The control of salivation is unique in two ways. First, it is mediated almost entirely by the nervous system. Note that both gut hormones and neuro-reflexes regulate secretion in other portions of the GI tract. Secondly, both the parasympathetic and sympathetic branches of the autonomic nervous system stimulate salivation. Note that parasympathetic and sympathetic nerves have opposing actions on most other organs. The parasympathetic division of the autonomic nervous system is the primary controller of salivation. Parasympathetic fibers are carried in the facial and glossopharyngeal nerves, cranial nerves VII and IX. Parasympathetic activity initiates and maintains salivation. In general, parasympathetic stimulation produces large amounts of watery saliva containing enzymes. The thought, smell, or taste of food, stimulates the salivary center in the medulla to increase parasympathetic activity and salivation. Acidic substances like a piece of lemon, and pressure of chewing food or non-food in the mouth, like a peach pit, are powerful stimuli for salivation. Intestinal irritation and accompanying nausea are also powerful stimulants of salivation. Fear, fatigue, sleep, and dehydration all inhibit salivation. Activity in the sympathetic nervous system produces a small volume of saliva that is thick with mucus. Because sympathetic stimulation accompanies frightening or stressful situations, the mouth may feel dry at such times. In summary, both parasympathetic and sympathetic activity increase salivation. Both also stimulate metabolism and growth of the salivary glands. The surface of the stomach has deep wells called gastric pits. Each pit leads to gastric glands. Throughout the stomach, gastric pits and glands contain cells that produce mucus and pepsinogen. In the fundus and body, gastric glands are deep and contain cells that produce both acid and intrinsic factor, and cells that produce histamine. Surface epithelium cells secrete thick, alkaline mucus. Mucous cells in the neck region of the gland secrete thin watery mucus. Parietal cells secrete acid and intrinsic factor. Chief cells secrete pepsinogen. These paracrine cells secrete the local chemical messenger histamine. In the pyloric region, gastric glands contain cells that produce gastrin and cells that produce mucus and pepsinogen. G cells secrete the hormone gastrin. Most digestion and absorption occurs in the small intestine. The essential secretions for digestion come from the pancreas and liver, not from the small intestine. We will study secretions of these accessory glands first beginning with the pancreas. The exocrine pancreas secretes a juice with two components that are regulated separately: enzymes to digest all major foodstuffs and a bicarbonate solution. CCK stimulates secretion of pancreatic enzymes, and secretin stimulates secretion of bicarbonate solution. Pancreatic juice is important for digestion and protection. Pancreatic juice is produced in structures called acini and carried through a network of ducts to enter the duodenum through the hepatopancreatic sphincter. Acinar cells secrete digestive enzymes for all major foodstuffs. They include: proteases to digest protein, pancreatic amylase to digest starch, and pancreatic lipase to digest fat. The major pancreatic proteases are trypsinogen, chymotrypsinogen, and procarboxypeptidase. Like pepsin, they are secreted in an inactive form. Enterokinase, an enzyme embedded in the intestinal cell membranes, activates trypsinogen. Trypsin activates more trypsinogen. This process is similar to activation of pepsinogen in the stomach, first by hydrochloric acid, then by pepsin. Trypsin also activates the other proteases. Carbohydrates and protein are partially digested prior to arriving in the small intestine. Fat is digested primarily by pancreatic lipase in the small intestine. Therefore, if the pancreas fails to secrete adequate amounts of digestive enzymes, the major disruption in digestion is the failure to digest fat. Duct cells secrete a watery solution containing bicarbonate. Bicarbonate neutralizes acidic chyme in the duodenum. A neutral-to-slightly alkaline intestinal environment is essential for maximal activity of pancreatic enzymes. Remember that the pancreas is a mixed gland with both exocrine and endocrine secretions. The endocrine pancreas secretes hormones including insulin and glucagon that regulate metabolic activities of the absorptive and postabsorptive states respectively. The major digestive function of the liver is the production of bile. Bile is produced continuously. When the hepatopancreatic sphincter is closed, bile goes to the gallbladder where it is stored and concentrated. Bile has two components that are regulated separately: organic compounds that are essential to emulsify fat and a bicarbonate solution. Recycled bile salts in portal blood regulate secretion of bile, and secretin stimulates secretion of bicarbonate solution. Bile is important for: digestion and absorption of fat and protection. The organic portion of bile is a mixture that includes: bile salts, lecithin, cholesterol, and bilirubin. Bile does not digest fat. Both bile salts, which are derived from cholesterol, and lecithin emulsify fat. They keep fat droplets from coalescing thus promoting enzymatic breakdown and absorption of fat. We will study digestion and absorption of fat in detail in the next topic. Cholesterol and bilirubin (a breakdown product of heme) are eliminated. Bile salts are recycled. Bile enters the duodenum during a meal, and travels through the small intestine. Bile salts are then actively reabsorbed in the terminal ileum, and return to the liver in the hepatic portal blood. In the liver, bile salts stimulate secretion of bile. This pathway is called the enterohepatic circulation. Bile salts may circulate through this pathway several times during digestion of a meal. Cells that line the bile ducts secrete a watery solution containing bicarbonate. This solution is identical to pancreatic bicarbonate solution and neutralizes acidic chyme in the duodenum. Secretin promotes secretion of both. The small intestine secretes a watery mucus solution and hormones that control GI activities. Small intestine secretions are important for: protection, digestion, and control. The intestinal mucosa is specialized for absorption. Mucus-secreting goblet cells are plentiful. Mucus protects the intestinal mucosa from digestion by acid and proteases, and lubricates the contents for ease of movement. The duodenum is at greatest risk for acid damage. The submucosa of the duodenum contains mucus-secreting duodenal glands that secrete alkaline mucus. Cells of the crypts secrete the water and electrolytes that combine with mucus to form intestinal juice. Water provides an environment for digestive reactions and adjusts osmolarity. Cells of the small intestine do not secrete any digestive enzymes into the lumen, but they do produce digestive enzymes. These enzymes, called brush border enzymes, are bound to microvilli cell membranes. We have already encountered the brush border enzyme enterokinase, which activates trypsinogen. In general, secretin and CCK promote intestinal activities and inhibit activities of the stomach. Contents in chyme stimulate secretion of the intestinal hormones, and both hormones have trophic effects on the pancreas. Acid in the duodenum stimulates secretion of secretin. Secretin stimulates duct cells of the pancreas and the liver to release bicarbonate solution. Because of its actions, secretin is called “nature’s antacid.” Fat (and to a lesser degree peptides) in the duodenum stimulates secretion of CCK into the bloodstream. CCK stimulates pancreatic acinar cells to release digestive enzymes. CCK is named for its second major function. Chole means bile; cysto means bladder; and kinin means mover. Therefore, CCK is the “bile bladder mover.” It causes gallbladder contraction and relaxation of the hepatopancreatic sphincter. Notice that CCK causes both enzymes and bile to enter the small intestine, thus providing all the essential compounds needed for digestion. In summary, let’s look at a table that lists the functions of all of the secretions that enter the small intestine. Mucus is a protection secretion that prevents acid and protease damage to the intestine Alkaline solutions function as both protection and digestion secretions. They neutralize acidic chyme. Neutrality reduces the possibility of acid damage to the intestinal wall and is essential for maximal digestive and absorptive activities. Secretin and CCK are important in both control and digestion. Secretin stimulates secretion of bicarbonate solutions from the pancreas and liver. CCK stimulates secretion of enzymes from the pancreas. It also stimulates contraction of the gallbladder and relaxation of the hepatopancreatic sphincter. Both CCK and Secretin inhibit gastric secretion and motility. And finally, in their role as digestion secretions, CCK and Secretin have trophic effects on the pancreas. Bile is important for both absorption and digestion. Its job is to emulsify fat. Emulsification is necessary for both digestion and absorption of fat. Other secretions that are important to digestion are: Enzymes which break down all major foodstuffs. Trypsin which activates chymotrypsin and procarboxypeptidase. And water which provides an environment for digestion and adjusts osmolarity. The large intestine secretes an alkaline mucus solution containing bicarbonate and potassium. Its sole function is protection. The alkaline mucus solution protects the intestine wall from damage by acids released by resident bacteria. Mucus eases the passage of feces and protects the wall from mechanical damage. Acid and mechanical stimulation, mediated by both long and short reflexes, increase the secretion of alkaline mucus.