Ulcerative colitis is a chronic inflammatory condition of the large intestine and a form of inflammatory bowel disease (IBD). It is characterized by inflammation and ulcers along the inner lining of the intestinal wall, leading to symptoms like bloody diarrhea and abdominal pain. Ulcerative colitis affects the mucosa and submucosa, the innermost layers of the colon. The inflammation begins in the rectum and can spread proximally in a continuous pattern.
Contributing Factors to Disease Development
The development of ulcerative colitis is multifactorial, involving genetic susceptibility, environmental inputs, and the gut microbiome. Dozens of gene variations have been linked to an increased risk. These genes are involved in regulating immune system functions and the protective barrier of the intestines. Specific genetic changes may predispose an individual to an overactive immune reaction to harmless gut bacteria.
Environmental factors also play a part in triggering the disease in genetically susceptible individuals. These can include dietary habits, high levels of stress, and certain medications like nonsteroidal anti-inflammatory drugs (NSAIDs). The gut microbiome is another element, and an imbalance in this microbial community, known as dysbiosis, is a contributor to the inflammatory process.
This dysbiosis can disrupt the peaceful coexistence between the host and their intestinal microbes, leading the immune system to misidentify friendly bacteria as harmful invaders. The interplay between these genetic, environmental, and microbial factors creates a scenario where the immune system is primed for a response that leads to chronic inflammation.
Intestinal Barrier Dysfunction
The intestinal barrier separates the contents of the gut from the rest of the body, and its failure is a feature of ulcerative colitis. A healthy barrier is formed by a single layer of specialized epithelial cells held together by protein complexes called tight junctions. This barrier is selectively permeable, allowing for the absorption of nutrients while preventing harmful substances from crossing into the bloodstream.
In ulcerative colitis, this barrier becomes compromised. The tight junctions that bind the epithelial cells together weaken, leading to increased intestinal permeability. This “leaky gut” state allows bacteria and other microbial products, known as luminal antigens, to penetrate the deeper layers of the intestinal wall, exposing the underlying immune cells.
The breakdown of the intestinal barrier is an active process influenced by the inflammatory environment. Inflammatory signals can directly impact the proteins that form the tight junctions, causing them to disassemble. This creates a vicious cycle where initial inflammation leads to a leakier barrier, which in turn allows more antigens to cross and provoke further immune responses.
The Aberrant Immune Response
Once the intestinal barrier is breached, the immune system launches an inappropriate response. Harmless bacteria that have crossed the barrier, and sometimes the body’s own intestinal cells, are mistakenly identified as pathogenic threats. This triggers the innate immune system to dispatch cells like neutrophils to the site of the breach. In this context, their activity contributes to tissue damage.
Following the innate response, the adaptive immune system becomes involved, leading to a more specific but damaging attack. A type of T-helper cell, the Th2 cell, plays a role by mounting a cytotoxic response against the colon’s own epithelial cells. This process is driven by signaling molecules called cytokines. In ulcerative colitis, there is an overproduction of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-alpha) and various interleukins.
These cytokines act as messengers that amplify and sustain the inflammatory cascade. Instead of the immune response resolving as it would after a typical infection, it becomes chronic and self-perpetuating. The persistent release of cytokines recruits more immune cells to the colon, leading to continuous inflammation and preventing the tissue from healing properly.
Manifestation of Tissue Damage
The chronic inflammation causes the physical damage seen in the colon. This sustained attack leads to the death of epithelial cells, resulting in the formation of ulcers, which are open sores on the intestinal lining. These ulcers are responsible for symptoms like bleeding and the presence of pus in the stool.
Microscopically, the inflammation manifests in other ways. Collections of neutrophils can accumulate in the base of the intestinal glands, forming what are known as crypt abscesses. The presence of these abscesses is an indicator of the active inflammatory process within the tissue.
Another consequence of prolonged inflammation is the depletion of goblet cells. These specialized epithelial cells produce mucus, which forms a protective layer over the intestinal lining. As these cells are lost, mucus production decreases, further weakening the barrier’s defenses and leaving the underlying tissue more vulnerable to damage from luminal contents and invading bacteria.