Anatomy and ultrastructure

The biliary system starts in the bile canaliculi, which are channels of uniform diameter between two or three adjoining hepatocytes. The walls of bile canaliculi are specialized segments of the hepatocyte cell wall bearing regularly shaped cylindrical microvilli which jut into the lumen of the canaliculi. Along the margin of the grooves which form the bile canaliculi the hepatocytes are attached to one another by junctional complexes. These include gap junctions which permit electrical communication between liver cells, desmosomes which act as fastening bodies, and so-called ‘tight junctions’ which form continuous bands along the entire length of the canalicular network. The bile canaliculi are surrounded by specialized pericanalicular cytoplasm which contains microtubules, vesicles, lysosomal-like structures and, frequently, a Golgi apparatus. Within the pericanalicular cytoplasm there is a rich network of actin microfilaments which also extend into the microvilli. These microfilaments maintain the shape of the hepatocyte including the microvilli and contribute to the structural integrity of the canaliculus. They also have a contractile function which requires the integrity of the Ca2+-calmodulin and actin-myosin systems to promote bile flow in the canalicular network within the hepatocyte plate towards the portal tract.

Bile leaves via channels lined by two spindle-shaped cells (canal of Hering) which drain into fine cholangioles at the periphery of the portal tracts. They have a diameter less than that of a liver cell and are lined by cuboidal epithelial cells. They drain to interlobular bile ductules lined by cells which are smaller than hepatocytes, have a clear cytoplasm, fewer mitochondria, but have up to 70 widely spaced microvilli on their epithelial surface. These ductules join ducts of ever-increasing calibre which form plexuses around portal vein branches as they carry bile towards the portahepatis, forming septal, then segmental ducts which drain into the major right and left hepatic ducts before emerging from the right and left lobes of the liver at the portahepatis to form the common hepatic duct (Figure 2.1). The lining cells of these larger ducts become more cylindrical but still bear many microvilli.

All of the intrahepatic biliary epithelium is surrounded by a dense capillary network derived from tributaries of the hepatic artery and draining via terminal branches of the portal vein into the sinusoids. Another feature of these major tributaries of the common hepatic duct are two diametrically opposed rows of glands which produce both serous and mucous secretions. These glands lie outside the ducts but open into them. Simpler, smaller, but less frequent glands are seen along the common bile duct. The common bile duct has a columnar epithelium with prominent microvilli. The mucosa is often arranged in longitudinal oblique folds or rugae with a highly vascular lamina propria. A few thin smooth muscle fibres are found in the connective tissues surrounding the duct.

The common hepatic duct is joined by the cystic duct from the gall bladder to form the common bile duct, which terminates at the choledocho-duodenal junction uniting with the main pancreatic duct in a complex ampulla which opens on to a papilla on the mediodorsal aspect of the second part of the duodenum. A sphincter is found at the lower end of the common bile duct with another within the ampulla and its papilla. The ampulla has a complex arrangement of valve-like structures with smooth muscle and mucus-producing glands which may assist in the mixing of bile and pancreatic juices. The usual gross anatomy of the extrahepatic biliary system is shown in Figure 2.2 but many variations in size, position, orientation and site of confluence occur.

The gall bladder is a pear-shaped highly vascular well enervated bag, the broad end of which is directed anteriorly towards the abdominal wall. The fasting volume in adults ranges from 10 to 50 ml. The body extends into a narrow neck continuing into the cystic duct which may have a sphinteric action. The mucosa of the gall bladder is lined by columnar epithelium bearing long, fine microvilli. The surface area is markedly increased in area by highly vascular rugae or interconnecting ridges. These mucosal folds extend into the cystic duct.

The wall of the gall bladder consists of muscular fibres without definite layers except in the neck and fundus where the muscle is particularly prominent. The muscle is embedded in elastic connective tissue. The gall bladder receives its rich blood supply from the tortuous cystic artery, usually a branch of the hepatic artery. The gall bladder stores and concentrates bile and secretes glycoproteins. The gall bladder contracts to 25 to 50% of its fasting volume with a t2 of 15 minutes in response to acid food in the duodenum while the sphincter of Oddi relaxes reciprocally under the influence of cholecystokinin and neural control.

Physiology of bile formation

Bile is formed in the bile canaliculi, modified in the bile ducts, concentrated in the gall bladder and ultimately is mixed with food in the intestines. There, certain organic acids, particularly bile salts, are reabsorbed, enter the circulation and return to the liver where they are avidly taken up by hepatocytes to undergo further enterohepatic circulation. Bile salts are believed to provide the main driving force in bile formation.

Bile is a complex solution of cholesterol (90–20 mg/dl; 2.4–8.5 mmol/litre), phospholipids in the form of phosphatidyl choline (1.4–8.0 g/litre), conjugated bile salts (3–45 mmol/litre), protein (0.3–3.0 g/dl) and electrolytes. The bile salts promote the secretion of lipids and stabilize these in bile. The osmolality of bile is that of plasma since cholesterol, phospholipid and bile salts are aggregated to form mixed micelles. The proteins include immunoglobulin IgA at a concentration 10 times that of plasma. The concentration of electrolytes reflects that in plasma except that the concentration of bicarbonate is higher.

Bile secretion is a complex process involving at least four steps: (a) uptake or synthesis of substances by the liver or bile duct cells; (b) metabolic transformation of these principally by the endoplasmic reticulum and Golgi on route to the bile; (c) transcytotic microtubular-dependent movement of vesicles (formed at the basolateral membrane or within hepatocytes) to the bile canaliculi; and (d) excretion of water, organic and inorganic material into the bile canaliculi. In addition, paracellular secretion of electrolytes, water and inert solutes occurs via the junctional complex (Figure...