The liver is an organ that serves many crucial metabolic functions. It processes nutrients, removes waste products and toxins, regulates metabolism and forms many important molecules. Thus it is easy to understand, why liver diseases can cause widespread metabolic changes. Fortunately, the liver has a large reserve capacity for many of its functions, causing the most severe metabolic changes only to occur in severe liver failure.


Liver failure reduces the liver’s capacity to produce albumin

All circulatory albumin is produced by the liver. Albumin is needed for maintaining blood oncotic pressure, as a carrier molecule, and for maintaining normal blood pH. When liver capacity is decreased by 60-80%, the liver is unable to produce sufficiently albumin to maintain a normal blood albumin concentration. Around 60% of dogs suffering from chronic liver diseases are hypoalbuminemic. Severe hypoalbuminemia causes water to leak out of blood vessels causing edema or ascites.

Glucose and lactate metabolism can be affected by liver failure

The liver has many metabolic functions associated with glucose metabolism; glycogen synthesis to store glucose, glycogenolysis to release stored glucose, and gluconeogenesis for forming glucose. The liver has a big reserve capacity for glucose metabolism. Hypoglycemia develops only in severe liver failure, when liver capacity for glycogenolysis and gluconeogenesis is declined.
Lactate is produced continuously as cells use anaerobic glycolysis for energy production. Normally 30-70% of circulatory lactate is removed by the liver, where it is converted into glucose. In severe liver diseases, especially during acute liver failure, lactate removal via the liver can be impaired, causing blood lactate concentrations to rise. In human medicine, hyperlactatemia has even been associated with increased mortality risk in ICU patients suffering from liver disease.

The ratio of aromatic to branched-chain amino acids changes in liver failure

The liver is responsible for the breakdown of the aromatic amino acids phenylalanine and tyrosine. The plasma concentration of these amino acids can rise in patients suffering from portosystemic shunts or chronic liver failure due to impaired breakdown of these amino acids. In contrast, the concentration of the branched-chain amino acids leucine, isoleucine and valine decline as the body tries to remove excess ammonia from the bloodstream. These changes have been associated with muscle wasting and hepatic encephalopathy. In human medicine, the usage of branched-chain amino acids as dietary supplements has been reported to improve the nutritional status, prognosis and quality of life of patients suffering from hepatic cirrhosis. The concentrations of branched-chain amino acids do not fall in acute liver failure, since these amino acids are released into the bloodstream from dying hepatocytes.
Changes in the concentrations of the amino acids alanine and glycine have also been associated with liver failure. Alanine is an amino acid, that has an important role in energy production during negative energy balance. When tissues break down amino acids for energy production, their amino groups are incorporated into alanine. Alanine is then transported to the liver, where it is used for gluconeogenesis. High alanine concentrations have been reported in severe acute liver failure and during liver removal. Increased alanine levels can be caused by both increased release, as well as reduced alanine removal from the bloodstream. The liver has an important role in glycine metabolism, as well, and high circulatory glycine concentrations have been reported during acute liver failure.

Creatinine concentrations can fall due to multiple reasons

Low creatinine concentrations are seen in both liver failure and portosystemic shunting, but are caused by slightly different mechanisms in both conditions. The renal filtration rate increases in portosystemic shunting, causing increased removal of creatinine via the kidneys. In liver failure, the liver’s capacity of forming creatine, the precursor of creatinine, is reduced, leading to reduced creatinine release into the bloodstream. Muscle wasting also contributes to the fall of creatinine, since the daily amount of  creatinine released by the muscles is largely affected by muscle mass.

Cholesterol can decrease in liver failure and increase in cholestasis

Most of the circulatory cholesterol of a fasted animal is produced by the liver. Hypocholesterolemia develops when the liver’s capacity for cholesterol formation is reduced. Hypocholesterolemia has been reported in hepatic cirrhosis, toxin-induced parenchymal damage and portosystemic shunting.  However, most dogs suffering from liver failure have their cholesterol concentration within reference ranges.
As opposed to other liver diseases, cholestasis can cause mild to moderate hypercholesterolemia. Hypercholesterolemia is caused by reduced biliary cholesterol secretion and reduced cholesterol intake into the liver. Lipoprotein metabolism has also been reported to change in cholestasis, increasing the proportion of LDL and decreasing the proportion of HDL.

Hyperlipidemia can be associated with liver disease

Two liver diseases; vacuolar hepatopathy and gallbladder mucocele, have been associated with hyperlipidemia, especially hypertriglyceridemia. Vacuolar hepatopathy has been reported especially in Miniature Schauzers suffering from idiopathic hyperlipidemia. Gallbladder mucocele has been associated with hypertriglyceridemia and hypocholesterolemia in Shetland Sheepdogs, Border Terriers and Miniature Schnauzers. High liver values ALT and AST have also been reported in asymptomatic Miniature Schanuzers suffering from idiopathic hyperlipidemia.


Direction of change
Associated with condition

Insufficient production
Chronic liver failure

Insufficient production
Liver failure

Impaired removal
Acute liver failure

Impaired removal
Portosystemic shunting, chronic liver failure

Impaired removal
Portosystemic shunting, chronic liver failure

Increased use
Muscle wasting, hepatic encephalopathy

Increased use
Muscle wasting, hepatic encephalopathy

Increased use
Muscle wasting, hepatic encephalopathy
Branched-chain amino acids

Increased use
Muscle wasting, hepatic encephalopathy

Increased renal filtration/insufficient production/decreased muscle mass
Portosystemic shunting, chronic liver failure, muscle wasting

Insufficient production
Chronic liver failure

Decreased hepatic uptake and biliary secretion/idiopathic
Gallbladder mucocele, biliary obstruction, vacuolar hepatopathy

Vacuolar hepatopathy, gallbladder mucocele

Additional information

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