IBD (Inflammatory bowel disease) pathophysiology - pnds.org · IBD (Inflammatory bowel disease)...

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IBD (Inflammatory bowel disease) pathophysiology Prof. Sina´ Aziz PhD (Paediatrics) KMDC/ASH 6/30/2012 1 PNDS/sina aziz

Transcript of IBD (Inflammatory bowel disease) pathophysiology - pnds.org · IBD (Inflammatory bowel disease)...

Page 1: IBD (Inflammatory bowel disease) pathophysiology - pnds.org · IBD (Inflammatory bowel disease) pathophysiology Prof. Sina´ Aziz ... • Ulcerative colitis- ... (Inflammatory bowel

IBD (Inflammatory bowel disease)pathophysiology

Prof. Sina´ Aziz PhD (Paediatrics)

KMDC/ASH6/30/2012 1PNDS/sina aziz

Page 2: IBD (Inflammatory bowel disease) pathophysiology - pnds.org · IBD (Inflammatory bowel disease) pathophysiology Prof. Sina´ Aziz ... • Ulcerative colitis- ... (Inflammatory bowel

Contents of this presentation• GI anatomy• Prevalence of IBD• IBD definition layman• IBS and IBD• Signs and symptoms of IBD• Pathophysiology IBD• Crohns disease-

etiology/anatomy/pathogenesis/signs and symptoms

• Ulcerative colitis-etiology/anatomy/pathogenesis/signs and symptoms

• Comparison between UC and CD• Research material

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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

http://kidshealth.org/parent/medical/digestive/ibd.html

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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

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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 diseaseand ulcerative colitis. In IBS, the structure of the bowel is not abnormal.

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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.

• .6/30/2012 6PNDS/sina aziz

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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).

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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.

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Multifactorial etiopathogenesis of CD

Cytokines

Cytokines chemokines, adhesion molecules

Eicosanoside nitrous oxide

Reactive oxygen metabolites Acute phase reaction

Neuropeptides intestinal permeability

Growth factors

immune down regulation

lack of immune down -regulation

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Triggering eventinfectious

Genetic predisposition Gut microflora

Abnormal mucosal immune response

Intestinal inflammationNormal homeostasis

Chronic IBD

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

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Anatomy and frequency of area involved

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CD-Pathology – anatomic distribution• Panenteric inflammatory process

• Endoscopy with biopsy identifies histologicabnormalities 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

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Data of hospital for sick children Toronto 1990-1999and

Gastroenterol clin north am 2002;31:307-27

% Intestinal involvement ( by colonoscopy and small bowel radiography)

29%38%

terminal ileum with or without cecal diseaseSmall intestine alone

9% More isolated proximal (ileal or jejunal) disease

42%38%

Ileocolonic inflammationIn combination with colon

20%20%

Colon involvementColon alone

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Macroscopic appearance

• Crohn's often involves the small intestine, the colon, or both.

• Internal tissues may develop shallow, crater-like areas or deeper sores and a cobblestone pattern, as seen here.

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Microscopic appearence- Endoscopic biopsy showing granulomatous inflammationof the colon in a case of Crohn's disease. H&E stain http://wikimediafoundation.org/wiki/Home

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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

UK and Ireland surveillanceN = 379

Abdominal pain 86 72

Diarrhea 78 56

Blood in the stool 49 22

Weight loss 80 58

fevers 38 Not stated

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 8 1

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Modes of presentation of CD- The hospital for sick children, Toronto 1980-89

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)1381111

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 2996/30/2012 17PNDS/sina aziz

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EXTRA INTESTINAL MANIFESTATIONS JOINTSSKINEYEHEPATOBILIARYPANCREASRENALVASCULARBONE

Crohns Disease complications - malnutrition and growth impairment

Factor Reason

Cytokines produced by chronically inflamed intestine

Direct role of inflammatory cytokines in linear growth inhibition (IGF-I) inhibition: interference in kinetics of bone growth

Insufficient caloric intake 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 Fever, chronic deficits

Cortico steroid treatment Inhibition of IGF-1 (insulin like growth factor)

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UC-Ulcerative colitis

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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

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Comparison of pathological features of UC & CD

Feature Ulcerative colitis Crohns disease

Gross/endoscopic

•Colonic involvement

•Rectal involvement

•Ileal involvement

•ulceration

Typically diffuse, continuous,

extending proximally from the

rectum

Almost always involved

Non-specific “backwash ileitis”

Broad and shallow

Focal disease characterized by skip

lesions

Frequently spared

Typically involved with ulceration

and nodularity

Early aphthous lesions, ulcer knife-

like and fissuring, intervening areas

of oedema may give cobblestone

appearence

Microscopic

Depth of inflammation

granulomas

Mucosal, except in severe disease

Absent except for occ. Giant cell

reaction to damagedcrypts

Typically transmural

Non-caseating granulomas seen

fibrosis unusual typical

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Etiologic factors in the pathogenesis of UC• Genetic predispostionFrequent positive F/H (15-25%)Higher rates of concordance in monozygotic twins than in dizygotic twinsAssociation with specific HLA class II genesAssociation with other genetic disorders e.g Turners syndrome

• Environmental factorsEarly childhood events e.g diarrheal illness; may increase riskAppendectomy at an early age: may decrease riskPsychological stress; may cause exacerbationsSmoking tobacco; decreases risk

• DrugsNSAID may cause exacerbationsOral contraceptives; conflicting data

• Microbial factors; important in pathogenesis

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Criteria for the diagnosis of severe UC

Feature Truelove and wittsBMJ 1955;2:1041

Werlin and GrandGastroenterology 1977;73:828-32

Bloody stools ≥ 6 per day ≥ 5 per day

Fever Mean evening

temperature > 37.3ºC

or temperature ≥ 37.8

at least 2 of 4 d

>100º during the first

hospital day

Tachycardia

Anemia

Hypoalbuminemia

ESR

> 90 bpm

Hb ≤ 75% of normal

value

> 30 mm/h

≥ 90 bpm

Hct ≤ 30%

s. Albumin ≤ 3.0 g/dL

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Extra intestinal manifestation of UC• Musculoskeletal

Peripheral arthopathyAnkylosing

spondylitis/sacroilitis EnthespathyHypertrophic

osteoarthropathyDecreased bone density

• Skin

Pyoderma gangrenosum Erythema nodosum Acne Alopecia

• Ophthalmologic Episcleritis Uveitis Cataracts Increased intracranial

pressure

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Extra intestinal manifestation of UC• Hepatobiliary Fatty liver disease Sclerosing cholangitis Autoimmune hepatitis Cholelithiasis

• Hematologic

Coagulation abnormalities Iron deficiency anemia Autoimmune hemolytic

anemia Neutropenia Thrombocytosis Immune thrombocytopenic

purpura

• Renal Nephrolithiasis

• Pancreas Pancreatitis

• Cardiorespiratory Pericarditis Pneumonitis

• Growth and development Delayed growth Delayed puberty

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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

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colonoscopy

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

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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

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• http://www.colitiscookbook.com/

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

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references

• NASPGHAN

• Allan Walker ed. Pediatric gastrointestinal disease 4rth edition

• http://www.medicinenet.com/inflammatory_bowel_disease_ibd_pictures_slideshow/article.htm

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Thank you

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