Immunology and Gut Health

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.