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GI Physiology Part 1: Metabolic Pathways Part 2: GI Physiology Part 3: GI Disorders 1 • For the quiz on Tuesday, there will be 5 questions from the Digestive anatomy flashcards and 5 questions from GI Physio flashcards. • For the physio, one question is about the definition of all those words that start with a "G" that people get mixed up, like glucagon, glycogen, glycolysis, glycogenolysis, gluconeogenesis. The other 4 questions are from the one-page table that lists all the digestive organs, what substances they secrete, and what those substances do. • All ten questions are multiple choice. 2 Simple and Complex Carbohydrates There are three main simple sugars (AKA monosaccharides or simple carbohydrates) Glucose Fructose (fruit sugar) Galactose If you join a glucose to any of these, you get a disaccharide Glucose + Glucose = Maltose (malt sugar) Glucose + Fructose = Sucrose (table sugar) Glucose + Galactose = Lactose (milk sugar) 3 Simple and Complex Carbohydrates If you join many monosaccharides and/or disaccharides together, it is called a polysaccharide (AKA complex carbohydrate). These are stored in the liver as glycogen. They can be broken down later into glucose as needed. The storage form of glucose in plants is called starch. When we eat starch, we convert it to glycogen and store it, or break it down to glucose to use it. 4 Glucagon and Insulin Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. So the Islets of Langerhans make two antagonistic hormones. The pancreas releases glucagon when blood sugar (glucose) levels fall too low. Glucagon (My glucose is gone!) causes the liver to beak down the stored glycogen into glucose, which is released into the bloodstream. Since glycogen is being broken down, this process is called glycogenolysis. Don’t confuse this with glycolysis (break down of glucose to ATP)! Glycogen Glucose ATP (glycogenolysis) (glycolysis) 5 Hormone = glucagon Glucagon and Insulin High blood glucose levels stimulate the release of insulin. Insulin allows glucose to be taken up and used by insulindependent tissues. Thus, glucagon and insulin are part of a feedback system that keeps blood glucose levels stable. 6 Glycolysis Glycolysis is the process where cells take in glucose and break it down into pyruvate, and ATP is released. This is how we get ATP from glucose. Fructose and galactose can also be broken down into pyruvate and ATP. During glycolysis, NAD (an energy molecule) is reduced to NADH. If you run out of NAD, glycolysis will stop. Therefore, we need to oxidize NADH to convert it back into NAD. This can be done by aerobic or anaerobic respiration, or fermentation. 7 Glycolysis Notice that 2 ATP molecules are used during glycolysis, but 4 are made (2 pyruvate molecules are made, each of which generates 2 ATP). There is a net gain of 2 ATP molecules. 8 After Glycolysis Immediately upon finishing glycolysis, the cell must get rid of the H+ on NADH by either an aerobic or anaerobic respiration. A cell that can perform aerobic respiration and which finds itself in the presence of oxygen will continue on to the aerobic citric acid cycle in the mitochondria. Oxygen will take two H+ and make water to be exhaled. If a cell able to perform aerobic respiration is in a situation where there is no oxygen (such as muscles under extreme exertion), it will move into anaerobic respiration. Some cells such as yeast are unable to carry out aerobic respiration and will automatically move into a type of anaerobic respiration called alcoholic fermentation. 9 The Activities of Major Digestive Tract Hormones 10 Figure 24.22 Aerobic vs. Anaerobic Respiration Aerobic respiration (in the mitochondria)will result in 6 ATP’s. Anaerobic respiration (in our cytoplasm) will result in only 2 ATP’s. More importantly, we get our NAD back, so glycolysis can continue. 11 Making ATP by Aerobic Respiration Takes place in the mitochondria Requires oxygen Breaks down glucose to pyruvate and produces ATP Waste products are CO2 and H2O (we exhale them) The good thing about making ATP from our mitochondria is that we can make a LOT of it. The bad things are that it takes longer to make it, and it requires oxygen, and a muscle cell may have used up all the oxygen during a sprinting run. Making ATP by Anaerobic Respiration Takes place in the cytoplasm Does not require oxygen Breaks down glucose to pyruvate and produces ATP Waste product is lactic acid The good thing about making ATP this way is that we can make it FAST. The bad thing is that it does not make much ATP, and we deplete the reserves quickly. Lactic Acid Build-up During strenuous workouts where oxygen becomes deficient, the pyruvate product of glycolysis does not have enough oxygen to use for aerobic respiration, so it has to undergo anaerobic respiration. The enzyme lactate dehydrogenase (LDH) is used to transfer hydrogen from the NADH molecule to the pyruvate molecule. Pyruvate with the extra hydrogen is called lactate. Lactic acid is formed from lactate. This causes muscle aches and fatigue. Lactic acid is deactivated by the addition of oxygen to it. Therefore, breathing heavily adds the oxygen to our system to deactivate lactic acid, and the muscle pains go away. Warm water or ultrasound will also increase oxygenated blood to the muscles, easing muscle cramps from lactic acid. When you add oxygen to lactic acid, it either goes back to being pyruvate, which is used to fuel the Krebs cycle (aerobic 14 respiration), or it is converted to glucose in the liver. ATP and Creatine Phosphate What do we do when we run out of ATP? Muscle fibers cannot stockpile ATP in preparation for future periods of activity. However, they can store another high energy molecule called creatine phosphate. Creatine phosphate is made from the excess ATP that we accumulate when we are resting. During short periods of intense exercise, the small reserves of ATP existing in a cell are used first. Then creatine phosphate is broken down to produce ATP. Aerobic vs. Anaerobic Respiration When do we use aerobic respiration? Resting (can breathe easily) Running marathons (can breathe easily on long runs) Marathon runners want to make sure there will be enough readily available energy for the muscles, so they eat a lot of carbohydrates over a two-day period before the marathon. That’s why they load up on pasta (carbo-loading)before a marathon. When do we use anaerobic respiration? Sprint running (can’t talk while sprinting!) Gluconeogenesis Gluconeogenesis (generating new glucose) is a metabolic pathway that results in the generation of new glucose from non-carbohydrate carbon substrates such as fatty acids and amino acids. Therefore, if we do not have enough glucose in our body, we will break down fat and proteins (muscles) to make glucose. It is one of the two main mechanisms to keep blood glucose levels from dropping too low (hypoglycemia). The other means of maintaining blood glucose levels is through the degradation of glycogen (glycogenolysis). Gluconeogenesis and glycogenolysis are the17 two ways to raise blood sugar. 18 GI Kit Line up the white label organs Place each colored substance under the proper organ Pancreas, acinar cells Liver Pancreas, Islets of Langerhans Alpha cells Salivary Glands Stomach Duodenum Pancreas, Islets of Langerhans Beta cells Pancreas, Islets of Langerhans Delta cells Stomach, Parietal Cells Stomach, Chief Cells Stomach, G-Cells Duodenum, K-Cells KEY Yellow = fat enzyme Green = protein enzyme Red = sugar enzyme Blue = hormones Orange = substances Carboxypeptidase Trypsin Pepsin Chymotrypsin Sucrase Maltase Lactase Amylase Lipase Lipase Lipase Lipase Gastrin Insulin Somatostatin Glucagon Bicarbonate Mucus Intrinsic factor Bile Motilin CCK Amylase GIP Secretin Prostaglandins HCl Pancreas, acinar cells Amylase Trypsin Chymotrypsin Carboxypeptidase Lipase Bicarbonate Pancreas, Islets of Langerhans Alpha cells Glucagon Pancreas, Islets of Langerhans Beta cells Insulin KEY Fat enzyme Protein enzyme Sugar enzyme Hormone Substances Pancreas, Islets of Langerhans Delta cells Somatostatin Stomach Lipase Prostaglandins Mucus Liver Salivary Glands Lipase Bile Amylase Lipase Stomach, Chief Cells Pepsin Stomach, Parietal Cells Intrinsic factor HCl Stomach, G-Cells Gastrin KEY Fat enzyme Protein enzyme Sugar enzyme Hormone Substances Duodenum Duodenum, K-Cells Sucrase GIP Maltase Lactase Secretin CCK Motilin KEY Fat enzyme Protein enzyme Sugar enzyme Hormone Substances Organ Pancreas Region of the Organ Acinar cells Acinar cells Acinar cells Acinar cells Islet of Langerhans; Alpha cells Islet of Langerhans; Beta cells Islet of Langerhans; Delta cells Liver Substances Amylase (enzyme) Lipase (enzyme) Protease enzymes (trypsin, chymotrypsin, carboxypeptidase) Bicarbonate (not an enzyme) glucagon (hormone) insulin (hormone) Somatostatin (hormone) Bile (a detergent) Lipase Amylase (enzyme) Lipase Mucous (not an enzyme) Prostaglandins (not an enzyme) Salivary glands Stomach Lipase Parietal cells Parietal cells Chief cells G cells Duodenum HCl (not an enzyme) Intrinsic factor (not an enzyme) Pepsinogen --> pepsin (enzyme) Gastrin (hormone) Secretin (hormone) CCK (hormone) Motilin (hormone) Maltase, Lactase, Sucrase (enzymes) K cells GIP (hormone) Function Breaks down starch and carbohydrates into glucose Breaks down fat into fatty acids Breaks down proteins into amino acids and also kills intestinal parasites and bacteria Raises pH in duodenum Causes glycogenolysis, the process which breaks down glycogen into glucose to raise blood glucose. Also causes gluconeogenesis to make new glucose molecules Removes glucose in bloodstream and brings it into cells. Lowers blood glucose levels. Inhibits gastrin, insulin, and glucagon (inhibits digestive system) Emulsifies fat Breaks down fat Breaks down starch and carbohydrates into glucose Breaks down fat Protect the stomach lining Protect the stomach lining Breaks down fat Allows Pepsinogen to be converted to pepsin, and it also kills bacteria Allows Vit B12 to be absorbed, which is needed to make RBCs. Without it, you get megaloblastic (pernicous) anemia. Breaks proteins into amino acids Tells parietal cells to secrete HCl Tells pancreas to secrete bicarbonate Tells pancreas to secrete proteases and lipase, and tells gallbladder to release stored bile (stimulates fat and protein digestion) Initiates peristalsis and tells Chief cells to secrete pepsinogen Break down complex carbohydrates into glucose 25 Tells pancreas to release insulin and also causes fat to be broken down into fatty acids Part 2 GI Physiology Figure 62-1; Guyton & Hall 26 Digestion Problems Incomplete digestion may be a contributing factor in the development of many ailments including flatulence, bloating, belching, food allergies, nausea, bad breath, bowel problems and stomach disorders. Digestive enzymes are primarily responsible for the chemical breakdown of food and constitute a large portion of digestive secretions. The human body makes approximately 22 different enzymes that are involved in digestion. 27 Digestive Enzymes Saliva is secreted in large amounts (1-1.5 liters/day) Salivary glands contain the enzyme salivary amylase. This enzymes breaks starch into smaller sugars and is stimulated by chewing. It is important to chew food thoroughly as this is the first stage of the digestive process. 28 Saliva The saliva serves to clean the oral cavity and moisten the food. It also contains digestive enzymes such as salivary amylase, which aids in the chemical breakdown of polysaccharides such as starch into disaccharides such as maltose. It also contains mucus, a glycoprotein which helps soften the food and form it into a bolus. 29 Swallowing The mechanism for swallowing is coordinated by the swallowing center in the medulla oblongata and pons (in the brain stem). The reflex is initiated by touch receptors in the pharynx (back of the throat)as the bolus of food is pushed to the back of the mouth. 30 Stomach The stomach is responsible for beginning the digestion of protein. Mucous cells (in the stomach) secrete mucous. The pancreas secretes bicarbonate. Mucous, bicarbonate, and prostaglandins protect the stomach lining from being digested. The parietal cells of the stomach secrete hydrochloric acid (gastric acid) and intrinsic factor. Hydrochloric acid (HCl), along with pepsin (from the chief cells), breaks down proteins to their individual amino acids. 31 Stomach Protection and Damage Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier © 2005 Elsevier Stimuli for Stomach Secretions Downloaded from: StudentConsult (on 23 April 2010 06:51 PM) © 2005 Elsevier Stomach Acid The acid itself does not break down food molecules. It provides an optimum pH for the activation of pepsin, and kills many microorganisms that are ingested with the food. It can also denature proteins. The parietal cells of the stomach also secrete a glycoprotein called intrinsic factor, which enables the absorption of vitamin B-12. 36 Stomach Acid Diseases Hypochlorhydria Diseases associated with low gastric acidity: Asthma, coeliac disease, eczema, osteoporosis and pernicious anemia. Hyperchlorhydria Diseases associated with high gastric acidity: Heartburn, gas and ulcers 37 Hypochlorhydria Deficient hydrochloric acid secretion Causes malabsorption and may result in a number of signs and symptoms. These include bloating, belching, flatulence, nausea, a sense of fullness immediately after meals, indigestion, diarrhea, constipation, food allergies, anemia (Folic acid, vitamin B12 and iron will not be absorbed if there is too little acid), undigested food in stool, chronic intestinal parasites, abnormal flora and weak, peeling and cracked fingernails. 38 • Small Intestine Duodenum – Absorption of minerals – Receives pancreatic digestive enzymes – Secretes hormones when acidic chyme enters duodenum • Secretin – Tells pancreas to secrete bicarbonate – Tells liver to make bile • Cholecystokinin (CCK) – Tells pancreas to release protein-digesting enzymes – Tells the gallbladder to release stored bile. – Therefore, it stimulates digestion of fat and protein. • GIP – Tells pancreas to secrete insulin • Motilin – Initiates peristalsis (increases GI motility) – Tells the Chief cells to secrete pepsinogen – Secretes enzymes to break down polysaccharides (-ase means an enzyme) • Maltase: breaks maltose down into glucose • Lactase: breaks lactose down to galactose plus glucose • Sucrase: breaks sucrose down into fructose plus glucose 39 Maltose Maltose (malt sugar) is made of two glucose molecules joined together. Maltose is the disaccharide produced when amylase breaks down starch. Amylase Maltase Starch Maltose Glucose Maltose is found in germinating seeds such as barley as they break down their starch stores to use for food. It is also produced when glucose is caramelized (browning of sugar during cooking). Foods containing maltose include malted milk shakes, malt liquor and beer. People who lack the maltase enzyme get diarrhea and gas if they ingest malt sugars. 40 Lactose Lactose is a milk sugar. It is made in the body by combining glucose with galactose. When milk products are consumed, lactose is broken down by the enzyme lactase. Many Asian and Hispanic people lack the enzyme lactase, so they are called lactose intolerant. If they consume milk products, they cannot break down lactose, so the E. coli in the colon get the sugar. E. coli metabolism then causes gas. The person may have diarrhea as well. 41 Sucrose and Fructose Sucrose is table sugar Fructose is fruit sugar All polysaccharide sugars and starches are broken down into glucose, which is needed by the body for metabolism. 42 Small Intestine Duodenum When there is no more chyme entering the duodenum, it secretes glucose-dependent insulinotropic peptide (GIP). GIP is synthesized by K cells, which are found in the duodenum and jejunum. GIP goes to the pancreas and tells it to secrete lipase (to break down fats) and to secrete insulin to lower blood glucose levels. 43 Lipid digestion and absorption Lipid digestion utilizes lingual and pancreatic lipases, to release fatty acids and monoglycerides. Bile salts improve chemical digestion by emulsifying lipid drops Lipid-bile salt complexes called micelles are formed 44 Fatty Acid Absorption INTESTINAL LUMEN: Bile salts form micelles (small droplets of lipids) Lipase breaks down the lipids into fatty acids and monoglycerides. INTESTINAL CELLS: Fatty acids and monoglycerides enter intestinal cells via diffusion; bile salts are then reused to ferry more lipids to the intestinal cell. Fatty acids are used to make triglycerides for storage. The rest of the fatty acids and monoglycerides are combined with proteins within the intestinal cells to make chylomicrons. Chylomicrons enter lacteals and are transported to the blood circulation via lymph 45 Protein and Fat Digestion During digestion, lipids are broken down into fatty acids plus glycerol by the enzyme lipase. Proteins are degraded by various proteolytic enzymes (proteases), and they break down into amino acids. Hydrolysis (water is added to break a bond) of proteins occurs in the stomach by pepsin, and this process requires the presence of hydrochloric acid in the stomach, but the rest of the proteins are broken down in the intestine. Both fat and protein digestion requires ATP. 46 Small Intestine Jejunum Absorbs water-soluble vitamins, protein and carbohydrates. The proteins began to be broken down into amino acids in the stomach by pepsin and acid. Proteins are further broken down into amino acids in the duodenum by trypsin and chymotrypsin (made by the pancreas and secreted into the duodenum). The carbohydrates are broken down in the duodenum by enzymes from the pancreas and duodenum into sugars. 47 Small Intestine Ileum Absorbs fat-soluble vitamins, fat, cholesterol, and bile salts. Fats are broken down into fatty acids in the duodenum. First, bile emulsifies the fat (breaks it down into droplets). Then, lipase (made in the pancreas) breaks the fat into fatty acids, which are small enough to be absorbed. 48 Pancreas Enzymes The pancreas secretes about one and a half liters of pancreatic juice a day! Pancreatic juice secretion is regulated by the hormones secretin and cholecystokinin (CCK), which is produced by the walls of the duodenum upon detection of acid food, proteins and fats. The enzymes produced by the pancreas include Lipases Amylases Proteases 49 Pancreas Enzymes Lipases Amylases Digestion of fats, oils, and fat-soluble vitamins Break down starch molecules into smaller sugars. Break down carbohydrates into maltose Proteases Break down protein into smaller amino acids Proteases include trypsin, chymotrypsin and carboxypeptidase. Proteases are also responsible for keeping the small intestine free from parasites (intestinal worms, yeast overgrowth and bacteria). A lack of proteases can cause incomplete digestion that 50 can lead to allergies and the formation of toxins. Regulation of Pancreatic Secretion Secretin and CCK are released when fatty or acidic chyme enters the duodenum CCK and secretin enter the bloodstream Upon reaching the pancreas: CCK induces the secretion of enzyme-rich pancreatic juice Secretin causes secretion of bicarbonate-rich pancreatic juice Vagal stimulation also causes release of pancreatic juice 51 The Pancreas Exocrine function (98%) Acinar cells make, store, and secrete pancreatic enzymes Endocrine function – α-cells (alpha)-Release glucagon β-cells (beta)release insulin cells (delta) release somatostatin (inhibitory to gastrin, insulin, and glucagon) 52 The Pancreas as an Endocrine Gland Insulin Beta cells Skeletal muscle and adipose tissue need functional glucose receptors Promotes glucose uptake Prevents fat and glycogen breakdown and inhibits gluconeogenesis Increases protein synthesis Promotes fat storage Epi/Norepi inhibit insulin! Help maintain glucose levels during times of stress and increase lipase activity in order to conserve glucose levels 53 Picture from:http://www.dkimages.com/discover/Home/Health-and-Beauty/Human-Body/Endocrine-System/Pancreas/Pancreas-1.html The Pancreas as an Endocrine Gland Glucagon Increases blood glucose levels Maintains blood glucose between meals and during periods of fasting by breaking down glycogen (stored in liver) into glucose. Initiates glycogenolysis in liver (within minutes). Stimulates gluconeogenesis. This process involves breaking down amino acids (proteins) into glucose. Stimulates amino acid transport to liver to stimulate gluconeogenesis Nervous tissue (brain) is heavily dependent on glucose levels! Image from: http://www.dkimages.com/discover/previews/768/74261.JPG 54 Liver and Gallbladder The liver produces bile that is either stored by the gallbladder or secreted into the small intestine. Bile emulsifies fats and fat-soluble vitamins. It also helps keep the small intestine free from parasites. The liver does not make the digestive enzymes for carbohydrates, amino acids and proteins (the pancreas and small intestine do that), but the liver does metabolize proteins, carbohydrates and cholesterol. It also is responsible for the detoxification of 55 toxins, drugs and hormones. Large Intestine The large intestine absorbs water, electrolytes and some of the final products of digestion. It allows fermentation due to the action of gut bacteria, which break down the substances which remain after processing in the small intestine; some of the breakdown products are absorbed. In humans, these include most complex saccharides (at most three disaccharides are digestible in humans) Food products that cannot go through the villi, such as cellulose (dietary fiber), are mixed with other waste products from the body and become hard and concentrated feces. 56 Physiology of the large intestine Reabsorption of water and electrolytes Coliform bacteria make: Vitamins – K, biotin, and B5 Organic wastes are left in the lumen – urobilinogens and sterobilinogens Bile salts Toxins Mass movements of material through colon and rectum Defecation reflex triggered by distention of rectal walls 57 Coliforms Coliforms is the term used for the bacteria that normally inhabit our colon (large intestine). E. coli is just one species of coliform. A ratio of 80% beneficial to 20% potentially harmful bacteria generally is considered normal within the intestines. Harmful microorganisms also are kept at a minimum by an extensive immune system comprising the gut-associated lymphoid tissue (GALT). 58 Phases of gastric secretion Cephalic phase Gastric phase Intestinal phase 59 Cephalic phase This phase occurs before food enters the stomach and involves preparation of the body for eating and digestion. Sight and thought stimulate the cerebral cortex. Taste and smell stimulus is sent to the hypothalamus and medulla oblongata. After this it is routed through the vagus nerve and release of acetylcholine. Gastric secretion at this phase rises to 40% of maximum rate. Acidity in the stomach is not buffered by food at this point and thus acts to stimulate Delta cells to secrete somatostatin. That causes the G cells to stop secreting gastrin. That caused the parietal cells to stop secreting HCl. 60 G cell secretion of gastrin D cell secretion of somatostatin 61 G cells and Gastrin G cells are found deep within the gastric glands of the stomach. When food arrives in the stomach, the parasympathetic nervous system is activated. This causes the vagus nerve to release a neurotransmitter called Gastrin-releasing peptide onto the G cells in the stomach. Gastrin-releasing peptide, as well as the presence of proteins in the stomach, stimulates the release of gastrin from the G cells. Gastrin tells parietal cells to increase HCl secretion, and it also stimulates other special cells to release histamine. Gastrin also tells the chief cells to produce pepsinogen. Gastrin is inhibited by low pH (acid) in the stomach. When enough acid is present, it turns off. 62 Gastrin Gastrin is released in response to Stomach distension Vagus nerve stimulation The presence of proteins or amino acids Gastrin release is inhibited by The presence of enough HCl in the stomach (negative feedback) Somatostatin also inhibits the release of gastrin 63 D cells D cells can be found in the stomach, intestine and the Islets of Langerhans in the pancreas. When gastrin is present, D cells increase somatostatin output. When D cells are stimulated by Ach, they decrease somatostatin output. 64 D cells Ach that comes from the Vegas nerve branch that lands on D cells will decrease somatostatin output so that digestion can occur. Ach that comes from the Vegas nerve branch that lands on G cells will cause gastrin to be released, and when gastrin is present but there is no food left, that excess gastrin will stimulate the D cells to increase somatostatin to try to turn off the system. 65 Somatostatin Somatostatin is also known as growth hormone-inhibiting hormone. It suppresses the release of gastrointestinal hormones Gastrin Cholecystokinin (CCK) Secretin GIP It suppresses the release of pancreatic hormones. It slows down the digestive process. It inhibits insulin release. It inhibits the release of glucagon. 66 Gastric phase This phase takes 3 to 4 hours. It is stimulated by distension of the stomach, presence of food in stomach and decrease in pH. Distention activates the vagus nerve. This activates the release of acetylcholine which stimulates the release of more gastric juices. As protein enters the stomach, it binds to hydrogen ions, which raises the pH of the stomach. Inhibition of gastrin and gastric acid secretion is lifted. This triggers G cells to release gastrin, which in turn stimulates parietal cells to secrete gastric acid. Gastric acid is about 0.5% hydrochloric acid (HCl), which lowers the pH to the desired pH of 1-3. Acid release is also triggered by acetylcholine and histamine. 67 Intestinal phase This phase has 2 opposing actions: the excitatory and the inhibitory. Partially digested food fills the duodenum. This triggers gastrin to be released. It also triggers the enterogastric reflex, which inhibits the Vagus nerve. This activates the sympathetic nervouse system, which causes the pyloric sphincter to tighten to prevent more food from entering the duodenum. 68 Digestive Enzymes (fats in yellow, proteins in green, and sugars in red) Salivary glands -amylase Lipase Stomach pepsin Lipase Liver Lipase Duodenum sucrase maltase lactase Pancreas amylase trypsin chymotrypsin carboxypeptidase Lipase 69 Digestive Hormones and Substances Stomach gastrin Intrinsic factor HCl Prostaglandins Mucous Liver Bile Duodenum Secretin CCK GIP Motilin Pancreas Glucagon Insulin Somatostatin Bicarbonate 70 The Activities of Major Digestive Tract Hormones 71 Figure 24.22 Organ Pancreas Region of the Organ Acinar cells Acinar cells Substances Amylase (enzyme) Lipase (enzyme) Acinar cells Acinar cells Protease enzymes (trypsin, chymotrypsin, carboxypeptidase) Bicarbonate (not an enzyme) Islet of Langerhans; Alpha cells Islet of Langerhans; Beta cells Islet of Langerhans; Delta cells Liver glucagon (hormone) insulin (hormone) Somatostatin (hormone) Bile (a detergent) Lipase Amylase (enzyme) Lipase Mucous (not an enzyme) Prostaglandins (not an enzyme) Salivary glands Stomach Lipase Function Breaks down starch and carbohydrates into glucose Breaks down fat into fatty acids Breaks down proteins into amino acids and also kills intestinal parasites and bacteria Raises pH in duodenum Causes glycogenolysis, the process which breaks down glycogen into glucose to raise blood glucose. Also causes gluconeogenesis to make new glucose molecules Removes glucose in bloodstream and brings it into cells. Lowers blood glucose levels. Inhibits gastrin, insulin, and glucagon (inhibits digestive system) Emulsifies fat Breaks down fat Breaks down starch and carbohydrates into glucose Breaks down fat Protect the stomach lining Protect the stomach lining Breaks down fat Parietal cells HCl (not an enzyme) Parietal cells Intrinsic factor (not an enzyme) Allows Vit B12 to be absorbed, which is needed to make RBCs. Without it, you get megaloblastic (pernicous) anemia. Chief cells G cells Pepsinogen --> pepsin (enzyme) Gastrin (hormone) Secretin (hormone) Breaks proteins into amino acids Tells parietal cells to secrete HCl Tells pancreas to secrete bicarbonate Duodenum CCK (hormone) Motilin (hormone) K cells Allows Pepsinogen to be converted to pepsin, and it also kills bacteria Tells pancreas to secrete proteases and lipase, and tells gallbladder to release stored bile (stimulates fat and protein digestion) Initiates peristalsis and tells Chief cells to secrete pepsinogen Maltase, Lactase, Sucrase (enzymes) Break down complex carbohydrates into glucose Tells pancreas to release insulin and also causes fat to be broken down GIP (hormone) into fatty acids 72 Where do the molecules go when you lose weight? • Think of fat as essentially a long-chain hydrocarbon CH3-(CH2)n-CH3. When your body uses that fat as fuel (either because you need fuel to exercise, or because you're not eating enough new fuel to support what you're doing), it burns that fat to extract the energy from it. That "burn" isn't a metaphor. The chemistry that your body does is exactly equivalent to literally burning it, just under more controlled conditions. 73 Where do the molecules go when you lose weight? • So, that hydrocarbon undergoes a controlled combustion with oxygen (O2) to produce a lot of energy, water (H2O), and carbon dioxide (CO2). Or, in chemical form: CH3-(CH2)n-CH3 + (3/2n+7/2)O2 ----> (n+2) CO2 + (n+3) H2O + Energy 74 Where do the molecules go when you lose weight? • So the carbon in the hydrocarbon goes to carbon dioxide and the hydrogen goes to water. But most of the mass of the hydrocarbon is carbon, so most of the mass gets converted to carbon dioxide, which is a gas and gets breathed out. • Now this is incomplete, because lipids and fat really aren't just hydrocarbons. They have phosphates and nitrogen and other things too, and those parts don't get converted to gases for excretion. Excess nitrogen gets converted to urea, for example, which gets excreted in the urine. And protein produces a lot more impurities when it gets broken down (though generally the body prefers to recycle proteins rather than burn them for energy). • But really, the way you lose most of your weight is just by 75 breathing it off. Good Website • http://uh.edu/sibs/tutorial/ap2.htm#digestive Part 3 GI Disorders Figure 62-1; Guyton & Hall 77 GI Disorders Peptic ulcers Pancreatitis Celiac Disease Inflammatory bowel disease (Crohn's disease and ulcerative colitis) Irritable bowel syndrome Appendicitis Diverticulitis Cancer Gastroenteritis ("stomach flu“); an inflammation of the stomach and intestines Cholera (bacteria in sewage-contaminated food or water) Giardiasis (protozoa in contaminated drinking water) Yellow Fever (virus transmitted by tropical mosquito) 78 Peptic Ulcers Classification By Region/Location Duodenum (called duodenal ulcer) Esophagus (called esophageal ulcer) Stomach (called gastric ulcer) Classification by Type Type I: Ulcer along the body of the stomach, most often along the lesser curve. Type II: Ulcer in the body in combination with duodenal ulcers. Associated with acid oversecretion. Type III: In the pyloric region. Associated with acid oversecretion. Type IV: Proximal gastroesophageal ulcer Type V: Can occur throughout the stomach. Associated with chronic NSAID use (such as aspirin). 79 Gastric and Duodenal ulcers Weakens H. pylori, aspirin, ethanol, NSAIDs, bile salts Strengthens mucus, HCO3- secretion, gastrin, PGs, epidermal growth factor Peptic ulcers occur when damaging effects of acid and pepsin overcome ability of mucosa to protect itself Gastric ulcers - main problem is decreased ability of mucosa to protect itself Duodenal ulcers - main problem is exposure to increased amounts of acid and pepsin 80 Two major causes of Peptic Ulcers: 1) 60% of gastric and up to 90% of duodenal ulcers are due to a bacterium called Helicobacter pylori. The body responds by increasing gastrin secretion, which erodes the stomach lining. 2) NSAIDs (non-steroidal anti-inflammatory drugs, such as aspirin) block prostaglandin synthesis. Prostaglandins promote the inflammatory reaction. They also are found in the stomach, protecting it from erosion. 81 Does stress cause ulcers? There is debate as to whether psychological stress can influence the development of peptic ulcers. Helicobacter pylori thrives in an acidic environment, and stress has been demonstrated to cause the production of excess stomach acid. 82 Diagnosis of Helicobacter pylori Urea breath test (noninvasive) Patient drinks a tasteless liquid which contains a radioactive carbon atom as part of the substance that the bacteria breaks down. After an hour, the patient will be asked to blow into a bag that is sealed. If the patient is infected with H. pylori, the breath sample will contain radioactive carbon dioxide. Biopsy Direct culture from a biopsy Histological examination and staining Direct detection of urease activity in a biopsy specimen by rapid urease test Measurement of antibody levels in blood Stool antigen test 83 Differential Diagnosis (DDx) A differential diagnosis is a list of possible things that may be causing a patient’s symptoms. DDx for H. pylori infection Peptic ulcer Gastritis Stomach cancer Gastroesophageal reflux disease Pancreatitis Hepatic congestion Cholecystitis Biliary colic Inferior myocardial infarction Referred pain (pleurisy, pericarditis) Superior mesenteric artery syndrome 84 Treatment Younger patients with ulcer-like symptoms are often treated with antacids or H2 antagonists (blocks the acid secretion of parietal cells). Patients who are taking NSAIDs may also be prescribed a prostaglandin analogue (Misoprostol) to help prevent peptic ulcers. When H. pylori infection is present, the most effective treatments are combinations of 2 antibiotics (e.g. Clarithromycin, Amoxicillin, Tetracycline, Metronidazole) and 1 proton pump inhibitor (PPI), sometimes together with a bismuth compound. An example of a PPI is Omeparazole (Prilosec). 85 Treatment Ranitidine (Zantac) and Cimetidine (Tagamet) provide relief of peptic ulcers, heartburn, indigestion and excess stomach acid and prevention of these symptoms associated with excessive consumption of food and drink. They decrease the amount of acid the stomach produces allowing healing of ulcers. Sucralfate, (Carafate) and strawberries have also been used in successful treatment of peptic ulcers. 86 Pancreas Disorders Gestational Diabetes Type I diabetes Type II diabetes Pancreatitis Cancer (death within 6 months) Chronic pancreatitis alcohol cystic fibrosis Acute pancreatitis Gallstones 87 Disorders of the Pancreas: Diabetes Mellitus Gestational Diabetes Occurs during pregnancy Type I diabetes – develops suddenly, usually before age 15 Destruction of the beta cells Skeletal tissue and adipose cells must use alternative fuel and this leads to ketoacidosis Hyperglycemia results in diabetic coma 88 Disorders of the Pancreas: Diabetes Mellitus Type II diabetes– adult onset Usually occurs after age 40 Cells have lowered sensitivity to insulin Controlled by dietary changes and regular exercise 89 Pancreatic Failure Digestion is abnormal when pancreas fails to secrete normal amounts of enzymes. Pancreatitis Removal of pancreatic head - malignancy Without pancreatic enzymes - 60% fat not absorbed (steatorrhea) 30-40% protein and carbohydrates not absorbed 90 Pancreatitis Pancreatitis means inflammation of pancreas. Autodigestion theory can explain condition. Chronic alcohol - most common cause in adults cystic fibrosis - most common cause in children pancreatitis - CF patients lack chloride transporter at apical membrane. Watery ductal secretion decreases which concentrates acinar secretions in ducts. Destroys pancreas gland by autodigestion. Acute pancreatitis Gallstones - most common cause 91 Uses of animal gut by humans The stomachs of calves have commonly been used as a source of rennet for making cheese. The use of animal gut strings by musicians can be traced back to the third dynasty of Egypt. In the recent past, strings were made out of lamb gut. With the advent of the modern era, musicians have tended to use strings made of silk, or synthetic materials such as nylon or steel. Some instrumentalists, however, still use gut strings in order to evoke the older tone quality. Although such strings were commonly referred to as "catgut" strings, cats were never used as a source for gut strings. Sheep gut was the original source for natural gut string used in racquets, such as for tennis. Today, synthetic strings are much more common, but the best gut strings are now made out of cow gut. Gut cord has also been used to produce strings for the snares which provide the snare drum's characteristic buzzing timbre. "Natural" sausage hulls (or casings) are made of animal gut, especially hog, beef, and lamb. Similarly, Haggis is traditionally boiled in, and served in, a sheep stomach. Chitterlings, a kind of food, consist of thoroughly washed pig's gut. 92 The oldest known condoms, from 1640 AD, were made from animal intestine. 93