Inflammatory Bowel Disease

1. Inflammatory Bowel Disease Alice Keyte ajk1g10@soton.ac.uk

2. IBD CROHN’S DISEASE ULCERATIVE COLITIS • ‘idiopathic, chronic, relapsing and remitting, inflammatory condition of the gastrointestinal tract’

3. ULCERATIVE COLITIS Acute, intermittent, chronic Inflammatory condition of unknown aetiology – affecting the large bowel Starts at rectum and extends proximally More common in women (20-35years) More common in non-smokers (smoking = protective) ASYMPTOMATIC or SYMPTOMATIC

4. Aetiology Environment IBD Atypical Immune Response Genetics Triggers: Bacteria Viruses Stress Less of link compared to CD. Unclear

5. Atypical Immune Response Normally: CD4 T lymphocytes T2 immune response – cytokine release

6. Anatomy – The Colon Colonic wall = simple columnar epithelium w. columnar absorptive cells + mucus-secreting goblet cells. Submucosa Inner circular + outer longitudinal SM layer (longitudinal = 3 bands – teniae coli haustrations Serosa Function = absorb water + small electrolytes into mesenteric vessels, causing stool to become solid.

7. Blood Supply

8. Ulcerative Colitis

9. Signs & Symptoms • General • Weight loss (due to malabsorption + inflammation) • Specific • Abdominal pain • Diarrhoea +/- blood, mucus (iron deficiency anaemia) • Urgency • Tenesmus (feeling of not finishing defecation) • Fever • Extra-Intestinal • Uveitis • Ankylosing spondylitis • Erythema nodosum

10. Complications Intestinal bleeding from ulcers Perforation, or rupture of bowel = peritonitis Strictures = large bowel obstruction Fistulae and perianal disease, disease in the tissue around the anus - more common in Crohn’s. Toxic megacolon- extreme dilation of the colon that is life-threatening; more common in ulcerative colitis. Colon cancer – more common in UC. Secondary arthritis

11. Investigations • Cultures: • Stool (rule out bacterial, viral, parasitic cause + blood) • Blood • Bloods: • FBC, U&Es (hypokalaemic w. severe diarrhoea), CRP/ESR, WBC, albumin • Imaging: • Erect chest X-ray (perforation = free air under diaphragm) • Abdo X-ray – (exclude toxic megacolon + strictures) • Barium enema (lead-piping, loss of haustra, granula mucosa) • CT • Scopic: • Sigmoidoscopy/colonoscopy (intestinal wall is visually examined for ulcers, inflammation + bleeding. Biopsies may be taken. Crypt abscesses, no serosal involvement)

12. Differential Dx Colonic Malignancy Megatoxic Colon Infective Cause - Gastroenteritis

13. Treatment CONSERVATIVE SURGICAL MEDICAL Aims: • reduce symptoms by inducing and maintaining remission • Increase quality of life • Suppress abnormal inflammatory response – promote healing • Decreasing frequency of flare-ups Dependant on extent and severity of disease

14. Truelove and Witts Criteria Used for classifying disease severity in UC.

15. Conservative Mx NBM Fluids Analgesia Diet

16. Diet Normal – avoiding trigger foods such as: ↑fibre, ↑ fat, skins. Low residue diet = reduces fibre + relieve symptoms (may need Vitamin supplements)

17. Medical Mx I - ACUTE • IV hydrocortisone 4-5days • Recal steroids- • Prednisolone. • Glucocorticosteroids • Anti-inflammatories • Water + Na absorption

18. Mx II • If improving + no complications: Oral Prednisolone (8wks, start: 40mg ↓ by 5mg each week) + Sulphasalazine/Mesalazine (Aminosalicylate + Anti-inflammatory) + Mebeverine(anti-spasmodic) • If complications develop or refractory to medical tx: • Total or sub-total colectomy with ileostomy, anastamosis or ileal pouch.

19. Side-Effects Iatrogenic Cushing’s Syndrome – prolonged administration Euphoria Depression ↑ risk of infection ↑ risk of peptic ulcers – OMEPRAZOLE Osteoporosis – CALCICHEW D3

20. Medical – If all else fails! • Azothioprine • Immunosuppressant • 2-3 months to take action • Regular blood tests • Safe in pregnancy • Use due to poor maintenance of remission and acute flare ups.

21. Mx III • Elective Surgery • Chronic symptoms • High grade dysplasia/carcinoma (UC = increased risk) • Fail to respond to Medical Tx

22. Surgery Curative. Entire colon is removed. Ileo-anal anastomosis created – stoma bag.OR Small intestine is reshaped to form an ileo-anal (PARK’s) pouch

23. CROHN’s DISEASE • “Inflammatory condition of unknown aetiology affecting entire length of the GI tract, mouth to anus” • M = F • Peak at 20-40 years • More common in smokers • Genetic link (disease concordance in genetic twins = 50%) • Characterised by: • Patchy transmural inflammation with non-caseating granulomas

24. Aetiology of CD • Unknown • Believed due to: • Immunodeficiency to maintain appropriate epithelial barrier

25. Pathophysiology Initial insult to gut from microbe Innate immune system responds to bacteria Chronic inflammatory response

27. Signs & Symptoms • Depends on site • General: • Weight loss • Fever in acute (low grade) • Specific (anything!): • Diarrhoea (blood/mucus) • Abdo. pain • Features of obstruction • Mouth ulcers • Extra-intestinal: • Ankylosingspondylitis (arthritis in lower spine) • Erythema nodosum (red rash on legs)

28. Examination • General: • Clubbing • Aphthous ulcers • Abdomen: • Tender • RIF mass • PR: • Perianal disease (e.g. skin tags, fistulas, fissures, perianal abscess)

29. Investigations • Cultures: • Stool (rule out bacterial, viral, parasitic cause + blood) • Blood • Bloods: • Venous - FBC, U&Es (hypokalaemic w. severe diarrhoea), CRP/ESR, WBC, albumin, Group + save for surgery • Imaging: • Erect chest X-ray (perforation = free air under diaphragm) • AbdoX-ray • Barium enema + FOLLOW-THROUGH (gives info of small intestine) • CT • Scopic: • Colonoscopy (Cobblestone appearance, fissuring, serosal involvement)

31. Mx I - Conservative Analgesia NBM Fluids

32. Mx II - Medical • Must not be taken for at least 6 months before trying for a baby – cause birth defects. • Avoided when breast feeding • Steroid (prednisolone) + immunosuppressant's (azathioprine/methotrexate) • Biological Therapies – treat moderate to severe CD, when standard tx is ineffective. • Infliximab • Anti-TNF agent • Powerful immunosuppressant

33. Additional Mx CD + perianal disease (complication) = give Antibiotic

34. Mx III - Surgical • 70% of CD patients will require surgery after 10years • EMERGENCY – tx complications • ELECTIVE – tx chronic problems • Options: • Limited resections of bowel • Ileocaecal resection • Removal of strictures via stricturoplasty

35. Macroscopic Pathology

36. Microscopic Pathology

37. Histology

38. Question 1 • Outline the main pathological differences in the bowel between Crohn’s disease and Ulcerative Colitis • Crohn’s – Affects mouth to anus, Skip lesions, Cobblestone mucosa, Fistulae, Transmural pathology, Granulomatous • UC – Affects only the colon (exception in backwash ileitis), Crypt abscesses, Severe ulceration, Goblet cell depletion.

39. Question 2