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| '''Portosystemic encephalopathy<br>

| '''Portosystemic encephalopathy<br>

'''Hepatic coma'''

'''Hepatic coma'''

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==Description==

==Description==

'''Hepatic encephalopathy''' is characterised by a complex of neurological abnormalities that may occur in the presence of advanced liver disease.  By far the most common cause in dog and cat is [[Portosystemic Shunt|portosystemic shunt]] (PSS), although a marked reduction in functional mass of hepatic tissue can also lead to hepatic encephalopathy.  In rare cases, when severe acquired shunt due to hepatobiliary disease and congenital PSS have been ruled out, congenital urea enzyme cycle deficiencies and organic acidaemias, where there is lack of ability to degrade ammonia to urea, can be considered.

'''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 [[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''', a by-product of protein degradation which is transported in the portal vein and metabolised to urea in the liver via the urea cycle.  Alterations at any stage in this pathway may result in HE.  Ammonia is generated in normal animals through the following physiological processes:

**Metabolism of glutamine by enterocytes of the small intestine, the source of 25% of the energy used by these cells.

*'''Aromatic amino acids''', 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.

*'''Endogenous benzodiazepine receptor ligands''' are of questionable importance.

This is a reversible abnormality of the cerebral metabolism.  Its pathogenesis is not yet fully understood.  Increased concentration of ammonia level is the most common cause of this disease manifestation, due to its toxicity effect on brain cells.  Due to the lack of urea cycle in the brain, ammonia in [[Cerebral Spinal Fluid - Anatomy & Physiology|cerebrospinal fluid (CSF)]] is detoxified into glutamine.  Level of glutamine can be shown to correlate with clinical signs.  Aromatic amino acids, especially tryptophan and its metabolites, share an antiport transporter with ammonia in CSF.  Consequently, dogs with congenital PSS are reported to have increased aromatic amino acid concentrations in CSF.  Increased ammonia concentrations also have a number of other effects on the central nervous system, including a reduction in serotonin activity, an increased in NMDA (N-methyl-D-aspartic acid) and peripheral-type benzodiazepine receptors.

HE represents a reversible alteration in cerebral metabolism whose pathogenesis is not yet fully understood.  An increased blood concentration of ammonia is the most commonly cited cause by HE and it is known that this metabolite is able to cross the blood brain barrier and exert a directly toxic effect on neurones of the central nervous system (CNS).  Since the cells of the CNS are not able to express the constituent enzymes of the urea cycle, they convert ammonia into glutamine rather than urea.  Glutamine is a potent neurotransmitter in the CNS and its levels correlate with the clinical signs observed in HE.  Increased concentrations of ammonia in the cerebro-spinal fluid are reported to have additional effects on cerebral metabolism, including reducing levels of the excitatory neurotransmitter serotonin and increasing the levels of NMDA (N-methyl-D-aspartate) and peripheral-type benzodiazepine receptors.  Aromatic amino acids (especially tryptophan and its metabolites) share an antiport transporter with ammonia in the blood brain barrier and dogs with congenital PSS are therefore reported to have increased levels of these amino acids in their CSF.   

The sources responsible for an increase in ammonia levels include:

 

HE occurs in those breeds that often develop 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.

*the bacterial and intestinal breakdown of urea by urease, which then diffuse into the [[Colon - Anatomy & Physiology|colon]] from the blood.

*the bacterial breakdown of undigested amino acids in the [[Colon - Anatomy & Physiology|colon]].

*the catabolic metabolism of glutamine as an energy source by small intestinal enterocytes.

*endogenous hepatic protein metabolism by excess dietary protein intake, breakdown of lean body mass and gastrointestinal bleeding.

==Diagnosis==

==Diagnosis==

===Clinical Signs===

===Clinical Signs===

====Dog====

====Dog====

Typical signs include:

Typical signs include:

*anorexia, depression and lethargy

*'''Anorexia, depression''' and '''lethargy'''.

*aimless wandering, head pressing, circling and pacing

*'''Bizarre behaviour''', including aimless wandering, head pressing, circling, pacing and compulsive eating and drinking.

*central blindness

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

*poor growth rate

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

*gastrointestinal signs such as [[Stomach and Abomasum Consequences of Gastric Disease - Pathology|vomiting]]

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

 

====Cat====

====Cat====

Typical signs include:

Typical signs include:

*well grown and in good body condition which in contrast to dogs

*'''Hypersalivation''' or ptyalism is the most commonly reported clinical feature but this is rarely reported in dogs.

*hypersalivation or ptyalism is the most commonly reported clinical feature, but rarely reported in dogs

*'''Seizures''' occur in 50% of cases but are uncommon in dogs.

*seizures, found in 50% of cases, but uncommon in dogs

*'''Compulsive behaviour''' is less common than in dogs.

*anorexia, vomiting and diarrhoea, polyuria and polydipsia are less common

*compulsive behaviour is less common compared to in dogs

 

===Laboratory Tests===

===Laboratory Tests===