IBD (Inflammatory bowel disease) pathophysiology

Transcription

1 IBD (Inflammatory bowel disease) pathophysiology Prof. Sina Aziz PhD (Paediatrics) KMDC/ASH 1

2 Contents of this presentation GI anatomy Prevalence of IBD IBD definition layman IBS and IBD Signs and symptoms of IBD Pathophysiology IBD Crohns diseaseetiology/anatomy/pathogenesis/signs and symptoms Ulcerative colitisetiology/anatomy/pathogenesis/signs and symptoms Comparison between UC and CD Research material 2

3 Prevalence of IBD Up to 1 million Americans are thought to have IBD, which occurs most often in ages 15 to 30, but can affect younger kids and older people. Most cases are reported in western Europe and North America 3

4 IBD definition Inflammatory bowel disease (which is not the same thing as irritable bowel syndrome, or IBS) refers to two chronic diseases that cause inflammation of the intestines: 1. ulcerative colitis and 2. Crohn's disease. Although the diseases have some features in common, there are some important differences 4

5 IBS Irritable bowel syndrome (IBS) is a disorder that leads to abdominal pain and cramping, changes in bowel movements, and other symptoms. IBS is not the same as inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. In IBS, the structure of the bowel is not abnormal. 5

6 Signs and symptoms-ibd Common symptoms of both ulcerative colitis and Crohn's disease are diarrhea and abdominal pain. Diarrhea can range from mild to severe (as many as 20 or more trips to the bathroom a day). If the diarrhea is extreme, it can lead to dehydration, rapid heartbeat, and a drop in blood pressure. And continued loss of small amounts of blood in the stool can lead to anemia. The loss of fluid and nutrients from diarrhea and chronic inflammation of the bowel can also cause fever, fatigue, weight loss, and malnutrition.. 6

7 Signs and symptoms Pain is usually from the abdominal cramping, which is caused by irritation of the nerves and muscles that control intestinal contractions At times, those with IBD may also be constipated. Crohn's disease, this can happen as a result of a partial obstruction (called stricture) in the intestines. Ulcerative colitis, constipation may be a symptom of inflammation of the rectum (known as proctitis). 7

8 Signs and symptoms IBD can cause other health problems that occur outside the digestive system. IBD can show signs of inflammation elsewhere in the body, including the joints, eyes, skin, and liver. Skin tags that look like hemorrhoids or abscesses may also develop around the anus. IBD might delay puberty or cause growth problems for some children because it can interfere with them getting nutrients from food. 8

9 Multifactorial etiopathogenesis of CD Genetic predisposition Triggering event infectious Gut microflora Cytokines Abnormal mucosal immune response Normal homeostasis Cytokines Eicosanoside Reactive oxygen metabolites Neuropeptides Growth factors immune down regulation chemokines, adhesion molecules nitrous oxide Acute phase reaction intestinal permeability Intestinal inflammation lack of immune down -regulation Chronic IBD 9

10 Environmental influences Specific microbial trigger Mycobacteria Viruses Role of enteric flora Role of diet Risk factors-early life exposures Other modulating factors Smoking Oral contraceptives Host environment interactions Defective mucosal barrier Immunoregulatory abnormalities Defective innate immunity- NOD2/CARD15 Adaptive immune response control of mucosal immune response 10

11 Anatomy and frequency of area involved 11

12 CD-Pathology anatomic distribution Panenteric inflammatory process Endoscopy with biopsy identifies histologic abnormalities GIT CD is characteristically segmental, with spared areas in the intestinal tract Terminal ileum is the most common affected area Colonoscopy and small bowel radiography Upper EGD with biopsy- microscopic involvement of esophagus/stomac and duodenum Gastroduodenal disease-only rarely the sole or predominant site of crohns disease 12

13 Data of hospital for sick children Toronto and Gastroenterol clin north am 2002;31: % Intestinal involvement ( by colonoscopy and small bowel radiography) 29% 38% terminal ileum with or without cecal disease Small intestine alone 9% More isolated proximal (ileal or jejunal) disease 42% 38% 20% 20% Ileocolonic inflammation In combination with colon Colon involvement Colon alone 13

14 Macroscopic appearance Crohn's often involves the small intestine, the colon, or both. Internal tissues may develop shallow, craterlike areas or deeper sores and a cobblestone pattern, as seen here. 14

15 Microscopic appearence- Endoscopic biopsy showing granulomatous inflammation of the colon in a case of Crohn's disease. H&E stain 15

16 Prevalence of individual symptoms at the time of diagnosis of CD Mendeloff et al Clin. Gastroenterology 1980;9: 258 symptom Toronto pediatric IBD data base N = 386 Abdominal pain Diarrhea Blood in the stool Weight loss fevers 38 Not stated UK and Ireland surveillance N = 379 Perianal lesions 8 fistula or abscess, 19 tags, 22 fissures 7 fistula or abscess Arthralgias/arthritis 17 8 Mouth ulcers 28 Not stated Skin lesions

17 Modes of presentation of CD- The hospital for sick children, Toronto Mode N (%) Classic presentation (abdominal pain, diarrhea, weight loss ± extra intestinal manifestations) 235 (78.6) Growth failure predomination 10 (3.3) Extraintestinal manifestation predominating Arthritis Recurrent fevers Recurrent oral ulcers Oral chelitis Pyoderma gangrenosum Recurrent acute pancreatitis 25 (8.4) Anemia as the major complaint 8 (2.7) Perianal disease predominating 11 (3.7) Anorexia, weight loss predominating 6 (2) Laparotomy for acute abdominal pain 4 (1.3) Total

18 Crohns Disease complications - malnutrition and growth impairment Factor Cytokines produced by chronically inflamed intestine Insufficient caloric intake Reason Direct role of inflammatory cytokines in linear growth inhibition (IGF-I) inhibition: interference in kinetics of bone growth Food avoidance because of exacerbation of Gi symptoms by eating: cytokine mediated anorexia Stool losses Mucosal inflammation leading to protein loosing enteropathy; steatorrhoea if extensive Increased nutritional needs Cortico steroid treatment Fever, chronic deficits Inhibition of IGF-1 (insulin like growth factor) EXTRA INTESTINAL MANIFESTATIONS JOINTS SKIN EYE HEPATOBILIARY PANCREAS RENAL VASCULAR BONE 18

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20 UC-Ulcerative colitis 20

21 Ulcerative colitis Is an inflammatory disease of the large intestine, or colon. Inner lining (mucosa) of the intestine becomes inflamed (red and swollen) and develops ulcers (open, painful wounds). Severe in the rectal area, which can cause frequent diarrhea. Mucus and blood often appear in the stool (feces or poop) if the lining of the colon is damaged 21

22 Comparison of pathological features of UC & CD Feature Ulcerative colitis Crohns disease Gross/endoscopic Colonic involvement Rectal involvement Ileal involvement ulceration Microscopic Depth of inflammation granulomas Typically diffuse, continuous, extending proximally from the rectum Almost always involved Non-specific backwash ileitis Broad and shallow Mucosal, except in severe disease Absent except for occ. Giant cell reaction to damagedcrypts Focal disease characterized by skip lesions Frequently spared Typically involved with ulceration and nodularity Early aphthous lesions, ulcer knifelike and fissuring, intervening areas of oedema may give cobblestone appearence Typically transmural Non-caseating granulomas seen fibrosis unusual typical 22

23 Etiologic factors in the pathogenesis of UC Genetic predispostion Frequent positive F/H (15-25%) Higher rates of concordance in monozygotic twins than in dizygotic twins Association with specific HLA class II genes Association with other genetic disorders e.g Turners syndrome Environmental factors Early childhood events e.g diarrheal illness; may increase risk Appendectomy at an early age: may decrease risk Psychological stress; may cause exacerbations Smoking tobacco; decreases risk Drugs NSAID may cause exacerbations Oral contraceptives; conflicting data Microbial factors; important in pathogenesis 23

24 Criteria for the diagnosis of severe UC Feature Truelove and witts BMJ 1955;2:1041 Werlin and Grand Gastroenterology 1977;73: Bloody stools 6 per day 5 per day Fever Tachycardia Anemia Hypoalbuminemia ESR Mean evening temperature > 37.3ºC or temperature 37.8 at least 2 of 4 d > 90 bpm Hb 75% of normal value > 30 mm/h >100º during the first hospital day 90 bpm Hct 30% s. Albumin 3.0 g/dl 24

25 Extra intestinal manifestation of UC Musculoskeletal Skin Peripheral arthopathy Ankylosing spondylitis/sacroilitis Enthespathy Hypertrophic osteoarthropathy Decreased bone density Pyoderma gangrenosum Erythema nodosum Acne Alopecia Ophthalmologic Episcleritis Uveitis Cataracts Increased intracranial pressure 25

26 Extra intestinal manifestation of UC Hepatobiliary Fatty liver disease Sclerosing cholangitis Autoimmune hepatitis Cholelithiasis Renal Nephrolithiasis Pancreas Pancreatitis Hematologic Coagulation abnormalities Iron deficiency anemia Autoimmune hemolytic anemia Neutropenia Thrombocytosis Immune thrombocytopenic purpura Cardiorespiratory Pericarditis Pneumonitis Growth and development Delayed growth Delayed puberty 26

27 Complications IBD > 8 yrs risk of colon cancer. risk greater when inflammation affects the entire colon. regular screening -- colorectal cancer is easiest to treat when it is found early. more than 90% of people with IBD do NOT get colon cancer 27

28 colonoscopy 28

29 Endoscopic findings in moderate-to-severe ulcerative colitis of circumferential mucosal inflammation, with ulcerations 29

30 Conclusion- UC Complex interplay between genetic and environmental factors Diagnosis and management is a challenge Esp. in children- who must complete their physical and emotional development Colectomy with ileoanal anastomosis in patients failing medical therapy Patients may develop chronic IBD True cure awaits further study of the genetic basis of UC and its pathogenesis 30

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34 Colitis book diet for UC and crohns disease-the Culinary Couple s Creative Colitis Cookbook: 100 Recipes for Low-Fiber, Low-Residue Diets used while treating Ulcerative Colitis or Crohn s Disease flare-ups 34

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36 references NASPGHAN Allan Walker ed. Pediatric gastrointestinal disease 4rth edition bowel_disease_ibd_pictures_slideshow/articl e.htm 36

37 Thank you 37