Lecture 12 GI Diseases Disorders1.pptx

Interdisciplinary School of Health Sciences Faculty of Health Sciences University of Ottawa HSS3305 Pathophysiology of Health Problems (3 credits) Pr...

Interdisciplinary School of Health Sciences Faculty of Health Sciences University of Ottawa HSS3305 Pathophysiology of Health Problems (3 credits) Professor: Dr. Karen Phillips Analysis and integration of concepts related to the pathology of acute, degenerative and chronic health problems using a system approach. Major diseases including cancer, cardiovascular disease, diabetes and neurological disorders will be examined. Interdisciplinary discussions of disease risk factors. Health professions involved in the treatment, study and regulation of disease will be identified. GERD GASTRITIS PEPTIC ULCER CONSTIPATION BOWEL OBSTRUCTION FOOD-BORNE ILLNESS DIARRHEA MICROBIOME DISTURBANCES INFLAMMATORY BOWEL DISEASE CROHN’S DISEASE ULCERATIVE COLITIS CELIAC DISEASE  GERD Gastroesophageal reflux disease (GERD) chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus transient or permanent changes in the barrier (esophageal sphincter) between the esophagus and the stomach Gastric Acid Secretion  Why Doesn’t Gastric Acid Damage Stomach Epithelium? Parietal cells produce gastric acid pH of stomach acid ~2 Mucosal epithelium produce NaHCO3 and mucus which protect/buffer acid Lower Esophageal Sphincter  Gastritis Multiple causes- alcohol, H. pylori Injury to the gastric mucosa associated with epithelial cell damage/ regeneration Gastritis- inflammation associated with mucosal injury Gastritis Symptoms Indigestion (dyspepsia) Heartburn Abdominal pain Hiccups Loss of appetite Nausea Vomiting, possibly of blood or material that looks like coffee grounds Dark stools Chronic Gastritis and Gastric Cancer Risk Helicobacter pylori (HP); chronic atrophic gastritis (CAG); NSAIDS- non-steroidal anti-inflammatory drugs e.g. ibuprofen (Advil)  Peptic Ulcers Ulcer in an area of the gastrointestinal tract that is usually acidic and thus extremely painful ~80% of ulcers are associated with Helicobacter pylori, a spiral-shaped bacterium that lives in the acidic environment of the stomach, however only 20% of those cases go to a doctor Caused by hyperacidity and excessive pepsin activity  Peptic Ulcers- H. Pylori Bacteria converts ammonia from urea which neutralizes gastric acid Inflammation, ulceration Proliferation, attract white blood cells Peptic Ulcers  Gastroenteritis Gastroenteritis: inflammation of the gastrointestinal tract, primarily the stomach and intestines Causes: infection with bacteria, viruses, or other parasites, or less commonly reactions to new foods or medications. Symptoms: stomach pain, diarrhea and/or vomiting Gastritis only directly affects the stomach and may include nausea or vomiting, while gastroenteritis affects both the stomach and the intestines.  generally described as having fewer than three bowel movements a week. Constipation may be extremely painful Causes Blockages in the colon or rectum Colon, rectal cancer Bowel obstruction Problems with the nerves around the colon and rectum MS, Parkinson Disease Stroke Spinal Cord Injury Risks Difficulty with the muscles involved in Older age elimination Female Conditions that affect hormones in the Being dehydrated Diet low in fibre body Little to no physical Diabetes activity  Bowel Obstruction bowel obstruction happens when either your small or large intestine is partly or completely blocked blockage prevents food, fluids, and gas from moving through the intestines in the normal way blockage may cause severe pain that comes and goes severe cases medical emergency, risk of sepsis, may require surgery  -low serum potassium -disease state where acidosis (pH less than 7.35) develops with an increase in ionic chloride  Symptoms of Foodborne Illness: Diarrhea Abdominal pain Bloating Nausea/vomiting Gastroenteritis Remember- none of these is influenza, all these might be referred to as stomach flu (slang) but it’s not influenza  Food Allergies vs. Food Intolerances CLARIFICATION! true food allergies are uncommon 1% of adults and 5% of children have true food allergies — an adverse reaction to foods that is triggered by the immune system Signs and symptoms of a food Hives, allergy usually develop itching or eczema within an Swelling of the lips, face, tongue and throat, or other parts of the body hour after eating the offending food Wheezing, nasal congestion or trouble breathing and may include: Abdominal pain, diarrhea, nausea or vomiting Dizziness, lightheadedness or fainting Food intolerance- irritation of GI tract, may be related to digestive enzymes  Pathology of Foodborne Illness For pathogens- Incubation period- hours + Some microbes attach to walls of GI tract Multiply in surface epithelium Some microbes stay in GI tract, other produce toxin that enters bloodstream Symptoms depend on causative agent diarrhea abdominal cramps vomiting/nausea  Gastroenteritis Gastroenteritis: inflammation of the gastrointestinal tract, primarily the stomach and intestines Causes: infection with bacteria, viruses, or other parasites, or less commonly reactions to new foods or medications. Symptoms: stomach pain, diarrhea and/or vomiting Gastritis directly affects only the stomach and may include nausea or vomiting, while gastroenteritis affects both the stomach and the intestines. E coli O157:H7 gram negative, rod shaped bacteria Severe, bloody diarrhea, abdominal cramps Bacteria live in cows etc. Consumption of food/water contaminated by feces containing E coli O157:H7 Complication- hemolytic uremic syndrome (HUS); 3-5% cases, occurs several weeks after initial infection; anemia, bleeding, kidney failure (Walkerton) E coli O157:H7 Campylobacter gram negative bacteria Fever, diarrhea, abdominal cramps Bacteria live in intestines of healthy birds, most raw poultry meat is contaminated by Campylobacter Walkerton Salmonella rod-shaped Gram-negative bacteria Fever, diarrhea, abdominal cramps Bacteria live in intestines of birds, reptiles, mammals Consumption of contaminated, improperly prepared meat reptiles, such as iguanas, which commonly host Salmonella species.  Norovirus (or Norwalk or Norwalk-like virus Usually more vomiting, than diarrhea, resolves within 2 days Exposure to virus- food or bodily fluids etc. Person-person transmission RNA virus non-enveloped RNA viruses that belong to the family Caliciviridae Unknown means of cell entry Cholera is an infection of the small intestine caused by the bacterium Vibrio cholerae. toxin released by the bacteria causes increased secretion of water and chloride ions in the intestine, which can produce massive diarrhea. Death can result from the severe dehydration brought on by the  Cholera Outbreak- Impacts occurs in epidemics when conditions of poor sanitation, crowding, war, and famine are present endemic areas include India, Asia, Africa, the Mediterranean, and more recently, South and Central America, and Mexico; Zimbabwe disrupt the social and economic structure impede development in the affected communities. restricted travel  Cholera- Mechanism Cholera toxin enters epithelial cell Permanently ‘activates’ Cl- channel Cl- transport is greatly increased, sending Cl- to lumen Na, H2O transport also ACE= Accessory Cholera Enterotoxin increased to lumen Increase in H2O transport  diarrhea  Review Recall: G-protein Coupled Receptor, Activation of subunit alpha required Cholera toxin causes ADP-ribose (ADPR) to attach to Galpha(s) subunit; resulting in permanent activation Cholera Toxin-Mechanism  Botulism caused by Clostridium botulinum (gram positive bacteria) Usually traced to eating improperly prepared foods in which the organism has grown and produced toxin Botulism is actually a poisoning caused by ingestion of toxin in food rather than a bacterial infection Produces potent neuroparalytic toxin Symptoms: double vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness.  Clostridium botulinum Blocks neurotransmitter release at: peripheral cholinergic nerve terminals Neuromuscular junction Autonomic nerve terminals: Sympathetic & Parasympathetic BOTOX Botulinum toxin is a neurotoxic protein produced by the bacterium Clostridium botulinum. Used in minute doses both to treat painful muscle spasms, and as a cosmetic treatment in some parts of the world. cosmetic effect of BTX-A was initially described by the Carruthers, a dermatologist/ophthalmologist husband and wife team working in Vancouver, Canada, although the effect had been observed by a number of independent groups.  Gut Microbiome internal microbial communities composed of bacteria, archaea, viruses, and eukaryotic microbes contribute metabolic, immune functions and protect against pathogens individual’s microbiome is quite stable over time Microbiome affected by Lifespan (very young/old) Diet Mode of birth Breastfeeding Environmental factors Individual factors Psychological stress  Development of Gut Microbiome babies are believed to be born with sterile gastro-intestinal tracts upon birth colonization of the gut by microbes begins Mode of birth (vaginal delivery compared to cesarean section) has been shown to be the primary initial influence of the developing infant microbiome Additionally, breast-fed vs formula-fed infants have very different trajectories of gut microbiome development Adult gut microbiome colony reached by age 3  Gut Microbiome alterations in the microbiota are recognized in a growing number of disease states  Gut Microbiome and Antibiotics antibiotics can dramatically change the type of bacteria in the gut reduced microbiota diversity reduced diversity does not necessarily mean a reduced number of bacteria overall  As the antibiotic-susceptible bacteria are eliminated, antibiotic- resistant bacteria multiply and take their place changes in the gut microflora/microbiome can lead antibiotic-associated diarrhea nausea/vomiting gastrointestinal side effects MicrobiologyOpen, Volume: 11, Issue: 1, First published: 13 January 2022, DOI: (10.1002/mbo3.1260) Inflammatory Bowel Disease Inflammatory condition of colon, small intestine Major types Crohn’s disease Ulcerative colitis  Crohn’s Disease Inflammatory bowel disease Pain, diarrhea, vomiting Associated problems- rashes, arthritis Causes- Autoimmune: impaired cell mediated response Genetics: CARD15 gene, XBP1 gene 3-microorganism biofilm could trigger the Environment: smoking, diet inflammation that causes the symptoms of Crohn's disease two types of bacteria (Escherichia coli and Serratia marcescens) and one fungus (Candida tropicalis)  Ulcerative Colitis Inflammation of colon, ulcerations develop Constant diarrhea, bloody stools Causes Genetics: twin studies, family history, ethnic patterns, putative markers Autoimmune? Environment: diet- low fiber?  Intestine The pathophysiology of inflammatory bowel disease remains unclear. clearly involves a disruption of the immune system genetic component (increased risk by 10-20x) environmental factors appear to act as a trigger composition of the intestinal flora and its interaction with the host seems to play a role NSAIDS- Non-steroidal anti-inflammatory drugs e.g ibupr Inflammatory Diseases of the Intestine  IBS- Irritable Bowel Syndrome affects the large intestine Signs and symptoms include cramping, abdominal pain, bloating, gas, and diarrhea or constipation, or both Chronic disorder Most people can control their symptoms by managing diet, lifestyle and stress doesn't cause changes in bowel tissue or increase risk of colorectal cancer BD= Inflammatory Bowel Disease  Coeliac/Celiac Disease Weight loss, pale stool, abdominal pain, diarrhea; variable symptoms Impacts: malabsorption of nutrients, vitamins A,D,E and K Anemia Weight loss Problems with coagulation due to vitamin K deficiency, abnormal bleeding Coeliac/Celiac Disease  Coeliac/Celiac Disease Pathology of small intestine Causes Autoimmune Genetic: HLA-DQ2 or HLA-DQ8 Diet Sensitivity to gliadin (glutin protein) normal celiac triggers inflammatory response, atrophy of intestinal villi Coeliac/Celiac Disease 1. Consider the anatomy of the stomach- how the design related to GERD? 2. Why don’t we vomit/reflux when upside down? Sphincters! 3. Recall that the histamine receptor from the allergy lecture is back again- this time different isoform and is involved in histamine-signaling for acid production the stomach! 4. Remember when everyone thought stomach ulcers were caused by stress, type A personality? Nope- mostly H. pylori infections. 5. Constipation and diarrhea- we don’t talk about them, everyone experiences them from time to time, but they can also be serious illnesses 6. Foodborne illness- this will teach us to wash hands, and keep a clean kitchen! 7. Does it seem to you that every other month there is a brand of bagged salad recalled due to E. coli? 8. So that’s why there are so many gluten-free products available. Lots of people eat gluten-free, but are they all celiac people? 9. IBS vs. IBD- that’s confusing, but remember that that although IBS can be difficult to live with- it won’t give you cancer