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كلية الطب المرحلة الثانية )GIT) physiology المحاضرة السادسة Pancreatic Digestive Enzymes: 1- The proteolytic enzymes for proteins digestion are trypsin, chymotrypsin, and carboxypolypeptidase.. Trypsin and chymotrypsin split digested proteins into peptides ,and carboxypolypeptidase does split some peptides into individual amino acid. 2- The digestive enzyme for carbohydrates is pancreatic amylase which hydrolyzes starches, glycogen and most other carbohydrates (except cellulose) to form disaccharides and a few trisaccharides.. 3- The main enzyme for fat digestion is(a) pancreatic lipase which is capable of hydrolyzing neutral fat into fatty acids (b) cholesterol esterase, which causes hydrolysis of cholesterol esters; and (c) phospholipase, which splits fatty acids from Phospholipids. Pancreas protects itself from auto digestion by proteolytic enzymes:by the following ways: A- When proteolytic enzymes synthesized in the pancreatic cells, they are in the inactive forms, These become activated only after they are secreted into the intestinal tract, they are activated by an enzymes are secreted by the intestinal mucous called enterokinase. B- The same cells that secrete the proteolytic enzymes into the acini of the pancreas secrete another substance called trypsin inhibitor. This substance is stored in the cytoplasm of the glandular cells surrounding the enzyme granules and it prevents activation of trypsin inside the secretary cells and in( the acini and ducts) of the pancreas. Regulation of Pancreatic Secretion Three basic stimuli are important in causing pancreatic secretion: 1. Acetylcholine, which is released from the parasympathetic vagus nerve endings and from other cholinergic nerves in the enteric nervous system 2. Cholecystokinin, which is secreted by the duodenal and upper jejunal mucosa when food enters the small intestine 3. Secretin, which is also secreted by the duodenal and jejunal mucosa when highly acid food enters the small intestine The first two of these stimuli, acetylcholine and cholecystokinin, stimulate the acinar cells of the pancreas, causing production of large quantities of pancreatic digestive enzymes but relatively small quantities of water and electrolytes to go with the enzymes, while secretin, in contrast to the first two basic stimuli, stimulates secretion of large quantities of water solution of sodium bicarbonate by the pancreatic ductal epithelium. pancreatic secretion normally results from the combined effects of the multiple basic stimuli, not from one alone. Phases of Pancreatic Secretion Pancreatic secretion occurs in three phases:1- Cephalic phase: The thought, smell, and taste of food produces the cephalic phase of pancreatic secretion. Both acinar and to less extent the ductal cell secretion are enhanced by vagal stimulation. Most the enzymes are stored in the acini . 2- Gastric phase: Pancreatic secretion is enhanced during the gastric phase by : A- Distention of the antrum and the body of the stomach which initiates avagovagal reflex resulting in a low volume of pancreatic secretion containing both bicarbonate ions and enzymes. B- Food breakdown products (amino acid and peptides) stimulate pancreatic secretion by release gastrin ( from G cells of antrum) which produces a low-volume, high enzyme pancreatic secretion. 3 - Intestinal phase: The most important for pancreatic secretion are hormone CCK( and secretin. They are released from endocrine cells in the duodenum and jejunum during the intestinal phase in response to the entrance of chyme into the small intestine. The amino acids, fatty acids are the major stimuli for (CCK) secretion from I cells which found in upper small intestine . CCK( in addition to its effect on the gallbladder, is a potent stimulant of pancreatic enzyme secretion ,by its effect on the acinar cells which trigger the second messenger inisitol tri phosphate(IP3) and then cells makes the enzymes. H⁺ or acid chyme from the stomach with (Low pH<4.5) stimulates release of Secretin From S cells that found in upper small intestine, secretin triggers cAMP in the ductal cells to stimulates large quantities of pancreatic juice containing HCO3 . Figure(11) Phenylalanine, methionine, tryptophan small peptides Fatty acids Figure(11) regulation of pancreatic secretion) Disorders of the pancreas Pancreatic Failure is failure of the pancreas to secrete pancreatic juice into the small intestine. Lack of pancreatic secretion frequently occurs (1) in pancreatitis (2) when the pancreatic duct is blocked by a gallstone at the papilla of Vater, or (3) after the head of the pancreas has been removed because of malignancy.Loss of pancreatic juice means loss of trypsin, chymotrypsin, carboxypolypeptidase, pancreatic amylase, pancreatic lipase, and still a few other digestive enzymes. Without these enzymes, as much as 60 per cent of the fat, as well as one third to one half of the proteins and carbohydrates entering the small intestine may be unabsorbed, As a result, large portions of the ingested food cannot be used for nutrition, and copious, fatty feces are excreted. The gallbladder is a thin walled green muscular sac on the inferior surface of the liver. The gallbladder stores bile that is not immediately needed for digestion and concentrates it. When the muscular wall of the gallbladder contracts bile is expelled into the bile duct. Bile secretion: Bile is necessary for digestion and absorption of lipids in the small intestine. Bile is a mixture of bile acids, bile pigments and cholesterol. Bile is produced and secreted by liver, stored in gallbladder, and ejected into the lumen of small intestine. It emulsify lipids to prepare them for digestion. When chyme reaches the small intestine CCK is secreted which stimulates contraction of gallbladder and relaxation of sphincter of Oddi, to flow bile into the lumen of the duodenum. When lipid absorption is complete, bile acids are recirculated to liver. figure(12) Figure (12)bile secretion The function of the gall bladder is :1-to store bile 2- to concentrate bile ( epithelial cells of gall bladder absorb ions and water) 3 -to eject bile into the lumen of the small intestine. Ejection of bile from gall bladder begins within 30 minutes after a meal. Bile is constituents of *bile acid (50%) *cholesterol (4%) *and phospholipids (40%).*Bile contains electrolytes and water.. 95% of secreted bill acids are recirculated to the liver, bile acid excreted in feces 5% , must be replaced by synthesis of new bile acids. Role of bile secretion A-detergent action : Bile secretion decrease the surface tension of the substance so it will brake them into smaller particle called micelles to increase the surface area to about 1000 times original one in which lipase will do it’s effect . B –hydrotropic effect : Which means makes lipid (water soluble) to pass easily via epithelial cell membrane bile secretion regarded as amphipathic molecule which means that it has 2 poles one is the hydrophilic pole which is formed from dissociate carboxyl group or hydroxyl group and the other is the methyl group which represent the hydrophobic pole of the bile salts .bile salts arrange themselves around the lipid molecule in such away that the hydrophilic group in the surface and the hydrophobic toward the lipid particles so the surface of lipid will be water soluble. Gallstone Formation:Bile salts are formed in the hepatic cells from cholesterol in the blood plasma. In the process of secreting the bile salts, about 1 to 2 grams of cholesterol are removed from the blood plasma and secreted into the bile each day. Cholesterol is almost completely insoluble in pure water, but the bile salts and lecithin in bile combine physically with the cholesterol to form ultramicroscopic micelles in the form of a colloidal solution. When the bile becomes concentrated in the gallbladder, the bile salts and lecithin become concentrated along with the cholesterol, which keeps the cholesterol in solution. Under abnormal conditions, the cholesterol may precipitate in the gallbladder, resulting in the formation of cholesterol gallstones. The amount of cholesterol in the bile is determined partly by the quantity of fat that the person eats, because liver cells synthesize cholesterol as one of the products of fat metabolism in the body. For this reason, people on a high-fat diet over a period of years are prone to the development of gallstones.