Your SlideShare is downloading. ×
pathogenesis of Crohn's disease presented on KMC,kol july, 2013
Upcoming SlideShare
Loading in...5
×

Thanks for flagging this SlideShare!

Oops! An error has occurred.

×
Saving this for later? Get the SlideShare app to save on your phone or tablet. Read anywhere, anytime – even offline.
Text the download link to your phone
Standard text messaging rates apply

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

660

Published on

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

  • Be the first to like this

No Downloads
Views
Total Views
660
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
31
Comments
0
Likes
0
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide

Transcript

  • 1. Pathophysiology of intestinal manifestations of Crohn’s disease Speaker: Dr. Dibbendhu Khanra Chairperson: Dr. K. D. Biswas
  • 2. Part I Pathology 19001950 Part II Immunology 19501990 Part III Genetics 19902010 Part IV Future & beyond 21st century Discourse along history
  • 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. Terminal ileitis Regional ileitis Granulomatous entreocolitis Crohn’s disease
  • 5. M=F Sedentary life style Developed nations OCP Smoking Appediculectomy Use of refrigerator
  • 6. Part I: Pathology
  • 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. Microscopic appearance Transmural ulcer Crypt abscess Non-caseating granuloma Aphthoid ulcer in Peyer’s patch
  • 9. Microscopic appearance: CD vs UC
  • 10. Radiological appearance String sign Fat halo sign Comb sign
  • 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. What kind of disease is Crohn’s disease? Is it infective disease?
  • 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. Part II: Immune dysregulations Power struggle & sensitivity issues
  • 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. 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. 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. Antibodies in Crohn’s disease ASCA is present in ITB (50%) and CD (50%) both
  • 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. What kind of disease is Crohn’s disease? Is it immunologic disease?
  • 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. Part III: Genetics & Innate Immunity - Days of glory
  • 23. Immune dysregulations 2 L/O oral tolerance L/O autophagy L/O NODing
  • 24. L/O Oral Oral tolerance T reg cells depleted Fox P3 transcription factor IL10 TGF-b Inflammation Antiinflammation
  • 25. L/O Autophagy ATG16L1 protein inadequate microbial elimination
  • 26. Role of NOD inadequate microbial elimination
  • 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. 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. What kind of disease is Crohn’s disease? Is it genetic disease?
  • 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. Part IV: What lies ahead Theory of everything
  • 32. NODophagy meets Autophagy
  • 33. Endoplasmic reticulum stress and unfolded protein response
  • 34. miRNA inadequate microbial elimination
  • 35. A magic trick Chronic diarrhea Abdominal cramps weight loss Intestinal inflammation Terminal ileum involved Granuloma +ve AFB -ve 2013 Rapamycin
  • 36. What kind of disease is Crohn’s disease? What we have learned today?
  • 37. Summary 1
  • 38. Summary 2
  • 39. Summary 3 Abdominal pain Diarrhea fistula Weight loss Mal nutrition Stricture Mass
  • 40. Crohn’s disease Defective GUT Genetic determinism Immune injustice Thank you

×