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GASTROINTESTINAL TRACT PHYSIOLOGY (PHG 222) by ADEJARE, A. A. Department of Physiology Faculty of Basic Medical Sciences College of Medicine University of Lagos OUTLINE • • • • • • • General organization/functional anatomy of the GIT Review of smooth muscle function GIT motility GIT secretions and hormones Digestion and absorption of food substances Nutrition and metabolism GIT disorders Digestion Process whereby the body breaks down food into absorbable nutrients. To digest food, five different body organs secrete digestive juices: the salivary glands, the stomach, the small intestine, the liver (via the gallbladder), and the pancreas. These secretions enter the GI tract at various points along the way, bringing an abundance of water and a variety of enzymes. Mouth Teeth grind food to reduce the size. Saliva released to help moisten food. Digestion of carbohydrate begins in the mouth, where the salivary glands secrete saliva, which contains water, salts, and enzymes Tongue pushes food to the back of the mouth to start swallowing reflex. Food passes through the esophagus and enters stomach. The salivary enzyme amylase begins digestion. Mouth • Protein • Chewing and crushing moisten protein-rich foods and mix them with saliva to be swallowed • Fat The sublingual salivary gland in the base of the tongue secretes as salivary lipase. Some hard fats majorly neutral fats and cholesterol begin to melt as they reach body temperature. The enzymes in the mouth do not affect the fats, proteins, vitamins, minerals, and fiber that are present in the foods people eat. Stomach Distended pouch. SME Secretes hydrochloric acid: Begins protein digestion. Kills microorganisms in food. Block salivary amylase activity mucus that coats and protects the stomach’s lining. Initiates breakdown of proteins. Both pepsin and the stomach acid involved. Protein is converted to proteoses, peptones and polypeptides the attachment of a protein carrier to vitamin B12. Nutrients not absorbed except water and alcohol. Stomach • HCl uncoils protein strands and activates stomach enzymes Fat The acid-stable salivary/lingual lipase splits one bond of triglycerides to produce diglycerides and fatty acids. The stomach’s churning action mixes fat with water and acid. A gastric lipase accesses and hydrolyzes a very small amount of fat. Small Intestine Most digestion and absorption occurs in the small intestine. Bile released to emulsify fat. Pancreatic enzymes released to digest carbohydrates, proteins and fats. Final digestive enzymes in intestinal lining break down carbohydrates, proteins and fats into absorbable units. α dextrinase Small intestine Protein Then enzymes on the surface of the small intestinal cells hydrolyze these peptides and the cells absorb them. • Only a small percentage of the proteins are digested all the way to their constituent amino acids by the pancreatic juices. • The last digestive stage of the proteins is achieved by the enterocytes that line the villi of the small intestine • Aminopolypeptidase and dipeptidases present in the microvilli of the enterocytes split the remaining polypeptides into tripeptides and dipeptides and a few into amino acids. • Both the amino acids plus the dipeptides and tripeptides are easily transported through the microvillar membrane to the interior of the enterocyte. • Finally, the enterocytes contain peptidases that are specific for the remaining types of linkages between amino acids. • the last dipeptides and tripeptides are digested to form single amino acids; • these then pass on through to the other side of the enterocyte and thence into the blood. • More than 99 per cent of the final protein digestive products that are absorbed are individual amino acids, Fat • The first step in fat digestion is physically to break the fat globules into very small sizes so that the water-soluble digestive enzymes can act on the globule surfaces. This process is called emulsification of the fat. • The emulsification is caused by bile salts and lecithin: make the fat globules fragmentable fat Bile is secreted continuously by the liver and is concentrated and stored in the gallbladder. Bile is not an enzyme but an emulsifier that brings fats into suspension in water .After the fats are emulsified, enzymes can work on them. Pancreatic lipase flows in from the pancreas (via the pancreatic duct): • Apart from causing emulsification, bile salts also cause formation of micelles that help to accelerate fat digestion • The bile salt micelles act as a transport medium to carry the monoglycerides and free fatty acids, both of which would otherwise be relatively insoluble, to the brush borders of the intestinal epithelial cells. • There the monoglycerides and free fatty acids are absorbed into the blood • the bile salts themselves are released back into the chyme to be used again and again for this “ferrying” process. DIGESTION IN THE LARGE INTESTINE Undigested residues, such as some fibers, are not absorbed but continue through the digestive tract as a semisolid mass. Fiber also retains water, keeping the stools soft, and carries some bile acids, sterols, and fat out of the body. Overview of Digestion & Absorption (Cont.) Vitamin Water and Minerals Mouth and salivary glands No action. The salivary glands add water to disperse and carry food. Stomach Intrinsic factor attaches to vitamin B12. Stomach acid (HCl) acts on iron to reduce it, making it more absorbable. The stomach secretes enough watery fluid to turn a moist, chewed mass of solid food into liquid chyme. Small intestine Bile emulsifies fatsoluble vitamins and aids in their absorption with other fats. Water-soluble vitamins are absorbed. The small intestine, pancreas, and liver add enough fluid so that approximately 2 gallons are secreted into the intestine in a day. Many minerals are absorbed. Vitamin D aids in the absorption of calcium. Large intestine Bacteria produce vitamin K, which is absorbed. More minerals and most of the water are absorbed. Fibers Most fiber passes intact through the digestive tract to the large intestine. Here, bacterial enzymes digest some fiber: Fiber holds water; regulates bowel activity; and binds cholesterol and some minerals, carrying them out of the body as it is excreted with feces Final Digestion Products Final digestion products absorbed by cells lining small intestine. Carbohydrates: Monosaccharides Proteins: Amino acids Chains of 2 or 3 amino acids Fats: Fatty acids Glycerol Monoglycerides Vitamins, minerals, water and some larger fat-like compounds such as cholesterol are not broken down before they are absorbed. The Absorptive System Most absorption takes place in the small intestine. Small intestine’s inner surface looks smooth, but viewed through a microscope, it turns out to be wrinkled into hundreds of folds (folds of Kerckring). Each fold is covered with thousands of fingerlike projections called villi. A single villus, magnified still more, turns out to be composed of several hundred cells, each covered with microscopic hairs called microvilli. Thus, the combination of the folds of Kerckring, the villi, and the microvilli increases the total absorptive area of the mucosa perhaps 1000-fold. A villus has A vascular system: for nutrient and water absorption Central lacteal: for absorption into the lymph Pinocytic vesicles Microvilli or brush border The Villus Absorption in the small intestine Water: by osmosis from chyme to plasma Sodium ions: active transport of sodium from inside the epithelial cells through the basal and side walls of these cells into paracellular spaces and by facilitated diffusion from lumen to the inside of the epithelial cells. Sodium is lost in diarrhea. Enhanced by aldosterone Chloride ions: passively “dragged” by the positive electrical charges of the sodium ions. Bicarbonate ions absorption in the duodenum and jejunum: hydrogen ions are secreted in exchange for the reabsorbed sodium. The hydrogen ions combine with bicarbonate ions to form carbonic acid (H2CO3), which then dissociates to form water and carbon dioxide. The water remains as part of the chyme in the intestines, but the carbon dioxide is readily absorbed into the blood and subsequently expired through the lungs. Bicarbonate ions are however secreted in the ileum and large intestine by HCO3-Cl antiport system: this bicarbonate is to help neutralise the acid products formed by bacteria in the large intestine Calcium ions: by active absorption. Regulated by PTH and Vitamin D. Iron ions, potassium, magnesium, phosphate and others: also by active absorption Absorption of nutrients Carbohydrates: mainly glucose, galactose and fructose Co-transport with sodium through intestinal membrane. it is the initial active transport of sodium through the basolateral membranes that provides the eventual motive force for moving glucose also through the membranes. Fructose is transported by facilitated diffusion all the way through the intestinal epithelium but not coupled with sodium transport. Much of the fructose becomes phosphorylated, then converted to glucose, and finally transported in the form of glucose the rest of the way into the blood. Proteins: mainly as amino acids, mono and dipeptides Also co-transport with sodium or through membrane transport proteins Fats: mainly as free fatty acids and monoglycerrides dissolved in bile micelles in chyme The micelles help to ferry them into the epithelial cells After entering the epithelial cell, the fatty acids and monoglycerides are taken up by the cell’s smooth ER where they are mainly used to form new triglycerides that are subsequently released in the form of chylomicrons through the base of the epithelial cell, to flow upward through the thoracic lymph duct and empty into the circulating blood. TRANSPORT OF LIPIDS: LIPOPROTEINS Within the circulatory system, lipids always travel from place to place bundled with protein, as lipoproteins. VLDL, LDL, HDL, and chylomicrons transport newly absorbed lipids from the intestinal cells to the rest of the body. The liver can assemble different lipoproteins, which are known as VLDL. As the body’s cells remove triglycerides from the VLDL, the proportions of their lipid and protein contents shift. As this occurs, VLDL become cholesterolrich LDL. Cholesterol returning to the liver for metabolism or excretion from other parts of the body is packaged in lipoproteins known as HDL. Indigestible Matter After digestion and absorption of nutrients, indigestible matter, such as fiber moves into the large intestine. Indigestible matter is compacted by removing water. Little nutrient absorption occurs in large intestine. Absorption in the large intestine • Sodium ions: by active transport • Chloride ions: by co transport with sodium • Bicarbonate ions: are secreted by counter transport with chloride ions • Water: osmosis Metabolism Chemical reactions that occur in the body: Building and maintaining body tissues Regulating body functions Supplying energy For metabolism to occur the body needs: Water Energy Oxygen Nutrients NUTRITION A proper diet requires a balance of carbohydrates, fats, and proteins. In addition the body requires many phytochemicals, vitamins, minerals, enzymes, and water. Food Intake Food energy measured in Calories Carbohydrates obtained primarily through plants Monosaccharides used for cellular fuel Minimum carbohydrates = 100 g/day Lipids < 30% of calories Mostly triglycerides Saturated fats usually from animals Cholesterol only from animals Neutral fats provide insulation and energy reserves Phospholipids for membranes and myelin Cholesterol for membranes, vitamin D, steroid hormones, and bile salts Proteins = 0.8 g/kg of body wt 8 Essential amino acids Plants usually lack 1 or more essential amino acids / Animal protein usually contains all Amino acids used to build structural proteins and enzymes VITAMINS: "vita" = Latin word for life. Vitamins are organic substances that act as coenzymes, chemicals that assist the enzymes in the bodies reactions. They do not provide energy or calories. Vitamins may be either Fat Soluble or Water Soluble. Fat soluble vitamins are stored in the body's fatty tissues. Fat soluble vitamins include the vitamins A D E K. Vitamin A Found in fish, liver, eggs, butter, yellow & green vegetables, fruits Needed for healthy skin, eyes, bones, teeth. Deficiency causes night blindness, skin disorders, kidney stones Vitamin D Found in liver, fish, eggs, milk, sunlight Needed for growth, healthy bones, metabolism of calcium & phosphorus Deficiency causes rickets, poor teeth and bones. Vitamin E Found in whole grains, leafy vegetables, milk, butter, vegetable oils Needed for healthy cell membranes, red blood cells Deficiency causes red cell rupture, muscle disorders Vitamin K Found in leafy vegetables, soybeans, made by intestinal bacteria Needed for normal blood clotting Deficiency causes slow clotting, hemorrhaging. Water soluble vitamins can be dissolved in water but cannot be stored in the tissues. They must be obtained each day from food. Water soluble vitamins include B1 (Thiamine) B2 (Riboflavin) Niacin B6 (Pyridoxine) Pantothenic Acid Biotin B12 Folic Acid C (Ascorbic acid) Vitamin B1 (Thiamine) Found in organ meats, whole grains, vegetables Needed for proper functioning of heart, nervous system, digestion Deficiency causes beriberi, cardiovascular disorders. Vitamin B2 (Riboflavin) Found in liver, poultry, milk, eggs, cheese, fish, green vegetables, whole grain Needed for metabolism of protein, carbohydrates, and fats, healthy skin Used to make FAD for metabolism Deficiency causes dim vision, premature aging, sore mouth Vitamin B6 (Pyridoxine) Found in meats, liver, whole grains, vegetables Needed for sodium and phosphorus balance Deficiency causes anemia, nausea, loss of appetite, nervousness Vitamin B12 Found in Liver, meats, eggs, cheese, dairy products Needed for red cell production, healthy nervous system. Deficiency causes pernicious anemia. Vitamin C Found in citrus and other fruits, leafy vegetables, tomatoes, potatoes Needed for healthy blood vessels, resistance to infection, healing Deficiency causes scurvy, bruising, bleeding gums Niacin Found in red meats, organ meats, fish, green vegetables Needed for metabolism, digestion, nerves, skin Used to make NAD for metabolism Deficiency causes pellagra, sore mouth, diarrhea, depression Folic Acid Found in green vegetables, liver, whole grains, legumes Needed for manufacture of proteins and red blood cells, needed for cell division, helps prevent spina bifida Deficiency causes inflamed tongue, diarrhea, B12 deficiency. MINERALS: Inorganic substances that are used in the chemical reactions of the body. Major minerals needed include: Calcium, Iodine, Iron, Magnesium, Phosphorus, Potassium, and Sodium. Calcium Found in milk, cheese, vegetables Needed for strong bones and teeth, blood clotting Iodine Found in seafoods, iodized salt Needed for normal thyroid metabolism, prevents goiter Iron Found in liver, meat, eggs Needed for red cell production, prevents anemia Magnesium Found in milk, meat, whole grains, legumes Needed for proper nerve and muscle functioning Phosphorus Found in milk, whole grains, meats, nuts, legumes Needed for tooth and bone development, ATP, nucleic acids Potassium Found in whole grains, fruits, legumes, meat Needed for proper nerve and muscle function Sodium Found in seafood, table salt Needed for water balance, proper nerve and muscle function Free Radicals charged molecules that become oxidized by combining with oxygen or the removal of hydrogen, causing electron deficiency. seek to regain the electron by removing it from other molecules, thus oxidizing them. set up a chain reaction that may damage cell structures such as DNA, cell membranes, or needed enzymes. Free radicals may be produced by normal metabolic processes, the immune system in response to disease, exposure to chemicals, toxins, or radiation. Free radical generation may be increased by exercise and stress. Damage caused by free radical generation is a major cause of the degenerative effects of aging, may cause cancers, damage to arterial walls leading to heart disease and/or stroke, and lead to other degenerative diseases such as Alzheimer’s. Antioxidants have a protective effect by neutralizing free radicals. best known antioxidants are Vitamin C, Vitamin E, and beta carotene. many others and possibly many yet to be discovered. proper number, types, and balance of is an important part of nutrition. METABOLISM Sum of all the chemical reactions occurring within the body Types of Metabolic Reactions Anabolic reactions - energy requiring synthesis reactions Catabolic reactions - energy releasing reactions that generate ATP Enzymes - globular proteins that act as catalysts Increase reaction rates Holoenzyme - a two-part enzyme consisting of a protein part and an organic cofactor Apoenzyme - the protein portion Coenzyme - the organic cofactor; usually a vitamin Energy Production Oxidation reactions - loss of an electron by an atom or molecule Reduction reactions - involves the gain of electrons by a molecule Coupled redox reactions Cellular Respiration Oxidation of Glucose Glucose Metabolism Glycolysis Acetyl Coenzyme A Krebs Cycle Electron Transport Chain Glycolysis Glucose molecules are broken down into two molecules of pyruvic acid in the cytoplasm of the cell Net gain of 2 molecules of ATP No oxygen required Fate of pyruvic acid depends on the oxygen availability Glycolysis Glucose C6H12O6 Glucose-6-phosphate ATP Fructose-6-phosphate ADP Fructose 1,6, diphosphate Glyceraldehyde-3-Phosphate or Dihydroxyacetone Phosphate 2Pyruvate (pyruvic acid) + 2NAD 2C3H4O3 + 2NADH+ ATP ADP + 4ATP + 2ATP (net) Acetyl CoA Formation Pyruvic acid is decarboxylated by the removal of CO2 into a two carbon acetyl group Occurs in the mitochondria of the cell Krebs Cycle - TCA Cycle Formation of citric acid when oxaloacetic acid combines with acetyl CoA Organic molecules are broken down, carbon dioxide is released and hydrogen atoms are removed & transferred by coenzymes NAD & FAD Kreb’s Cycle Acetyl CoA + Oxalocetic Acid Citric Acid Isocitric Acid CO2 NADH2 alpha-Ketoglutaric Acid CO2 NADH2 Succinyl CoA ATP Succinnic Acid FADH2 Fumaric Acid Malic Acid NADH2 Electron Transport Involves electron carrier molecules that will release energy in a controlled way This energy is used to generate ATP Occurs inner mitochondrial membrane Chemiosmosis Glucose Anabolism Glycogenesis - conversion of glucose to glycogen; stimulated by insulin Glycogenolysis - hydrolysis of glycogen to form glucose; stimulated by glucagon Gluconeogenesis - synthesis of glucose from non-carbohydrates such as fats and amino acids Lipid Metabolism Lipid Catabolism - Lipolysis Hydrolysis of triglycerides into glycerol and fatty acids Glycerol converted to G 3-P and then into pyruvic acid, then into the Kreb’s cycle Beta -oxidation of fatty acids occurs forming two-carbon fragments which is then attached to coenzyme A, forming acetyl CoA Protein Metabolism Proteins are converted into substances than can enter the Kreb’s cycle by deamination - loss of (NH2) from amino group decarboxylation - loss of CO2 molecule dehydrogenation - loss of hydrogen atom Protein synthesis involves transcription and translation The Central Pathway of Energy Metabolism Basal Metabolic Rate What Is Your BMR? • Your BMR measures the minimum calorie requirement your body needs to stay alive in a resting state • It is the amount of calories your body would need if you were to stay in bed all day How Many Calories Is This? • About 70% of your calorie intake is responsible for just supplying your BMR • You need calories to: – Pump your heart – Breathe – Control your body temperature – Any many other things Do We All Have The Same BMR? • We all have different BMR and there are many things that will affect what that rate is • Your BMR is the largest factor in determining your overall metabolic rate (how your body burns calories) Genetics • Some people are born with slower metabolisms than others • Some people are born with faster metabolisms than others Gender • Men have a greater muscle mass and a lower body fat percentage (10-15% higher BMR than womem) • The higher your muscle mass, the higher your metabolism Age • Your BMR will reduce as you age • After 20 years of age, your BMR drops about 2% every year Weight • The more you weigh, the higher your BMR • The BMR of an obese woman is 25% higher than a woman of an appropriate weight Body Surface Area • The greater your body surface area, the higher your BMR • Tall, thin people have higher BMRs Body Fat Percentage • The lower your body fat percentage, the higher your BMR Diet • If you reduce your calorie intake suddenly, your BMR can drop by 30% • Your body wants to ensure that it always has the calories it needs to survive, so cutting calories quickly will switch your body into a “survival” mode Body Temperature • For every 1 degree increase in your body temperature, your BMR increases by approximately 14% • Chemical reactions occur faster in your body at higher temperatures • You burn a lot more calories while you are sick or have fever External Temperature • Exposure to cold temperatures will increase your BMR • Prolonged exposure to heat will also increase your BMR Glands • Your thyroid gland (butterfly-shaped gland in your neck) is responsible for making thyroxin • The more thyroxin produced, the higher your BMR Exercise • Exercise helps to build lean muscle tissue • The more lean muscle tissue, the higher your BMR • This means you will burn more calories – even when you are sleeping! 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