The Exocrine Pancreas, Liver And Gallbladder
The exocrine pancreas secretes a major digestive fluid called pancreatic juice. This juice is secreted into the duodenum via the pancreatic duct that opens into the gastrointestinal (GI) tract at the same site as the common bile duct (see later). When food is present in the duodenum, a small sphincter (sphincter of Oddi) relaxes, allowing both bile and pancreatic secretions to enter the tract (Fig. 40a).
Pancreatic juice is made up of a number of enzymes, secreted by the acinar cells of the pancreas, which break down the major constituents in the diet. The enzymes include pancreatic amylase, which breaks down carbohydrates to monosaccharides; pancreatic lipase, which breaks down fats to glycerol and fatty acids; ribonuclease and deoxyribonuclease, which are involved in the breakdown of nucleic acids and free mononucleotides; and a variety of proteolytic enzymes (trypsin, chymotrypsin, elastase and carboxypeptidase), which break down proteins into small peptides and amino acids. The hormone cholecystokinin (CCK), released into the bloodstream by the duodenal cells in response to the presence of amino acids and fatty acids in the chyme, is responsible for the secretion of the pancreatic enzymes from the acinar cells of the pancreas. The other major secretions, besides the enzymes, are water and bicarbonate ions. The volume of pancreatic juice secreted precisely neutralizes the acid content of the chyme delivered by the stomach to the intestines. This is caused by the acid in the duodenum releasing secretin from its walls into the bloodstream. Secretin stimulates the production of water and bicarbonate ions from the duct system and, in particular, from the epithelial cells lining the duct. Approximately 1 L of pancreatic juice is secreted per day from a normal individual (Fig. 40b).
The liver is the largest organ of the body, weighing over 1 kg in the normal adult. The functions of the liver can be divided into two broad categories. First, it is involved with the processing of absorbed sub- stances, both nutrient and toxic. In other words, it is responsible for the metabolism of a vast range of substances produced by the digestion and absorption of food from the intestine. Second, it has an important exocrine function in that it is involved in: (i) the production of bile acids and alkaline fluids used in the digestion and absorption of fats and for the neutralization of gastric acid in the intestines; (ii) the breakdown and production of waste products following digestion; (iii) the detoxification of noxious substances; and (iv) the excretion of waste products and the detoxification of substances in bile.
The majority of waste metabolites and detoxified substances are excreted from the body in the bile, from the GI tract, or via secretions from the liver into the bloodstream for subsequent excretion by the kidney. The relationship between the liver, gallbladder and duodenum is shown in Figure 40a. The liver consists of four lobes, with each lobe made up of tens of thousands of hexagonal lobules, 1–2 mm in diameter, which are the functional unit of the liver. Each lobule (Fig. 40c) consists of a central vein that eventually becomes part of the hepatic vein. Surrounding the central vein are single columns of liver cells (hepatocytes) radiating outwards; between the hepatocytes are small canaliculi which begin as blind-ended structures at the end nearer the central vein, but drain into the bile duct on the periphery of the lobule. At each of the six corners of the lobules lies a ‘portal triad’ comprising branches of the hepatic artery, the portal vein and the bile duct. The bile ducts eventually drain into the terminal bile duct.
Bile and the gallbladder
The hepatocytes secrete a fluid called hepatic bile. It is isotonic and resembles plasma ionically. It also contains bile salts, bile pigments, cholesterol, lecithin and mucus. This fraction of bile is called the bile acid-dependent fraction. As it passes along the bile duct, the bile is modified by the epithelial cells lining the duct by the addition of water and bicarbonate ions; this fraction is called the bile acid-independ- ent fraction. Overall, the liver can produce 500–1000 mL of bile per day. The bile is either discharged directly into the duodenum or stored in the gallbladder. The bile acid-independent fraction is made at the time it is required, i.e. during digestion of the chyme. The bile acid- dependent fraction is made when the bile salts are returned from the GI tract to the liver, and is then stored in the gallbladder when the sphincter of Oddi is closed. About 95% of the bile salts that enter the small intestine in bile are recycled and reabsorbed into the portal circulation by active transport mechanisms in the distal ileum (the so-called enterohepatic circulation; Fig. 40d). Many of the bile salts are returned unaltered, some are broken down by intestinal bacteria into secondary bile acids and then reabsorbed, and a small proportion escapes reabsorption and is excreted in the faeces.
The gallbladder not only stores the bile, but also concentrates it by removing non-essential solutes and water, leaving the bile acids and pigments. The process of concentration is mainly by active trans- port of Na+ ions into the intercellular spaces of the lining cells and this, in turn, draws water, HCO − and Cl− ions from the bile and into the extracellular fluid, thereby concentrating the bile held in the gallbladder.
The formation of bile is stimulated by bile salts, secretin, glucagons and gastrin. The release of bile stored in the gallbladder, however, is stimulated by the secretion of CCK into the bloodstream when chyme enters the duodenum and, to a lesser extent, by the actions of the vagus nerve. Within a few minutes of a meal, particularly when fats are consumed, the muscles of the gallbladder contract; this forces the contents into the duodenum through the now relaxed sphincter of Oddi. CCK relaxes the sphincter and stimulates the pancreatic secretions at the same time. The gallbladder empties completely 1 h after a fat-rich meal and maintains the level of bile acids in the duodenum above that necessary for the function of the micelles.