Gastrointestinal (GI) Lecture Notes Chapter 11 PDF

[EXCI461 Lecture Notes: Chapter 11 Gastrointestinal (GI)] ===================================================================== [11.1 Objectives: explain GI physiology, explain the prostaglandins, and proton pump and its role in acidity of stomach.] =================================================...

[EXCI461 Lecture Notes: Chapter 11 Gastrointestinal (GI)] ===================================================================== [11.1 Objectives: explain GI physiology, explain the prostaglandins, and proton pump and its role in acidity of stomach.] ===================================================================================================================================== [Physiology of gastrointestinal system:] ---------------------------------------------------- - The gastrointestinal (GI) system is made up of the mouth, esophagus, lower esophageal sphincter, the stomach, pylorus, intestine (includes duodenum and colon), and rectum. Here is a diagram of the stomach and its connections: - The sphincter and the pylorus keep stomach acid in it\'s proper place, and the pylorus also keeps bile from duodenum from getting into the stomach. - Esophagus is not protected from acidity, so stomach acid can hurt it. - pH of 1-5 is extremely acidic From Hydrochloric Acid (HCl, gastric acid). - Food gets from esophagus to stomach where the acidification and digestion processes begin. The parietal cell is in the stomach lining, it plays a key role in digestion. When food is smelled, or is being eaten, the parietal cell starts to secrete HCl into the stomach. Acid turns pepsinogen (pro-enzyme) into pepsin which is a digestive enzyme. Pepsin is an enzyme that digests proteins. - Three hormone/transmitters are produced by stomach: gastrin, acetylcholine, and histamine. - The parietal cells have receptors called the gastrin receptor, acetylcholine receptor, and H2 receptor (for histamine). - These receptors will activate a proton pump called the H+K+-ATPase which pumps protons through the parietal cell and into stomach. - Protons (H+) combine with Cl- to produce hydrochloric acid. The acid rises.  - The stomach & duodenum must be protected from acidity otherwise tissues can be damaged, the helpful bacteria can die, and the pathogenic bacteria may take over. A protective layer of mucus is produced to neutralize the acidity. - The production of mucus requires prostaglandins to be functional. - If NSAIDS are used, they may block this prostaglandin leading to GI damage over time. - Once food is digested, it moves through the intestines by peristalsis. - Peristalsis is the rhythmic movement of the intestine which moves the bowel movement along. - Parasympathetic nerves (cholinergic) promote peristalsis allowing bowel movements to occur. - Sympathetic nerves (adrenergic) oppose this process, which slows down a bowel movement. - For these reasons, drugs that affect cholinergic or adrenergic system may affect the digestion process. - Finally, when digestion in the stomach is not needed anymore, prostaglandin version PGE2 inhibits acid secretion from parietal cells, and version PGI2 restores the protective mucus and bicarbonate buffer to prepare for next meal. [**11.2 Objectives:** Know pathophysiology signs and symptoms of GI disorders, summarize effects of exercise on GI problems] ======================================================================================================================================== [Heartburn:] ------------------------ - Acid indigestion. Feels like a burning chest pain primarily behind the sternum but can move up towards the neck. - Spontaneous regurgitation due to reflux - Bronchial constriction in people with asthma - About 1/3 adults experience heartburn once a month. - Similar feeling to a myocardial infarction [Gastro esophageal reflux disease (GERD):] ------------------------------------------------------ - Means heartburn happens regularly\--\> twice a week. - Can go untreated, causing damage to esophagus and inflammation - Leads to erosion of the esophagus - Can lead to barrettes esophagus and esophageal cancer in rare cases. - Also, ulcers can be a complication. - Continuous acidity prevents healing of esophagus - The symptoms of GERD are felt most when lying down. - The cause of GERD is that the lower esophageal apogeal sphincter (LES) does not function well allowing acid and pepsin into the esophagus. Contributing factors to GERD symptoms including: - Straining - Bending over - Coughing - Eating - Pregnancy - Spicy food - Carbonated beverages, caffeine - Certain drugs like NSAIDs inhibit prostaglandins which impairs protection - Exercise can negatively impact on GERD symptoms: - High intensity and high impact exercise causes acid to reflux - Eating before exercise increases acid, then makes it worse - Age is also a factor. With increasing age, the protective mucosa diminishes. Age of 65 or over this problem becomes more common. [Peptic Ulcer Disease (PUD)] ---------------------------------------- - PUD is caused by erosion of the mucosa of the stomach, also called a gastric ulcer. The ulcer may be in the small intestine, called a duodenal ulcer. - PUD is very common, can be life threatening. - [Signs and symptoms of PUD include]: - Abdominal pain the most common symptom, the pain awakens a person, burning or cramping. - Pain begins 1-3 hours after eating, alleviated by ant-acids. - GI bleeding and perforation of stomach can happen. Internal bleeding could occur. - [There are several causes of PUD]: - Overuse or overdose of NSAID drug can damage stomach lining result in ulcer. NSAIDs cause direct irritation to the stomach lining, and they block prostaglandins that protect stomach, and NSAID may slow the healing process. - Cigarettes will exacerbate severity - Perhaps stress causes ulcer, but this idea is controversial because it is not supported by data. - *h. Pylori* infection, a bacteria, treatable with antibiotics. - [*H. Pylori* is a very common infection]: - it is a gram-negative bacteria that can live between the mucosa and the stomach lining. - It is transmitted through fecal-oral route that would mean contaminated meat usually, or dirty vegetables that were contaminated with farm run-off. Farm run-off is when animals on the farm make waste, and that gets into the water and on the vegetables at the farm. Vegetables should be rinsed and cooked if possible. With meat, like ground beef, it contains fecal matter at a low percentage, must be fully cooked. - Some people with *H. Pylori* develop ulcers, which can be treated with antibiotics. - *H. Pylori* is the most common cause of gastric and duodenal ulcers. [Constipation] -------------------------- - Constipation is when bowel movement is unusually slow or stopped. Less than three bowel movements per week, stool hard and dry. - When this happens, then too much water is absorbed and the stool is hard, dense, and may be painful cramping. - Straining is necessary, common in 65 and up. - It is not a really a disease or disorder. It has many causes. - Associated with endocrine diseases, diabetes, hypothyroidism, or drugs with anti-cholinergic effects (opioids, MAOIs, antidepressants, antihistamines), some antacids, ageing, and a busy lifestyle. [Diarrhea] ---------------------- - Diarrhea is when the bowel movement is unusually fast, and the stool is watery (diarrhea). - Increased frequency of bowel movements, and/or decreased consistency of stool (watery, less dense). - When bowel moves fast the water can not be absorbed efficiently, can lead to dehydration. - Usually brief, but can be chronic and potentially fatal due to dehydration - The bowel has to absorbs \~9 liters of water per day! - Lasting more than a few weeks requires medical attention. - Like constipation, it is more of a symptom not a disorder in itself. There are many causes: - Illness such as acquired immune deficiency syndrome (AIDS) - Irritable bowel syndrome (IBS), - Inflammatory bowel disease (IBD), - Disruption of bacterial flora , for example by tetracycline - Damage of GI epithelial cells by drugs or infections. - Drugs that accelerate peristalsis - Foods with laxative effects like fatty foods - Dairy products for lactose intolerant people - Infection of GI with bacteria, virus, protozoa [Irritable bowel Syndrome (IBS) (also called spastic colon, \"colitis\")] ------------------------------------------------------------------------------------- - Common disorder where the colon is more sensitive than usual. - Onset early adulthood, triggered by stress - Symptoms can include gassiness, bloating, diarrhea, constipation - The cause may be psychological stress, depression and certain foods cause enhanced contraction of intestine [Inflammatory bowel Disease (IBD) (Auto-immune diseases)] --------------------------------------------------------------------- - Refers to two diseases Crohn\'s disease, and ulcerative colitis. - Crohn\'s involves intestine but can affect any part of digestive tract. Painful cramps, fever, diarrhea, rectal bleeding, anemia, weight loss. - Ulcerative colitis is inflammation of the colon and rectum. - The cause is genetic factors and autoimmunity. Must be supervised by a physician. [Hemorrhoids (piles)] --------------------------------- - Noticed as painful swelling of the anus of the haemorrhoidal blood vessels - Mild hemorrhoids include symptoms of bleeding, itching, burning, inflammation. - Severe hemorrhoids has increased bleeding, anal pain, protrusion outside anal canal, seepage, blood clot. These can resemble polyps and cancer. - Many causes of hemorrhoids including pregnancy, constipation, diarrhea, straining, lifting, sitting or standing, - Risk of hemorrhoids may be genetic, inherited [**11.3 S**uggest non-drug and drug interventions for Gi issues] ============================================================================ [Non-drug treatments for GERD (also relevant for PUD, heartburn)] ----------------------------------------------------------------------------- - Avoid certain foods and beverages that irritate GI such as caffeine, spicy food, - Avoid cigarettes & alcohol - Elevate the head of the bead during sleeping - This does not mean elevate the person\'s head, since adding a pillow does nothing. - Tilting the bed makes the acid stay towards bottom of stomach. - Lie on left side while sleeping - For most people gravity will cause the acid to stay in the stomach, because the stomach has a curved shape. - Avoid large meals 2-3 hours before lying down, sleeping, or strenuous exercise - meals induce acid, lying down pushes it to the esophagus. - Loose body weight, avoid tight clothes, avoid straining - Minimize antihistamines, tricyclic anti-depressants, opioids - Minimize NSAID drugs or take a lot of water when taking drugs such as NSAIDs. [Drug treatments for GERD (also relevant for PUD, heartburn):] -------------------------------------------------------------------------- - The goal of drug treatments for GERD is to neutralize acidity, inhibit acid production, block effect of acid on tissue, increase effects of mucus. These same goals are used to treat PUD and even regular heartburn. - [Proton pump inhibitor (PPI)]: - Proton pump inhibitor, blocks proton pumps - Prevents pepsin-pepsinogen conversion - Increases stomach pH - Treating GERD: PPI more effective than H2 inhibitors. - Inhibits an actively proton pumping stomach, doesn\'t do much to a resting stomach. Thus, take during meal. - Can be sold over the counter and can easily be combined with other drugs - [Histamine 2 receptor (H2) antagonists]: - Blocks the H2 receptor - Can be used alone or in combination with ant-acids. - Lifestyle changes and a few weeks is enough for mild heartburn, but GERD takes longer to treat. - Most of them are OTC - [Antacids]: - These are substances that neutralize the stomach pH. - The work really fast when someone takes them, go directly to the stomach - Sold over the counter, but potential adverse reactions is high! - Constipation or diarrhea common side effects. - Gassiness common (acid/base reaction) - Antacids might not be drugs, however, they can all interfere with other drugs directly, or by lowering bioavailability of other drugs. So better to check with doctor or pharmacist if combining antacids with other drugs. - - - - - [Drug treatment specifically for PUD treatment] ----------------------------------------------------------- - Must get tested for *h. Pylori* - *If positive, a combination therapy with antibiotics and PPI is the preferred to treat PUD caused by h. pylori.* [Non-drug treatment for IBS:] ----------------------------------------- - Managing diet and stress. - Keep a food diary. - Eliminate carbonated beverage or chewing gum which both put gas and air into the stomach. - Along with psychological therapy if applicable, for stress! [Drugs to treat IBS] -------------------------------- - Loperamide (Imodium, it is an opioid-receptor agonist) used as anti-diarrheal - Bulk forming laxatives preferred for constipation (e.g. psyllium) - Anti-depressants for depression commonly given, along with psychological therapy if applicable, for stress! [Non-drug treatment for constipation] ------------------------------------------------- - To treat constipation: - Lifestyle changes such as more fibre like bran, fruits, vegetables - Drink more water - Exercise help to improve abdominal muscle tone which facilitates peristalsis. - Regular exercise to move the body. - If persistent or serious should see doctor. [Drugs and substances to treat constipation ] --------------------------------------------------------- - Laxatives to treat constipation: - Bulk forming - Stool softener - Osmotic - Stimulant - Can be administered rectally as an enema or suppository which is faster than oral (minutes versus hours) - Bulk forming better for long term medication- should see a physician - Osmotic better for short term result - Stool softener more of a preventative - or can lubricate the stool - Stimulant drugs promote peristalsis of smooth muscle cells. [Drug treatments for diarrhea] ------------------------------------------ - Opioids act through mu-receptor to decrease smooth muscle contractibility - Loperamide is the only OTC because of low abuse potential - Bismuth Subsalicylate (Pepto bismal): - Acidity converts it into salicylic acid (NSAID) and bismuth oxychloride - Bismuth has anti-bacterial functions. - Used to treat traveller\'s diarrhea - Used in multi-drug combinations for h. pylori - Bad in combination with blood thinners, NSAIDs [Drugs to treat IBD:] --------------------------------- - Anti-inflammatory, immunosuppressant, corticosteroids, antibiotics are used depending on symptoms. - Must be followed closely by a physician, these drugs are toxic, and their effectiveness varies a lot in a patient. - Heavy immunosuppression can cause opportunistic infections - There are surgical options to remove scar tissue in GI [Drugs and substances to treat Hemorrhoids] ------------------------------------------------------- - Treatment goal is to relieve the symptoms of pain, itching, swelling and burning. Drug categories are below, many are available OTC. - Corticosteroids- Low dose topical to reduce inflammation - Local anesthetics- Temporary relief blocks nerve impulse (e.g. benzocaine) - Astringents- Relieves irritation and inflammation by protecting skin - Vasoconstrictors-Reduces swelling (adrenergic effect) (there is an error in the textbook on this point- it probably meant alpha-adrenergic effect) - Protectants- Physical barrier on skin (e.g. cocoa butter) - Counterirritants- Distract from pain and itching through cooling, tingling or warmth (e.g. menthol) - Keratolytics- Helps remove dead dermal tissue to allow access of other medications [**1.4 Objectives:** know the role of the AT in advising people with GI issues]. ============================================================================================ [Role of the AT:] - GI medicine is perhaps of the more overused medicines. - Many people do not seek help for GI disorders from a doctor. Instead, they buy over the counter medicine to treat symptoms. The underlying cause is therefore not determined. - A person\'s lack of knowledge and self-diagnosis leads to errors in choosing an OTC medicine. Their symptom may be a more serious disease or disorder treatable with non-drug method, or prescription drugs - \"Dr. Google\" is not always right! - Exercise can exacerbate symptoms of IBS and GERD. - Exercise can help treat signs of constipation. - Some of the symptoms of GERD resemble myocardial infarction (heart attack). - Know that chest pain below the sternum that occurs on exertion, and that radiates to jaw and arm may not be [GERD]. - Could be myocardial infarction or angina, but hard to tell. - If such pain is detected, follow emergency procedures, call emergency number. - Once properly diagnosed, the AT can help with compliance and could recommend lifestyle changes. - For example, with constipation: need to drink more water, fibre and exercises. - Diarrhea: reduce fatty foods.