1. Inflammatory bowel disease
    1. (Crohn disease & Ulcerative colitis) Distinction between the 2 is based on: Distribution of affected sites Morphologic expression of disease
      1. 1- Crohn disease
        1. can affect any region in the GIT, but the most commonly affected areas are the terminal ileum + cecum (40%) (Regional enteritis). Terminal ileum + colon (30%) & Colon alone (30%)
          1. (Gross morphology) Distribution of lesions in the form of Skip lesions (multiple, separate, sharply delineated areas of disease) which is very characteristic for Crohn
          2. Bowel wall is thickened & rubbery (Edema, inflammation, fibrosis) causing narrowing of lumen contributing to stricture formation which is seen radiographically as “String sign”
          3. Inflammation is Transmural ( involve all layers )
          4. Affected serosa is reddish, erythematous احمر, edematous متورم & granular محبب
          5. In cases of extensive transmural disease, mesenteric fat extends over the serosal surface (Creeping fat)
          6. Earliest lesion is shallow mucosal aphthous ulcer. Multiple lesions often coalesce into elongated, serpentine ulcers (creeping ulcer) قرحه زاحفه
          7. Mucosal folds are edematous & lost with sparing of interspersed mucosa giving rise to the characteristic Cobblestone appearance (diseased tissue is depressed below level of normal mucosa)
          8. Fissures develop between mucosal folds. Can extend deeply to become fistula tracts ثقب
        2. (Microscopic picture) non caseating granulomas (Multiple non necrotizing granuloma) this is the hallmark of Crohn disease (35% of cases) may occur in areas of active disease or uninvolved regions. Seen in submucosa & serosa
        3. clinical features : intermittent attacks of diarrhea, abdominal pain & fever. In between the attacks, the patients remains asymptomatic for weeks-many months Disease reactivation can be associated with a variety of triggers as stress, dietary factors, smoking
          1. Extensive cases are associated with malabsorption, weight loss, malnutrition, Loss of Albumin (Protein-losing enteropathy), Iron deficiency anemia &/or vitamin B12 deficienc
          2. Fibrosis & strictures develop in terminal ileum & require surgical resection
          3. Fistulas develop between loops of bowel & may involve the bladder, vagina, perineal skin
          4. Extraintestinal manifestations: Migratory polyarthritis, Ankylosing spondylitis, Uveitis & erythema nodosum
          5. The risk for development of colonic adenocarcinoma is high in patients with long-standing Crohn disease
      2. 2- Ulcerative colitis
        1. Usually starts in the distal colon & rectum then extends proximally in a continuous fashion (no skip lesions seen) to involve part or entire colon
        2. - If entire colon is affected, this is termed: Pancolitis , If disease is only limited to the rectum or rectosigmoid, this is termed: Ulcerative proctitis or Ulcerative proctosigmoiditis
        3. (Gross morphology)small intestine is normal except in severe cases of Pancolitis, where the distal ileum shows mild mucosal inflammation ”Backwash ileitis”
          1. Involved colonic mucosa is red with granular appearance and exhibit broad-based ulcers (which look different from the Crohn disease serpentine ulcers) Sharp demarcation between diseased & uninvolved colon is seen
          2. Chronic disease may lead to mucosal atrophy with smooth mucosal surface lacking normal folds
          3. Pseudopolyps are also found (islands of regenerating mucosa protruding or seen bulging into the lumen)
          4. Inflammation is mural. Hence, Serosal surface is normal
          5. Bowel wall is not thickened. Hence, strictures do not occur
          6. In severe cases, inflammation can extend to muscularis propria + neuromuscular dysfunction lead to Dilation & Toxic megacolon
        4. (Microscopic picture) Architectural crypt distortion (crypts are haphazardly arranged)
          1. Lymphocytic infiltration of colonic mucosa (evidence of chronic inflammation)
          2. Clusters of neutrophils infiltrating the crypts “Cryptitis”
          3. “Crypt abscess” (Crypts are filled with mixed inflammatory infiltrate)
          4. Mucosal atrophy with loss of crypts and ulceration
          5. Epithelial metaplasia including pseudopyloric metaplasia (presence of gastric antral appearing glands) one form of metaplasia can be seen
          6. Inflammation is only limited to mucosa & submucosa Muscularis propria is not involved. Skip lesions are absent There are No Granulomas and No fissures
        5. clinical features : Intermittent attacks of bloody mucoid diarrhea with abdominal pain that can persist for days up to months
          1. Extraintestinal manifestations similar to those seen with Crohn disease
    2. Laboratory tests: 1-CBC: low Hb concentration (Anemia), Total leukocytosis ( high TLC) 2-Inflammatory markers: high ESR & CRP
  2. A chronic condition
    1. resulting from : Complex interaction between intestinal microbiota (normal flora) & host immunity in genetically predisposed ( المعرضين للإصابه) leading to inappropriate mucosal immune activation
  3. More in females , teens & early 20s , More common in Caucasians & in the USA , Among Eastern European ( Ashkenazi ) Jews ( Genetic factors )
  4. pathogenesis : combination of abnormalities in immune regulation , host-microbe interactions & epithelial barrier function in genetically predisposed individuals
    1. > 200 IBD-associated genes have been identified. These account for < 50% of disease risk in Crohn disease and even small contributions to ulcerative colitis Polymorphisms of NOD2 is the strongest risk gene for Crohn (10-fold increased risk of disease)
      1. normally the transepithelial flux of microbes activates innate & adaptive responses
      2. In a genetically susceptible host, TNF release & other inflammatory signals increase tight junction permeability lead to establishes a self-amplifying cycle of microbial influx & host immune responses leading to IBD
      3. a) Epithelial defects Defects in the intestinal epithelial tight junctions, transporter genes, polymorphisms in ECM proteins or metalloproteinases are all associated with IBD
        1. b) Immune regulation defects Inadequate development of regulatory processes that limit mucosal immune responses, allowing some mucosa-associated microbes to trigger persistent & chronic inflammation Genetic polymorphisms in both proinflammatory (Il-12, IFN-ɣ), & anti-inflammatory (IL-10 & IL-10 receptor) signaling are involved. Mutations in IL-10 receptor are associated with severe, early-onset colitis Defects in T regulatory cells especially the IL-10 producing subset are also involved in IBD pathogenesis
          1. c) Host-microbial interactions defects Composition of GIT flora especially those populating the intestinal mucus layer may influence pathogenesis by affecting innate & adaptive immune responses
  5. treatment : Combination of lifestyle & diet changes (Eliminating high gas foods , decrease gluten intake , increase fiber consumption) , Medications
  6. Differential diagnosis : Inflammatory bowel disease ,Enteric infection
  7. Diagnosis ; Endoscopic & microscopic = normal , Diagnosis depends on clinical symptoms , Female , 20- 40 years , Abdominal pain or discomfort ( at least 3 times/month over 3 months ) , pain improves by defecation , change in stool frequency or form
  8. causes : muscle contraction , nervous system , inflammation , severe infection , change in microflora
  9. pathogenesis : "poorly defined", psychological stressors, food sensitivity , Abnormal gut motility , Abnormal of gut microbiome
  10. 1-chronic relapsing abdominal pain 2- bloating (abdominal distention) 3- changes in bowel habits
    1. 3 include : Diarrhea , constipation , mixed subtype
  11. irritable bowel syndrome