Small intestine secretions

Diarrhea is a common problem that is usually self-limiting and of short duration. Increased accumulations of small intestinal and colonic contents are known to be responsible for producing diarrhea. The former may be caused by increased intestinal secretion which may be enterotoxin-induced, eg, cholera and E. col] or hormone and dmg-induced, eg, caffeine, prostaglandins, and laxatives decreased intestinal absorption because of decreased mucosal surface area, mucosal disease, eg, tropical spme, or osmotic deficiency, eg, disaccharidase or lactase deficiency and rapid transit of contents. An increased accumulation of colonic content may be linked to increased colonic secretion owing to hydroxy fatty acid or bile acids, and exudation, eg, inflammatory bowel disease or amebiasis decreased colonic absorption caused by decreased surface area, mucosal disease, and osmotic factors and rapid transit, eg, irritable bowel syndrome. 

FIGURE 24.3 (a) A duct at the junction of the pancreas and duodenum secretes pancreatic juice into the duodenum, the first portion of the small intestine, (b) Hydrolysis of triacylglycerols by pancreatic and intestinal lipases. Pancreatic lipases cleave fatty acids at the C-1 and C-3 positions. Resulting monoacylglycerols with fatty acids at C-2 are hydrolyzed by intestinal lipases. Fatty acids and monoacylglycerols are absorbed through the intestinal wall and assembled into lipoprotein aggregates termed chylomicrons (discussed in Chapter 25). 

AQP10 has only been identified in the small intestine so far and is thought to play a role in hormonal secretion. AQP11 is expressed in kidney, liver, testis and brain, but no function has been found so far. AQP12 has been identified in pancreatic acinar cells, where it is thought to facilitate the release of digestive enzymes into the pancreatic duct. 

GLUT2 is a glucose/fructose transport facilitator expressed in liver, small intestine, kidney, and pancreatic p-cells. GLUT2 has low-affinity for glucose (Km= 60 mM) and fructose (ivm=65 mM), and is an essential part of the glucose sensor of pancreatic (3-cells which controls insulin secretion and biosynthesis. 

Motilin is a 22-amino acid peptide hormone, secreted by the enterochromaffin cells of the small intestine,... 

Vitamin B12 is special in as far as its absorption depends on the availability of several secretory proteins, the most important being the so-called intrinsic factor (IF). IF is produced by the parietal cells of the fundic mucosa in man and is secreted simultaneously with HC1. In the small intestine, vitamin B12 (extrinsic factor) binds to the alkali-stable gastric glycoprotein IF. The molecules form a complex that resists intestinal proteolysis. In the ileum, the IF-vitamin B 12-complex attaches to specific mucosal receptors of the microvilli as soon as the chymus reaches a neutral pH. Then either cobalamin alone or the complex as a whole enters the mucosal cell. 

Zollinger-Ellison syndrome (ZES) is characterized by the development of a tumor (gastrinoma) or tumors that secrete excessive levels of gastrin, a hormone that stimulates production of acid by the stomach. In most cases, the tumor or tumors arise within the pancreas and/or the upper region of the small intestine (duodenum). 

There are two main classes of proteolytic digestive enzymes (proteases), with different specificities for the amino acids forming the peptide bond to be hydrolyzed. Endopeptidases hydrolyze peptide bonds between specific amino acids throughout the molecule. They are the first enzymes to act, yielding a larger number of smaller fragments, eg, pepsin in the gastric juice and trypsin, chymotrypsin, and elastase secreted into the small intestine by the pancreas. Exopeptidases catalyze the hydrolysis of peptide bonds, one at a time, fi"om the ends of polypeptides. Carboxypeptidases, secreted in the pancreatic juice, release amino acids from rhe free carboxyl terminal, and aminopeptidases, secreted by the intestinal mucosal cells, release amino acids from the amino terminal. Dipeptides, which are not substrates for exopeptidases, are hydrolyzed in the brush border of intestinal mucosal cells by dipeptidases. 

The proteases are secreted as inactive zymogens the active site of the enzyme is masked by a small region of its peptide chain, which is removed by hydrolysis of a specific peptide bond. Pepsinogen is activated to pepsin by gastric acid and by activated pepsin (autocatalysis). In the small intestine, trypsinogen, the precursor of trypsin, is activated by enteropeptidase, which is secreted by the duodenal epithelial cells trypsin can then activate chymotrypsinogen to chymotrypsin, proelas-tase to elastase, procarboxypeptidase to carboxypepti-dase, and proaminopeptidase to aminopeptidase. 

A wide diversity of herbal remedies have purported abilities to stimulate defense functions. Complexes of carbohydrate and lignin, which are present in some herbs, modulate enteric immune functions (Kiyohara et al, 2000), and the changes in cytokine secretion (Matsumoto and Yamada, 2000) can trigger systemic responses. The polysaccharides present in other herbal medicines augment production of immunoglobulin (Ig) A by the Peyer s patches in the small intestine (Sakushima et al, 1997 Yu et al, 1998). The responses of the enteric immune system to lectins are variable (Pusztai 1993), and can elicit systemic responses (Lavelle et al, 2000). Other phytochemicals provide protection by inducing detoxification pathways in mucosal cells (Williamson et al, 1998). 

Bicarbonate is only one of the digestive chemicals that get secreted into the small intestines. Bile acids play a role as well. Bile is made in the liver, stored in the gallbladder, and, when needed, secreted into the small intestines via the bile duct. Bile plays an essential role in the breakdown of fat by dissolving it in the small intestine, much like soap dissolves oil on a frying pan. This breaks the fat down into small droplets. These fat droplets are broken down even further by other intestinal enzymes so that they can be absorbed by the body. 

A schematic representation of the metabolism of lipoproteins is shown in Fig. 12 [170]. Chylomicrons are synthesized and secreted by the small intestine. They are hydrolyzed in blood by the enzyme lipoprotein lipase... 

The Leggett Model simulates lead biokinetics in liver with two compartments the first simulates rapid uptake of lead from plasma and a relatively short removal half-life (days) for transfers to plasma and to the small intestine by biliary secretion a second compartment simulates a more gradual transfer to plasma of approximately 10% of lead uptake in liver. Different transfer rates associated with each compartment are calibrated to reproduce patterns of uptake and retention of lead observed in humans, baboons, and beagles following intravenous injection, as well as blood-to-liver concentration ratios from data on chronically exposed humans. Similarly, the Leggett Model simulates lead biokinetics in three compartments of soft tissues, representing rapid, intermediate, and slow turnover rates (without specific physiologic correlates). 

Bile is produced continuously by the liver bile salts are secreted by the hepatocytes and the water, sodium bicarbonate, and other inorganic salts are added by the cells of the bile ducts within the liver. The bile is then transported by way of the common bile duct to the duodenum. Bile facilitates fat digestion and absorption throughout the length of the small intestine. In the terminal region of the ileum, the final segment of the small intestine, the bile salts are actively reabsorbed into the blood, returned to the liver by way of the hepatic portal system, and resecreted into the bile. This recycling of the bile salts from the small intestine back to the liver is referred to as enterohepatic circulation. 

The return of the bile salts to the liver from the small intestine is the most potent stimulus of bile secretion. In fact, these bile salts may cycle two to five times during each meal. The intestinal hormone secretin, which is released in response to acid in the duodenum, enhances aqueous alkaline secretion by the liver. Secretin has no effect on the secretion of bile salts. During the cephalic phase of digestion, before food even reaches the stomach or intestine, parasympathetic stimulation, by way of the vagus nerve, promotes bile secretion from the liver. 

Bile is secreted by the liver, stored in the gallbladder, and used in the small intestine. It is transported toward the small intestine by the hepatic duct (from the liver) and the cystic duct (from the gallbladder), which join to form the common bile duct. Pancreatic juice is transported toward the small intestine by the pancreatic duct. The common bile duct and the pancreatic duct join to form the hepatopancreatic ampulla, which empties into the duodenum. The entrance to the duodenum is surrounded by the Sphincter of Oddi. This sphincter is closed between meals in order to prevent bile and pancreatic juice from entering the small intestine it relaxes in response to the intestinal hormone cholecystokinin, thus allowing biliary and pancreatic secretions to flow into the duodenum. 

Water and electrolytes. Each day in an average adult, about 5.51 of food and fluids move from the stomach to the small intestine as chyme. An additional 3.5 1 of pancreatic and intestinal secretions produce a total of 9 1 of material in the lumen. Most of this (>7.5 1) is absorbed from the small intestine. The absorption of nutrient molecules, which takes place primarily in the duodenum and jejunum, creates an osmotic gradient for the passive absorption of water. Sodium may be absorbed passively or actively. Passive absorption occurs when the electrochemical gradient favors the movement of Na+ between the absorptive cells through "leaky" tight junctions. Sodium is actively absorbed by way of transporters in the absorptive cell membrane. One type of transporter carries a Na+ ion and a Cl ion into the cell. Another carries a Na+ ion, a K+ ion, and two Cl ions into the cell. 

K. E. Thummel, and P. B. Watkins. Identification of a novel route of extraction of sirolimus in human small intestine roles of metabolism and secretion, J. Pharmacol. Exp. Ther. 2002, 301, 174-186... 

Gramatte, T., Oertel, R., Terhaag, B., Kirch, W., Direct demonstration of small intestinal secretion and site-dependent absorption of the beta-blocker talinolol in humans, Clin. Pharmacol. Ther. 1996, 59, 541-549. 

Bile acids secreted into the small intestine facilitate absorption of fat-soluble vitamins and cholesterol. The majority of bile acids are reabsorbed from the intes-... 

Terao, T., Hisanaga, E., Sai, Y., Tamai, I., Tsuji, A., Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier,... 

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