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
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.
