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كلية الطب المحاضرة السادسة ) GIT) physiology المرحلة الثانية Disorders of the Small Intestine:1-Malabsorption or “sprue'' In this case nutrients are not adequately absorbed from the small intestine even though the food has become well digested. Can occur when large portions of the small intestine have been removed or Several diseases can cause decreased absorption by the mucosa like:A- Nontropical Sprue:One type of sprue called idiopathic sprue or(celiac disease) occur in children, its autoimmune disease occur genetically ,or called gluten enteropathy in adult, results from the toxic effects of gluten present in certain types of grains, especially wheat and rye. Only some people are susceptible to this effect, gluten has a direct destructive effect on intestinal enterocytes. This case either milder forms ,only the microvilli are destroyed, or more severe forms, the villi themselves disappear ,this will lead to reducing the absorptive area of the GIT tract. Removal of wheat and rye flour from the diet frequently results in cure within weeks, especially in children with this disease. B-Tropical Sprue. Frequently occurs resulting from unidentified infectious agents and can often be treated with antibacterial agents. Digestion I t is chemical breakdown of ingested food into absorbable molecules, The digestive enzymes are secreted by salivary gland, gastric gland, pancreatic glands, and apical membrane of intestinal epithelial cells. Digestion of carbohydrates:Three major sources of carbohydrates exist in the normal human diet. These are sucrose (table sugar) disaccharide, lactose (disaccharide) in milk and starches (polysaccharides) present in all non animal foods, and grains. Other carbohydrates ingested are glycogen, alcohol . The diet also contains a large amount of cellulose, which is a carbohydrate, however, no enzymes capable of hydrolyzing it , then it expelled out. Digestion of carbohydrates in the mouth:ptyalin (an a-amylase) in saliva hydrolyzes starch into the disaccharide maltose and other small polymers of glucose that contain three to nine glucose molecules, the food remains in the mouth only a short time, 5 % of all the starches will have become hydrolyzed by the time, when the food is swallowed.. Digestion of carbohydrate in the stomach: salivary ptyalin can continue be active for as long as1 hour after the food has entered the stomach ,then blocked by acid of gastric secretions. 30-40 % of the starches will have been hydrolyzed mainly to maltose. Digestion of carbohydrate in small intestine: a-amylase in Pancreatic secretions continue splitting starches into maltose and other small polymers of glucose,before passing the duodenum or upper jejunum,then the brush border epithelial cells which lining the small intestine contain enzymes lactase, sucrase, maltase and a-dextrinase which are capable of splitting the disaccharide lactose, sucrose and maltose into their monosaccharide, Lactose splits into galactose and glucose. Sucrose splits into fructose and a glucose. Maltose and other small glucose polymers all split into multiple molecules of glucose ,which are absorbed and delivered to the liver by way of the hepatic portal vein. After the liver processes, the nutrients enter into the blood stream circulating throughout the body . Digestion of carbohydrate Lactose intolerance: It is the most common cause of carbohydrate malabsorption. It result from inability of the intestinal mucosa to produce lactase in the infant. The diarrhea produce dehydration can be life threatening. Digestion of protein: The dietary proteins are derived from meats and vegetables. Digestion of proteins in stomach: Pepsin hydrolysis the peptide linkages between the amino acid and convert the protien to proteosis,peptons and polypeptides. Collagen is a major constituent of the intercellular connective tissue of meats, its an albuminoid type of protein , pepsin digest this protien that is affected little by other digestive enzymes.; it is first necessary that the collagen fibers be digested to penetrate meats and digest the other meat proteins, Pepsin digestion represents 10-30 % of total protein digestion. Digestion of protein by pancreatic secretion: Most protein digestion occur in small intestine under proteolytic enzymes of the pancreatic secretion. Trypsin, chymotrypsin, and carboxypolypeptidase which split protein molecules into small polypeptides. Digestion of peptides by epithelial peptidase of small intestine: The brush border of small intestine contains several different enzymes for hydrolyzing the peptides linkage of the remaining dipeptides and other small polypeptides as they come in contact with epithelium of the villi.The enzymes responsible are aminopolypeptidase and several dipeptidase. About 98 % of all the proteins finally become either amino acids or dipeptides that can be absorbed into the blood. All of these smaller protein fragments go directly to the liver by the hepatic portal vein. Once in the liver one of three things happens to the proteins: 1. It converts to glucose 2. It converts to fat 3. It is directly released into the blood as amino acids. Protien digestion Digestion of fat: Dietary lipids include triglycerides ,cholesterol (more in food of animal origin), phospholipid , and cholesterol esters(fats). The lipids must be solubilized to be digested and absorbed. small amount of triglycerides is digested in the stomach by lingual lipase from saliva represent 10 % its unimportant. The first step in fat digestion is emulsification of the fat by (bile) which break the fat globules into very small sizes called micelles and makes lipid water soluble in which lipase will do it’s effect. The lipase enzymes are water-soluble compounds and can attack the fat globules only on their surfaces when it become water soluble. The bile salt play role in converted cholesterol into monoglycerides and fatty acids, which is essential to absorption of cholesterol. However 60 % of triglycerides can be digested and absorbed even in the absence of bile salt. Most of the triglycerides of the diet are split by pancreatic lipase into free fatty acids and 2-monoglycerides. When foods with high lipid content enter the stomach, the hormone – gastric inhibitory peptide is released, slowing down movement flow out of the stomach. This is why we feel full after eating high fat foods. Absorption It is movement of nutrients, water and electrolytes from the lumen of the intestine into the blood. There are two path for absorption, a cellular path and paracellular path. In the cellular path the substance must cross the apical (luminal) membrane, then enter the tight junction intestinal epithelial cell, and be extruded from the basolateral membrane. In paracellular, through intercellular spaces between intestinal epithelial cells, and to the blood. The structure of intestinal mucous is suited for absorption of large quantities of nutrients though villi and microvilli which increase the surface of a small intestine. The villi are largest in the duodenum, where digestion and absorption occur and shortest in the terminal ileum.. The villi and microvilli increases total surface area by 600 fold. The epithelial cells of small intestine are replaced every 3-6 days. Absorption of carbohydrates: Glucose and galactose are absorbed in separate mechanisms involving Na-depend cotransport.,while Fructose is absorbed by facilitated diffusion. Na-glucose cotransport and Na-galactose cotransport, using a gradient as the energy source on basolateral membrane because the intracellular Na⁺ concentration is low in intestinal cells ,as it in other cells ,Na⁺moves into the cell along gradient. Glucose and galactose are extracted across the basolateral membrane into blood by facilitated diffusion. Fructose is transported across luminal membrane by facilitated diffusion, then extruded into blood. Epithelial cell of the small intestine blood lumen absorption of monosaccharide Absorption of protein: Amino acid are transported from the lumen into the cell by Na-amino acid cotransporter in apical membrane energy by a gradient. There are four separation cotransporters; each one for neutral, acidic, basic, and other amino acids. The amino acids then are transported across the basolateral membrane into the blood by facilitated diffusion. Again by separation mechanism most ingested protein is absorbed by intestinal epithelial cells in dipeptides and tripeptide form and free amino acids. Inside the cell, most of dipeptides and tripeptides are hydrolyzed to amino acid by cystosolic peptidases, the remaining dipeptides and tripeptides are Absorbed unchanged. lumen Epithelial cell of the small intestine blood absorption of protein Absorption of lipid 1- the product of lipid digestion are solubilized in the intestinal lumen in mixed micelles except glycerol, which is water soluble. The outer layer of micelle which is cylindrical shape is composed of bile acids. 2- The micelles diffuse to apical membrane of the intestinal epithelial cells. The lipids are released from the micelle diffuse down concentration gradients into the cell. The micelles do not enter the cell. The bile acid are left behind in the intestinal lumen. Most of the digested lipid is absorbed by the mid jejunum. The work of bile acid is completed in side the intestine before they are returned to the liver via entrohepatic circulation . 3- The product of lipid (fatty acids) are re-esterified on the smooth endoplasmic reticulum to form the original ingested lipid, triglyceride, cholesterol ester and phospholipids. 4- Inside cells, lipids are packaged with lipid-carrying particle called chylomicrons. The chylomicrons , with an average diameter of 1000 A°, phospholipid cover 80 % of outside of it, and remaining 20 % of surface covered with apoproteins which are synthesized by intestinal epithelial cells, are essential for absorption of it. 5- The chylomicrons are packaged in secretary vesicles on the Golgi apparatus. The secretary vesicles migrate to the basolateral membranes and there is exocytosis of the chylomicrons. They are too large to enter vascular capillaries, they can enter the lymphatic capillaries. The lymphatic circulation carries them to the thoracic duct which empties into the blood stream.