My Clinical Notes

• Chronic, relapsing, idiopathic inflammation of the GIT, thought to be due to local immune responses to the intestinal flora
• Two disorders – UC and Crohn’s with common features but different clinical manifestations
• The incidence in 1 in 200 in people of northern European decent
  • Crohn disease – granulomatous IBD affecting any portion of the gut but most commonly the distal small intestine and colon
  • Ulcerative colitis – IBD without granuloma formation affecting only the colon and rectum

 

Aetiology and pathogenesis

• IBD results from unregulated and exaggerated local immune responses to commensal microbes in the gut, in genetically susceptible individuals
• Genetic susceptibility
  • There is familial clustering, multigenetic aetiology
  • NOD2 gene mutations have been associated with CD. It encodes for a protein which regulates proinflammatory cytokine production and innate defences against intracellular microbes
  • Knock out animal models e.g. IL-10 KO get disease
• Role of intestinal flora
  • If animal models of disease are raised in a germ free environment they don’t get disease
  • No specific microbe has been identified
• Abnormal T cell responses
  • Exaggerated T cell activation and deficits in T cell regulation

 

• Is disease autoimmune or directed against the microbial antigens?;
  • Disease caused by CD4 T cells, some of which recognise self antigens such as tropomyosin but it is unclear if these antibodies have a pathogenic role
  • Crohn disease appears to be due to a chronic delayed type hypersensitivity response induced by IFN-γ producing Th1 cells
  • Some suggestion from animal models that UC is a Th2 disease but IL4 is not found in the lesions in humans

 

Crohn Disease

 

• Characterised pathologically by;
  • Sharply delimited and typically transmural involvement of the bowel by an inflammatory process with mucosal damage
  • The presence of noncaseating granulomas
  • Fissuring with the formation of fistula

 

Epidemiology

• Primarily occurs in the West
• Incidence is between 4 and 10 per 100000 with incidence and prevalence steadily rising
• Peak age of detection are the second and third decades of life, F>M and whites more than nonwhites

 

Morphology

• There is gross involvement of the SI alone in around 40% of cases, the SI and colon in 30% of cases and the colon alone in 30% of cases
• Other areas such as the mouth, oesophagus and stomach can be affected but less commonly
• Gross findings;
  • Skip lesions with granular and inflamed seros and adherent ‘creeping’ mesenteric fat
  • Rubbery thick bowel wall with oedema, inflammation, muscular hypertrophy and often strictures. As a result the lumen is generally narrowed
  • Punched out mucosal aphthous ulcers and linear ulcers
  • As the intervening mucosa tends to be relatively spared the mucosa acquires a cobblestone appearance
• Histological characteristics
  • Mucosal inflammation and ulceration with intraepithelial neutrophils (earliest lesion) and crypt abscesses. Mononuclear inflammation of the LP
  • Chronic mucosal damage – this is the hallmark of IBD with villus blunting and atrophy in the colon the crypts display irregularity and distortion. The mucosa may undergo atropy
  • Ulceration – may be superficial of penetrate into deeper layers
  • Transmural inflammation with lymphoid aggregates in the submucosa, muscle wall and subserosal fat
  • Noncaseating granulomas – may be rpesent throughout the gut even in uninvolved segments

 

Clinical

• Manifestations are very variable
• There may be intermittent attacks of fever, diarrhoea, abdo pain, anorexia and weight loss
• There may be complications from fibrotic strictures; fistula to adjacent viscera, abdominal and perineal skin, bladder or vagina. There may be malabsorption and malnutrition and loss of albumin
• There is increased risk of bowel cancer (risk is greater with UC)
• There may be extraintestinal manifestations;
  • Migratory polyarthritis
  • Sacroilitis
  • AS
  • Erythema nodosum
  • Clubbing of the fingers
  • Uveitis
  • Cholangitis
  • Amyloidosis

 

Ulcerative Colitis

 

• Disease is limited to the colon and generally only affects the mucosa and submucosa
• Unlike CD it extends in a continuous fashion proximally from the rectum
• Well formed granulomas are absent
• Like CD, UC is a systemic disorder which is associated in some patients with;
  • Migratory polyarthritis
  • Sacroilitis
  • AS
  • Uveitis

 

Epidemiology

• Slightly higher incidence compared with CD of 4 to 12 per 1000000
• Again more common in white populations and females are more affected than women
• Onset of disease peaks around 20-25
• Non smoking is associated with UC

 

Morphology

• Pancolitis, no skip lesions
• Gross findings
  • Mucosa may be reddened, granular and friable
  • There may be ulceration of the mucosa and isolated islands of regenerating mucosa bulge upwards to create pseudopolyps
  • The mucosa may also be atrophic and flattened
  • Unlike CD, mural thickening doesn’t occur and the serosal surface is generally normal
• Microscopic findings
  • Mucosal inflammation is similar to CD with crypt abscesses, ulceration, chronic mucosal damage, glandular architectural distortion and atrophy
  • Fissures, aphthous ulcers and granulomas are absent
  • In treated or inactivated disease, the mucosa may revert to near normal
  • Particularly significant in UC is the spectrum of epithelial change signifying dysplasia and the progression to frank carcinoma

 

Clinical

• Intermittent attacks of bloody mucoid diarrhoea and abdominal pain
• Rarely presents as an explosive illness with severe electrolyte disturbances and toxic megacolon (a massively dilated non-functional colon)
• The risk of carcinoma developing from dysplasia is highest in patients with pancolitis of greater than 10 years duration

This entry was posted on Monday, February 25th, 2008 at 5:11 pm and is filed under Gastrointestinal. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.