Medicine

Last updated on: October 2nd, 2022

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Ulcerative Colitis

Introduction

Definition

Ulcerative colitis (UC) is a chronic inflammatory bowel condition with a relapsing and remitting disease course that often presents with hematochezia, abdominal pain, rectal urgency and tenesmus, among other symptoms. UC begins in the rectum and extends proximally. Though it primarily affects the lower gastrointestinal (GI) tract, multiple extra-gastrointestinal systems can be affected.

Classification

UC is classified according to the Montreal classification. This describes UC by disease extent according to the area of the gastrointestinal tract affected. E1 or proctitis is disease limited to the rectum; E2 is left-sided disease distal to the splenic flexure; and extensive colitis or E3 is disease extending proximal to the splenic flexure.

Etiology

The development of UC is influenced by the interaction between external environmental factors (so-called “exposomes”), immune system dysregulation, epithelial and mucosal barrier defects in the colon, dysbiosis, and disruption of GI homeostasis in a genetically susceptible individual.

Pathogenesis

UC's disease process involves epithelial and mucosal dysfunction in the colon which allows the infiltration of luminal gut bacteria. This initiates an inflammatory cascade within the colonic mucosa, leading to gut dysbiosis. Depleted goblet cells, a porous mucus barrier and inflammatory cytokines facilitate this process. Immune dysregulation in the form of T helper cells leads to the perpetuation of cellular apoptosis and inhibits mucosal healing. Though an autoimmune link has been considered due to the detection of anti-colon, perinuclear anti-neutrophil cytoplasmic antibodies and anti-neutrophil cytoplasmic antibodies, these have not been found in high enough concentrations to be causative.

Epidemiology

Though UC can occur at any age, most cases are in the 15-40-year age group. UC has been found to be at a higher incidence in westernized, developed countries, although rates in developing countries are increasing.

Disease complications

UC has many complications. These include, but are not limited to:

  1. Acute severe ulcerative colitis (ASUC): ASUC is a worrying complication of UC that requires hospitalization and can require a colectomy to treat. It is defined by the modified Truelove and Wits criteria as 6 or more bloody stools a day with symptoms of systemic toxicity, including a temperature of ≥37.8 ˚C, hemoglobin (Hb) <10.5g/dL, erythrocyte sedimentation rate (ESR) >30mm/hr, or a pulse ≥90bpm.
  2. Toxic megacolon: Toxic megacolon is a rare but potentially fatal complication of UC, inflammatory bowel disease (IBD), or any condition that causes inflammation of the colon. It is diagnosed by a colonic dilatation >6cm, plus any three of the following: fever (>38.6 ˚C), tachycardia (>120 bpm), leukocytosis (>10.5 x 103 µl), or anemia with either hypotension, hypovolemia, altered mental status or electrolyte disturbances.
  3. Primary sclerosing cholangitis (PSC): PSC is a cholestatic liver disease that involves inflammation and fibrosis of the biliary tract. It is diagnosed by a cholestatic pattern on liver function tests (elevated alkaline phosphatase and gamma-glutamyl transferase), and a pattern of strictures and dilatations in the biliary tracts. Histologically, lymphocytic infiltration is appreciated in the bile ducts. PSC increases the risk of colorectal cancer and mortality in UC patients.
  4. Venous thromboembolism: The risk of venous thromboembolism is 3-4 times higher in UC patients, particularly those being treated with corticosteroids for a flare.
  5. Hepatobiliary complications: Hepatitis can arise in multiple ways in UC. Firstly, in those infected, immunosuppressant regimens can lead to reactivation of Hepatitis B or other viruses (EBV, CMV). They can also cause drug-induced inflammation through their own effects on the liver. Autoimmune hepatitis and granulomatous hepatitis are autoimmune and inflammatory conditions respectively which are also associated with UC.
  6. Cardiovascular events: Due to systemic inflammation and endothelial dysfunction, patients with UC are at an increased risk of developing both arterio-vascular and cardiovascular insults.
  7. Benign strictures: Benign strictures are structural adhesions that can occur in the colon secondary to colonic inflammation of UC. Together with chronic colonic inflammation, these can contribute to colonic dysmotility and anal dysfunction.
  8. Malabsorption and malnutrition: Malnutrition in UC can occur for a range of reasons. Firstly, UC symptoms can act as a deterrent to normal food intake, leading to loss of appetite and under-eating. Secondly, medications may cause GI discomfort and lead to food avoidance, while specific medications such as glucocorticoids, may disrupt the absorption of calcium, phosphorus, and zinc and lead to osteopenia. Chronic mucosal inflammation can lead to the loss of electrolytes, proteins, and blood across the lumen. Iron, Vitamin B12 and folic acid deficiencies are common in UC.

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