What are the functions of the liver?

Functions of the Liver

Core Metabolic and Synthetic Functions

The liver serves as the body's central metabolic organ with four major functions: metabolism and synthesis, excretion, storage, and detoxification of potential poisons. 1

Protein Synthesis and Coagulation

• Albumin production occurs exclusively in the liver and serves multiple biological actions including maintenance of oncotic pressure, binding of substances (fatty acids, bilirubin, thyroid hormone, drugs), lipid metabolism, and antioxidant properties 2
• Clotting factors (II, V, VII, IX, and X) are synthesized in the liver, and significant liver injury (>70% loss of synthetic function) results in coagulopathy with prolonged prothrombin time (PT) or INR 2
• Thrombopoietin production occurs in the liver, with levels declining in chronic liver injury and contributing to thrombocytopenia 2

Bilirubin Metabolism and Excretion

• The liver converts insoluble unconjugated bilirubin into soluble conjugated bilirubin for excretion 2
• Bilirubin is transported to the liver from the reticuloendothelial system where it undergoes conjugation via glucuronyltransferase enzyme 2
• Conjugated hyperbilirubinaemia typically indicates parenchymal liver disease or biliary obstruction, while unconjugated hyperbilirubinaemia suggests haemolysis or impaired conjugation 2

Carbohydrate and Lipid Metabolism

Glucose Regulation

• The liver controls hepatic glucose production, with dysfunction leading to impaired glucose tolerance and progression to type 2 diabetes 2
• The liver maintains homeostasis of numerous blood metabolites essential for physiological function 3

Lipid and Lipoprotein Processing

• The liver plays a central role in regulating carbohydrate and lipid/lipoprotein metabolism, with impairment having major impact on cardiovascular disease and diabetes risk 2
• Portal circulation delivers free fatty acids to the liver, where excess accumulation leads to hepatic steatosis 2
• The liver produces apolipoprotein B, with dysfunction leading to hypertriglyceridemia 2

Detoxification and Clearance Functions

Xenobiotic Metabolism

• The liver is fundamentally important for detoxification of xenobiotics (drugs) and potential poisons 1, 3
• Phase-I xenobiotic metabolism occurs in hepatocytes, with function impaired in malnutrition and liver disease 2
• The liver clears plasminogen activators, with impaired clearance anticipated in advanced liver disease 2

Metabolic Clearance

• Galactose elimination capacity serves as a measure of quantitative liver function 2
• The liver removes fibrin degradation products, with elevated levels in liver disease due to impaired hepatic clearance 2

Immunologic and Inflammatory Functions

Acute Phase Response

• The liver produces mediators of the acute phase response 3
• C-reactive protein plasma levels are produced by the liver and can be impaired in infected malnourished children 2
• The liver participates in immune-regulatory functions essential for maintaining physiological homeostasis 4

Endotoxin Processing

• The diseased liver incompletely removes coagulation factors activated in the low-flow portal system 2
• Endotoxin absorption from intestines into systemic circulation triggers sustained inflammation when hepatic clearance is impaired 2

Hormone Metabolism

Sex Hormone Regulation

• The liver produces sex hormone-binding globulin (SHBG), with synthesis stimulated by estrogens 2
• Altered estrogen metabolism occurs in advanced liver disease due to disruption of the hypothalamic-pituitary axis 2
• Increased peripheral conversion of androgens to estrogen occurs with portosystemic shunting 2

Storage Functions

• The liver stores essential nutrients and biochemicals necessary for digestion and growth 1
• The liver maintains ion homeostasis and participates in cellular energy homeostasis through mitochondrial function 5

Clinical Implications

Assessment Limitations

• Standard liver function tests primarily measure hepatocellular injury and cholestasis rather than actual liver function, with true functional assessment requiring measurement of synthetic capacity (albumin, INR) and metabolic clearance 6
• Multiple hepatic functions can be impaired simultaneously, requiring at least five different tests to assess liver function adequately 1