WEEK 4 - Inflammatory Bowel Conditions

UC: colon only, continuous retrograde inflammation beginning at rectum, mucosal inflammation, no granulomas, crypt distortion, loss of haustra , pseudopolyps CD: anywhere (mouth to anus), discontinuous inflammation (skip lesions), transmural inflammation, granulomas may be present, extracolonic disease (abscesses, fistulae, perianal disease), thickened wall, “cobble stoning”

Inflammation doesn’t resolve normally - prolonged inflammatory response. Lack of clear resolution. Inflammation is self perpetuating. Persistent. Damage of tissue. New connective tissue formation (scarring, fibrosis). Granuloma formations in CD

Diffuse inflammation of the mucous membrane of the colon. Confined to colon only. Clinical manifestations vary with location, extent and severity of disease.

Inflammation confined to the rectum. Main symptom = passing fresh blood of blood stained mucous. May have diarrhoea, normal stools or constipation. Inflammation can causes urgent need to pass stool. Tenesmus - feeling of incomplete stool excretion.

Inflammation starts in the rectum and extends up through the left side of the colon up to the splenic flexure. Symptoms = bloody diarrhoea, mucous, pain in L) side of abdo, urgency, tenesmus.

Inflammation of an extensive length of the colon. Symptoms = frequent diarrhoea with blood, mucous, sometimes pus, severe abdo cramps & pain, tenesmus, weight loss.

Very severe diarrhoea with blood, mucous, sometimes pus. Severe abdo cramps & pain, tenesmus, weight loss. Nocturnal diarrhoea. Medical emergency - usually requires hospitalisation.

Change of structure & function of bowel Anaemia Haemorrhage Perforation Toxic megacolon

Affects any part of the GIT from mouth to anus. Most common = terminal ileum (1st) then colonic (2nd). Patchy inflammation, skip lesions. Inflammation of the bowel wall. Clinical manifestations vary with extent, severity of disease & complications.

Right lower abdo pain Impaired bile salt absorption Impaired vit B12 absorption Diarrhoea or constipation

Abdo pain and diarrhoea. The diarrhoea is unlikely to be blood stained as blood will be degraded by digestive processes.

Blood stained diarrhoea. Frequent bowel actions, especially if sigmoid & rectum involves. Often called Crohn’s colitis.

Anal fissures Skin tags Fistulas Abscesses Perforation

Ongoing episodes of inflammation & healing - fibrotic tissue - stricture. Symptoms = cramping abdo pain, nausea, abdo bloating, constipation, loud bowel noises. Strictures can lead to partial or complete bowel obstruction. Solutions: dilatation, strictureplasty, bowel resection.

Malnutrition Osteoporosis Anaemia Fatigue IBS Psychosocial

Joint: arthritis, arthralgias Ankylosing spondylitis Primary sclerosing cholangitis Eye inflammation Renal/biliary stones Skin: erythema nodosum, pyoderma gangrenosum

Largely unknown Ethnicity: Jewish, Caucasian, developed countries Age: 26-30, typical onset 20s Smoking: Crohn’s disease, protective factor in ulcerative colitis Crohn’s disease: more common in females and younger children than UC Genetic influences are stronger in CD than UC

Environmental factors Genetic predisposition Gut microbiota Host immune response (innate/adaptive)

• Altered microbiota (less diverse?), over abundance of pro-inflammatory flora. • Degradation & loss of mucosal layers (loss of protective mechanisms) • Loss of epithelial junctions - leaky gut • ? Disordered response to micro flora by TLR & antigen presenting cells • Over expression of pro inflammatory cytokines (phagocytes, neutrophils, macrophages) & production of prostaglandins (pain) • Activation, differentiation & proliferation of lymphocytes - vasodilation (redness & swelling) - increase in vascular permeability - tethering & extravasation of WCs - leakage of plasma (swelling)

Time course of illness: Gastroenteritis = common & short lived, abrupt onset, symptoms worse at onset, history of contacts. IBD = onset more gradual & insidious with crescendo or fluctuating pattern, symptoms longer than initially acknowledged.

Organic vs. functional Inflammation acute or chronic? Is there damage or structural change?

Functional gastrointestinal disorder Disturbance in bowel function affecting sensorimotor function of the gut More common Without alarm bells or abnormal blood tests Has some similar symptoms to IBD

Clinical presentation Blood examination (FBE, biochemical, inflammatory markers, iron studies, coeliac antibody testing) Stool testing (culture, faecal calprotectin) Imaging (abdo X-ray, CT, MRI, US) Endoscopy & histology

Goals: Treat acute disease … - reduce or control intestinal inflammation - mucosal healing - minimise side effects & long term adverse effects - eliminate symptoms Improve & maintain General well being & quality of life Correct nutrition deficiencies Maintain steroid free remission Prevent disease progression & complications Type/location/severity of disease/existing complications/risk factors will direct type of treatment & mode of delivery