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Biological Sciences
Stephen Reid

1    Lecture 22: The Intestines, Pancreas and Liver 1. The Small Intestine The stomach empties into the small intestine through the pyloric valve. The small intestine itself consists of three main sections. The duodenum is the small section closest to the pyloric valve, about 30 cm long. Chyme from the stomach enters the duodenum as do digestive enzymes from the pancreas and bile from the liver and gallbladder. The jejunum follows the duodenum, and is much longer - a little over a meter. The ileum is the final section of the small intestine, it is approximately 1.5 meters long and connects via the illeocecal valve to the large intestine. The small intestine is the predominant site of nutrient absorption with the vast majority of nutrient absorption occurring within the first 20%. The small intestine is anatomically designed for large rates of absorption. The inner wall of the small intestine contains numerous protrusions called villi which face into the lumen of the intestine. Each villus contains an artery, a vein, capillaries, and a blind-ended lymphatic lacteal. The villi enhance the surface area available for absorption. The available surface area is increased even further as the villi themselves are covered with smaller protrusions called microvilli. There can be thousands of microvilli on a single intestinal epithelial cell. In between the villi are large pits, called crypts of Lieberkuhn which also enhance the surface area available for absorption. They contain cells that produce bicarbonate and release it into the intestinal lumen. This is necessary to decrease the acidity of the stomach contents entering the small intestine. Many intestinal enzymes (i.e., from the pancreas) cannot function in an acidic environment therefore the bicarbonate-induced alkalinisation of the intestinal lumen is critical for enzymatic digestion. Surface epithelial cells in the intestine are replaced every 3-5 days, meaning that millions of intestinal cells are shed each day. 2    2. The Large Intestine The large intestine is connected to the small intestine via the illeocecal sphincter which itself leads into a small region of the large intestine called the cecum. The cecum connects to the colon, the area of the intestine in which the final process of water/ion absorption occurs. Also attached to the cecum is the appendix, a small, vestigial part of the intestine. It has no know function in digestion in humans. The colon itself consists of the ascending colon (on the right side of the body), transverse colon, the descending colon (on the left side) and the sigmoid colon which leads to the rectum. Finally, the rectum empties via the anus, the opening of which is under the control of and external and an internal anal sphincter. 3. Disorders of the Large Intestine The appendix can become blocked by digested foodstuffs, which can cause inflammation and infection. This is called appendicitis and, should the appendix rupture, the resulting bacterial infection throughout the body cavity (peritonitis) is usually fatal. 3    Another disorder of the large intestine (colon) is the formation of a fecalith which is compacted feces. This can be caused by a lack of fibre in the diet, and results in chronic constipation. In the worst cases, fecaliths need to be removed surgically. Diverticulosis and diverticulitis are primarily disorders of the sigmoid colon. Diverticulosis is due to a weakening of the muscle surrounding the colon that causes the intestinal lining to form extruding 'pouches', called divertuculi. Diverticulitis is when these pouches become infected and inflamed, which leads to intense abdominal pain (on the left side) and, in severe cases, perforation of the intestines and peritonitis. Again, it is usually caused by a low fibre diet. These diseases of the large intestine are frequently detected or confirmed using a colonoscopy. This is a procedure in which a camera on the end of the flexible tube is inserted into the rectum and moved through the colon. 4    4. The Pancreas The pancreas is located underneath the liver close to the curvature of the duodenum. Secretions from the pancreas enter the duodenum via the pancreatic duct. The pancreatic duct terminates in the ampulla of Vater which is a common ending for the pancreatic duct and the bile duct. The opening into the duodenum is via the Sphincter of Odi. There are many blind-ended ducts in the pancreas that arise from the pancreatic duct. These blind-ends are lined by unique enzyme-secreting cells called acinar cells, which produce a variety of enzymes. Pancreatic amylase breaks down carbohydrates; pancreatic proteases break down proteins; pancreatic lipase is produced to break down fats; and finally deoxynuclease and ribonuclease are produced to break down nucleic acids. The proteases are secreted in an inactive form, to prevent them from breaking down proteins within the acinar cells. These pancreatic enzymes are referred to as exocrine secretions. The blind-ended ducts are also lined by cells which produce bicarbonate and secrete it into the fluid containing pancreatic enzymes. The bicarbonate helps to raise the pH of the intestinal contents thereby creating the alkaline environment which the pancreatic enzymes require to function. 5    The pancreas also produces what are referred to as endocrine secretions that come from groups of cells within the pancreas called the islets of Langerhans. The islets of Langerhans consist of three main cell types: alpha cells, towards the outer surface of the cell group, secrete glucagon; beta cells, on the inside, secrete insulin; and delta cells, scattered around the border between the two, produce the hormone somatostatin. The islets of Langerhans are supplied by numerous capillaries into which these hormones are secreted. 5. Insulin, Glucagon and Blood Glucose Regulation Insulin is a small dipeptide hormone whose main role in the body is to lower blood glucose levels by signaling cells (such as muscle, kidney or fat cells) to take up glucose from the blood. It also stimulates the conversion of glucose into glycogen in the liver. The primary stimulus for insulin release is an increase in plasma glucose levels. Glucagon plays the opposite function; it raises blood glucose levels when they fall too low. It does this by stimulating the breakdown of glycogen in the liver providing glucose that can enter the blood. 6    Insulin release from the beta cells in the pancreas occurs primarily in response to an increase in blood glucose levels. There is some release triggered by the presence of carbohydrates in the gut prior to the elevation of blood glucose levels. Glucose molecules are taken up into the beta cells by a GLUT2 glucose transporter. Inside the cells the enzyme glucokinase (similar to hexokinase) phosphorylates glucose and starts the process of glycolysis leading to the production of ATP. The elevation of ATP + + levels causes the close of ATP-sensitive K channels on the beta cell plasma membrane. K ions are therefore retained within the cell causing the plasma membrane to depolarise. This leads to the opening of voltage-dependent Ca channels allowing for the influx of Ca . The rise in intracellular [Ca ] ++ triggers the release of insulin by exocytosis.
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