pathophysiology Prof. Sina Aziz PhD (Paediatrics) KMDC/ASH - - PowerPoint PPT Presentation

IBD (Inflammatory bowel disease) pathophysiology

• Prof. Sina´ Aziz

PhD (Paediatrics) KMDC/ASH

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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

• f 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 disease and 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.

• .

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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
• f inflammation of the rectum (known as

proctitis).

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Signs and symptoms

• IBD can cause other health problems that
• ccur 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 event infectious Genetic predisposition Gut microflora Abnormal mucosal immune response Intestinal inflammation Normal homeostasis Chronic IBD

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

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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 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
• f 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 1990-1999 and

Gastroenterol clin north am 2002;31:307-27

% 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% Ileocolonic inflammation In combination with colon 20% 20% Colon involvement Colon 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 inflammation

• f 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 surveillance N = 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) 13 8 1 1 1 1 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 299

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EXTRA INTESTINAL MANIFESTATIONS JOINTS SKIN EYE HEPATOBILIARY PANCREAS RENAL VASCULAR BONE

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

• f 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

• f 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 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

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Criteria for the diagnosis of severe UC

Feature Truelove and witts

BMJ 1955;2:1041

Werlin and Grand

Gastroenterology 1977;73:828-32

Bloody stools ≥ 6 per day ≥ 5 per day Fever Mean evening temperature > 37.3ºC

• r 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 arthopathy
• Ankylosing

spondylitis/sacroilitis

• Enthespathy
• Hypertrophic
• steoarthropathy
• Decreased 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/articl e.htm

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Thank you

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