What is the underlying pathophysiology of ulcerative colitis and how does it differ to Crohn’s disease? Within this section, you can gain an overview of the pathophysiology of ulcerative colitis, its presentation and disease management.
The general principles of the pathogenesis of ulcerative colitis are similar to those described for Crohn’s disease. However, there are also some important differences (Ungaro et al., 2017).
While changes in defensins adversely affect innate immunity in ileal Crohn’s disease, in ulcerative colitis such changes may arise after inflammation (Matricon et al., 2010). In ulcerative colitis, thinning of the mucus layer contributes to impairment of the epithelial mucosal barrier (Wehkamp et al., 2016).
Following increased intestinal epithelial permeability, innate immune cells, such as macrophages, recognise bacterial antigens via toll-like receptors (TLRs) and become activated (Ordás et al., 2012). The transcription of pro-inflammatory genes is stimulated via nuclear factor kappa B pathways (NF-κB), leading to increased levels of pro-inflammatory cytokines — tumour necrosis factor α (TNFα), interleukin (IL)-1β, IL-6, IL-12 and IL-23 (Ordás et al., 2012). Processed antigens are presented to T helper (Th) cells via T cell receptors (TCRs), facilitating an adaptive immune response, while natural killer T (NKT) cells produce IL, further disrupting the epithelial barrier. Furthermore, leucocyte recruitment increases through mechanisms such as upregulation of pro-inflammatory chemokines (CXCL) and binding of integrin (α4β7)-bearing T cells to colonic endothelial cells via mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) (Ordás et al., 2012).
Ulcerative colitis is a chronic disease with relapsing and remitting inflammation (Ungaro et al., 2017). The inflammation is confined to the mucosa (Abraham and Cho, 2009) and starts in the rectum but may extend to the rest of the colon (Abraham and Cho, 2009, Danese and Fiocchi, 2011, Ungaro et al., 2017). Symptoms can vary according to the extent of colonic involvement (Ungaro et al., 2017) with bloody diarrhoea the hallmark symptom (Ordás et al., 2012).
The changing physical features of ulcerative colitis as it becomes more severe can be explored in the below animations. Endoscopy in patients with ulcerative colitis can help in the classification of the disease as proctitis, left-sided disease or pancolitis. The animations help depict the changing physical manifestations seen within the bowel as inflammation increases as well as highlighting the differences between ulcerative colitis’ proximal distribution of lesions versus the skip lesions seen in Crohn’s disease.
Take a virtual journey through the bowel of a patient with ulcerative colitis.
These animations are taken from the Gastro Ex app that allows gastroenterologists from all around the world to virtually diagnose conditions and perform life-like interventional procedures. Free for healthcare providers, the app can be downloaded from the App Store or on Google Play.
Compare this to virtual journey through the bowel of a patient with Crohn’s disease here.
Based primarily on the daily number of stools and the presence of inflammatory signs, ulcerative colitis can also be classified as mild, moderate, severe or fulminant (Table 1) (Feuersten and Cheifitz, 2014).
Table 1: Classification of ulcerative colitis (Feuersten and Cheifitz, 2014).
Around one-third of patients have extra-intestinal manifestations (Ungaro et., 2017). These can include effects on the skin, joints or eyes (Neurath, 2014; Danese and Fiocchi, 2011).
Use of 5-aminosalicylates is more effective in ulcerative colitis than Crohn’s disease (Neurath, 2017). Consequently, these are the main treatment option for ulcerative colitis patients with mild to moderate disease (Feuerstein and Cheifitz, 2014). Traditional step-up approaches are used (Feuerstein and Cheifitz, 2014; Ungaro et al., 2017), whereby patients can receive steroids and immunosuppressants, as well as the biological therapies that address pro-inflammatory targets as described in the inflammatory targets section of this Knowledge Centre. However, around 15% of patients may still need colectomies (Feuerstein and Cheifitz, 2014; Ungaro et al., 2017).
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