Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
GI Lecture #51 Tues, March, 4, 11:00AM Dr. Gwirtz Leslie Reddell for Adib Asrabadi Page 1 of 13 Integration of GI Function Everything in this lecture should be a review of all GI functions covered in previous lectures. A copy of Dr. Gwirtz’s overheads can be found on the class bulletin outside the mailroom or in Lubiel for anyone who would like to make copies. -------------------------------------------------------------------------------------------------------------------------------------------------- Various stages of eating a meal o Interdigestive period o Digestive period Cephalic Phase Gastric Phase Early Intestinal Phase Late Intestinal Phase Interdigestive Period o OVERVIEW OF PICTURE: This period is characterized by low output of digestive secretions and the interdigestive migrating motility complex (IMMC). The contractile patterns in the stomach (B) and intestine (D) are correlated to the plasma concentration of motilin (C). Water and electrolytes are being absorbed in the gallbladder (A) and cecum (E). o The IMMC is initiated by released of MOTILIN (graph C) IMMC starts at the gastric antrum and continues as a peristaltic wave (ONE peristaltic contraction) to the terminal ileum (ileocecal junction) Occur 3 per min if the wave begins in the stomach Housekeeping function Clears out the GI tract before eating another meal o Clean of food, secretions, &/or sloughedoff cells Prepares system for ingestion of next meal Contractions become stronger & stronger the longer the interdigestive period o That’s why you have such stronger “hunger contractions” in the morning o o o o o o o o o GI Lecture #51 03/04/03 11:00AM Page 2 of 13 NOTE: even people who have had their stomach removed still feel hunger contractions, but they are probably feeling the intestinal contractions You spend 12-15 hours in interdigestive period Most amount of time spent in this phase Low basal rate of motor, secretary, digestive activity due to low levels of parasympathetic drive (main reason) Salivary, gastric, liver and pancreatic secretions are at their MINIMUM Periodic SYMPATHETIC stimulation cause secretions Circulating GI hormones are also at basal levels and are secreted due to parasympathic activity Continual exfoliation & regeneration of mucosal epithelium Regeneration of mucosal cells Differentiation of stem cells Due to trophic factor = GASTRIN from the G-cell Endocrine & Exocrine cells replenishing stores of hormones and enzymes SALIVARY GLANDS Secretion at basal rate Low levels of salivary secretion to moisten mouth & prevent bacterial overgrowth Keeps mouth moist and clean Upper esophageal sphincter (UES) & lower esophageal sphincter (LES) are contracted Esophagus collapsed = empty esophagus Swallow saliva periodically STOMACH Decreased volume Secretion at basal rate Decreased vagal drive = a very acidic secretion in stomach = low pH REMEMBER THAT WHEN ACID pH DROPS BELOW 2, THE D-CELL IS STIMULATED IN THE ANTRUM OF THE STOMACH TO RELEASE SOMATOSTATIN WHICH INHIBITS GASTRIN SECRTION FROM THE G-CELL = NEGATIVE FEEDBACK MECHANISM To much acid has the potential to overpower the mucosal border of the stomach which can lead to back diffusion of the acid and digestion of the stomach Swallowing the salivary secretions helps to buffer this acid Decreased HCO3 Low level of motility (graph B) Burst of activity = IMMC Occurs every hour or so in response to the release of motilin form the small intestine SMALL INTESTINE Empty due to IMMC (graph D) Contractions due to IMMC LIVER Secretions at basal rate Increased synthesis of bile salts Due to low portal bile concentrations = increased synthesis The bile will go to the gall bladder for storage Decreased secretion of bile salts Decreased portal bile concentrations decreases the stimulus for secreting bile Any bile that is synthesized and secreted by the liver at this time will go into the bile duct and then into the gallbladder to be concentrated since the sphincter of Oddi is contracted NOTE: bile synthesis is an ongoing process, secretion is not GALLBLADDER Concentrating bile salts (graph A) GI Lecture #51 03/04/03 11:00AM Page 3 of 13 o o o Water decreases because of absorption of water across the wall of the gallbladder due to active absorption of sodium Bile salt, cholesterol, bilirubin, etc…increased up to 20 fold Periodically empties due to relaxation of the sphincter of Oddi PANCREAS Decreased volume of secretion Secretion at basal rate Due to vagal stimulation Decreased HCO3 Low secretin, CCK Periodically empties as sphincter of Oddi relaxes COLON Haustrations = Mixing contractions for maximal absorbtion Absorptions of H2O & electrolytes H2O volume is decreased overtime due to increased time allowed for absorption (graph E) SIGMOID COLON & RECTUM Empty Digestive Period: Cephalic Phase o OVERVIEW OF PICTURE This period is characterized by an activated parasympathetic system and a small rise in plasma gastrin (D). These neurohumoral factors increase salivary (B), gastric (C), and pancreatic (E) secretions. The gallbladder contracts (A) and the sphincter of Oddi relaxes. o Anticipation of a meal activates neural canters & parasympathetic efferents Stimulated by: Sight, smell, thought of food Eating-chewing reflex o Vagal stimulation leads to secretion of glands to prepare the GI tract Prepares GI tract for incoming food Increased parasympathetic activity stimulates everything Stimulation = increase in metabolic activity = metabolic vasodilation = increased splanchnic blood flow o Food in Pharynx = swallowing reflex = initiation of primary peristaltic contraction o Increased activity of glands = Increased splanchnic blood flow Increased salivary glands, gastric glands, pancreas, begin contraction of gallbladder o Motor activity of the small intestine & large intestine is not significantly influenced o Swallowing reflex o Receptive relaxation of the LES & STOMACH o SALIVARY GLANDS Increased salivary flow up to 6X the basal rate (graph B) GI Lecture #51 03/04/03 11:00AM Page 4 of 13 Lubricates mouth For chewing & swallowing = via diluting food Breaks starches into glucose via salivary α-amylase Parasympathetic stimulation Salivation is increased to PEAK production o STOMACH Receptive relaxation Adaptive reflex = Stretch relaxation Allows for only a small increase in gastric pressure as stomach fills Stomach is empty at this point Increased acid output due to vagal stimulation (graph C) o Increased acid & intrinsic factor secretion via stimulation of parietal cells o Increased pepsinogen secretion via chief cell stimulation BOTH vagal stimulation and gastrin release will stimulate the chief cells to secret pepsinogen Increased plasma gastrin due to increased vagal stimulation (graph D) o Gastrin released into the bloodstream via stimulation of the G-cells which leads to increased acid release from the parietal cells o PANCREAS Increased pancreatic secretion (graph E) Acinar cells releasing enzymes o Major influence of vagal stimulation at this point is to secrete pancreatic enzymes Will see a small increase in bicarbonate release from ductal cells Due to vagal stimulation Increased gastrin leads to increased enzyme secretion o LIVER Synthesis of bile Low secretion of bile because there will still be low portal bile concentrations Bile will start to empty into the small intestine because the gallbladder is beginning to contract o SPHINCTER OF ODDI Relaxes due to vagal stimulation (graph A) o SMALL INTESTINES May still have the IMMC occurring Will secrete a watery solution o LARGE INTESTINE Haustrations still occurring in the colon NOTE: IMMC may still be occurring = ongoing contractions will complete themselves but no new IMMC waves are initiated GI Lecture #51 03/04/03 11:00AM Page 5 of 13 Digestive Period: Gastric Phase o OVERVIEW OF PICTURE: This period is characterized by a decreased parasympathetic drive and a further increase in plasma gastrin (E). Salivary secretion returns toward the basal level (C), whereas gastric (D) and pancreatic (F) secretions are further augmented. Gastric volume increases rapidly and subsequently declines as it empties (B). THE gallbladder continues to empty (A). Motor reflexes from the stomach initiate ileal and colonic contractions; chime moves into the cecum where it is mixed. o Food has entered the stomach = stomach filled with food Have stopped eating and swallowing food o Parasympathetic influence has decreased o Gastrin becomes the dominant regulating factor o Blood flow remains elevated Due to increased motility and secretions Blood flow needed to bring the nutrients to the cells of the gut to make ATP in order to contract smooth muscle and to make the secretions o SALIVARY GLANDS Salivary flow starts to decrease back to basal levels (graph C) Because have stopped eating and swallowing food o STOMACH Mixing contractions in body Peristaltic contractions in the antrum/pylorus Controlled gastric emptying Regulated by many factors Distention of the stomach (graph B) Increased gastrin volume Stomach at its fullest for this particular meal Vagal reflex (graph D & E) Increased HCl & gastrin o Acid secretion at its PEAK Due to vagal stimulation Due to gastrin synthesis/secretion at its peak Gastrin secretion is stimulated by the release of bombesin (AKA Gastrin Releasing Hormone) & Ach released at the G-cell from the parasympathetic nerves o Proteins in chyme, alcohol, Ca2+ directly stimulate G-cells to produce gastrin Due to distention of the stomach = G-cells to release gastrin & parietal cells to release acid GI Lecture #51 03/04/03 11:00AM Page 6 of 13 o o o o Pepsin digests proteins o Pepsin released due to gastrin Intrinsic factor secreted Increased plasma gastrin o Due to vagal stimulation, amino acids and Ca2+ LIVER/GALLBLADDER Vagal stimulation causes bile secretion Will see a decrease in gall bladder volume (graph A) Gall bladder is contracting o Caused by vagal stimulation and gastrin Sphincter of Oddi is relaxing PANCREAS Increased pancreatic secretion (graph F) More enzymes being secreted than HCO3 Bicarb is still being released Due to vagal stimulation and gastrin of the pancreatic acinar & ductal cells o Synergistic effect SMALL INTESTINE Ileal motility increase due to gastrin Ileocecal sphincter relaxes = gastrocolic reflex via gastrin LARGE INTESTINE Gastrocolic reflex = stronger haustral contractions in the colon initiating a mass movement Initiates a mass movement due to parasympathetic activity and gastrin Mass movement moves everything from the transverse colon to the sigmoid colon and into the rectum Distention of the rectum is going to initiate the defecation reflex Occurs 15 min or so after eating Digestive Period: Early Intestinal Phase o OVERVIEW OF PICTURE: This period is characterized by a reduction in plasma gastric levels (D) and a concomitant raise in plasma levels of secretin and CCK (F). The stomach continues to slowly empty its contents (B), while acid output falls dramatically (C). The pancreas elaborates an enzymeand bicarbonate-rich secretion (E). There is an intense contraction of the gallbladder (A). The motor pattern in the small bowel shifts from the IMMC to irregular segmental and propulsive contractions, which mix the chime with digestive secretions. Colonic motility includes patterns such as mass movements and retropulsion. o Chyme is present in the intestine o Stomach empties over a long period of time The higher the fat content the GI Lecture #51 03/04/03 11:00AM Page 7 of 13 o o o o o o o longer the meal/chime is going to stay in the stomach Events during the early intestinal phase include release of CCK & secretin, digestion, absorption STOMACH Controlled emptying (graph B) Feedback inhibition of gastric emptying o Humoral o Neural o Osmotic Acid output starts to decrease due to DECREASED pH (graph C) Due to CCK and secretin o CCK released in response to fats in the duodenum = DECREASED gastric motility = DELAYS gastric emptying o Secretin released due to acid in the chime = DECREASE gastric motility = DELAYS gastric emptying o CCK and secretin also decrease gastric secretions DELAYED gastric emptying allows for maximal absorption in the small intestine before the emptying of new material Plasma gastrin levels DECREASE (graph D) Due to vagal reflexes originating in the small intestine due to effects of secretin and CCK, LIVER Bile acid secretion GALLBLADDER Contraction of gallbladder Reduced volume (graph A) CCK causes contraction of the gallbladder PANCREAS PEAK level of pancreatic secretions (graph E) CCK major hormone for stimulating secretion by acinar cells Secretin major hormone stimulating for HCO3- secretion by ductal cells Maximal level of HCO3- to neutralize chyme Plasma secretin and CCK at maximum (graph F) Secretin and CCK potentiate each other SMALL INTESTINE IMMC stops with the presence of food Segmentation contractions to mix the chyme with the secretions of the gallbladder, pancreas, and intestinal cells Forms an iso-osmotic, watery, chyme-like substance Allows for max digestion by the enzymes Max exposure of chyme to epithelial cells to allow for absorption LARGE INTESTINE Mass movement This lecture & textbook demonstrates that the mass movement occurs in the early intestinal phase….most other textbooks disagree stating that the initiation of the mass movement occurs in the gastric phase Distention of rectum Leads to defecation reflex o Intrinsic reflex o Parasympathetic reflex GI Lecture #51 03/04/03 11:00AM Page 8 of 13 Digestive Period: Late Intestinal Phase o OVERVIEW OF PICTURE: This period is characterized by a gradual return of the intestinal hormones (secretin and CCK) to their interdigestive plasma levels (D,F). Gastric (C) and pancreatic (E) secretion rates and gastric volume (B) fall toward their basal rates. Bile salts, absorbed from the terminal ileum, stimulate hepatic bile salt secretion and inhibit bile salt synthesis. The gallbladder slowly fills with hepatic bile (A). When the rectum distends sufficiently, the urge to defecate is felt and the stool is passed. o The upper small intestine is virtually empty due to absorption of nutrients o Stimuli for hormonal release from the duodenum, jejunum, etc. is removed Decreased CCK, secretin levels o The rate of gastric and salivary secretions returns to basal levels o Gastric and small intestine motility shifts to the interdigestive MMC pattern o STOMACH Decreased gastric volume (graph B) Decreased acid output (graph C) Decreased plasma gastrin (graph D) o LIVER Increased bile salt secretion Goes to be stored in the gallbladder Decreased bile salt synthesis (because returning bile to the liver) Increased secretion and decreased synthesis due to an increase in portal bile concentrations o GALLBLADDER Increased filling of the gallbladder (graph A) Closure of the sphincter of Oddi o PANCREAS Decreased pancreatic enzyme secretion (graph E) Returning to basal levels Decreased plasma secretin and CCK (graph F) o SMALL INTESTINE Chyme in the ileum Ileum allows for final absorption What is not absorbed goes into the large intestine Segmentation contractions occurring The terminal ileum absorbs the bile slats Increases blood concentration of bile salt Inhibits the liver’s synthesis of bile Stimulates the liver’s secretion of bile o LARGE INTESTINE Chime moves into the colon Continued colonic motility Haustrations occurring GI Lecture #51 03/04/03 11:00AM Page 9 of 13 LOTS of digestive enzymes are being secreted during the digestive periods o Salivary Glands Secrete α-amylase Digests starch o Stomach Secretes Pepsin (pepsinogen) Stimulated/converted to pepsin by HCl Begins digestion of proteins and polypeptides Secretes Gastric Lipase Of little significance o Exocrine Pancreas Responsible for the secretion of the major peptidases, lipases, and amylases Responsible for most of the digestion that occurs in the small intestine Trypsin is activated by enterokinase that is part of the small intestinal brush border Trypsin then activates all other proteases secreted by the pancreas o Intestinal Mucosa Has enterokinase and a number of other brush border enzymes (i.e. amino peptidases, dipeptidases, maltase, sucrase, lactase etc…) Peptidases o Breaks polypeptides into di- & tri- peptides so they can move into the epithelial cells where they are digested by epithelial cell cytoplasmic peptidases into amino acids Can be absorbed by the bloodstream once they are amino acids Maltase, Sucrase, Lactase o Makes disaccharides into monosaccharides o The only monosaccharides we are absorbing are the glucose, the galactose, and the fructose Lipase o Digests the lipids into free fatty acids and glycerol o Digests cholesterol esters into cholesterol o Can then become micelles that are transported to the epithelial cells and absorbed Carbohydrate Digestion o Begins in the mouth by α-amylase and then by pancreatic α-amylase So…starch is broken down to glucose so it can be absorbed o Lactose + Lactase = Glucose & Galactose Glucose & galactose are absorbed by what mechanism? Na+ co-transport o Sucrose + Sucrase = Glucose & Fructose How is fructose absorbed? Facilitated diffusion o All monosaccharides absorbed across the brush border o So if you destroy the intestinal brush border enzymes (i.e. you have celiac disease, an immune response to gluten in wheat in rye, so you have no villi and no brush border enzymes) which sugar can you still digest and adequately absorb? You can still eat starch because it is digested by the α-amylase o If you have a genetic disorder where you are missing the enzyme lactase, you can not digest lactose. Lactose goes into the colon where it is acted on by the bacteria in the colon resulting in gas formation and diarrhea GI Lecture #51 03/04/03 11:00AM Page 10 of 13 Protein Digestion o Proteases are secreted in the stomach Pepsinogen activated by acid to Pepsin Begins the digestion of proteins o Small intestine trypsinogen which is secreted by the pancreas is activated by enterokinase in the intestinal brush border into trypsin All other proteases are activated by trypsin Digests protein into di- & tri- peptides and some amino acids Amino acids and di- & tri- peptides are taken up into the epithelial cells mainly by a Na+ co-transport mechanism o Di- & tri- peptides are broken down to amino acids by intracellular peptidases which are then absorbed into the blood stream o NOTE: Brush border enzymes are bound to the brush border so…THEY ARE NOT SECRETED INTO THE LUMEN Lipid Digestion o Lipid digestion takes more time to digest and occurs by a more complex mechanism o Major lipids we ingest are triglycerides, cholesterol esters, and phospholipids o We begin lipid digestion with lingual lipases o Most lipids will be digested by pancreatic lipases Triglycerides = monoglycerides + free fatty acids Cholesterol esters = cholesterol + fatty acid Phospholipid = lysolecithin + fatty acid o Once digested, the lipids will be absorbed across the wall of the epithelial cell What component is crucial for this digestion to occur? Bile acids o Surround the micelle so the micelle can transport the lipid globule over to the epithelial cell o Lipid components freely diffuse across epithelial cell o Once taken into the epithelial cell, cholesterol esters, triglycerides, and phospholipids are made again Surround these with an apoprotein coat = forms a chylomicron inside the epithelial cell Chylomicron moves by exocytosis into the intercellular space where it is then taken up into the lymph because it is to big to go into the blood capillary THE ONLY EXCEPTION: small chain lipid can freely move around in the lumen of the gut and be absorbed completely through the epithelial cell and move into the bloodstream o 40% of dietary lipids are small chain lipids o So…can absorb small chain lipids in the absence of bile acids LOTS of Electrolytes absorbed in the small intestine o Na+ absorption Occurs in the duodenum and jejunem Mechanisms o Co-transport with glucose and amino acids o Counter transport of Na+ in exchange for H+ o Na+ diffusing between the intercellular spaces o Transport bringing Na+ & Cl- inside the cell o Na+ actively transported outside the cell across the basolateral membrane where it will enter the bloodstream GI Lecture #51 03/04/03 11:00AM Page 11 of 13 o o o o In the Ileum Mechanisms o Na+ and Cl- co-transport o Exchange of Na+ for H+ o Na+ actively transported out of the cell REMEMBER: water is following the osmotic gradient moving by simple diffusion going from low osmotic pressure to high osmotic pressure There is a passive diffuse of K+ as water flows In colon Plays an important role in the absorption of electrolytes and water Absorption of Na+ from the lumen of the colon into the epithelial cell o This process can be stimulated by aldosterone o Where else can Na+ movement be affected by aldosterone? The salivary glands o Na+ actively transported out the basal membrane into the bloodstream Cl- secretion From the crypt cells Stimulated Cl- secretion by cholera toxin or bacterial infection Cl- moved out into the lumen and water follows in response Where in the gut are you going to see bicarbonate being absorbed rather than secreted? In the colon…Why? Will have bicarbonate-Cl- exchange in the terminal ileum and colon so you are secreting bicarb rather than absorbing it Ca2+ and Iron absorbed according to the body’s need for these nutrients Ca2+ absorption stimulated by the amount of calcium binding protein inside the cell Determined by the plasma levels of calcium Decreased calcium plasma levels = release of parathyroid hormone = synthesis of the calcium binding protein Calcium binding protein moves into the enterocyte where presence of the binding protein causes calcium to move into the cell and then out of the cell into the blood plasma Iron Ingested in the form of meat iron = heme iron Moves into the enterocyte where it become bound to ferritin If the body is in need of iron we produce more transferrin = an iron binding protein produce in the liver o high plasma levels of transferrin signals the release of iron from ferritin where the iron is taken back to the liver bound by transferring o if transferrin is free, we absorb more iron from the epithelial cells o if there are high levels of transferrin in the bloodstream already bound to iron, the iron in the epithelial cells bound to ferritin will be sloughed off and excreted since it is not needed by the body Vitamin B12 Parietal cells secretes intrinsic factor which complexes with the vitamin B12 In the ileum, it allows the vitamin B12 to be absorbed into the epithelial cell and released into the bloodstream GI Lecture #51 03/04/03 11:00AM Page 12 of 13 The Hormones o Know actions! Hormone/ Paracrine/ Neurotransmitter Acetylcholine Bombesin Cholecystokinin (CCK) Gastric Inhibitory Polypeptide (GIP) Site of Production Parasympathetic, enteric nerves ● neural reflexes Enteric neurons in stomach mucosa Duodenal mucosa ● neural reflexes ● dietary protein Duodenal mucosa ● fatty chyme ● glucose containing chime ● protein in gastric chyme ● elevated gastric pH ● gastric distension ● neural reflexes Gastrin Stomach mucosa – antrum Histamine Stomach mucosa (enterochromaffin cells; mast cells) Motilin Nitric Oxide Stimulus for Production Duodenal mucosa Enteric neurons ● fatty chyme ● partially digested proteins, amino acids ● gastrin ● food in stomach ● acetylcholine (reflexes) ● irritation ● unknown ● Neural reflexes Norepinephrine, Epinephrine Sympathetic nerves, adrenal medulla ● neural reflexes Opioids/ Enkephalins Enteric neurons ● Neural reflexes Target Organ and Action ● Salivary glands: stimulate secretion ● Esophagus: stimulates motility ● Stomach: stimulates motility and secretions of acid, pepsinogen ● Small intestine: stimulate motility and secretion ● Gallbladder: stimulates contraction ● Pancreas: stimulates enzyme secretion ● Stomach: stimulates release of gastrin ● Pancreas: stimulates secretion ● Stomach: decreases motility and delays emptying; inhibits acid secretion ● Small intestine: stimulates motility ● Gallbladder: stimulates contraction to expel stored bile; relaxes sphincter of Oddi ● Pancreas: stimulates enzyme secretion; potentiate action of secretin ● Stomach: inhibits acid secretion ● Small intestine: inhibit motility ● Pancreas: stimulates insulin release ● Stomach: stimulates motility (to enhance gastric emptying) and secretions of acid, pepsinogen ● Small intestine: stimulate motility ● Ileocecal valve: relaxation ● LES: contraction ● Large intestine: stimulate mass movement ● Gallbladder: mild contraction ● Pancreas: mild stimulation of enzyme, HCO3 secretion ● Trophic hormone ● Stomach: stimulate acid secretion ● Small intestine: stimulate secretions ● regulates interdigestive migrating myoelectric complex ● Relaxes intestinal smooth muscle, including sphincters ● Relaxes GI smooth muscle, except constricts sphincters ● Inhibits secretions ● Decreases blood flow ● Circular smooth muscle contraction ● Intestine: decreases secretion ● Inhibits release of VIP, acetylcholine, substance P GI Lecture #51 03/04/03 11:00AM Page 13 of 13 Duodenal mucosa ● acidic chyme ● partially digested proteins, fats, hypertonic or hypotonic fluids ● irritants in chyme Somatostatin Enterochromaffin cells in gastric and duodenal mucosa ● food in stomach ● acidic pH in stomach ● neural reflexes Substance P Enteric neurons ● Neural reflexes ● Distension ● Food in gut ● chyme containing partially digested foods Secretin Vasoactive Intestinal Peptide (VIP) Duodenal mucosa ● Stomach: inhibit motility (delay emptying) and secretions ● Small intestine: inhibit motility ● Liver: increase bile output, especially ductal secretion of HCO3 ● Gallbladder: potentiate CCK’s action to contract ● Pancreas: stimulate secretion of HCO3; potentiate CCK’s action on enzyme secretion ● Inhibits release of neuroendocrine factors ● Stomach: inhibits secretion ● Small intestine: ● Gallbladder: ● Pancreas: inhibits secretion ● Relaxes intestinal smooth muscle, including sphincters ● Intestine: stimulates secretion ● Relaxes GI smooth muscle, including sphincters ● Intestine: stimulates secretion