Lect 6-inf bowel dis


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inflammatory bowel disease

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  • Crohn's disease shows a transmural pattern of inflammation , meaning that the inflammation may span the entire depth of the intestinal wall. [1]
  • Slide 5 Ideally, treatment for active Crohn's disease should rapidly improve symptoms. Non-specific anti-inflammatory drugs are the mainstay of treatment for Crohn's disease. Examples are: glucocorticoids 5-aminosalicylates (5-ASA) immunosuppressants antimetabolites methotrexate.
  • Lect 6-inf bowel dis

    2. 2. INFLAMMATORY BOWEL DISEASE IBD is a group of inflammatory conditions of large intestine ,in some cases small intestine.
    3. 3. Intestines - Pathology Idiopathic Inflammatory Bowel Diseases <ul><ul><li>Etiology & Pathogenesis </li></ul></ul>Crohn’s disease Ulcerative Colitis
    4. 4. <ul><li>Idiopathic Inflammatory Bowel Diseases </li></ul><ul><li>Etiology & Pathogenesis </li></ul><ul><li>Characterized by= A chronic, relapsing inflammatory conditions </li></ul><ul><li>unknown etiology. </li></ul><ul><li>speculations involve= Genetic factors, unknown infectious agents, special susceptibility factors, altered immuno-reactivity to dietary </li></ul><ul><li>or infectious antigens & altered regulatory controls of the inflammatory responses </li></ul>
    5. 5. Idiopathic Inflammatory Bowel Diseases <ul><li>Distinguished into two clinicopathologic entities : </li></ul><ul><ul><li>Crohn’s disease (CD) </li></ul></ul><ul><ul><li>Ulcerative colitis (UC) </li></ul></ul><ul><li>Crohn’s disease (CD) </li></ul><ul><li>Transmural granulomatous inflammation of the bowel, with mucosal ulcerations, fissures & fistulas in Young (20s)whites Females </li></ul><ul><li>Skip lesions (cobble stone app.) </li></ul><ul><li>Ulcerative colitis (UC) </li></ul><ul><li>crypt abscesses, psudopolyps & ↑risk of carcinoma (adenocarcinoma ) </li></ul>
    6. 6. Different Clinical, Endoscopic, and Radiographic Features of Crohn’s & Ulcerative Colitis Ulcerative Colitis Crohn's Disease   CLINICAL Gross blood in stool Yes Occasionally   Mucus Yes Occasionally   Systemic symptoms Occasionally Frequently   Pain Occasionally Frequently   Abdominal mass Rarely Yes   Significant perineal disease No Frequently   Fistulas No Yes   Small intestinal obstruction No Frequently   Colonic obstruction Rarely Frequently   Response to antibiotics No Yes   Recurrence after surgery No Yes   ANCA-positive Frequently Rarely  
    7. 7. Ulcerative Colitis Crohn's Disease ENDOSCOPIC Rectal sparing Rarely Frequently Continuous disease Yes Occasionally &quot;Cobblestoning&quot; No Yes Granuloma on biopsy No Occasionally RADIOGRAPHIC Small bowel significantly abnormal No Yes Abnormal terminal ileum Occasionally Yes Segmental colitis No Yes Asymmetrical colitis No Yes Stricture Occasionally Frequently
    8. 8. Intestines - Pathology Idiopathic Inflammatory Bowel Diseases (CD) (UC) Fissuring Ulcer noncaseating granulomas
    9. 9. Pathogenesis <ul><li>The common end pathway is inflammation of the mucosal lining of the intestinal tract, causing ulceration, edema, bleeding, and fluid and electrolyte loss. </li></ul><ul><li>Persons with IBD have a genetic predisposition (or perhaps susceptibility) for the disease. </li></ul><ul><li>The triggering event for the activation of the immune response has yet to be identified. </li></ul><ul><li>Possible factors related to this event include a pathogenic organism (as yet unidentified), an immune response to an intraluminal antigen (eg, protein from cow milk), or an autoimmune process whereby an appropriate immune response to an intraluminal antigen and an inappropriate response to a similar antigen is present on intestinal epithelial cells (ie, alteration in barrier function). </li></ul>
    10. 10. ULCERATIVE COLITIS <ul><li>Ulcerative colitis ( Colitis ulcerosa , UC ) is a form of inflammatory bowel disease (IBD). </li></ul><ul><li>Ulcerative colitis is a form of colitis, a disease of the intestine, specifically the large intestine or colon, that includes characteristic ulcers, or open sores, in the colon. </li></ul><ul><li>The main symptom of active disease is usually diarrhea mixed with blood, of gradual onset. </li></ul><ul><li>however, a systemic disease that affects many parts of the body outside the intestine </li></ul>
    11. 12. AETILOGY <ul><li>Exact cause is unknown. </li></ul><ul><li>Several causes have been suggested .it includes </li></ul><ul><li>Genetic Factors </li></ul><ul><li>Environmental Factors </li></ul><ul><li>Auto Immune Disease </li></ul><ul><li>Several Other Theories </li></ul>
    12. 13. Genetic factors <ul><li>A genetic component to the etiology of ulcerative colitis can be hypothesized based on the following </li></ul><ul><li>Aggregation of ulcerative colitis in families . </li></ul><ul><li>Diet: as the colon is exposed to many different dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis </li></ul><ul><li>Breastfeeding: There have been conflicting reports of the protection of breastfeeding in the development of inflammatory bowel disease . </li></ul><ul><li>3. Other childhood exposures, or infections </li></ul>
    13. 14. Autoimmune disease <ul><li>Some sources list ulcerative colitis as an autoimmune disease </li></ul><ul><li>Disease in which immune system malfunctions, attacking some parts of body. </li></ul><ul><li>But it is seen that surgical removal of large intestine cures disease, including manifestations outside digestive system. </li></ul><ul><li>This suggests cause of disease is in colon itself, not in immune system. </li></ul>
    14. 15. <ul><li>Ulcerative colitis involves only the mucosa; it is characterized by the formation of crypt abscesses and a coexisting depletion of goblet cell mucin. </li></ul><ul><li>In severe cases, the submucosa may be involved ; in some cases, the deeper muscular layers of the colonic wall is also affected. </li></ul><ul><li>Increased intensity of the cellular infiltrate in the lamina propria with alterations of the composition. </li></ul><ul><li>Infiltrate is more extensive and extends diffusely towards the deeper part (transmucosal) </li></ul><ul><li>Accumulation of plasma cells near the mucosal base , in-between the crypt base and the muscularis mucosae (basal plasmacytosis </li></ul>Pathological Feature
    15. 16. <ul><li>An irregular surface or a villiform surface and a disturbed crypt architecture. </li></ul><ul><li>Mucosal atrophy characterized by a combination of crypt drop-out and shortening of crypts. </li></ul><ul><li>Mucosal ulcerations and erosions , mucin depletion, </li></ul><ul><li>Paneth-cell metaplasia and diffuse thickening of the muscularis mucosae </li></ul>
    16. 18. Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips , palate and pharynx   Endoscopic image of ulcerative colitis showing loss of vascular pattern of the sigmoid colon, granularity and some friability of the mucosa.
    17. 19. Clinical presentation <ul><li>Diarrhoea mixed with blood and mucus. </li></ul><ul><li>Gradual onset. </li></ul><ul><li>Signs of weight loss. </li></ul><ul><li>Different degrees of abdominal pain ranging from mild discomfort to severely painful cramps. </li></ul>
    18. 20. CLASSIFICATION <ul><li>Extent of involvement </li></ul><ul><li>The disease is classified by the extent of involvement, depending on how far up the colon the disease extends. </li></ul><ul><li>1.Distal colitis </li></ul><ul><ul><li>a. Proctitis : Involvement limited to the rectum. </li></ul></ul><ul><ul><li>b. Proctosigmoiditis : Involvement of the rectosigmoid colon, the portion of the colon adjacent to the rectum. </li></ul></ul><ul><ul><li>c. Left-sided colitis : Involvement of the descending colon, which runs along the patient's left side, up to the splenic flexure and the beginning of the transverse colon . </li></ul></ul><ul><li>2.Extensive colitis , inflammation extending beyond the reach of enemas: </li></ul><ul><ul><li>Pancolitis : Involvement of the entire colon </li></ul></ul>
    19. 22. <ul><li>Mild disease : fewer than 4 stools daily,no signs of systemic toxicity,normal ESR,mild abdominal pain . </li></ul><ul><li>Moderate disease : more than 4 stools daily,minimal signs of toxicity,anaemia,moderate abdominal pain,low grade fever. </li></ul><ul><li>Severe disease : more than 6 bloody stools,evidence of toxicity with fever,tachycardia,elevated ESR </li></ul><ul><li>Fulminant disease : more than 10 stools,bleeding,toxicity,abdominal tenderness,blood transfusion requirement.unless treated will lead to death. </li></ul>Severity of disease
    20. 23. Extraintestinal features <ul><li>Iritis </li></ul><ul><li>Episcleritis </li></ul><ul><li>Aphthous ulcers involving tongue,lips,palate,pharynx. </li></ul><ul><li>Arthritis </li></ul><ul><li>Ankylosing spondylitis </li></ul><ul><li>Erythema nodusum </li></ul><ul><li>Deep venous thrombosis </li></ul><ul><li>Pulmonary embolism </li></ul><ul><li>Auto immune hemolytic anaemia </li></ul><ul><li>Clubbing of fingers </li></ul>
    21. 24. Diagnosis <ul><li>Complete blood count-anaemia,thrombocytosis,high platelet count. </li></ul><ul><li>Electrolyte studies-hypokalemia,hypomagnesia </li></ul><ul><li>Renal function tests </li></ul><ul><li>Liver function tests </li></ul><ul><li>X-ray </li></ul><ul><li>Stool culture </li></ul><ul><li>ESR </li></ul><ul><li>C-reactive protein </li></ul>
    22. 25. H&E stain of a colonic biopsy showing a crypt abscess:a classic finding in ulcerative colitis [ edit ] General
    23. 26. Crohn's Disease
    24. 27. Contents <ul><li>Introduction and definition of Crohn’s Disease </li></ul><ul><li>Classification </li></ul><ul><li>Cause </li></ul><ul><li>Pathology </li></ul><ul><li>Complications </li></ul><ul><li>Clinical features </li></ul><ul><li>Diagnosis </li></ul><ul><li>Investigations </li></ul><ul><li>Disease at glance </li></ul>
    25. 28. Definition: <ul><li>Crohn's disease (also known as regional enteritis ) is a chronic, episodic, inflammatory condition of the gastrointestinal tract characterized by </li></ul><ul><li>transmural inflammation (affecting the entire wall of the involved bowel) and skip lesions (areas of inflammation with areas of normal lining between). </li></ul><ul><li>Crohn's disease is a type of inflammatory bowel disease (IBD) and can affect any part of the gastrointestinal tract from mouth to anus ; as a result, </li></ul><ul><li>the symptoms of Crohn's disease vary between affected individuals. </li></ul>
    26. 29. Introduction to Crohn’s disease: <ul><li>This is a chronic inflammatory disease which causes stomach pains, diarrhoea, and weight loss. </li></ul><ul><li>The disease is characterised by periods of activity and remissions. </li></ul><ul><li>It typically affects the lower part of the small intestine (ileum) or the large intestine (colon), but it can affect any part of the digestive system. </li></ul>
    27. 30. <ul><li>Crohn Disease </li></ul><ul><li>any level of alimentary tract </li></ul><ul><li>a) small intestine alone  40% </li></ul><ul><li>b) sm. Intestine + colon  30% </li></ul><ul><li>c) colon alone  30% </li></ul><ul><li>“ skip” lesions </li></ul><ul><li>pathological characteristics: </li></ul><ul><li>a) mucosal damage (transmural) </li></ul><ul><li>b) well demarcated regions </li></ul><ul><li>c) noncaseating granulomas </li></ul><ul><li>d) formation of fissures </li></ul><ul><li>e) narrowed lumen (obstruction) </li></ul>www.freelivedoctor.com
    28. 31. <ul><li>The affected areas become red and swollen and ulceration may occur. </li></ul><ul><li>As the ulcers heal, the formation of scar tissue makes the intestine increasingly narrow, leading to obstruction. </li></ul><ul><li>There is no cure for Crohn's disease, but the symptoms can be treated and the periods of remission can be made to last several years. </li></ul>
    29. 32. Classification: <ul><li>Based on location. </li></ul>
    30. 33. Classification contd..
    31. 34. Classification <ul><li>Based on behaviour of disease </li></ul><ul><li>Stricturing disease. </li></ul><ul><li>Penetrating disease. </li></ul><ul><li>Inflammatory disease. </li></ul>
    32. 35. Cause <ul><li>The exact cause of Crohn's disease is unknown. However, genetic and environmental factors have been invoked in the pathogenesis of the disease. </li></ul><ul><li>Mutations in the CARD15 gene (also known as the NOD2 gene ) are associated with Crohn's disease and with susceptibility to certain phenotypes of disease location and activity. </li></ul><ul><li>Recently, research has indicated that Crohn's disease has a strong genetic link. </li></ul>
    33. 36. Cause contd.. <ul><li>Abnormalities in the immune system </li></ul><ul><li>Many environmental factors. </li></ul><ul><li>Diets </li></ul><ul><li>Smoking </li></ul><ul><li>Methods of hormonal contraception </li></ul><ul><li>Some bacteria: </li></ul><ul><li>Eg Mycobacterium avium subsp. Paratuberculosis, mannose , anti saccharomyces cerevisiae antibodies and E. coli </li></ul>
    34. 37. Pathology: <ul><li>Odeomatous and thickened bowel wall </li></ul><ul><li>Cobblestone </li></ul><ul><li>Patchy inlammation </li></ul><ul><li>Skip lessions </li></ul><ul><li>Transmural inflammation </li></ul><ul><li>H and E section of colectomy showing transmural inflammation . </li></ul>
    35. 38. www.freelivedoctor.com
    36. 39. Clinical Features <ul><li>Ileal Crohn’s Disease </li></ul><ul><li>Abdominal pain </li></ul><ul><li>Diarrhea </li></ul><ul><li>Weight loss </li></ul><ul><li>Crohn’s colitis </li></ul><ul><li>Bloody diarrohea </li></ul><ul><li>Passage of mucus </li></ul><ul><li>Lethargy </li></ul><ul><li>Malaise </li></ul><ul><li>Anorexia </li></ul><ul><li>Weight loss </li></ul>
    37. 40. f) chronic course may lead to: i) fibrosing strictures - terminal ileum - fistulas other areas ii) protein loss iii) Vit B 12 loss iv) bile salt loss - steatorrhea v) linear serpentine ulcers www.freelivedoctor.com
    38. 41. Complications: <ul><li>Intestinal:- </li></ul><ul><li>Severe, life-threatening inflammation of colon. </li></ul><ul><li>Perforation of the small intestine or colon. </li></ul><ul><li>Life-threatening acute haemorrhage. </li></ul><ul><li>Fistulae and perianal disease. </li></ul><ul><li>Cancer. </li></ul>
    39. 42. Differential Diagnosis <ul><li>Indium- or technetium- labelled white scanning. </li></ul>
    40. 43. Investigations: <ul><li>Endoscopic image of Crohn's colitis showing deep ulceration. </li></ul>
    41. 44. Contd….. <ul><li>Bacteriology </li></ul><ul><li>Barium studies </li></ul><ul><li>Other investigations </li></ul><ul><li>X-ray </li></ul><ul><li>Radio labelled white cell scan </li></ul><ul><li>Ultrasound </li></ul><ul><li>MRI scans </li></ul>
    42. 45. Contd.. <ul><li>CT scan showing Crohn's disease in the fundus of the stomach . </li></ul>
    43. 46. Crohn’s Disease at Glance: <ul><li>Crohn's disease is a chronic inflammatory disease of the intestines. </li></ul><ul><li>The cause of Crohn's disease is unknown. </li></ul><ul><li>Crohn's disease can cause ulcers in the small intestine, colon, or both. </li></ul><ul><li>Abdominal pain, diarrhea, vomiting, fever, and weight loss are symptoms of Crohn's disease. </li></ul><ul><li>Crohn's disease of the small intestine may cause obstruction of the intestine. </li></ul>
    44. 47. Contd.. <ul><li>Crohn's disease can be associated with reddish, tender skin nodules, and inflammation of the joints, spine, eyes, and liver. </li></ul><ul><li>The diagnosis of Crohn's disease is made by barium enema, barium x–ray of the small bowel, and colonoscopy. </li></ul><ul><li>The choice of treatment for Crohn's disease depends on the location and severity of the disease. </li></ul><ul><li>Treatment of Crohn's disease includes drugs for suppressing inflammation or the immune system, antibiotics, and surgery. </li></ul>
    45. 48. Comparison of UC and CD ULCERATIVE COLITIS CROHN’S Age Any Any Sex m=f M=f Anatomical distribution Colon only Any part of G.I Presentation Bloody diarrhoea Variable; pain diarrhoea, Weight loss Risk factors more common in non smokers More common in smokers
    46. 49. Treatment of Inflammatory Bowel Disease
    47. 50. TREATMENT <ul><li>Treatment for IBD may include: </li></ul>DIETARY CHANGES LIFESTYLE CHANGES DRUG THERAPY SURGERY
    48. 51. Dietary Changes <ul><li>Taking specific nutritional supplements, </li></ul><ul><li>Limiting dairy products, </li></ul><ul><li>Eating low-fat foods, </li></ul><ul><li>Avoiding foods high in undigestible fiber </li></ul><ul><li>Following doctor-recommended diets and </li></ul><ul><li>Eating smaller, more frequent meals. </li></ul>
    49. 52. LIFESTYLE CHANGES <ul><li>. </li></ul>Taking rest nonsmoking Stress reduction Doing exercise
    50. 53. Drug Therapies <ul><li>5-Aminosalicylates (5-ASA) </li></ul><ul><li>Glucocorticoids (steroids) </li></ul><ul><li>Antibiotics </li></ul><ul><li>Immunosuppressants </li></ul><ul><li>Biological Therapy </li></ul>
    51. 54. Aminosalicylates <ul><li>Sulfasalazine (5-aminosalicylic acid and sulfapyridine as carrier substance) </li></ul><ul><li>Mesalazine (5-ASA), e.g. Asacol, Pentasa </li></ul><ul><li>Balsalazide (prodrug of 5-ASA) </li></ul><ul><li>Olsalazine (5-ASA dimer cleaves in colon) </li></ul><ul><li>Oral, rectal preparation </li></ul>