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Phases of Pancreatic SecretionPancreatic 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 byvagal 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 .

Regulation of pancreatic secretion )

Disorders of the pancreasPancreatic Failure Is failure of the pancreas to secrete pancreatic juice into the small intestine.occurs (1) in pancreatitis (2) by a gallstone at the papilla of Vater, (3) removed of head of the pancreas in malignancy.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:

Phenylalanine, methionine, tryptophansmall peptides

Fatty acids

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.

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 break 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.

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,thenthe 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.

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

Digestion of carbohydrate

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

Epithelial cell of the small intestineblood

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 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.

enitsetni llams eht fo llec lailehtipE

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.

absorption of monosaccharide

lumenblood

Figure(14)absorption of monosaccharide

Figure(14)absorption of monosaccharide

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 inside 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.

enitsetni llams eht fo llec lailehtipE

Epithelial cell of the small intestine

bloodlumen

Figure (13)absorption of lipid

lumenblood

Figure (15)absorption of lipid