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2-10-10 Digestion Absorption-SI LI pancreas liver color

2-10-10 Digestion Absorption-SI LI pancreas liver color -...

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Unformatted text preview: Clicker Question Barry Marshall drank a beaker full of Helicobacter Helicobacter pylori because he wanted to fulfill Koch’s postulates and he did not have an animal model for ________. Where Where are We? • Last time I discussed: – The role of the mouth and stomach in the chemical and mechanical process of digestion. – That digestion is regulated by the nervous system (e.g. conditioned reflexes) and the endocrine system (e.g. the fight or flight response). – How Warren and Marshall discovered the microbial How cause 75cause of 75-80% of ulcers. – Stress ulcers—the other 20%. ulcers— A) scurvy B) ulcers C) pellagra D) beriberi E) stress • This time I will discuss: – The role of the small and large intestines, the pancreas, the liver and the gall bladder in digestion and absorption. absorption. – Intestinal gas Various Views of th Dig the Di estive Tract Food Museum 1 The Digestive Canal as a Chemical Factory canal…may be compared to a chemical factory, where the raw materials materials—the foodstuffs—are foodstuffs are submitted submitted to an essentially chemical process. In this factory, the foods are brought into a condition in which they are capable of being absorbed into the body fluids and made use of for the maintenance of the processes of life.” According to Ivan Pavlov Ivan (1910), “The digestive The Digestive Canal as a Chemical Factory “The factory consists of a series of compartments, in each of which the food, according to its properties, is either retained for a time or at once sent on to the next; and each single compartment is provided with suitable reagents. These reagents are either prepared in adjoining little workshops, burrowed into the walls of the laboratory itself, or else in distant and separate organs, connected, as in other large chemical factories, with the main workshop by a system of transmitting tubes. These latter are the so-called secreting glands with their soexcretory ducts.” 2 Food Processing in the Body Ingestion: The consumption of food (eating and drinking), which takes place in the mouth. Digestion: The mechanical and chemical breakdown of food by the chemical breakdown of food by the mouth, mouth, stomach and small intestine to a form that can be absorbed. Absorption: The uptake of nutrients across the mucosa of the small intestine into the blood or lymph. Elimination: The storage and removal of undigested food through the large intestine, rectum and anus. Digestion of Foodstuffs: Carbohydrates, Proteins and Lipids • We begin to digest starch and starch convert it into maltose in the maltose mouth and digest protein and protein convert it into protein fragments protein in the stomach. These components of food, along with the lipids, th li continue being digested in the small intestine. The The view of the duodenum (the first 12 finger widths in length of the small intestine) seen by a nutrient as it leaves the stomach. • The small intestine is the major organ of digestion and absorption. In the small intestine, chyme the food changes from chyme to chyle chyle, which is an opaque white substance that resembles cream. Neutralization of Stomach Acids • The liquidy chyme, discharged from the stomach to the small intestine, has a pH of approximately 2. It is very very acid (sour) and as sour as a lemon. Neutralization of Stomach Acids CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3HCO Do you know what becomes of the Do you know what becomes of the CO produced CO2 produced in the small intestine? Hint: At body temperature CO2 is a gas. Don’t you wish that our intestines could fix carbon like green plant cells can? • Glands that line the duodenum, secrete bicarbonate ions, which bicarbonate combine with the acid (H+) coming from the stomach in order to partially neutralize it by producing neutralize it CO2 and H2O according to the following reaction: 3 The Mucosa of the Small Intestine is Deeply Folded to Increase the Surface Area Necessary for Secretion and Absorption Infoldings Along Different Regions of the Digestive Tract http://www.vivo.colostate.edu/hbooks/pathphys/digestion/basics/gi_microanatomy.html The Duodenum Secretes Enzymes that Break Down Disaccharides into Monosaccharides • Lactase breaks down milk breaks sugar (the disaccharide lactose lactose) into the monosaccharides, monosaccharides, glucose and galactose and galactose. The Duodenum Secretes Enzymes that Break Down Disaccharides into Monosaccharides • Invertase breaks down table sugar (the disaccharide sucrose into disaccharide sucrose) into the the monosaccharides glucose and fructose. • There is individual individual • variation in our ability to make this enzyme (e.g. lactoselactose-intolerant people). people). LactoseLactose-intolerant people can get lactase by ingesting Lactobacillus Lactobacillus acidophilus. • There is individual individual variation in our ability to make this enzyme. The Duodenum Secretes Enzymes that Break Down Disaccharides into Monosaccharides • Maltase breaks down beer sugar (the disaccharide maltose disaccharide maltose) into into the monosaccharide glucose. glucose. The Duodenal Juice Alone Cannot Digest Proteins Evidence: If a sample of protein is treated with purified duodenal juice from the small intestine from the small intestine, it is not digested. Dr. William Beaumont and Alexis St. Martin found that pancreatic juices are important for digestion. • There is individual individual variation in our ability in to make this enzyme. 4 Dr. William Beaumont and Alexis St. Martin Discovered that Secretions from the Pancreas and Liver are also Necessary for Digestion The Breakdown of Foodstuffs in the Small Intestine Requires Enzymes Produced by the Pancreas • Starch breakdown requires amylase. amylase – Produces maltose (and then glucose) Produces maltose (and then glucose) “Pancreatic juice [from an ox], combined [from with the chyme of roast beef, formed both in and out of the stomach increased its in and out of the stomach, increased its thin, pastethin, paste-like consistence, and gave it more of a cream color. Bile [from the [from liver], added to this, produced fine added coagulae, coagulae, suspended from the top to the bottom, without depositing any distinct sediment.” • Protein breakdown requires proteases. proteases – Produces amino acids • Lipid breakdown requires lipases. lipases – Produces fatty acids and glycerol Figure 21.2B Chemical digestion: the breakdown of polymers to monomers Polymer Proteindigesting enzymes Protein Amino acids Monomers Pancreatic Enzymes and Pre-Digested PreProtein Supplements Polysaccharide Carbohydratedigesting enzymes Monosaccharides Disaccharide Nucleic aciddigesting enzymes Nucleic acid Nucleotides Fat-digesting enzymes Fat Glycerol Fatty acids Nature Nature goes to great lengths to make sure proteases do not run wild and digest the body • Protein treated with purified juice from either either • • the the small intestine or the pancreas is not digested digested. However, the protein is digested by a mixture of mixture of duodenal juice and pancreatic juice. Ivan Pavlov discovered that the duodenum produces an enzyme he named enterokinase enterokinase that converts trypsinogen (an inactive trypsinogen protease), secreted by the pancreas, to trypsin trypsin (an active protease). Enzymes Secreted by the Pancreas The pancreas is an exocrine gland that secretes exocrine many enzymes into a duct that empties into the duct duodenum region of the small intestine. 5 Enzymes Secreted in an Alkaline Solution of Sodium Bicarbonate • The enzymes, including amylase lipase amylase, lipase and trypsinogen trypsinogen are secreted in a solution of sodium bicarbonate solution of sodium bicarbonate that supplements the bicarbonate secreted by the duodenum itself. The bicarbonate neutralizes neutralizes the acids in the small intestine that come from the stomach. Hydrolysis of Foodstuffs • The digestive enzymes split the large food molecules • • into their component parts by introducing water water molecules into the large molecules. Since the enzymes introduce water to split the molecule, we say that the enzyme “hydrolyzes” the foodstuff and that these digestive enzymes are hydrolytic hydrolytic enzymes. Biodegradation and Biosynthetic Reactions in an Aqueous Environment • Adding water to a molecule in an aqueous environment in the course of biodegradation biodegradation reactions is easy and usually releases energy. The reaction is exergonic: the reactants reaction is exergonic: the reactants have have more energy than the products. Removing water from a molecule in an aqueous environment in the course of biosynthetic reactions is difficult biosynthetic reactions and usually requires an input of energy from ATP. Such a reaction is endergonic: endergonic: the products have more energy than the reactants. Exergonic Reactions Release Energy Endergonic Reactions Require Energy • Intracellular Secretory Pathway • Cells are composed of a multitude of membranous motifs, including the ER, the Golgi apparatus, the vacuole and the plasma membrane. The relationships between the various membranes were revealed to a large extent by studying the secretory secretory process in Intracellular Secretory Pathway within the cell that the secretion of the fluid peculiar to each organ is effected….The cell is the secreting organ par excellence It is the secreting organ par excellence. It secretes, secretes, inside itself, substances which are, in some cases, destined to be transported to the outside of the body by way of the excretory ducts, and, in other cases, destined to remain within the cell which has produced them….” Henri Dutrochet (1824) postulated that “it is “it • pancreatic pancreatic exocrine cells. 6 Intracellular Secretory Pathway • Dutrochet was right, but he was ahead of his time. Intracellular Intracellular Secretory Pathway • Heidenhain correlated the disappearance of the disappearance appearance apical granules with the appearance of digestive enzymes in the pancreatic juices that he he measured biochemically. • In the eighteen seventies and eighties, Rudolf Heidenhain Heidenhain studied the secretory cells of the pancreas (as well as those of the stomach). He noticed that shortly after an animal ate, microscopic granules disappeared from the apical part of the pancreatic cells, and reappeared a few hours later. • He concluded that the granules, which he dubbed zymogen zymogen granules, contained the precursors of the digestive enzymes. The zymogen granules, he supposed, represented an available store of digestive enzymes that could be released upon eating. A Century-Long Collaboration Century• Limited by technology, Heidenhain was unable to • intracellular elucidate the intracellular pathways involved in secretion. Impressed with Heidenhain’s work, George Palade Palade (1959) (1959) set out to understand the intracellular part of the the secretory process using the newly developed technique of electron microscopy. electron Palade considered these studies to be “a collaboration over “a almost a century between Rudolf Heidenhain…and myself.” The Rough Endoplasmic Reticulum • The Golgi Apparatus Intracellular Secretory Pathway •Palade put thin slices of pancreatic tissue in 3Hleucine, an amino acid, and then used autoradiography autoradiography to follow the pathway of the newly synthesized proteins. •The digestive enzymes were synthesized on the The digestive enzymes were synthesized on the rough rough endoplasmic reticulum at the basal region of the cell. •Then they traveled through the Golgi Golgi apparatus. •After approximately 1 h, they were in the zymogen zymogen vesicles at the apical end of the cell. at 7 Intracellular Secretory Pathway Then the pancreatic enzymes are secreted into the small intestine though a duct Nervous Communication? • Ivan Pavlov could stimulate the secretion of pancreatic juices if he treated the duodenum with acid (that mimicked the arrival of mimicked the arrival of chyme chyme from the stomach). Another Another Form of Communication? • William Bayliss and Ernest Starling Ernest saw that they could get the same effect even after they severed all the nerves that would communicate between the small would communicate between the small intestine intestine and the pancreas. They guessed that there must be another another between the small intestine and the pancreas. Perhaps it was through the blood stream. • He guessed that there was • an internal reflex reaction that took place through the nervous system. But… and novel form of communication 8 Postulating a Chemical Messenger • Since acid injected into the blood would not stimulate pancreatic secretion, Bayliss and Starling guessed that the acid caused the mucosa of the small intestine to mucosa produce chemical produce a chemical that traveled traveled through the blood stream and caused blood the pancreas to secrete pancreatic juice into the small intestine. They at once did an experiment that confirmed their hypothesis. The Experiment: Live Dissection • They isolated the mucus membrane from the small intestine of a dog and treated the membrane with acid. They neutralized the extract and They neutralized the extract and injected injected it into a vein in the dog. Almost instantly, the pancreas started secreting pancreatic juices. The extract from the small intestine was specific since extracts from other organs were unable to cause the pancreas to secrete. • • • • Secretin: The First Hormone • They called the chemical that • They postulated that there They postulated that there is is a class of molecules that chemical would act as chemical messengers between causes the pancreas to secretin secrete, secretin. Endocrine Endocrine vs. Exocrine • Endocrine glands • • • secrete chemicals into the blood stream. Exocrine glands secrete chemicals into ducts. The small intestine contains both endocrine contains both endocrine glands glands and exocrine glands. The pancreas also contains endocrine and exocrine glands. It secretes insulin directly into the blood stream and digestive enzymes into ducts. different parts of the body and proposed that they be called hormones hormones, from the Greek meaning “I set in motion.” William Bayliss and Ernest Starling Bayliss Giving a Lecture 9 The Little Brown Dog Animal Rights Some people feel that animals do not have the right to informed consent and that animal experimentation is justified to relieve the suffering of humans. There are others who feel strongly that animals have the same rights as humans and all animal experimentation is unjust. Perhaps, with the setting of priorities, there is a middle road. http://www.peta.org/ Balancing the Costs and Benefits of Animal Use antivivisectionists are the second of the two types Theodore Roosevelt described when he said, ‘Common sense without conscience may lead to crime, but conscience without common sense may lead to folly, which is the handmaiden of crime.’” According to Walter B. Cannon (1892), “The Which Characteristic Would You Choose to Decide Who Assumes the Risk in Medical Experiments? • Species-based? Species• Religion-based? • Race-based? Race– Experiments on dogs, cats, mice, rats, guinea pigs, chimps – Experiments in Nazi Germany – Tuskegee Syphilis Experiment – Birth control pill trials in Puerto Rico – Use of embryonic stem cells • Economic-based? Economic- • Developmental-based? Developmental- Judgment at Nuremberg: “…the charge is that of conscious participation...” Spencer Tracy: Judgment at Nuremberg http://www.ushmm.org/museum/ http://ohsr.od.nih.gov/guidelines/nuremberg.html 10 “Thom Gunn has written powerfully of the ‘occasions’ of poetry. Science has its occasions no less than art: sometimes a dream-metaphor, like Kekule’s snakes; sometimes an analogy, like Newton’s apple; sometimes a literal event, the thing-in-itself, which suddenly explodes into hi unimagined significance, like Archimedes’s “Eureka!” in his bath. Every such occasion is a eureka or epiphany. The occasions of medicine are provided by sickness, injury, patients.” Reverence for Life Studying Studying the biological basis of life and health, like eating, requires some sadness, risk of life and even killing. Scientific Scientific progress requires that there must be some sacrifice. sacrifice I described to you the heroic deeds of Joseph described heroic Goldberger (pellagra) and Barry Marshall (ulcers). Who Who or what, in which way and how many are sacrificed is an important bioethical question. bioethical I believe that every sacrifice that is made or believe done to understand the biological basis of life and health can and should be done or made with a reverence for life. reverence Fat Digestion Requires that the Fats Be Emulsified • The lipases themselves that are secreted lipases by the pancreas are not able to digest the waterwater-insoluble fats that enter the small intestine intestine. These fats must be emulsified. That is, emulsified. they must be broken into little pieces that are small enough to remain suspended in solution so that they can be hydrolyzed by the water-soluble lipases. waterEmulsify = homogenize homogenize Homogenization Homogenization (an aside) • Milk is homogenized so that the fat does homogenized • During homogenization, fat is ground into not separate from the aqueous liquid. such small particles, that gravity is not gravity is strong enough to cause the fat to rise to the top. This is because the surface to volume ratio of the small particles is so large, that the fat droplets stick to the protein and water molecules due to electrostatic forces. electrostatic When the particles are small enough, the electrostatic electrostatic forces are much greater gravitational than the gravitational forces. • • • • Homogenization of Milk The Liver Produces Bile • The liver produces a yellowish green bile bile from cholesterol and bilirubin, a cholesterol bilirubin, pigment which is produced from hemoglobin hemoglobin that has been reclaimed from damaged red blood cells. The bile is transported to the gall gall bladde bladder where it is stored before it enters the duct going to the small intestine. Secretin stimulates the secretion of bile from the liver to the gall bladder. Gallstones form when there is either too much cholesterol or too much bilirubin, bilirubin, or when there is not enough salt and water to keep the bile fluid. The gallstones block the normal flow of bile. • • • 11 Yellow Bile, The Humor Once Thought to be Responsible for Aggression • In antiquity, health and temperament were thought to be based on the balance of four four humor humors. Emulsification of Lipids Once the bile reaches the small intestine, it binds to the fat droplets and emulsifies emulsifies them lipases so that the lipases secreted by the pancreas can hydrolyze them. • Too much yellow bile yellow was was associated with a choleric or bilious personality with too much anger, aggression and “gall”. alli (Xenical) Binds to Lipase and Inhibits its Ability to Break down Fats Users lose weight because the fats pass straight though the small intestine The small intestine. The passage passage of so many fats through the small intestine result in “treatment effects” resulting from bacteria in the large intestine metabolizing the lipids. xenical myalli.com Isozymes are Variants in the Amino Acid Sequence of Enzymes • The hydrolytic enzymes produced by the small small pancreas intestine and pancreas and the bile produced by the liver result in the degradation of: liver result – carbohydrates into monosaccharides monosacc – lipids into fatty acids and glycerol fatty glycerol – and proteins into amino acids amino The digestive enzymes (isozymes) released may depend on environment (e.g. diet) and similar heredity (e.g. alleles) and are similar and unique in individuals. • Absorption of Nutrients • In the small intestine, the small molecules mucosa are taken up by the cells of the mucosa. surface The surface area of the mucosa is enormous ...
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