoles|metronidazole]].

*'''Antibiotics''' given orally or per rectum to reduce the number of colonic bacteria.  Suitable products include [[Penicillins|ampicillin]], [[Aminoglycosides|neomycin]] (which, although highly toxic when administered systemically, is also highly polar and therefore restricted to the GI tract) or [[Nitroimidazoles|metronidazole]].

*[[Lactulose|'''Lactulose''']] can be given orally or by enema.  It is a synthetic disaccharide which, when metabolised by the acidifying colonic bacteria, donates a hydrogen ion to ammonia to form ammonium ions.  Because these ions are charged, the are not absorbed freely and are rather trapped in the colon and excreted in faeces.  Lactulose also acts as an osmotic laxative, preventing constipation and reducing the time that colonic bacteria are able to act on undigested amino acids to form ammonia.  

*[[Lactulose|'''Lactulose''']] can be given orally or by enema.  It is a synthetic disaccharide which, when metabolised by the acidifying colonic bacteria, donates a hydrogen ion to ammonia to form ammonium ions.  Because these ions are charged, the are not absorbed freely and are rather trapped in the colon and excreted in faeces.  Lactulose also acts as an osmotic laxative, preventing constipation and reducing the time that colonic bacteria are able to act on undigested amino acids to form ammonia.  

*When the animal is to be fed, a '''diet with a high carbohydrate, low protein (2g/kg/day) and low fat''' content is recommended.  Both soluble and insoluble fibre may be beneficial in appropriate quantities as the former traps ammonia in the colon and the latter reduces intestinal transit time and prevents constipation.  In an animals with PSS or severe hepatic insufficiency, it may not be advisable to restrict protein too assiduously as these animals are likely to be [[Hypoalbuminaemia|hypoalbuminaemic]].

*When the animal is to be fed, a '''diet with a high carbohydrate, low protein (2g/kg/day) and low fat''' content is recommended.  Both soluble and insoluble fibre may be beneficial in appropriate quantities as the former traps ammonia in the colon and the latter reduces intestinal transit time and prevents constipation.  In an animals with PSS or severe hepatic insufficiency, it may not be advisable to restrict protein too assiduously as these animals are likely to be [[Hypoalbuminaemia|hypoalbuminaemic]].

*'''Seizures''' should be treated with anticonvulsant medication but [[Benzodiazepines|benzodiazepines]] should be avoided as they may worsen the HE.

*'''Seizures''' should be treated with anticonvulsant medication but [[Benzodiazepines|benzodiazepines]] should be avoided as they may worsen the HE.

 

==Prognosis==

==Prognosis==

In cases of PSS, the prognosis in dogs for resolution of clinical signs after total surgical ligation is excellent.  However, the response of cat to surgical intervention in cats is less promising than in dogs.

In cases of PSS, the prognosis in dogs for resolution of clinical signs after total surgical ligation is excellent.  However, the response to surgical intervention in cats is less promising than in dogs.

==References==

==References==

 

[[Category:Liver_-_General_Pathology]]

[[Category:Liver_-_General_Pathology]]

[[Category:Dog]][[Category:Cat]]

[[Category:Liver Diseases - Dog]][[Category:Liver Diseases - Cat]]

[[Category:To_Do_-_James]]

[[Category:Neurological Diseases - Dog]][[Category:Neurological Diseases - Cat]]

[[Category:To_Do_-_Review]]

[[Category:Expert_Review]]