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Lipid Mobilisation Syndrome  

Also known as: '''''Lipid Mobilisation Syndrome '''''

 

== Introduction ==

== Introduction ==

Hepatic lipidosis describes a syndrome caused by derangements in lipid and protein metabolism. It occurs in both cats and dogs but it produces a more important clinical syndrome in cats. Similar phenomena occur in horses, donkeys, cattle and sheep when they are exposed to periods of metabolic stress. Hepatic lipidosis may be '''primary''' (or idiopathic) or it may be '''secondary''' to another disease.  

Hepatic lipidosis describes a syndrome caused by derangements in lipid and protein metabolism. It occurs in both cats and dogs but produces a more important clinical syndrome in cats. Similar phenomena occur in [[Hyperlipaemia - Horse|horses]], [[Hyperlipaemia - Donkey|donkeys]], [[Fatty Liver Syndrome|cattle]] and [[Pregnancy Toxaemia|sheep]] when they are exposed to periods of metabolic stress. Hepatic lipidosis may be '''primary''' (or idiopathic) or it may be '''secondary''' to another disease.  

=== Primary Lipidosis ===

=== Primary Lipidosis ===

'''Primary or idiopathic hepatic lipidosis''' is most commonly recognised in obese indoor cats following a period of anorexia or stress. It is the most common hepatic disease of cats in North America but it is becoming more common in Europe. It occurs due to the accumulation of large amounts of lipid in hepatocytes, altering the morphology of the cells and producing an acute hepatopathy. The mortality rate of this disease is high unless it is treated aggressively.  

'''Primary or idiopathic hepatic lipidosis''' is most commonly recognised in '''obese indoor cats''' following a period of anorexia or stress. It is the most common hepatic disease of cats in North America but it is becoming more common in Europe. It occurs due to the accumulation of large amounts of lipid in hepatocytes, altering the morphology of the cells and producing an acute hepatopathy. The mortality rate of this disease is high unless it is treated aggressively.  

The lipid that accumulates within hepatocytes is composed of triglyceride which is synthesised from circulating fatty acids in the liver. Circulating fatty acid concentrations are regulated by a number of hormonal factors that act on the enzymes hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL). HSL is responsible for releasing fatty acids from adipose tissue and its action is stimulated by catecholamines, glucagon, corticosteroids and thyroid hormones but inhibited by insulin. LPL degrades circulating lipoprotein complexes allowing fatty acids to be taken back up into adipose stores. The liver and other tissues usually oxidise fatty acids via the Krebs cycle within mitochondria but this pathway is downregulated in animals that receive excessive dietary calories. Additionally, hepatocytes are able to package fatty acids into very low lipoprotein complexes (VLDLs) that are released back into the circulation. If the apolipoproteins that partly constitute the VLDLs are deficient, fatty acids may not be dispatched from the liver. The accumulation of triglycerides in the liver reflects an imbalance between the processes that cause lipid mobilisation, those that lead to fatty acid oxidation and dispatch and those that encourage storage in adipose tissue. One or more mechanisms may be involved and these include increased activation of HSL by '''catecholamines''' released in response to stress, failure to produce sufficient '''insulin''' (in [[Diabetes Mellitus|diabetes mellitus]]) results in uncontrolled HSL activity and excessive lipid mobilisation induced by '''anorexia''', '''starvation''' or '''illness''', partly under the influence of glucagon on HSL. '''Deficiency of dietary proteins''' and other nutrients, which reduces the capacity of the liver to produce lipid transport (apolipo-)proteins and to metabolise fat. Recognised micronutrient deficiencies include '''arginine''', '''carnitine''', '''taurine''' and '''methionine'''. Carnitine has a vital role in carrying fatty acids across the inner mitochondrial membrane and also disturbances in the neural and hormonal mechanisms that control '''appetite''' and satiety resulting in inappropriate anorexia, are other factors.  

The lipid that accumulates within hepatocytes is composed of triglyceride which is synthesised from circulating fatty acids in the liver. Circulating fatty acid concentrations are regulated by a number of hormonal factors that act on the enzymes hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL). HSL is responsible for releasing fatty acids from adipose tissue and its action is stimulated by catecholamines, [[glucagon]], corticosteroids and [[Thyroid Gland - Anatomy & Physiology#Thyroid Hormone Physiology|thyroid hormones]] but inhibited by [[insulin]]. LPL degrades circulating lipoprotein complexes allowing fatty acids to be taken back up into adipose stores. The liver and other tissues usually oxidise fatty acids via the Krebs cycle within mitochondria but this pathway is downregulated in animals that receive excessive dietary calories. Additionally, hepatocytes are able to package fatty acids into very low lipoprotein complexes (VLDLs) that are released back into the circulation. If the apolipoproteins that partly constitute the VLDLs are deficient, fatty acids may not be dispatched from the liver. The accumulation of triglycerides in the liver reflects an imbalance between the processes that cause lipid mobilisation, those that lead to fatty acid oxidation and dispatch and those that encourage storage in adipose tissue. One or more mechanisms may be involved and these include increased activation of HSL by '''catecholamines''' released in response to stress, failure to produce sufficient '''insulin''' (in [[Diabetes Mellitus|diabetes mellitus]]) results in uncontrolled HSL activity and excessive lipid mobilisation induced by '''anorexia''', '''starvation''' or '''illness''', partly under the influence of glucagon on HSL. '''Deficiency of dietary proteins''' and other nutrients, which reduces the capacity of the liver to produce lipid transport (apolipo-)proteins and to metabolise fat. Recognised micronutrient deficiencies include '''arginine''', '''carnitine''', '''taurine''' and '''methionine'''. Carnitine has a vital role in carrying fatty acids across the inner mitochondrial membrane and also disturbances in the neural and hormonal mechanisms that control '''appetite''' and satiety resulting in inappropriate anorexia, are other factors.  

=== Secondary Lipidosis ===

=== Secondary Lipidosis ===

'''Secondary hepatic lipidosis''' is a neuroendocrine response to other diseases, including [[Pancreatitis|pancreatitis]], [[Diabetes Mellitus|diabetes mellitus]], [[Inflammatory Bowel Disease|inflammatory bowel disease]] and primary hypertriglyceridaemia. Secondary hepatic lipidosis is therefore less closely associated with obesity and it may be seen in normal or even thin cats. In dogs, this secondary lipid accumulation rarely contributes to the clinical syndrome but in cats, it may greatly exacerbate the disease suffered by the affected animal. Secondary lipidosis is much more common than primary in cats in the UK.  

'''Secondary hepatic lipidosis''' is a neuroendocrine response to other diseases, including [[Pancreatitis|pancreatitis]], [[Diabetes Mellitus|diabetes mellitus]], [[Inflammatory Bowel Disease|inflammatory bowel disease]] and primary hypertriglyceridaemia. Secondary hepatic lipidosis is therefore less closely associated with obesity and it may be seen in normal or even thin cats. In dogs, this secondary lipid accumulation rarely contributes to the clinical syndrome but in cats, it may greatly exacerbate the disease suffered by the affected animal. ''Secondary lipidosis is much more common than primary in cats in the UK. ''

 

== Signalment ==

== Signalment ==

Indoor and obese cats are more prone to the development of primary hepatic lipidosis during periods of stress or anorexia. Most cases occur in middle-aged cats with no apparent breed predisposition.  

Indoor and obese cats are more prone to the development of primary hepatic lipidosis during periods of stress or anorexia. Most cases occur in middle-aged cats with no apparent breed predisposition.  

== Clinical Signs ==

== Clinical Signs ==

 

[[Image:Jaundiced cat.jpg|thumb|Image of a jaundiced cat that was suffering from hepatic lipidosis.  Note the icteric pinnae.<br><small>Copyright Sabar 2007 Wikimedia Commons</small>]]

[[Image:Jaundiced cat.jpg|thumb|Image of a jaundiced cat that was suffering from hepatic lipidosis.  Note the icteric pinnae.<br /><small>Copyright Sabar 2007 Wikimedia Commons]] Clinical signs may appear to be non-specific at first. These include severe persistent '''anorexia''' with lethargy. Cats may lose weight and have an unkempt appearance.[[Icterus|'''Jaundice''']] may or may not occur. It is a form of intra-hepatic icterus as the swollen hepatocytes partially obstruct the flow of bile in the canaliculi.&nbsp;[[Hepatic Encephalopathy|'''Hepatic encephalopathy''']] may manifest mainly as depression and hypersalivation. [[Diarrhoea|'''Diarrhoea''']] and [[Vomiting|'''vomiting''']] do not occur with all cases of hepatic lipidosis. '''Palpable hepatomegaly''' may be appreciable as the liver enlarges with the storage of lipid in hepatocytes.&nbsp;'''Coagulopathies''' sometimes occur in affected animals and may manifest as spontaneous subcutaneous, intra-articular or intra-cavitatory haemorrhage. The syndrome develops due to reduced absorption of vitamin K or failure to reclaim vitamin K in the liver due to diffuse hepatic disease.  

Clinical signs may appear to be non-specific at first. These include severe persistent '''anorexia''' with lethargy. Cats may lose weight and have an unkempt appearance.[[Icterus|'''Jaundice''']] may or may not occur. It is a form of intra-hepatic icterus as the swollen hepatocytes partially obstruct the flow of bile in the canaliculi. [[Hepatic Encephalopathy|'''Hepatic encephalopathy''']] may manifest mainly as depression and hypersalivation. [[Diarrhoea|'''Diarrhoea''']] and [[Vomiting|'''vomiting''']] do not occur with all cases of hepatic lipidosis. '''Palpable hepatomegaly''' may be appreciable as the liver enlarges with the storage of lipid in hepatocytes. '''Coagulopathies''' sometimes occur in affected animals and may manifest as spontaneous subcutaneous, intra-articular or intra-cavitatory haemorrhage. The syndrome develops due to reduced absorption of vitamin K or failure to reclaim vitamin K in the liver due to diffuse hepatic disease.  

 

== Diagnosis ==

== Diagnosis ==

Urinalysis may reveal '''bilirubinuria''' as the serum bilirubin concentration is increased as in any cholestatic disease.  

Urinalysis may reveal '''bilirubinuria''' as the serum bilirubin concentration is increased as in any cholestatic disease.  

Cats with hepatic lipidosis often become deficient for vitamin B12 (cyanocobalamin), especially if they concurrent [[Inflammatory Bowel Disease|inflammatory bowel disease]] of [[Pancreatitis|pancreatitis]].  

Cats with hepatic lipidosis often become deficient of vitamin B12 (cyanocobalamin), especially if they also suffer from [[Inflammatory Bowel Disease|inflammatory bowel disease]] or [[Pancreatitis|pancreatitis]].  

=== Diagnostic Imaging ===

=== Diagnostic Imaging ===

==== Ultrasonography ====

==== Ultrasonography ====

 

[[Image:Sono Hepatische Lipidose Katze 0.jpg|thumb|Ultrasonographic image of a feline liver affected by hepatic lipidosis.  The liver has a similar echogenicity to the surrounding fat.<br /><small>Copyright Kalumet 2009 Wikimedia Commons</small>]] An abdominal ultrasound scan will reveal an enlarged and '''diffusely hyperechoeic''' liver. The underlying cause of the liver disease may also be apparent.  

[[Image:Sono Hepatische Lipidose Katze 0.jpg|thumb|Ultrasonographic image of a feline liver affected by hepatic lipidosis.  The liver has a similar echogenicity to the surrounding fat.<br /><small>Copyright Kalumet 2009 Wikimedia Commons]] An abdominal ultrasound scan will reveal an enlarged and '''diffusely hyperechoeic''' liver. The underlying cause of the liver disease may also be apparent.  

=== Pathology ===

=== Pathology ===

 

Grossly, the liver will appear to be enlarged with rounded edges. The tissue may be white/yellow in colour and the cut surface will be uniform and greasy to handle.  

Grossly, the liver will appear to be enlarged with rounded edges. The tissue may be white/yellow in colour and the cut surface will be uniform and greasy to handle.  

Histopathology[[Image:Hepatic lipidosis histology.jpg|thumb|right|250px|Histological image of a section of liver with lipidosis.  Note the many vacuoles that push the hepatocyte nuclei aside.<br /><small>Copyright Karin Allenspach 2008 RVC]] Fine needle aspiration of the liver (preferably under ultrasound guidance) is often sufficient to make a diagnosis of hepatic lipidosis. Cytological examination of the sample reveals that the hepatcoytes are swollen with lipid which pushes the nuclei aside. Where possible, biopsy of liver tissue and aspiration of bile are indicated to determine the underlying cause of the disease.

Histopathology:

== Treatment ==

== Treatment ==

 

Intensive treatment of cats is required as the disease has a high mortality if not managed aggressively. Owners should be warned that long-term nutritional support will be required to achieve a successful outcome. In cases of secondary lipidosis, the underlying cause of disease should be treated.  

Intensive treatment of cats is required as the disease has a high mortality if not managed aggressively. Owners should be warned that long-term nutritional support will be required to achieve a successful outcome. In cases of secondary lipidosis, the underlying cause of disease should be treated.  

Nutritional Support[[Image:FelineHepaticLipidosisEsophagealFeedingTube.jpg|thumb|Image of a cat receving nutritional support via an oesophagostomy tube<br /><small>Released into the Public Domain]]&nbsp;is generally required for a period of 4 - 6 weeks but longer durations may be necessary if the animal fails to eat voluntarily. The two major considerations are the route of feeding and the composition of the diet that is fed.  

Nutritional Support is generally required for a period of 4 - 6 weeks but longer durations may be necessary if the animal fails to eat voluntarily. The two major considerations are the route of feeding and the composition of the diet that is fed.  

==== Route of Feeding ====

==== Route of Feeding ====

Specific nutrients such as arginine, taurine, or carnitine may also be added and there is some evidence to suggest that carnitine supplementation may be beneficial in cats with hepatic lipidosis. B vitamins, particularly B12 in cats, should be supplemented if they are thought to be deficient. Antioxidants (including s-adenosyl methionine (SAMe) and vitamin E can be added to the diet to limit oxidative Heinz body anaemia that occurs with hepatic lipidosis and to limit inflammatory liver pathology.  

Specific nutrients such as arginine, taurine, or carnitine may also be added and there is some evidence to suggest that carnitine supplementation may be beneficial in cats with hepatic lipidosis. B vitamins, particularly B12 in cats, should be supplemented if they are thought to be deficient. Antioxidants (including s-adenosyl methionine (SAMe) and vitamin E can be added to the diet to limit oxidative Heinz body anaemia that occurs with hepatic lipidosis and to limit inflammatory liver pathology.  

=== [[Hepatic Encephalopathy#Medical_Management|Hepatic Encephalopathy]] ===

=== [[Hepatic Encephalopathy#Medical_Management|Hepatic Encephalopathy]] ===

This is dependent on the underlying cause and the way in which the patient is managed. If treated appropriately, 85% of severely affected animals will recover. In cats this percentage is only around 50%.

This is dependent on the underlying cause and the way in which the patient is managed. If treated appropriately, 85% of severely affected animals will recover. In cats this percentage is only around 50%.

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== References ==

== References ==

*Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) '''BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition)''' ''BSAVA''  

*Hall, E.J, Simpson, J.W. and Williams, D.A. (2005) '''BSAVA Manual of Canine and Feline Gastroenterology (2nd Edition)''' ''BSAVA''  

*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''.  

*Tilley, L. P. &amp; Smith, F. W. K. (2007) '''Blackwell's Five-minute Veterinary Consult: Canine &amp; Feline (Fourth Edition)''' ''Blackwell Publishing''

*Tilley, L. P. &amp; Smith, F. W. K. (2007) '''Blackwell's Five-minute Veterinary Consult: Canine & Feline (Fourth Edition)''' ''Blackwell Publishing''

 

 

 

 

 

 

 

 

[[Category:Liver_-_Degenerative_Pathology]] [[Category:Liver_Diseases_-_Cat]] [[Category:To_Do_-_Review]] [[Category:Liver_Diseases_-_Dog]]

[[Category:Liver_-_Degenerative_Pathology]] [[Category:Liver_Diseases_-_Cat]] [[Category:Expert_Review]] [[Category:Liver_Diseases_-_Dog]]