Phys II GI Secretion (Gastro Day 3 & 4)

Volumes of the secretions in the GI tract
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Volumes of the secretions in the GI tract
- The highest secretion is from the small intestine (1800 mL, pH 7.5-8)
- The lowest are from the colon and the brunner's glands (200 mL, pH between 7.5 and 9)
Two general types of glands in the digestive tract
- Those that secrete digestive enzymes
- Those that secrete mucous

- Most digestive secretions occur only in response to the presence of food in the alimentary tract
- The amount secreted matches the amount needed
Typical function of a glandular cell for formation and secretion of enzymes and other secretory substances.
Image: Typical function of a glandular cell for formation and secretion of enzymes and other secretory substances.
Basic mechanisms of glandular stimulation
1) Effect of food contact with the epithelium. Mechanical presence of food in a segment of the GI tract usually causes the glands of that region to secrete.
- The mechanism, especially for mucus secretion, results from the direct contact stimulation of the surface glandular cells.

2) Autonomic stimulation. Both parasympathetic and sympathetic stimulation work here.

3) Hormonal stimulation (see below)
Parasympathetic stimulation for GI secretion
- Stimulation here almost invariably increases the rates of glandular secretion.
- This is especially true of the glands innervated by CN IX and X, such as salivary glands, esophageal glands, gastric glands, pancreas, and Brunner's glands in the duodenum
Sympathetic stimulation of GI secretion
- Sympathetic stimulation constricts blood vessels that supply the glands
- Thus sympathetic stimulation slightly increases secretion, but can also decrease secretion induced by the parasympathetic system or hormonal induced secretion
Hormonal stimulation for GI secretion (help regulate the volume and character of secretions)
- Acetylcholine, gastrin, histamine, and many others
- These hormones originate in the GI mucosa and are absorbed into the blood and carried to the glands
- Chemically, the GI hormones are usually polypeptides or polypeptide derivatives
The principal salivary glands
- The parotid (largely serous)
- Submandibular (mixed serous and mucous)
- Sublingual (largely mucous)

- In addition, there are many buccal glands
The daily secretion of saliva ranges from _____________ mLs.
800-1500
Saliva contains two major types of protein secretion:
1) a serous secretion that contains ptyalin (a-amylase), which digests starches
2) a mucous secretion which contains mucin for lubrications.
The parotid glands secrete entirely ______________, and the submandibular and sublingual glands secrete _________________.serous fluid a mix of serous and mucous secretionsThe acini secrete enzymes or mucus while the ducts secreted bicarbonate and reabsorb sodium.The parotid gland has a _________ structure and large connective tissue septa separating the lobules. The gland is also almost exclusively __________ seecreting.lobular serousThe structure of the duct system in salivary glandsThe duct system of salivary glands- In the duct system, secretory end pieces empty into intercalated ducts, which are lined by cuboidal epithelial cells. These cells can divide and differentiate into secretory or ductal cells. - Several of these short intercalated ducts join to form striated ducts, which are characterized by radial striations that extend from the bases of the cells to the level of the central nuclei. - These striations are infoldings of the basal membrane with numerous mitochondria that are aligned parallel to the infolded membranes. This is characteristic of ion-transporting cells. - Both intercalated and striated ducts are intralobular ducts because of their location within lobules. - Striated ducts of each lobule secrete and drain into ducts located in the connective tissue septae separating the lobules, where they become interlobular, or excretory ducts. - They are initially lined with pseudostratified or stratified cuboidal epithelium, but more distal parts are lined with stratified columnar epithelium. The main duct of each salivary gland ultimately empties into the oral cavity and is lines with nonkeratinized-stratified squamous epithelium.Structure of the submandibular glandSalivation is regulated by the PS nervous systemBrainstem nuclei- The brainstem nuclei two nuclei at the ponto-medullary junction called the superior and inferior salivatory nuclei. These are excited by both taste and tactile stimuli from the tongue and other areas of the mouth a pharynx. - Salivation can be stimulated or inhibited by higher centers of the CNS which project to the salivatory nuclei. For example, when a person smells or eats foods, salivation is activated. - The appetite area of the brain, located close to the parasympathetic centers in the anterior hypothalamus, responds to signals from the taste and smell areas of the cerebral cortex and amygdala. - Some taste stimuli, such as sour taste (caused by acids), elicit copious amounts of saliva secretion. Also, smooth objects cause more salivation than rough shaped objects.Axons from neurons in these nuclei go out as follows:- The parotid gland receives its parasympathetic input from the glossopharyngeal nerve(CN IX) via the otic ganglion, - The submandibular and sublingual glands receive their parasympathetic input from the facial nerve (CN VII) via the submandibular ganglion. These nerves release acetylcholine and substance P. - Direct sympathetic innervation of the salivary glands takes place via preganglionic nerves in the thoracic segments T1-T3 which synapse in the superior cervical ganglion with postganglionic neurons that release norepinephrine, which is then received by β-adrenergic receptors on the acinar and ductal cells of the salivary glands - Both parasympathetic and sympathetic stimuli result in an increase in salivary gland secretions. The sympathetic nervous system also affects salivary gland secretions indirectly by innervating the blood vessels that supply the glands.Secretions of ions in the saliva- Saliva contains large quantities of K+ and -HC03, and relatively low concentrations of Na+ and Cl-.- Saliva secretion is a two-stage operation:- The first involves the acini and the second the ducts. - First, the acini secret a primary secretion that contains ptyalin and/or mucin in a solution of ions which is very similar to the extracellular fluid. - Second, as this primary secretion flows through the tubes, two major active transport processes modify the secretion. •In the first, Na+ are actively reabsorbed from all the salivary ducts, and K+ are secreted in their place. - However, since more Na+ is absorbed than K+ secreted, the potential in the salivary ducts is about -70mV. - This causes Cl- to be reabsorbed passively, down its electrochemical gradient. This is how both sodium and chloride ions become very low in concentration in the saliva.Secretion of bicarbonate- The second tubular process to modify the saliva is the secretion of -HC03 by the ductal epithelium. - This is caused partially by the exchange of -HC03 for Cl-, and partly from active bicarbonate secretion. - During maximal salivation, the ducts may not have the time to modify the saliva as described above, and so the saliva becomes more salty. - In contrast, in the presence of high aldosterone levels, Na+ and Cl- reabsorption become maximal, consistent with the function of aldosterone on the kidney (i.e. causes salt reabsorption).Esophageal secretion- Esophageal secretions are mucoid in character and function to provide lubrication for swallowing. - The esophageal glands are both simple and compound mucous glands. - The mucous serves to lubricate the food to aid in its passage down the esophagusGastric secretion- In addition to mucus-secreting cells that line the entire surface of the stomach, the stomach mucosa has two types of tubular glands: oxyntic (gastric) and pyloric glandsA typical stomach oxyntic gland has various cell types:1) surface lining cells, secreting mucous 2) peptic (chief) cells, secreting pepsinogen 3) parietal (oxyntic) cells, secreting HCl 4) Enteroendocrine cells; ex. G cellsParietal cellThese figures show the structure of a parietal cell. Note the large, branching canaliculi. HCl is formed at the files-like projections inside these canaliculi and secreted to the stomach lumen.Mechanism of acid productionPostulated mechanism for secretion of hydrochloric acid. (The points labeled "P" indicate active pumps, and the dashed lines represent free diffusion and osmosis.)Pyloric glands and surface mucous cells- The pyloric glands are structurally similar to the oxyntic glands, but contain few peptic cells and almost no parietal cells. Instead, they contain mostly mucous cells - These cells secrete a small amount of pepsinogen, and a large amount of mucus that lubricates the food movement - Pyloric glands also secrete gastrinThe basic factors that stimulate gastric secretion:- Acetylcholine (from the vagus) - Gastrin (from the gastric G cells) - Histamine (from the enterochromaffin cells)The role of acetylcholine- Vagal stimulation: This is elicited when you think of or smell food, and is part of the cephalic phase. The vagus works through a direct and indirect pathway - Direct pathway: vagal fibers directly innervate parietal cells, and through a muscarinic cholinergic receptor that utilizes a PLC pathway, it increases HCL production. - Indirect pathway: vagal fibers innervate G cells and induce gastrin release, which increases HCL secretion by the mechanism described below. - The neurotransmitter here is not ACh (as it is on the parietal cells), but rather GRP (gastrin releasing peptide) - Thus atropine, an ACh antagonist, inhibits the direct, but not the indirect pathway because it does not block GRP binding to G cells, whereas vagotomy inhibits both pathwaysRole of distention of the stomachDistention of the stomach, when food enters, elicits a local reflex where the enteric nerves of the submucosal plexus (Meissner's plexus) also release ACh and cause gastric acid secretionThe role of histamine- The secretion of HCL by parietal cells is directly related to the amount of histamine secreted by enterochromaffin cells - These enterochromaffin cells lie adjacent to the gastric glands, and therefore release their histamine directly to the parietal cells. - Histamine then works on H2 receptors on the parietal cells to cause HCl release. - The drug cimetidine inhibits the H2 receptor; the second messenger is cAMPThe role of gastrin- Gastrin, is released from G cells in the antral gastric glands in response to proteins in the chyme - Gastrin is a class of hormones consisting of a 34 amino acid polypeptide and a 17 amino acid peptide2 mechanisms for Gastrin:1) After secretion in response to proteins from meat in the chyme, the vigorous mixing in the stomach transports the gastrin to the enterochromaffin cells, which release histamine, which stimulates acid secretion. 2) Gastrin interacts directly with the parietal cells, through an unknown receptor, to increase HCL secretion.Inhibition of gastric acid secretion by factors originating in the stomach:- When the acidity of the gastric juices increases to less than 3.0 pH, the gastrin mechanism becomes blocked - This is because the low pH block release of gastrin itself, possibly through the mediator somatostatin (see above figure) and also the acid induces an inhibitory nervous reflex - Obviously, this feedback mechanism protects the stomach against acid damageFood in the intestine inhibits gastric secretion, with the purpose of slowing the release of chyme from the stomach when the small intestine is already filled. This is accomplished in the following ways:1) Food in the small intestine initiates a reverse enterogastric reflex, via the myenteric nervous system and extrinsic autonomic fibers. This was discussed in the last topic 2) The presence of acid, fat, protein breakdown products, or any irritating factor in the upper small intestine induces the release of the following hormones: -- secretin, which induces pancreatic secretion -- gastric inhibitory peptide -- vasoactive intestinal polypeptide -- somatostatin All of these inhibit gastric secretionRegulation of pepsinogen secretionTwo signals that stimulate pepsinogen secretion: 1) acetylcholine from the vagus (or from the enteric nervous system) 2) acid in the stomach Pepsinogen is a protein with a molecular weight of about 42.5Kd, and is activated only when split by pepsin plus HCl, into a protein (Pepsin) of 35Kd. Pepsin is a proteolytic enzyme with a pH optima between 1.8 and 3.5Phases of gastric secretion1) cephalic phase - originating in the cerebral cortex, acting through the vagus 2) gastric phase - once food hits the stomach, vagovagal reflexes, local enteric reflexes and the gastrin mechanism all kick in 3) Intestinal phase - Food in the duodenum causes the stomach to secrete small amounts of gastric juice, partly because of the small amounts of gastrin released by the duodenal mucosaGastric secretion during the interdigestive period- When not digesting, a small amount of digestive juice is secreted each hour, but it is mainly mucus wilt little pepsin and almost no acid - Emotional stimuli, however, can increase gastric secretion, in much the same way that the cephalic phase releases gastric secretion - This is believed to be one of the causative factors in development of peptic ulcersPancreatic secretion- The pancreas forms digestive enzymes and sodium bicarbonate; the combined product of these flow through a long pancreatic duce that joins the hepatic duct just before it empties into the duodenum - A smooth muscle sphincter, the sphincter of Oddi, regulates this releaseThe pancreas- Is a gland that lies posterior to the stomach - Produces enzymes that digest carbohydrates, proteins, fats, and nucleic acids - Produces sodium bicarbonate which buffers stomach acid - Empties its contents into the duodenumPancreatic digestive enzymes- Secreted by the cell in the acini, the major enzymes for protein digestion include •trypsin •chymotrypsin •carboxypolypeptidase - Generally, the proteolytic enzymes are secreted in an inactive form, but are activated by being cleaved by trypsin (hence trypsinogen, chymotrypsinogen, procarboxypolypeptidase) - Also, some secondary enzymes include •elastases •nucleasesPancreatic amylase- The pancreatic digestive enzyme for carbohydrates is pancreatic amylase, which hydrolyzes starches glycogen and most other carbohydrates with a-glycosidic bonds - Note that the only enzyme in humans which can digest b-glycosidic bonds, such as occurs in plant leaves, is b-galactosidase, which digests only lactose. Thus plant material, such green leafy vegetables, with b -glycosidic bonds are not digested by humans and contribute to roughage in the dietThe main enzymes for fat digestion- pancreatic lipase, which cleaves fats into fatty acids and monoglycerides - cholesterolesterase, which cleaves cholesterol esters - phospholipase, which splits fatty acids from phospholipidsSecretion of bicarbonate ions- Bicarbonate ions and water are secreted not by the cells of the acini, as the digestive juice is, but by the epithelial cells of the ducts and ductules which lead from the aciniThe figure that shows the secretion of isosmotic sodium bicarb solution by the pancreatic ductules and ductsThree basic stimuli that cause pancreatic secretion1) Acetylcholine, released from the vagus nerve 2) Cholecystokinin, secreted by duodenal and upper jejunal mucosa 3) Secretin, also secreted by duodenal and upper jejunal mucosaPicture explaining the pancreatic secretionSince Acetylcholine and cholecystokinin act on the acinar cell more than the ductal cells, they cause the release of much pancreatic digestive enzymes and only a little bicarbonate. The opposite happens with __________; since it stimulates the ductal cells more, it produces a secreted fluid rich in what the ductal cells produce, which is bicarbonate (see above).secretinWhen all the different stimuli of pancreatic secretion occur at once, the secretion is far _______ than the sum of the secretions caused by each one separately.greaterSecretion of bile by the liver and gallbladder- The most potent stimulus for gallbladder contraction is cholecystokinin, which also causes secretion of digestive enzymes by pancreatic acinar cells. CCK is released by duodenal mucosa in response to fat in the duodenum. - A secondary, but still important signal for gallbladder emptying is acetylcholine, released by both the vagus and the enteric nervous systemThis is the figure that outlines bile secretionThis is another figure for bileLiver and gallbladder functions- The liver makes bile, important in the emulsification of fats - The gallbladder stores bile until it is neededSchematic drawing of the structure of the liver. The liver lobule in the center is surrounded by the portal space (dilated here for clarity). Arteries, veins, and bile ducts occupy the portal spaces. Nerves, connective tissue, and lymphatic vessels are also present but are (again, for clarity) not shown in this illustration. In the lobule, note the radial disposition of the plates formed by hepatocytes; the sinusoidal capillaries separate the plates. The bile canaliculi can be seen between the hepatocytes. The sublobular (intercalated) veins drain blood from the lobules.Three-dimensional aspect of the normal liver. In the upper center is the central vein; in the lower center is the portal vein. Note the bile canaliculus (green thing), liver plates, Hering's canal, Kupffer cells, sinusoid, fat-storing cell, and sinusoid endothelial cells.Name each of the areas on these stainsThis is what happens to oxygen, extrahepatic hormones, key glycolysis enzymes, key glucose liberating enzymes, key fatty acid oxydation enzymes, and key fatty acid synthesizing enzymes in the peritubular cells and the centrolobular cellsMechanism of secretion of bile acids. About 90% of bile acids are derived from the intestinal epithelium and transported to the liver. The remaining 10% are synthesized in the liver by the conjugation of cholic acid with the amino acids glycine and taurine. This process occurs in the smooth endoplasmic reticulum (SER).•An extensive array of compound mucous glands, called Brunner's glands, is located in the first few centimeters of the duodenum. These glands secrete large amounts of alkaline mucous in response to:1) Tactile stimuli 2) Vagal stimuli 3) GI hormones, mostly secretionLocated over the entire surface of the small intestine are small pits called the _________. These lie between the intestinal villi, and contain _________, which secrete mucus, and _________, which secrete water an electrolytes.crypts of Leiberkuhn Goblet cells enterocytesBrunner's, or submucosal mucous glands, help protect the duodenal wall from the acidic contents of the stomach. These cells are only present in the _______.duodenum________, along with goblet cells, enterocytes, and enteroendocrine cells, represent the principal cell types of the epithelium of the small intestine.Paneth cellsPaneth cells are identified microscopically by their location ________________________ and the large eosinophilic refractile granules that occupy most of their cytoplasm.just below the intestinal stem cells in the intestinal glands (crypts of Lieberkühn)Paneth cell granules consist of several anti-microbial compounds and other compounds that are known to be important in immunity and host-defense. When exposed to bacteria or bacterial antigens, Paneth cells secrete some of these compounds into the lumen of the intestinal gland, thereby contributing to ____________.maintenance of the gastrointestinal barrierA crypt of Lieberkühn, found in all parts of the small intestine between the villi, which secretes almost pure ___________.extracellular fluid