PPT
description
Transcript of PPT
![Page 1: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/1.jpg)
Inflammatory Bowel Disease
Francisco A. Sylvester, MD
Associate Professor of Pediatrics
![Page 2: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/2.jpg)
Goals - IBD
1. Definitions: Crohn disease – ulcerative colitis
2. Epidemiology
3. Pathophysiology - Genetics
4. Diagnosis
5. Treatment
![Page 3: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/3.jpg)
Definitions
Crohn disease – Ulcerative colitis
![Page 4: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/4.jpg)
Normal colon
![Page 5: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/5.jpg)
IBD - ColonCrohn Disease Ulcerative Colitis
![Page 6: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/6.jpg)
IBD – Disease Location
http://www.hopkins-gi.org/
Crohn disease Ulcerative colitis
![Page 7: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/7.jpg)
Distribution of Crohn Disease
http://www.hopkins-gi.org/
![Page 8: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/8.jpg)
Types of Crohn Disease
http://www.hopkins-gi.org/
![Page 9: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/9.jpg)
Diagnostic Certainty
Crohn Disease Ulcerative Colitis
IBD-U
![Page 10: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/10.jpg)
Dr. Burrill B. Crohn(1884-1983)
![Page 11: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/11.jpg)
Epidemiology
• ~1.4 million Americans have IBD
• Mean age at diagnosis ~30 years of age
• 25% diagnosed as children
• M = F (in children with Crohn M > F)
• At CCMC: ~80-90 new patients/year
![Page 12: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/12.jpg)
Crohn’s Disease
Ulcerative Colitis
Ulcerative Colitis(< 20 years of age)
Appendicitis - Appendectomy
Smoking
Crohn’s Disease
![Page 13: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/13.jpg)
North-To-South Gradient
![Page 14: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/14.jpg)
Pathophysiology
![Page 15: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/15.jpg)
![Page 16: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/16.jpg)
Intestinal Flora
Stomach 0-10²Duodenum 10²
Distal Ileum 107 - 108
Colon 1011 - 1012
Jejunum 10²Proximal Ileum 103
Sartor B. Gastroenterology 2008;134:577-94
![Page 17: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/17.jpg)
“Our” DNA
90% Bacterial
10% Human
![Page 18: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/18.jpg)
So, Why Doesn’t Everybody Have IBD?
![Page 19: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/19.jpg)
Microbial Molecular Patterns
Muramyl dipeptide (MDP) Flagellins
Bacterial DNALipopolysaccharide (LPS)
![Page 20: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/20.jpg)
Intestine: Steady State
~ ~~~~
~~
~Microbes
DC
Intestinal Lumen
T cells
IntactEpithelial Cell Barrier
~
MLN
TregIntestinal LP
~ ~
~
Blood
~
M Cells
![Page 21: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/21.jpg)
“Controlled Inflammation”
![Page 22: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/22.jpg)
~ ~~~~
~~
~ ~Microbes
Activated T cellsCytokines/Chemokines
DC
Intestinal Lumen
T cells
Damage toEpithelial Cell Barrier
Microbial Invasion
~~
~~
Intestinal Inflammation
Intestinal LP
~
![Page 23: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/23.jpg)
http://www.randymays.com/Rugersr9-1.jpg
![Page 24: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/24.jpg)
IBD - Genetics
• NOD2/CARD15 (chromosome 16q12)– 20-40-X risk in individuals carrying 2
abnormal alleles– Ileal Crohn disease– Stricturing – penetrating– Caucasians only
![Page 25: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/25.jpg)
IBD - Genetics
• GWAS– ATG16L1 (Crohn disease)– IL-23R (Crohn disease and ulcerative colitis)– IL-23/Th17 pathway– > 30 novel loci
![Page 26: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/26.jpg)
What is Changing?
Genes vs. Jeans?
![Page 27: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/27.jpg)
Environmental Factors
• Microbial Ecology– Hygiene (Parasites)– Antibiotics– Refrigeration– Diet– Vaccines
• Tobacco
• North-to-south gradient– Vitamin D deficiency?
![Page 28: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/28.jpg)
Pathophysiology - IBD
• Genetic predisposition
• Defective innate immunity
• Hyperactivation of effector cells
• Microbial ecology alterations
• Environmental factors
![Page 29: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/29.jpg)
Genes Environment
Microbiota
![Page 30: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/30.jpg)
Diagnosis
• History – Physical Exam
• Laboratory– CBC, ESR, CRP, albumin– Stool culture– Serology (antibodies to PAMPs)
• Endoscopy
• Imaging
![Page 31: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/31.jpg)
Extraintestinal Manifestations
• Skin• Mouth• Joints• Bone
• Liver• Hypercoagulability• Kidney• Eye
•Present in ~50% patients•25% patients may have more than one•May be presenting symptom!
![Page 32: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/32.jpg)
Growth Failure – Pediatric IBD
![Page 33: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/33.jpg)
Complications
• Intra-abdominal sepsis (Crohn disease)
• Fecal incontinence
• Short gut syndrome (Crohn disease)
• Colon cancer
• Infertility
• Medication adverse effects (infection, cancer)
![Page 34: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/34.jpg)
Arrow shows narrowing of the distal ileum
![Page 35: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/35.jpg)
Arrow shows a phlegmon
![Page 36: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/36.jpg)
Mesalamine (5-ASA)/Corticosteroids
AZA/6-MPCD: MTX
Biologics
Steroids/5_ASA
AZA/6-MPCD: MTX
Biologics
Step Up vs. Top Down
Crohn disease: Nutritional therapy
![Page 37: PPT](https://reader036.fdocuments.net/reader036/viewer/2022081602/5461b23eaf795930398b61d8/html5/thumbnails/37.jpg)
Challenges for School-Aged Children
• School absences
• Bathroom needs
• Psychosocial issues– Self-perception and self-esteem– Peer relationships
• Special diets (nutritional therapy)