Lecture 24 ? Gastrointestinal System Semi-Quantitative Analysis Of Amounts Of Substances Ingested, Secreted, Absorbed And Excreted Per Day In Human Adult (Slide 1) 1. The gut is responsible for absorbing a large amount of substances in one day. 2. We ingest a volume of 2 liters, or a mass of 2 kg, of total substance in one day. Most of that is liquid. 3. You consume water in three forms: directly (Poland Spring), indirectly (coffee or tea) and intrinsically (water from naturally produced foods). 4. They all have to be absorbed into the GI. Most of this water comes from the bloodstream (it is recirculated). Physiology Of The Stomach?s Various Functions (Slide 2) 1. The stomach is the greatest producer of water in a 24 hour period. The salivary glands during the absorptive state are the first glands that secrete a significant amount of water. 2. The aqueous medium contains electrolytes (Na+, K+, Cl- HCO3-) and proteins (enzymes). 3. An important enzyme is salivary amylase. It is secreted by the salivary glands and is used to break down sugars in the mouth. It is the first enzyme that comes in contact with food. 4. The stomach is divided into several regions depending on what the mucosa in the stomach does. a. The gastric pits, or glands, contains mucosa with several different cell types. They run from the surface down the neck to the base of the pit. Somewhere in the neck there are stem cells. They are pleuripotent, which means they can reproduce the other cells. b. At the surface, you have mucosal epithelial cells. They produce a gelatinous mucous that eventually coats the pit and lining of the stomach. c. There are also chief cells, which secrete pepsinogen in response to proteins. Parietal cells secrete HCl in response to everything in the diet. Selected Secretory Products Of Gastric Pits Of Stomach (Slide 3) 1. Pepsinogen is secreted by chief cells. a. Precursor for pepsin, enzyme that digests proteins. 2. Hydrogen ions secreted by parietal cells. a. maintain acidic environment of stomach 3. Intrinsic factor secreted by parietal cells. a. Necessary for absorption of vitamin B12 4. Gastrin secreted from G cells (hormone). 5. Mucus secreted from neck cells. Diffusion Barrier In Gastric Mucosa (Slide 4) 1. Mucosal neck cells (yellow) produce a mucosa layer that is quite thick. a. When bicarbonate is released by the neck cells after it has been cotransported into the cells with Na+, the bicarbonate is trapped in the gel. It cannot escape into the lumen. The rich gelatinous material behaves as a barrier against the acid. 2. The pH ranges from very acidic in the lumen (1-2) to fairly neutral in the mucosal neck cells. a. The mucus layer prevents H+ ions from getting into the interstitial space or blood. Tight junctions prevent that from happening. There is a 1,000,000-fold difference in H+ concentration between the lumen of the gut and the lumen of blood vessels. 3. If the epithelium fails to produce or has a disrupted gelatinous coat, the acid can cause peptic/gastric ulcers, bleeding in the stomach or GI tract. It can also activate cells called mast cells. Mast cells have secretory granules containing many things, the most important being histamine. It can do many things to blood vessels: increase their permeability and also constrict them. So blood flow can become ischemic (inadequate blood supply), and the lack of O2 delivery is damaging to the area. 4. So there is a gradient between the lumen of the stomach and the interstitial spaces for H+ concentration. What separates the two spaces are tight junctions between mucosa epithelial cells. Also, secretory cells lay down a mucosal gelatinous material. Finally, there is a diffusion gradient of H+ and HCO3-. When the barrier is gone, all cells in the gastric pit are affected by the acidosis. Histamine causes parietal cells to produce more acid, which complicates the matter. Breakdown Of Gastric Mucosal Barrier (Slide 5) 1. Integrity of barrier judged by transepithelial potential (-60 mV). 2. Agents that alter diffusion barrier: aspirin, alcohol, bile acids, coffee, wine 3. Allow acid to damage mast cells which release: histamine, PAF, platelet-activating factor, leukotrienes, endothelins, thromboxanes, oxidants (collectively cause inflammation, ischemia, tissue damage) 4. Acid reflux and diseases of the esophageal mucosa a. Acid reflux can affect everything from the stomach to the mouth. b. The rate of cancer of these tissues is on the rise, partly due to increased acid reflux. 5. Helicobacter pylori: gram negative bacillus colonizing entral mucosa; causes gastritis and peptic ulcer 6. Prostaglandins are protective to the mucosa barrier. Control Of The Secretion Of Gastric Acid (Slide 6) 1. The distension of the stomach by food: a. Activates enteric nervous system (small brain or little brain) and reflexes within it. The enteric nervous system is a group of nerves that are confined to the walls of the GI tract and are important in all factors of GI function. The system interacts with the autonomic and somatic nervous systems as well as circulating factors in the blood. b. This releases acetylcholine and GRP. These act on G cells, whose primary function is to release stored gastrin. This stimulates parietal cells to release acid. c. The gastrin also stimulates ECL cells to release histamine. This histamine acts on parietal cells to release acid as well. 2. You have a positive feedback system. The acid enhances protein digestion by activating some of the enzymes important with digesting. They also stimulate G cells, which augments acid release. Movement Of Newly-Synthesized Proteins Through The Secretory Pathway (Slide 7) 1. The investigator radiolabels cells; he administers an amino acid that has 3H or 14C. He can follow this atom and find out the rate of protein synthesis. 2. At time 0, 100% are found in the rough ER. 3. At 10 minutes, if you sample other organelles as well as the ER, we find that less than 50% of the radiolabel is in the ER. Almost 50% is in the Golgi vesicles. By 30 minutes, most of it has left the ER. 4. It takes less than two hours for new proteins to be synthesized and readied to release from the GI tract. Summary Secretions (Slide 8) 1. All GI tissues are secretory. 2. Secretions moisten, lubricate, digest, release and transport. 3. Excess secretions (H+ and ulcers) 4. H. Pylori, stomach, esophageal erosion and Barrett?s syndrome (cancer of the upper esophageal Region, i.e. larynx, pharynx) Summary (Slide 9) 1. Gastric acid is important to protein digestion. 2. Several mechanisms are involved in acid secretion. 3. Pernicious anemia (lack parietal cells, high plasma gastrin but no H+ secretion)
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