Physiology and function of the hepatobiliary tract

Chapter 1.7
Physiology and function of the hepatobiliary tract

Yiannis N. Kallis and David Westaby

¹Barts Health NHS Trust, London, UK

²Imperial College Healthcare NHS Trust, London, UK

1.7.1 Anatomy, physiology and function

The liver is situated in the right hypochondrium and is split into right and left lobes. It can be further divided into eight functional segments according to vascular supply and biliary drainage [1]. Inflow of blood is via a dual supply, with approximately 25% derived from the hepatic artery and 75% from the portal vein, which drains the gastrointestinal tract, pancreas and spleen. Both vessels enter the liver at the hilum and subdivide into smaller branches, running in structures called portal tracts, also composed of bile ducts and lymphatics. Blood perfuses the liver within sinusoids before draining via tributaries to form the hepatic vein, which enters the inferior vena cava just beneath the diaphragm.

Histologically, liver parenchyma is arranged into units called lobules, defined by a central hepatic venule and multiple peripheral portal tracts [2]. Hepatocytes are organised into three-dimensional plates separated by sinusoids, which are lined by fenestrated endothelium through which blood can readily permeate. Kupffer cells (liver macrophages) and hepatic stellate cells (fibroblast-like collagen-producing cells) lie in close approximation [3]. Spatially, hepatocytes are classified into three zones, with those around portal tracts in zone 1 receiving the most oxygenated blood and those in zone 3 around hepatic venules the least [4].

Bile caniliculi form a dense meshwork around hepatocytes and fuse to form bile ducts within portal tracts. The right and left hepatic ducts join at the hilum to form the common hepatic duct. The cystic duct drains the gallbladder and fuses with the common hepatic duct to form the common bile duct. The latter enters the duodenum at the ampulla of Vater (see Chapter 1.5).

The gallbladder is located in the abdomen under the right lobe of the liver. It is a pear-shaped sac, with average volume of 50 mL and length of 9 cm in healthy adults (range 4–14 cm), and is connected to the gastrointestinal tract via the cystic duct and common bile duct [5]. Its function is to concentrate and store bile produced in the liver and to release this into the duodenum when required for digestion. Release of bile is achieved by muscular contraction of the gallbladder in response primarily, but not exclusively, to gut hormones, especially cholecystokinin (CCK), that are stimulated by the products of digestion in the gastrointestinal tract. In the small intestine, bile is essential for the emulsification of dietary fat.

Carbohydrate metabolism

The liver plays a major role in glucose homeostasis and is the main store of glycogen. It assimilates excess glucose into glycogen within hepatocytes under insulin control. Conversely, hepatic glycogenolysis makes glucose readily available to other organs as the first response to starvation. Thereafter, the liver can also release glucose via gluconeogenesis from non-carbohydrate substrates such as lactate, amino acids (alanine and glutamine) and glycerol. During prolonged starvation, hepatic fatty acids are metabolised by beta-oxidation to ketone bodies, an important energy source for organs such as the brain.

Protein metabolism

The liver regulates plasma amino acid levels by controlling amino acid transamination and gluconeogenesis. All circulating plasma proteins except gamma-globulins are synthesised by the liver. Approximately 10–12 g of albumin is produced daily, helping to maintain oncotic pressure and transport water-insoluble compounds. Coagulation cascade factors, including fibrinogen, are produced in the liver, as are acute phase and complement proteins. The liver is the primary site of nitrogen excretion via amino acid transamination and oxidative deamination, leading to the formation of ammonia, which is subsequently converted to urea and excreted renally.

Lipid metabolism

Following dietary fat absorption, the liver synthesises triglycerides from free fatty acids for redistribution around the body within very low-density lipoproteins (VLDL). Likewise, hepatic fatty acid oxidation can be utilised for energy release. The liver controls production of circulating lipoproteins which transport insoluble fats through the bloodstream. Cholesterol formation, excretion and redistribution are also under hepatic regulation. Circulating cholesterol is taken up via hepatic low-density lipoprotein (LDL) receptors, and cholesterol can be formed de novo from hepatic acetyl-CoA. Cholesterol esterification to fatty acids also takes place in the liver.

The liver is a store for several vitamins and minerals, including vitamins A, D, B12, iron and copper, and is the site of 25-hydroxylation of cholecalciferol.

Bile acid and bilirubin metabolism

Bile is composed of water, electrolytes, bile acids, bilirubin, phospholipids, cholesterol and conjugated waste products, with approximately 600 mL produced each day [6]. In fasted states, approximately half is syphoned off to the gallbladder where it is concentrated. It is actively secreted at the hepatocyte canalicular membrane via bile transporter proteins, with biliary ductular epithelium also contributing. It facilitates the emulsification and digestion of fats and provides an alkaline pH for optimal pancreatic enzyme function. It is also the main vehicle for the elimination of hydrophobic waste products such as bilirubin. Bile formation is stimulated by secretin and inhibited by somatostatin. After ingestion of a meal, cholecystokinin stimulates gallbladder contraction and sphincter of Oddi relaxation.

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