pathogenesis of Crohn's disease presented on KMC,kol july, 2013

2,084 views

Published on

0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,084
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
64
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide

pathogenesis of Crohn's disease presented on KMC,kol july, 2013

  1. 1. Pathophysiology of intestinal manifestations of Crohn’s disease Speaker: Dr. Dibbendhu Khanra Chairperson: Dr. K. D. Biswas
  2. 2. Part I Pathology 19001950 Part II Immunology 19501990 Part III Genetics 19902010 Part IV Future & beyond 21st century Discourse along history
  3. 3. 1900: Sorrow of Prince Albert Chronic diarrhea Bleeding PR Abdominal cramps Severe weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve ?
  4. 4. Terminal ileitis Regional ileitis Granulomatous entreocolitis Crohn’s disease
  5. 5. M=F Sedentary life style Developed nations OCP Smoking Appediculectomy Use of refrigerator
  6. 6. Part I: Pathology
  7. 7. Macroscopic appearance Aphthous ulcer  Mycobacterium paratuberculosis  E. coli  Yersinia  Listeria  Measles ‘Cobblestone’ Perianal disease  Inflammatory symptoms Small Bowel : 70 - 80 % Small And Large Bowel : 50 % Large Bowel Only : 15 - 20 %  Obstructive symptoms  Fistulous symptoms  Perianal diseases
  8. 8. Microscopic appearance Transmural ulcer Crypt abscess Non-caseating granuloma Aphthoid ulcer in Peyer’s patch
  9. 9. Microscopic appearance: CD vs UC
  10. 10. Radiological appearance String sign Fat halo sign Comb sign
  11. 11. Sorrow of Prince Charming Chronic diarrhea Bleeding PR Abdominal cramps Severe weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve Crohn’s disease antimicrobials Surgery
  12. 12. What kind of disease is Crohn’s disease? Is it infective disease?
  13. 13. 1950: Sorrow of Miss America Chronic diarrhea Bleeding PR Abdominal cramps Severe weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve Crohn’s disease
  14. 14. Part II: Immune dysregulations Power struggle & sensitivity issues
  15. 15. POWER V/S INJUSTICE JUSTICE Blood vessels Gut Innate Innate Immunity Immunity Organized Disorganized war Microbial Invasion Immune response Adaptive Adaptive Immunity Immunity Inflammation Barrier function Epithelial damage Increased small intestinal permeability Malabsorption & deficiency
  16. 16. Adaptive immunity inadequate inadequate Genetic innate microbial predisposition immunity elimination Adaptive immunity Neutrophil IL12 Th0 IL4, 23 Th1 CAMIntegrin Extraintestinal manifestations Macrophage Lymphocyte Th2 IFN gamma IL4, 5 13 Granulomatous inflammation Superficial ulceration IL6, TGFb Th17 IL17, 21 Neutrophilic recruitment TNFa, IL1, IL6 Extraintestinal manifestations
  17. 17. Abdominal pain 1. Stretch receptors stimulated as a food bolus passes through stenotic bowel 2. ganglia of the myenteric plexuses increased in size and number 3. Substance P receptors have increased around lymphoid follicles, microvasculature, and enteric neurons Diarrhea Fever & weight loss: TNF-alpha 1. Increased mucosal permeability 2. Cytokines, PG, ROS 3. imbalance in the luminal concentration of bile salts relative to dietary fat 4. Bacterial overgrowth 5. Disordered colonic motility
  18. 18. Antibodies in Crohn’s disease ASCA is present in ITB (50%) and CD (50%) both
  19. 19. 1950: Sorrow of Miss America Chronic diarrhea Bleeding PR Abdominal cramps Severe weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve 1950 1960 Steroid Immuno modulators Surgery
  20. 20. What kind of disease is Crohn’s disease? Is it immunologic disease?
  21. 21. 2000: Sorrow of a Rock diva Chronic diarrhea Bleeding PR Abdominal cramps Severe weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve Crohn’s disease
  22. 22. Part III: Genetics & Innate Immunity - Days of glory
  23. 23. Immune dysregulations 2 L/O oral tolerance L/O autophagy L/O NODing
  24. 24. L/O Oral Oral tolerance T reg cells depleted Fox P3 transcription factor IL10 TGF-b Inflammation Antiinflammation
  25. 25. L/O Autophagy ATG16L1 protein inadequate microbial elimination
  26. 26. Role of NOD inadequate microbial elimination
  27. 27. NOD2/ CARD15 Chr 16 Genetic determinism ATG16L1 Chr 2 TLR4 LPS signaling defect Microbial invasion Innate Immunity Adaptive Immunity TNFSF15 IL23R CTLA4 Mucosal integrity DLG 5 Chr 10 OCTN 1 Chr 15
  28. 28. Crohn’s victim to Crohn’s survivor Chronic diarrhea Bleeding PR Abdominal cramps Severe weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve Crohn’s disease 2000 Biologics
  29. 29. What kind of disease is Crohn’s disease? Is it genetic disease?
  30. 30. 2010: a magician in trouble Chronic diarrhea Abdominal cramps Weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve Crohn’s disease
  31. 31. Part IV: What lies ahead Theory of everything
  32. 32. NODophagy meets Autophagy
  33. 33. Endoplasmic reticulum stress and unfolded protein response
  34. 34. miRNA inadequate microbial elimination
  35. 35. A magic trick Chronic diarrhea Abdominal cramps weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve 2013 Rapamycin
  36. 36. What kind of disease is Crohn’s disease? What we have learned today?
  37. 37. Summary 1
  38. 38. Summary 2
  39. 39. Summary 3 Abdominal pain Diarrhea fistula Weight loss Mal nutrition Stricture Mass
  40. 40. Crohn’s disease Defective GUT Genetic determinism Immune injustice Thank you

×