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==Description==

==Description==

Hepatic lipidosis describes a syndrome caused by derangements in lipid and protein metabolism.  It occurs in both cats and dogs but it is more clinically significant 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 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.

===Primary Lipidosis===

===Primary Lipidosis===

'''Primary or idiopathic hepatic lipidosis''' is most commonly recognised in obese indoor cats following a period of anorexia.  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, 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 pathogenesis involves a number of 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 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.  Oneore more of the following mechanisms may be involved:

*Excessive lipid mobilisation induced by anorexia, starvation, illness or stress.

*Deficiency of dietary proteins and other nutrients, which reduces the capacity of the liver to produce lipid transport proteins and to metabolise fat.  Recognised micronutrient deficiencies include arginine, carnitine, taurine and methionine.

*Disturbances in the neurohormonal control of appetite resulting in inappropriate anorexia.

*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.

*Disturbances in the neural and hormonal mechanisms that control '''appetite''' and satiety resulting in inappropriate anorexia.

===Secondary Lipidosis===

===Secondary Lipidosis===

'''Secondary hepatic lipidosis''' is a neuroendocrine response in dogs and cats to other diseases, including [[Pancreatitis - Dog and Cat|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.

'''Secondary hepatic lipidosis''' is a neuroendocrine response to other diseases, including [[Pancreatitis - Dog and Cat|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.

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.

==Diagnosis==

==Diagnosis==

===Clinical Signs===

===Clinical Signs===

*Anorexia and lethargy

*Severe persistent '''anorexia''' with lethargy.  Cats may lose weight and have an unkempt appearance.

*[[Icterus|Jaundice]]

*[[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 #Clinical Signs|Hepatic Encephalopathy]]

*[[Hepatic Encephalopathy|Hepatic encephalopathy]] may manifest mainly as depression and hypersalivation.

*[[Diarrhoea|Diarrhoea]] (sometimes)

*[[Diarrhoea|Diarrhoea]] and [[Vomiting|vomiting]] do not occur with all cases of hepatic lipidosis.

*Palpable hepatomegaly (sometimes)

*'''Palpable hepatomegaly''' may be appreciable as the liver enlarges with the storage of lipid in hepatocytes.

*Coagulopathies (sometimes)

*'''Coagulopathies''' sometimes occur in affected animals and may manifest as spontaneous subcutaneous, intra-articular or intra-cavitatory haemorrhage.

===Laboratory Tests===

===Laboratory Tests===

====Biochemistry====

====Biochemistry====

*Markedly increased level in alanine

Cholestatic enzymes are usually elevated due to intra-hepatic cholestasis but the exact pattern observed varies between species.  In cats, an elevated concentration of '''ALP''' is more sensitive for the detection of hepatic lipidosis and this enzyme is often greatly elevated while the level of GGT remains normal.  In dogs, an elevated serum concentration of '''GGT''' is more sensitive than ALP for the detection of hepatic lipidosis.

*Low gamma-glutamyltransferase (GGT) concentration

[[Image:Hepatic lipidosis histology.jpg|thumb|right|250px|Hepatic Lipidosis Histology - Copyright Karin Allenspach's lecture RVC]]

[[Bilirubin|'''Hyperbilirubinaemia''']] often occurs and this may be clinically evident as [[Icterus|icterus]].

 

===Diagnostic Imaging===

===Diagnostic Imaging===

====Radiography====

====Radiography====

Abdominal radiography shows a marked hepatomegaly.

'''Plain radiographs of the abdomen''' usually show only marked hepatomegaly with a right shift of the gastric axis when viewed on a right lateral film.  The borders of the liver lobes will be rounded and extensive intra-abdominal fat reserves may be evident in obese cats giving excellent serosal detail.

====Ultrasonography====

====Ultrasonography====

On ultrasound, an enlarged and diffusely hyperechoeic liver is seen.

An abdominal ultrasound scan will reveal an enlarged and '''diffusely hyperechoeic''' liver.

===Pathology===

===Pathology===

*enlarged [[Liver - Anatomy & Physiology|liver]] with round edges

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.

*lightish yellow in colour

*cut surface is uniform and greasy to handle

==Histopathology==

==Histopathology==

Fine needle aspirate of the liver is normally sufficient for a diagnosis.  Cytology demonstrates hepatocytes swollen with lipid.

Biopsy and culture of the liver tissue is always indicated to determine the underlying cause of the disease.

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.

 

==Treatment==

==Treatment==

*Intensive treatment of cats is required for best outcome

Intensive treatment of cats is required as the disease has a high mortality if not managed aggressively.

===Nutritional support===

===Nutritional Support===

*For a period of 4 - 6 weeks.

*For a period of 4 - 6 weeks.

*This is the most important treatment in hepatic lipidosis.  It is vital to ensure that the diet is of adequate calorific content with an increase in protein content.  Specific nutrients such as arginine, taurine, or carnitine may also be added.

*This is the most important treatment in hepatic lipidosis.  It is vital to ensure that the diet is of adequate calorific content with an increase in protein content.  Specific nutrients such as arginine, taurine, or carnitine may also be added.

===[[Hepatic Encephalopathy #Medical Management|Hepatic Encephalopathy]]===

===[[Hepatic Encephalopathy #Medical Management|Hepatic Encephalopathy]]===

*Treat this if presented.

This syndrome should be treated specifically if it occurs.

===Gastrointestinal drugs===

===Gastro-intestinal Drugs===

*Anti-emetics and porkinetics such as [[Gastroprotective Drugs #Histamine (H2) Receptor Antagonists|ranitidine]] and [[Drugs Acting on the Intestines#Drugs Acting on 5-HT4 Receptors|metoclopromide]] if vomiting for delayed gastric emptying is present

*Anti-emetics and porkinetics such as [[Gastroprotective Drugs #Histamine (H2) Receptor Antagonists|ranitidine]] and [[Drugs Acting on the Intestines#Drugs Acting on 5-HT4 Receptors|metoclopromide]] if vomiting for delayed gastric emptying is present

===Fluid therapy===

===Fluid Therapy===

*Intravenous fluid therapy in early stages of disease.

*Intravenous fluid therapy in early stages of disease.

*Blood glucose and electrolytes especially potasium and phosphate should be monitored.

*Blood glucose and electrolytes especially potasium and phosphate should be monitored.

===Coagulopathy===

===Coagulopathy===

*Vitamin K supplement may be required if coagulopathy is significant.

*Vitamin K supplement may be required if coagulopathy is significant.

==Prognosis==

==Prognosis==

This is dependent on the underlying cause.  If treated appropriately, 85% of severely affected animals will recover.

This is dependent on the underlying cause.  If treated appropriately, 85% of severely affected animals will recover.

==References==

==References==

**dietary factors: obesity and starvation

**dietary factors: obesity and starvation

**increased demand for energy: pregnancy, lactation, and starvation in physiological states

**increased demand for energy: pregnancy, lactation, and starvation in physiological states

 

 

 

====Feline====

====Feline====

 

*Survival rate is only 50-60%

*Survival rate is only 50-60%

*Pathophysiology:

*Pathophysiology: