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What is the result of targeted disruption of the genes for the T-cell receptor and the cytokine IL-2 in mice?
What is the result of targeted disruption of the genes for the T-cell receptor and the cytokine IL-2 in mice?
What is the primary mechanism by which the hygiene hypothesis contributes to the development of IBD?
What is the primary mechanism by which the hygiene hypothesis contributes to the development of IBD?
During which period does the patterning activity of certain aspects of the immune system strongly influence immune responses in the adult?
During which period does the patterning activity of certain aspects of the immune system strongly influence immune responses in the adult?
What is the role of interleukin-10 in mice models of IBD?
What is the role of interleukin-10 in mice models of IBD?
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What is thought to be an important component of the pathogenesis of IBD?
What is thought to be an important component of the pathogenesis of IBD?
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What is the effect of monoclonal antibodies to tumor necrosis factor alpha (TNFa) on inflammation in mice models of IBD?
What is the effect of monoclonal antibodies to tumor necrosis factor alpha (TNFa) on inflammation in mice models of IBD?
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What is a common presentation of Crohn's disease in approximately 20% of patients?
What is a common presentation of Crohn's disease in approximately 20% of patients?
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What is the role of the gut microbiota in the pathogenesis of IBD?
What is the role of the gut microbiota in the pathogenesis of IBD?
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What is a potential trigger for disease reactivation in Crohn's disease?
What is a potential trigger for disease reactivation in Crohn's disease?
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What is a potential complication of colonic disease in Crohn's disease?
What is a potential complication of colonic disease in Crohn's disease?
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What is the relationship between the development of regulatory processes in the neonatal immune system and the risk of IBD?
What is the relationship between the development of regulatory processes in the neonatal immune system and the risk of IBD?
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What is the effect of smoking on the risk of developing IBD?
What is the effect of smoking on the risk of developing IBD?
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What is the primary mechanism by which mothers influence the development of the immune system in their offspring?
What is the primary mechanism by which mothers influence the development of the immune system in their offspring?
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What is the typical pattern of disease activity in Crohn's disease?
What is the typical pattern of disease activity in Crohn's disease?
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What is the role of genetic risk in the development of IBD?
What is the role of genetic risk in the development of IBD?
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What is the category of susceptibility genes that is associated with IBD?
What is the category of susceptibility genes that is associated with IBD?
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What is the relationship between smoking and Crohn's disease?
What is the relationship between smoking and Crohn's disease?
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What is the effect of infections on the development of IBD?
What is the effect of infections on the development of IBD?
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What is the impact of the neonatal period on the development of the immune system?
What is the impact of the neonatal period on the development of the immune system?
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What is the relationship between the development of IBD and autoimmune diseases?
What is the relationship between the development of IBD and autoimmune diseases?
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What is a common complication of extensive small bowel disease?
What is a common complication of extensive small bowel disease?
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Where does the disease typically occur?
Where does the disease typically occur?
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What is the characteristic appearance of the involved mucosa?
What is the characteristic appearance of the involved mucosa?
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What is a common extraintestinal manifestation of Crohn's disease?
What is a common extraintestinal manifestation of Crohn's disease?
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What is a common complication of fibrosing strictures?
What is a common complication of fibrosing strictures?
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What is a common therapy for Crohn's disease?
What is a common therapy for Crohn's disease?
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What is a common symptom of Crohn's disease?
What is a common symptom of Crohn's disease?
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What is a common location for fistula formation?
What is a common location for fistula formation?
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What is a rare complication of Crohn's disease?
What is a rare complication of Crohn's disease?
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What is a characteristic feature of Crohn's disease?
What is a characteristic feature of Crohn's disease?
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What is the current treatment for Celiac Disease?
What is the current treatment for Celiac Disease?
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What is a complication of untreated or undiagnosed Celiac Disease?
What is a complication of untreated or undiagnosed Celiac Disease?
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What is the minimum amount of gluten that can induce inflammatory changes in the small intestine?
What is the minimum amount of gluten that can induce inflammatory changes in the small intestine?
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What is a characteristic of Crohn's disease?
What is a characteristic of Crohn's disease?
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What is a complication of refractory Celiac Disease?
What is a complication of refractory Celiac Disease?
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What is the name of the two disorders that comprise Inflammatory Bowel Disease (IBD)?
What is the name of the two disorders that comprise Inflammatory Bowel Disease (IBD)?
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What is the difference between Ulcerative Colitis and Crohn's Disease?
What is the difference between Ulcerative Colitis and Crohn's Disease?
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What is a urogenital complication of untreated or undiagnosed Celiac Disease?
What is a urogenital complication of untreated or undiagnosed Celiac Disease?
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What is a musculoskeletal complication of untreated or undiagnosed Celiac Disease?
What is a musculoskeletal complication of untreated or undiagnosed Celiac Disease?
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What is a hematopoietic complication of untreated or undiagnosed Celiac Disease?
What is a hematopoietic complication of untreated or undiagnosed Celiac Disease?
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What is the primary tumor location in Zollinger-Ellison Syndrome?
What is the primary tumor location in Zollinger-Ellison Syndrome?
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What is the effect of hypergastrinemia in Zollinger-Ellison Syndrome?
What is the effect of hypergastrinemia in Zollinger-Ellison Syndrome?
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What is the best single screening test for Zollinger-Ellison Syndrome?
What is the best single screening test for Zollinger-Ellison Syndrome?
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What is a common complication of Zollinger-Ellison Syndrome?
What is a common complication of Zollinger-Ellison Syndrome?
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What is the goal of medical treatment in Zollinger-Ellison Syndrome?
What is the goal of medical treatment in Zollinger-Ellison Syndrome?
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What is the most common cause of massive lower GI bleeding in the elderly?
What is the most common cause of massive lower GI bleeding in the elderly?
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What is the primary mechanism of achalasia?
What is the primary mechanism of achalasia?
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What is a characteristic of Esophageal Achalasia?
What is a characteristic of Esophageal Achalasia?
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What is the main treatment approach for Esophageal Achalasia?
What is the main treatment approach for Esophageal Achalasia?
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What is the primary risk factor for Gastroesophageal Reflux Disease (GERD)?
What is the primary risk factor for Gastroesophageal Reflux Disease (GERD)?
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What is the percentage of gastric ulcers associated with H. pylori infection?
What is the percentage of gastric ulcers associated with H. pylori infection?
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What is the effect of bile on the mucosal barrier in the stomach?
What is the effect of bile on the mucosal barrier in the stomach?
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What is the consequence of delayed emptying of gastric contents into the duodenum?
What is the consequence of delayed emptying of gastric contents into the duodenum?
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What is the effect of prostaglandins (PG) on mucosal blood flow and bicarbonate secretion?
What is the effect of prostaglandins (PG) on mucosal blood flow and bicarbonate secretion?
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What is a common cause of gastritis?
What is a common cause of gastritis?
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Study Notes
Inflammatory Bowel Disease (IBD)
- Targeted disruption of genes for T-cell receptor and cytokine IL-2 in mice results in GI tract disease resembling ulcerative colitis.
- Patterning activity of the immune system during the neonatal period strongly influences immune responses in adults.
- Early exposure to intestinal microbiota may be an important component of the pathogenesis of IBD.
- Maternal effects are thought to be a contributing factor to GI disease, as composition of the intestinal microbiota is in large part transmitted by the mother.
Crohn's Disease
- Clinical manifestation:
- Disease begins with intermittent attacks of mild diarrhea, fever, and abdominal pain.
- Approximately 20% of patients present acutely with RLQ pain, fever, and bloody diarrhea.
- Periods of active disease are typically interrupted by asymptomatic periods that last for weeks to many months.
- Disease reactivation can be associated with external triggers, including physical or emotional stress, specific dietary items, and cigarette smoking.
- Individuals with colonic disease may develop iron deficiency anemia due to blood loss.
Epidemiology
- Exact causes of IBD are unknown despite progress in understanding its pathogenesis.
- The hygiene hypothesis suggests that increasing incidence of IBD is related to improved food storage conditions, decreased food contamination, and changes in gut microbiome composition.
- Some mucosa-associated microbes trigger persistent and chronic inflammation in response to susceptible hosts.
- Other potential explanations for increased IBD prevalence include the idea that preservatives and other materials added to processed foods induce low-grade mucosal damage that predisposes to IBD.
Pathogenesis
- Results from a combination of genetic risk and environmental factors.
- Genetic risk includes abnormalities in susceptibility genes related to immune regulation, host-microbiome interactions, and epithelial barrier functions.
- Environmental factors include pathogenic microorganisms, the repertoire of indigenous intestinal microbes, dietary factors, smoking, and defective immune responses.
- Psychosocial factors may also contribute to the pathogenesis of IBD.
Complications
- Undiagnosed or untreated CD may lead to complications, including:
- Gastrointestinal complications, such as pharyngeal or esophageal cancer, lymphoma, or cancer of the small intestine.
- Hematopoietic complications, such as non-Hodgkin lymphoma.
- Urogenital complications, such as infertility, recurrent miscarriage, premature birth, and premature menopause.
- Musculoskeletal complications, such as osteoporosis and increased risk of bone fractures.
Treatment of Celiac Disease
- The only current available treatment is adherence to a strict gluten-free diet (GFD).
- Even very small amounts of gluten (50mg or a breadcrumb) can induce inflammatory changes in the small intestine and trigger symptoms in patients with CD.
Hemostasis and Diverticular Bleeding
- Hemostasis can be attempted by endoscopic methods (cautery, injection, or clips) or by interventional radiology.
- Diverticula are a source of bleeding in 3-5% of patients with diverticulosis.
- Diverticular bleeding is typically painless and not believed to be associated with a focus of inflammation.
- The differential diagnosis of painless bleeding per rectum also includes internal hemorrhoids and angiodysplasia.
Esophageal Achalasia
- Esophageal achalasia is a motor disorder in which the lower esophageal sphincter (LES) fails to relax properly in response to swallowing.
- Characteristics of achalasia include:
- LES more tightly contracted and loss of normal peristalsis in the esophageal body.
- Failure of a hypertensive LES to relax and the absence of esophageal peristalsis.
- Clinical manifestations of achalasia include:
- Dysphagia (inability to swallow).
- Regurgitations.
- Chest pain.
- Tremendous enlargement of the esophagus.
- Esophagus can hold as much as 1 L of putrid, infected material → risk of aspiration pneumonia.
- Progressive severe weight loss.
- Mucosal ulceration.
- Infections.
- Esophageal rupture.
- Death.
- Etiology of achalasia includes:
- Degeneration of the myenteric plexus.
- Loss of inhibitory enteric neurons that release VIP, nitric oxide.
- Diagnosis of achalasia is based on:
- A failure of the LES to completely relax with swallowing, confirmed via esophageal manometry, a contrast esophagram, or esophagoscopy.
- Differentiation of achalasia includes:
- Chagas' disease.
- Malignancies.
- Treatment of achalasia includes:
- Reducing the pressure at the lower esophageal sphincter.
- Medications: long-acting nitrates or calcium channel blockers.
- Injection with botulinum toxin (Botox).
- Widening (dilation) of the esophagus at the location of the narrowing.
- Surgery (esophagomyotomy).
Reflux Esophagitis: Gastroesophageal Reflux Disease (GERD)
- Chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus.
- Backflow of gastric or duodenal contents or both into the esophagus.
- Due to:
- Incompetence of the LES.
- Transient LES relaxation.
- Impaired expulsion of gastric reflux from the esophagus.
- A hiatus hernia.
- LES provides an effective barrier to reflux of acid from the stomach back into the esophagus.
- Effectiveness of the barrier can be altered by:
- Increased frequency of transient LES relaxations.
- Loss of secondary peristalsis after transient LES relaxations.
- Loss of LES tone.
- Hiatal hernia.
- Increased stomach volume or pressure.
- Increased production of acid.
- Alkaline injury: pancreatic juice reflux.
- Factors influencing the rate of spontaneous transient LES relaxation:
- Hormones.
- Neural agents.
- Foods.
- Other factors.
- Clinical presentation of GERD:
- Burning chest pain (heartburn).
- Dysphagia.
- Hemorrhage.
- Perforation.
- Hoarseness.
- Coughing.
- Wheezing.
- Aspiration pneumonia.
- Barrett's esophagus.
- Diagnosis of GERD:
- Barium swallow radiograph.
- Upper endoscopy.
- pH monitoring examination.
- Treatment of GERD:
- Drugs: antacids, H2 blockers, proton pump inhibitors, prokinetics.
- Surgery: fundoplication (Nissen).
Acid-Peptic Disease: (APD)
- Disorder of the GIT which results from superficial or deep lesion of the GI mucosa as a consequence of imbalance between protective and aggressive factors.
- Different forms of APD:
- Duodenal ulcer.
- Gastric ulcer.
- Gastritis.
- Etiology of APD:
- Bacterium Helicobacter pylori.
- Zollinger-Ellison Syndrome:
- Caused by gastrin-secreting tumor (gastrinoma).
- Stimulates the acid-secreting cells of the stomach to maximal activity.
- Hyperproliferation of gastric glands and parietal cells.
- Excess secretion of gastric acid.
- Consequently: gastrointestinal mucosal ulceration.
- May occur:
- Sporadically.
- As part of an autosomal dominant familial syndrome Multiple Endocrine Neoplasia type I (MEN I).
- Symptoms of Zollinger-Ellison Syndrome:
- Secondary to hypergastrinemia.
- Gastrointestinal mucosal ulceration.
- Diarrhea.
- Malabsorption.
- Abdominal pain.
- Diarrhea.
- Heartburn.
- Other symptoms.
- Physical examination:
- May be normal.
- Paleness in GI bleeding.
- Jaundice.
- Epigastric tenderness.
- Dental erosions.
- Hepatomegaly.
- Diagnosis of Zollinger-Ellison Syndrome:
- Fasting serum gastrin.
- Gastric acid secretory tests.
- Complications of Zollinger-Ellison Syndrome:
- Abdominal perforation.
- Esophageal stricture.
- Obstruction.
- GI bleeding.
- Gastric carcinoids.
- Prognosis of Zollinger-Ellison Syndrome: excellent in patients without metastatic disease.
- Goals of treatment:
- Medical control of gastric acid hypersecretion.
- Surgical resection of the tumor.
- Chemotherapy.
- Liver transplantation.
- Surgical resection or thermoablation in single confined liver metastatic lesion.
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Description
This quiz covers the relationship between the immune system and gut health, including the role of T-cells, cytokines, and microbiota in the development of inflammatory bowel disease (IBD).