Liver Anatomy and Function

• The liver is a vital organ responsible for many essential functions to keep the body healthy
• The liver is the largest internal organ in the human body, located in the upper right quadrant of the abdomen, below the diaphragm
• It has a reddish-brown color and a rubbery texture

Liver Anatomy

• The liver is divided into two main lobes: the large right lobe and the smaller left lobe
• These lobes are separated by the falciform ligament, which attaches the liver to the anterior abdominal wall
• The liver has a unique dual blood supply, receiving blood from both the hepatic artery and the portal vein
• The hepatic artery supplies oxygenated blood from the heart, while the portal vein carries nutrient-rich blood from the digestive system
• Blood from both sources mixes in the liver sinusoids, which are capillaries located between hepatocytes
• The liver is composed of functional units called lobules, which are hexagonal structures consisting of hepatocytes arranged around a central vein
• Hepatocytes are the primary cells of the liver and are responsible for most of its functions
• Bile canaliculi are small channels located between hepatocytes that collect bile, which is produced by the liver
• The bile ducts merge to form the common hepatic duct, which joins the cystic duct from the gallbladder to form the common bile duct
• The common bile duct empties into the duodenum, the first part of the small intestine

Liver Function

• The liver performs a wide range of functions essential for maintaining homeostasis and overall health
• It plays a crucial role in metabolism, detoxification, storage, and synthesis
• One of the primary functions of the liver is carbohydrate metabolism
• The liver helps regulate blood glucose levels by storing glucose as glycogen and releasing it when needed
• The liver also performs gluconeogenesis, the synthesis of glucose from non-carbohydrate sources
• In lipid metabolism, the liver synthesizes cholesterol, triglycerides, and lipoproteins
• It also breaks down fatty acids for energy production through beta-oxidation
• The liver plays a central role in protein metabolism
• It synthesizes non-essential amino acids, converts ammonia to urea for excretion, and produces plasma proteins such as albumin and clotting factors
• The liver is responsible for detoxifying harmful substances, such as drugs, alcohol, and toxins
• It metabolizes these substances and converts them into less toxic forms that can be excreted by the kidneys or in bile
• The liver stores several important substances, including glycogen, vitamins (A, D, E, K, and B12), and minerals (iron and copper)
• The liver synthesizes a variety of essential compounds, including albumin, clotting factors, complement proteins, and acute phase proteins
• Bile production is another critical function of the liver
• Bile is a fluid that contains bile salts, cholesterol, bilirubin, and electrolytes
• Bile salts emulsify fats in the small intestine, aiding in their digestion and absorption
• Bilirubin, a breakdown product of heme, is excreted in bile
• The liver plays a role in immune function by producing acute phase proteins and removing bacteria and debris from the bloodstream via Kupffer cells, specialized macrophages in the liver

Hepatic Diseases

• Hepatic diseases encompass a wide range of conditions that affect the liver, leading to impaired liver function and potentially severe health consequences
• Viral hepatitis is inflammation of the liver caused by viral infections, such as hepatitis A, B, C, D, and E viruses
• Chronic hepatitis can lead to cirrhosis and liver cancer
• Cirrhosis is the irreversible scarring of the liver, resulting from chronic liver diseases such as hepatitis, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD)
• Cirrhosis impairs liver function and can lead to complications like ascites, variceal bleeding, and hepatic encephalopathy
• NAFLD is the accumulation of excess fat in the liver in individuals who do not consume excessive alcohol
• Nonalcoholic steatohepatitis (NASH) is a more severe form of NAFLD characterized by liver inflammation and damage
• Alcohol-related liver disease (ARLD) is liver damage caused by excessive alcohol consumption
• It includes alcoholic fatty liver, alcoholic hepatitis, and cirrhosis
• Liver cancer includes hepatocellular carcinoma (HCC), which arises from hepatocytes, and other less common types
• HCC is often associated with chronic liver diseases
• Autoimmune liver diseases involve the immune system attacking the liver
• Examples include autoimmune hepatitis, primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC)
• Genetic and metabolic disorders, such as hemochromatosis (iron overload) and Wilson's disease (copper accumulation), can lead to liver damage
• Drug-induced liver injury (DILI) occurs when certain medications or herbal supplements cause liver damage
• Cholestatic liver diseases involve impaired bile flow, leading to the accumulation of bile in the liver
• Examples include PBC and PSC

Liver Metabolism

• Liver metabolism is a complex and multifaceted process that encompasses a wide range of biochemical reactions essential for maintaining homeostasis

Carbohydrate Metabolism

• Involves the liver playing a central role in regulating blood glucose levels through several key processes
• Glycogenesis: The liver stores glucose as glycogen when blood glucose levels are high
• Glycogenolysis: The liver breaks down glycogen into glucose when blood glucose levels are low
• Gluconeogenesis: The liver synthesizes glucose from non-carbohydrate precursors like amino acids, lactate, and glycerol

Lipid metabolism

• Sees the liver involved in the synthesis, breakdown, and transport of lipids
• Lipogenesis: The liver synthesizes fatty acids and triglycerides from glucose and amino acids
• Beta-oxidation: The liver breaks down fatty acids into acetyl-CoA, which can be used for energy production
• Lipoprotein synthesis: The liver synthesizes lipoproteins (e.g., VLDL, HDL) that transport fats, cholesterol, and other lipids in the blood
• Cholesterol metabolism: The liver synthesizes cholesterol and converts it into bile acids

Protein metabolism

• Includes the liver being actively involved in amino acid metabolism and protein synthesis
• Amino acid deamination: The liver removes amino groups from amino acids, converting them into ammonia
• Urea cycle: The liver converts ammonia into urea, which is excreted in the urine
• Protein synthesis: The liver synthesizes a variety of proteins, including albumin, clotting factors, and acute-phase proteins
• The liver is the primary site for the metabolism and detoxification of drugs, alcohol, and other xenobiotics
• Phase I reactions: Oxidation, reduction, and hydrolysis reactions, often catalyzed by cytochrome P450 enzymes, modify the chemical structure of drugs
• Phase II reactions: Conjugation reactions, such as glucuronidation, sulfation, and glutathione conjugation, make drugs more water-soluble for excretion
• The liver processes bilirubin, a breakdown product of heme, for excretion in bile
• Bilirubin uptake: The liver takes up unconjugated bilirubin from the blood
• Bilirubin conjugation: The liver conjugates bilirubin with glucuronic acid, making it water-soluble
• Bilirubin excretion: The conjugated bilirubin is excreted into bile and eventually eliminated in the feces
• The liver plays a vital role in vitamin and mineral metabolism
• Vitamin storage: The liver stores vitamins A, D, E, K, and B12
• Mineral storage: The liver stores iron (as ferritin) and copper
• Activation of vitamins: The liver converts some vitamins into their active forms (e.g., vitamin D)

Liver Regeneration

• Liver regeneration is the remarkable ability of the liver to repair and restore its tissue after injury or partial removal
• The liver can regenerate up to 70% of its original mass
• This regenerative capacity is essential for maintaining liver function and survival after liver damage
• Hepatocytes, the primary cells of the liver, are capable of proliferation and contribute to liver regeneration
• Following liver injury, hepatocytes enter the cell cycle and undergo DNA replication and cell division
• This proliferation helps to replace damaged or lost hepatocytes and restore liver mass
• Liver progenitor cells (LPCs), also known as oval cells, are stem cell-like cells that can differentiate into hepatocytes and biliary epithelial cells
• LPCs play a role in liver regeneration, particularly when hepatocyte proliferation is impaired
• These cells can proliferate and differentiate to repopulate the liver and restore its function
• Several growth factors and cytokines are involved in the regulation of liver regeneration
• These factors stimulate hepatocyte proliferation, inhibit apoptosis, and promote liver growth
• Examples include hepatocyte growth factor (HGF), transforming growth factor alpha (TGF-α), epidermal growth factor (EGF), and interleukin-6 (IL-6)
• The extracellular matrix (ECM) provides structural support and regulates cell behavior during liver regeneration
• Remodeling of the ECM is essential for proper liver regeneration
• Matrix metalloproteinases (MMPs) degrade the ECM, while tissue inhibitors of metalloproteinases (TIMPs) inhibit MMP activity
• In chronic liver diseases, such as cirrhosis, the regenerative capacity of the liver is impaired
• Chronic inflammation and fibrosis interfere with hepatocyte proliferation and promote the formation of scar tissue
• This can lead to the development of liver failure and other complications
• Research is ongoing to identify strategies to enhance liver regeneration and improve outcomes for patients with liver diseases
• These strategies include the use of growth factors, cell-based therapies, and gene therapy