Chapter 9: Hepatobiliary System
Detailed discussion of the hepatic physiology is beyond the scope of this book. However, understanding the roles of the liver is necessary when considering the microscopic anatomy.
Nutritional metabolic functions
The liver functions in the modification and transport of nutritional molecules, and therefore plays a critical role in energy metabolism. This includes the generation, breakdown, modification, and storage of nutritional molecules including glucose/glycogen, proteins, and lipids.
Xenobiotics include any compounds that are “foreign” to an animal. An example of xenobiotics are medications such as the class pain relief drugs referred to as NSAIDs (NSAIDs = non-steroidal anti-inflammatory drugs), but xenobiotics also include non-therapeutic compounds.
Xenobiotics are metabolized by hepatocytes via biotransformation, the process by which xenobiotics are chemically modified and excreted into bile. Hepatocytes are rich in cytochrome P450, a metabolic enzyme responsible for biotransformation. Biotransformation of a xenobiotic aims to render the agent less toxic and soluble for excretion. Occasionally, activation of the xenobiotic during biotransformation may result in an intermediate compound that is more toxic than the original form, leading to toxicity! Nonetheless, hepatocytes are the workhorses of xenobiotic biotransformation, and as such, they serve a major protective role in preventing the build-up and toxicity of xenobiotics.
Production of circulating plasma proteins
Hepatocytes produce many of the most abundant circulating plasma proteins including albumin, lipoproteins (LDL, VLDL, and HDL), and glycoproteins. These hepatocyte-produced proteins function in diverse areas such as energy and molecular transport and inflammation. The liver is also the primary source of proteins of the coagulation cascade. Hepatocytes produce almost all of the clotting factors (except Factor VIII, produced by endothelium) required in the coagulation cascade, including fibrinogen, prothrombin, antithrombin III, Protein C and Protein S.
Storage and conversion of vitamins and minerals
The liver is a major site of storage and conversion of various vitamins and minerals that include Vitamin A (retinol), Vitamin D, Vitamin B12, Vitamin K, iron and copper.
The liver receives red blood cell fragments from the spleen and further processes these products for recycling or excretion. Hemoglobin from red blood cells is broken down into heme and globin. The iron containing heme is further processed into bilirubin. Hepatocytes conjugate bilirubin, converting unconjugated (insoluble) bilirubin to conjugated (soluble) bilirubin, and is excreted and incorporated into bile to be excreted into the gastrointestinal tract.