Liver toxicology

• The liver stores and synthesises glucose
• The liver synthesises clotting factors and albumin
• The liver plays roles in bioactivation and detoxification
• Hepatocytes contain most of the metabolising enzymes
• Kupfer cells are described as the macrophages of the liver
• Bile ducts contain uptake and efflux transporters
• The ACINUS is the smallest unit in the liver and contains 3 zones
• Zone 1 is closest to the portal vein
• Zone 1 has a high oxygen supply and high levels of antioxidants
• Zone 3 is located near the central hepatic vein
• Zone 3 has low levels of oxygen and high levels of metabolising enzymes
• The liver can be a target for toxicology due to the rich blood flow
• Metabolites can cause oxidative stress. This can lead to mitochondrial damage and lipid peroxidation
• Oxidative stress and damaged cellular components cause necrosis
• Necrosis can lead to leakage of hepatocellular enzymes into the circulation
• The leakage of cellular compartments is recognised by kupfer cells
• Kupfer cell activation causes inflammation of the liver. This can cause hepatitis.
• Mitochondrial damage can activate stellate cells, this causes production of collagen and can cause fibrosis
• Inhibition of bile efflux transporters causes leakage of bile into circulation. This leads to cholestasis
• Steatosis is the abnormal fat build up
• Altered fatty acid B oxidation can lead to reduced fatty acid metabolism. This can lead to steatosis of the liver
• Granulocytes release high levels of ROS this causes tissue damage.
• Kupfer cells produce IL6 which regenerates damaged tissues
• Iron binds to ferrin and stored in hepatocytes. Saturation of ferrin can increase levels of ROS
• Carbon tetrachloride can be dangerous when metabolically activates due to the formation of free radicals
• Carbon tetrachloride most impacts zone 3 due to requiring metabolism
• Idiosynchratic injury is drug induced liver damage
• In idiochratic injury damage occurs at normal theraputic drug levels