Gastrointestinal Physiology PDF

Structure of the gastrointestinal tract Parasympathetic innervation Vagus nerve uppergastrointestinal tract 1/3 upper of the esophagus=>ascending and a portion of the transverse colin Pelvic nerve lower gastrointestinal tract including wall of transeverse, descending and sigmoid colons Vagovagal ref...

Structure of the gastrointestinal tract Parasympathetic innervation Vagus nerve uppergastrointestinal tract 1/3 upper of the esophagus=>ascending and a portion of the transverse colin Pelvic nerve lower gastrointestinal tract including wall of transeverse, descending and sigmoid colons Vagovagal reflexes is a kind of reflex that both afferent and effecrent limbs are containd in the vagus nerve Celiac Innervation of the gastrointestinal tract Superior mesenteric sympathetic innervation Four ganglia inferior mesenteric hypogastric intrinsic innervation (enteric nervous system) The enteric nervous system is located in ganglia in the myenteric and submucosal plexuses and controls the contractile, secretory, and endocrine functions of the gastrointestinal tract Subtopic 1 Characteristic of gastrointestinal peptides to promote hydrogen ion (H+) secretion by the gastric parietal cells. meal, gastrin is secreted from G cells located in the antrum of the stomach. Protein digestion secretion of Gastrin Physiologic stimuli that initiate Gastrin seccretion Phenylalanine and truptophan are the most potent stimuli for gastrin secretion Distention of the stomach by food Vagal stimulation Gastrin( secreted by G cell) neurocrine releashed from vagal nerve ending onto the G cells is gastrin-releasing peptide (GRP or Bombesin) Gastrin secretion is inhibited by low pH and Somatostatin Stimulate H+ secreation by gastric parietal cells Actions of Gastrin Growth of the gastric mucosa Caused by excesive gastrin secretion by tumor in pancrea non beta cell Zolinger-Elison syndrome Symptoms: - increase H+ secretion in the parietal cells - hypertrophy of the gastric mucosa - duodenale ulcers Because of over secretion of H+ => acidification of the intestinal lumen, which inacivates paceatic lipase, an enzyme necessary for fat digestion. => seatorrhea ( tiêu chảy mỡ) treatment H2 recepotr blocking drugs: cimetidine inhibitor of the H+ pump: Omeprazole contraction of the gallbladder cause relaxation of Sphincer of Oddi => ejects bile from the gallbladder into the lumen secretion of pancreatic enzymes Functions Promote fat digestion and absorption Secretion of bicarbonate (HCO3-) from the pancreas NOT a major effect of CCK Growth of the exocrine pancreas and gallbladder Gastrointestinal Hormones Cholecystokinin (secreted by I cells) inhibition of gastric emptying Inhibit or slow gastric emptying and increases gastric emptying time. => facilitate the fat digestion and absorption due to the increasement of digest time. Monoglycerides and fatty acids in chyme Physiologic stimuli Gastrointestinal regulatory substances Small peptides and amino acids in chyme Physiologic stimuli Secretin ( Secreted by S cells) Fucntions initiated when the acidic gastric contents (pH classify as Increatin (hormone that promote insulin secretion) inhibit gastric H+ secretion and gastric emptying Increase gastrointestinal motility Motilin initiate the interdigestive myoelectric complexes that occur at 90 minute intervals candidate hormones Pancreatic pollypeptide inhibits pancreatic secretion of HCO3- and enzymes eneroglucagon increase glycogenolysis and gluconeogenesis Glucagon-like peptide-1 (GLP-1, Secreted by L cells) classified as an incretin Physiology role is uncertain Ihibits secretion of the other gastrointestinal hormones and inhibites gastric H+ secretion Somatostatin (secreted by D cells) Somatostain secreted by hypothalamus and by the delta cells of teh endocrine pancreas Paracrines Histamin Histamin stimulates H+ secretion along with gastrin and ACh Neurocrines Satiety center: inhibits appetite even in the presence of food Notions Arcuate nucleus lead information about food to the feeding center Satiety Leptin (Secreted by fat cells) Stimulates anorexigenic neurons and inhibits orexigenic neurons => decreasing appetite and increasing energy expenditure Insulin similar to leptin GLP-1 SImilar to Leptin and inssulin Ghrelin (secreted by gastric cells) increasing appetite Peptide YY decrease appetite Subtopic 1 Slow waves Chewing Chewing and Swallowing Swallowing Esophageal motility extrinsic innervation by the autonomic nervous system Structure and innervation of the stomach Intrinsic innervation from the myenteric and submucosal plexues receptive relaxation Receptive relaxation is a vagovagal reflex, meaningthat both afferent and efferent limbs of the reflex are carried in the vagus nerve. wave of contraction begin in the body of the stomach. the more close to the pylorus the more force the pylrus contraction used. Have retropulsion to ensure all the chyme is small enough Parasympathetic system, gastrin and motilin increase teh frequency of action potentials and the force of gastric contractions Sympathetic, secretin and GIP decrease the frequency of action potentials and the froce of contractions if the food does not small enough (>1mm) it will go through retropulsion Retropulstion is when the stomachj wave conract also close the pylorus cause the food to propelled back to the stomach Gastric motility Mixing and digestion gastric emptying Motility THe presence of fat when fatty acid appear in the duodenum=> CCK secreted and slow the gastric emptying => there is enough time for HCO3- to neutralize The presence of H+ ions (mediated by enteric nervous system) when there are H+ in the duodenum => H+ bind to H+ receptors in the duodenal mucosa => send signal to the smooth muscle => decrease contraction => decrease gastric emptying => increase gastric empyting time major factors slow or inhibit gastric emptying serve to mix the chyme Segmentation contractiosn Produce no forward Small intestinal motility peristaltic contractions The food bolus is snsed by enterochomaffin like (ECL) cells => these cells then releashed serotonin (5-HT) => these serotonin bind to receptros on intrinsic primary affernet neurons( IPANs) => activate peristaltic reflex. Behind the bolus, excitatory transmitters (e.g., ACh, substance P, neuropeptide Y) are released in circular muscle, while these pathways are simultaneously inhibited in the longitudinal muscle; thus this segment of small intestine narrows and lengthens In front of the bolus, inhibitory pathways (e.g., VIP, NO) are activated in circular muscle, while excitatory pathways are activated in longitudinal muscle; thus this segment of small intestine widens and shortens. afferent informations comiting center from the vestibuar system at the back of the throat Vomitting begin with reverse peristaltic contractions that starting at the small intestine and move up into the stomach segmentation contractions Subtopic 1 Mass movements large intestinal motility defecation the intra-abdominal pressure created for defecation can be increased by Valsava maneuver Gastrocolic reflex Distention of the stomach by food increases the motility of the colon and increases the frequency of mass movements in the large intestine. This long arc reflex, called the gastrocolic reflex, structure of the salivary galnds formation of saliva Salivary secretion effect of flow rate on composition of Saliva Regulation of Salivary secretion Structure and cell types of the gastric mucosa 1. In intracellular fluid, carbon dioxide (CO2) Cellular mechanism produced from aerobic metabolism combines with H2O to form H2CO3, catalyzed by carbonic anhydrase. H2CO3 dissociates into H+ and HCO3−. The H+ is secreted with Cl− into the lumen of the stomach, and the HCO3 − is absorbed into the blood, as described in Steps 2 and 3, respectively. 2. At the apical membrane, H+ is secreted into the lumen of the stomach via the H+-K+ ATPase. The H+-K+ ATPase is a primary active process that transports H+ and K+ against their electrochemical gradients (uphill). H+-K+ ATPase is inhibited by the drug omeprazole, which is used in the treatment of ulcers to reduce H+ secretion. Cl− follows H+ into the lumen by diffusing through Cl− channels in the apical membrane. 3. At the basolateral membrane, HCO3 − is absorbed from the cell into the blood via a Cl−-HCO3 − exchanger. The absorbed HCO3 − is responsible for the “alkaline tide” (high pH) that can be observed in gastric venous blood after a meal. Eventually this HCO3 − will be secreted back into the gastrointestinal tract in pancreatic secretions. 4. In combination, the events occurring at the apical and basolateral membranes of gastric parietal cells result in net secretion of HCl and net absorption of HCO3 Histamin - Apical membrane have H+-K+ ATPase and Clchannels - basolateral membranes contain Na+-K+ ATPase and Cl- HCO3- Subtopic 1 Subtopic 1 Bind to H2 receptors which coupled to Gs protein on paretal cells => activated cAMP => cAMP activates protein kinase A => caused secretion of H+ Subtopic 1 Subtopic 1 Subtances that alter HCL secretion ACh ACh is released from vagus nerves innervating the gastric mucosa and binds directly to muscarinic (M3) receptors on the parietal cells. The second messengers for ACh are IP3/Ca2+. When ACh binds to muscarinic receptors, phospholipase C is activated. Phospholipase C liberates diacylglycerol and IP3 from membrane phospholipids, and IP3 then releases Ca2+ from intracellular stores. Ca2+ and Diacylglycerol activate protein kinases that produce the final physiologic action: H+ secretion by the parietal cells Gastrin Gastrin binds to cholecystokinin B (CCKB) receptors on the parietal cells. (The CCKB receptor has equal affinity for gastrin and CCK, whereas the cholecystokinin A [CCKA] receptor is specific for CCK.) Like ACh, gastrin stimulates H+ secretion through the IP3/Ca2+ second messenger system. The stimuli that trigger gastrin secretion from the G cells HCl secretion Gastric secretion Stimulations are smelling and tasting, chewing, swallowing, and conditioned reflexes cephalic phase DIrect stiumlation of the parietal cells by vagus nerves Secretion Mechanism Phases Subtopic 1 indirect stimulation of the parietal cells by gastrin Stimulation are distetion of the stomach and presence of amino acids and small peptides distention causes direct vagal stimulation of the parietal cells Gastric phase Mechanisms Indirect stimulation of the parietal cells by gastrin relseased Distention of the stomach cause gastrin reflexes direct effect of amino acids and small peptides on the G cells to stimulate gastrin release Intestinal phase Pepsinogen secretion accounts for only 10% of HCl secretion (not shown in Figure 8.19) and is mediated by products of protein digestion pepsinogen is converted to pepsin, beginning the process of protein digestion. In the cephalic and gastric phases of H+ secretion, vagal stimulation is the most important stimulus for pepsinogen secretion. H+ also triggers local reflexes, which stimulate the chief cells to secrete pepsinogen intrinsic factor secretion Stucture of the panceatic exocrine glands Include Acinar cells and ductal cells Formation of pancreatic secretion Effect of flow rate on compostion of pancreatic juice - At the highest pancreatic flow rate the HCO3- concentration in the juice is highest - At the lowest flow rate, the opposite happened Phase - Cephalic phase: initiated by smell, taste - Gastric phase: initiated by distention of the stomach and mediated by Vagus nerve - intestinal phase: is the most imortance phase acoounted for 80% of the pancreatic secretion gastrointestinal  physiology Subtopic 1 Pancreatic secretion CCK (secreted by I cells) Regulation of pancreatic secretion Acinar cells (enzymatic secretion) pancreatic acinar cells have receptors for CCK (CCKA receptors) and muscarinic receptors for ACh. During the intestinal phase, CCK is the most important stimulant for the enzymatic secretion. The I cells are stimulated to secrete CCK by the presence of amino acids, small peptides, and fatty acids in the intestinal lume Hace 2 receptors Subtopic 1 muscarinic receptros for ACh Ductal cells Overview of the billiary system Have receptors for CCK, ACh and Secretin Secretin is the major stimulate of Subtopic 1 Subtopic 1 ACh stimulate enzyme secretion and potentiates the action of CCK by vagovagal reflexes HCO3- CCK stimulates contraction of the gallbaldder and relaxation of the sphincter of Oddi Composition of Bile Bile secretion Carbonhydrates Function of the gallbladder Concentration of bile, ejection of bile Enterohepatic circulation of Bile Salts In the ileum, the bile salts are transported from the intestinal lumen into the portal blood by Na+-bile salt cotransporters => then the portal vien blood carries bile salts to the liver = Digestion of carbohydrates by amylase in the pancrea and small proportion in the salivary gland absorption of carbohydrates Subtopic 1 Subtopic 1 Subtopic 1 disorder of carbohydrate digestion and absorption Tripsinogen turen into Tripsin by enterokinase. From then tripsin activates all the others pancrea protease Subtopic 1 Subtopic 1 Subtopic 1 Digestion of proteins Subtopic 1 Pepsinogen secreted by chief cell Protein Absorption of proteins L-amino acid abosrp through Na+-amino cotransoport - dipeptide and tripeptide go in side the cell by H+-dependent cotransporters Subtopic 1 Subtopic 1 Subtopic 1 Subtopic 1 Disorders of protein disgestion and absorption have to be emulsifications to produces small dropletst of lipid => easy to absorb Digestion and absorption digestion of lipids micelles per se do not enter the cell, however, and the bile salts are left behind absorption of lipids Surface of the chylomicron made up with 80% is Phospholipid, the remaining 20% is approtein. - Apoproteins are essential for the absorption of chylomicrons. Failure to synthesize Apo B (or abeta-lipoprotein) results in betalipoproteinemia, a condition in which a person is unable to absorb chylomicrons and therefore is also unable to absorb dietary lipids. Subtopic 1 in the small intestine steps: 1. The products of lipid digestion (cholesterol, monoglycerides, lysolecithin, and free fatty acids) are solubilized in the intestinal lumen in mixed micelles, except glycerol, which is water soluble. Mixed micelles are cylindrically shaped disks with an average diameter of 50 Å. As discussed earlier, the core of a micelle contains products of lipid digestion and the exterior is lined with bile salts, which are amphipathic. The hydrophilic portion of the bile salt molecules dissolves in the aqueous solution of the intestinal lumen, thus solubilizing the lipids in the micellar core. 2. The micelles diffuse to the apical (brushborder) membrane of the intestinal epithelial cells. At the apical membrane, the lipids are released from the micelle and diffuse down their concentration gradients into the cell. The Lipid pancreatic lipase A potential problem in the action of pancreatic lipase is that it is inactivated by bile salts. Bile salts displace pancreatic lipase at the lipid-water interface of the emulsified lipid droplets. This “problem” is solved by colipase. Colipase is secreted in pancreatic juices in an inactive form, procolipase, which is activated in the intestinal lumen by trypsin. Colipase then displaces bile salts at the lipid-water interface and binds to pancreatic lipase. With the inhibitory bile salts displaced, pancreatic lipase can proceed with its digestive functions. in the intestinal lumen to be absorbed downstream in the ileum. 3. Inside the intestinal epithelial cells, the products of lipid digestion are reesterified with free fatty acids on the smooth endoplasmic reticulum to form the original ingested lipids, triglycerides, cholesterol ester, and phospholipids. 4. Inside the cells, the reesterified lipids are packaged with apoproteins in lipid-carrying particles called chylomicrons. 5. The chylomicrons are packaged in secretory vesicles on the Golgi apparatus. The secretory vesicles migrate to the basolateral membranes, and there is exocytosis of the chylomicrons. The chylomicrons are too large to enter vascular capillaries, but they can enter the Subtopic 1 Subtopic 1 lymphatic capillaries (lacteals) by moving between the endothelial cells that line the lacteals. The lymphatic circulation carries the chylomicrons to the thoracic duct, which empties into the bloodstream. abnormalities of lipid disgestion and absorption fat solube vitamin like the absorption of lipid Na+-dependent cotransport Vitamin Is absorb in the illeum. water-solube vitamins B12 occurs in the following steps: (1) Dietary vitamin B12 is released from foods by the digestive action of pepsin in the stomach. (2) Free vitamin B12 binds to R proteins, which are secreted in salivary juices. (3) In the duodenum, pancreatic proteases degrade the R proteins, causing vitamin B12 to be transferred to intrinsic factor, a glycoprotein secreted by the gastric parietal cells. (4) The vitamin B12–intrinsic factor complex is resistant to the degradative actions of pancreatic proteases and travels to the Calcium Iron Free iron then binds to apoferritin and is transported across the basolateral membrane into the blood. In the circulation, iron is bound to a Betaglobulin called transferrin, which transports it from the small intestine to storage sites in the liver Jejunum is the major site for Na+ absorption in the small intestine jejunum - the apical membrane: Na+-glucose, Na+galactose, Na+-amino acid cotransporter and Na+-H+ exchanger - Subtopic 1 Subtopic 1 Subtopic 1 Subtopic 1 Intestinal absorption ileum The cellular mechanisms in the colon are similar to those in the principal cells of the late distal tubule and collecting ducts of the kidney (Fig. Subtopic 1 Subtopic 1 Subtopic 1 colon Subtopic 1 Intestinal fluid and electorlyte transport The apical membrane have Na+ and K+ channel => reabsorp Na+ but secrete K+ intestinal secretion Decreased surface area for absorption osmotic diarrhea Diarrhea Secreatoryh diarrhea Cholera toxin (Step 1).Inside the cells, the A subunit of the toxin detaches and moves across the cell to the basolateral membrane. There, it catalyzes adenosine diphosphate (ADP) ribosylation of the %s subunit of the Gs protein that is coupled to adenylyl cyclase (Step 2). ADP-ribosylation of the %s subunit inhibits its GTPase activity, and as a result, GTP cannot be converted back to GDP. With GTP permanently bound to the %s subunit, adenylyl cyclase is permanently activated (Step 3), cAMP levels remain high, and the Cl− channels in the apical membrane are kept open (Step 4). The resulting Cl− secretion is accompanied by secretion of Na+ and H2O. Subtopic 1 Subtopic 1 Subtopic 1 routes. The permeability of tight junctions between the epithelial cells determines whether fluid and electrolytes will move via the paracellular route or whether they will move via the cellular route. The tight junctions in the small intestine are “leaky” (have low resistance) and permit significant paracellular movement, whereas the tight junctions in the colon are “tight” (have a high resistance) and do not permit paracellular movement. Bile formation and secretion Bilirubin production and excretion liver physiology Metabolic functions of the liver Detoxification of subtances Main Topic 8