Chron Disease Video

Overview of Crohn's Disease

• Crohn's disease, often referred to simply as Crohn disease, is classified as an inflammatory bowel disease

• It causes inflammation throughout the gastrointestinal tract, impacting areas from the mouth to the anus

• Different from ulcerative colitis, which is limited to the large intestine

Classification and Classification Differences

• Crohn Disease vs. Autoimmune Disease

  • Ulcerative colitis is classified as an autoimmune disease

  • Crohn disease is categorized as an immune-related disorder

  • Key Concept:

  • Autoimmune disease: Immune system attacks self-cells and proteins

  • Crohn disease: Immune system reacts to foreign pathogens present in the gastrointestinal tract

Pathogens Implicated in Crohn's Disease

• Specific pathogens associated with Crohn disease include:

  • Mycobacterium paratuberculosis

  • Pseudomonas species

  • Listeria species

Immune Response Mechanism

• The immune system's response involves several steps:

  • Pathogens activate immune response via antigen presentation

  • Example: Gastrointestinal cells signal the presence of an infectious molecule

  • Activation of T helper cells (Th1 cells)

  • These cells release cytokines:

    • Interferon gamma

    • Tumor necrosis factor-alpha (TNF-α)

  • Cytokines promote further inflammatory response, attracting inflammatory cells such as macrophages

Unregulated Inflammation

• In individuals with Crohn's disease, the inflammatory response becomes uncontrolled:

  • Large amounts of inflammatory substances like proteases, platelet activating factor, and free radicals are produced

  • Leads to destruction of healthy gastrointestinal tissue

• Genetic Component

  • Family history significantly increases risk for developing Crohn disease

  • Genes identified related to Crohn disease include:

  • NOD2 gene (CARD15)

Genetic Mutations and Their Implications

• Frameshift Mutation

  • Definition: Occurs when nucleotides are added or removed, altering the reading frame

  • Results in the production of different amino acids and likely dysfunctional proteins

Anatomy of Gastrointestinal Wall

• Structure of the intestinal wall consists of layers:

  • Mucosal Layer

  • Submucosal Layer

  • Muscle Layer

  • Serosa

Barrier Defect Hypothesis

• It is hypothesized that defects in the epithelial barrier allow pathogens to penetrate the intestinal wall:

  • Upon penetration, the immune system is activated, mirroring the process outlined for antigen presentation

Granuloma Formation

• As inflammation escalates, immune cells organize into granulomas:

  • Function: Encapsulate perceived foreign entities

• Resulting structural damage leads to the formation of ulcers on the intestinal wall, resembling craters

Nature of Inflammation in Crohn’s Disease

• Distinctions between Crohn disease and ulcerative colitis include:

  • Inflammation in Crohn's extends beyond the submucosal layer, affecting the entire depth of the intestinal wall

  • This condition is termed transmural inflammation

  • Areas of inflammation are discontinuous, with healthy tissue interspersed, creating a cobblestone appearance

Areas Affected by Crohn's Disease

• Commonly affected regions include:

  • Ileum and colon (most common)

  • Ileum only (second most common)

  • Colon only (third most common)

  • Potential for involvement anywhere along the GI tract

Symptoms of Crohn's Disease

• Patients may experience various symptoms:

  • Abdominal Pain

  • Most common in the right lower quadrant

  • Diarrhea

  • Caused by compromised reabsorption of water due to intestinal damage

  • Blood in Stool

  • Resulting from damage to intestinal wall tissue

• Malabsorption issues may occur if the small intestine is predominantly affected, impacting nutrient absorption

Treatment Options for Crohn's Disease

• Treatment commonly includes:

  • Anti-inflammatory medications

  • Antibiotics

  • Helps control symptoms by reducing bacterial overgrowth and mitigating immune response

  • Some antibiotics have inherent anti-inflammatory effects

  • Immunosuppressants

  • Such as corticosteroids for severe symptoms

  • Surgery may be indicated for tissue removal

  • Important distinction: Removal of affected tissue does not cure the disease since inflammation may recur in other areas of the GI tract.