Inflammatory Bowel Disease

Both forms of IBD are idiopathic, lifelong, and relapsing-remitting: patients cycle through remissions "that can last for weeks or years" and then relapse, and neither disease has a medical cure. The shared model is a chain: genetic susceptibility plus an environmental trigger produce a defective epithelial barrier — in ulcerative colitis (UC) a defect in colonic mucin and tight junctions — which lets more luminal microbial antigens cross into the lamina propria, where dendritic cells bristling with TLR2/TLR4 mount a dysregulated mucosal immune response to the gut microbiota. The result is chronic inflammation aimed, in effect, at the body’s own bacteria. Genes, abnormal immune reactions, the microbiome, and the environment all play a role; family history is the single most important independent risk factor for UC, and in Crohn’s disease (CD) NOD2/CARD15 mutations are tied to ileal involvement, earlier onset, and more severe disease.

The two diseases then diverge at the T-cell. UC runs an atypical Th2-skewed response — IL-13, NK-T cells, TNF-α, and a disproportionate IgG1 rise — that is directly cytotoxic to the epithelium. CD is a Th1/Th17 cascade: interferon-γ, IL-2, IL-12, IL-18, and TNF-α poured out by macrophages, neutrophils, and T-helper cells. Both share the leukocyte-recruitment step that modern drugs exploit: UC upregulates the chemoattractant CXCL8 and the endothelial adhesion molecule MAdCAM-1, which pulls leukocytes out of the bloodstream into the mucosa — the exact handshake vedolizumab blocks by binding the α4β7 integrin.

Two systemic consequences follow the inflammation wherever it lives. IBD "promotes a hypercoagulable state": thromboembolic events arise from chronic systemic inflammation, occur independently of how the bowel looks, and escalate during flares — hospital immobility stacks on top, which is why VTE prophylaxis is part of every IBD admission. And chronic inflammation plus malabsorption and gut losses produce malnutrition early: at diagnosis roughly 60% of CD and 35% of UC patients are already underweight.

UC is "an idiopathic inflammatory condition of the colon that results in diffuse friability and superficial erosions on the colonic wall and associated bleeding." Two rules define it. Depth: inflammation is restricted to the mucosa and submucosa — it does not tunnel through the wall. Pattern: "the disease starts in the rectum and extends proximally in a continuous manner" — never skipping. The Montreal classification names the reach: E1 proctitis (rectum only), E2 left-sided colitis, E3 pancolitis (the whole colon, past the splenic flexure). UC is a colon disease; it spares the small bowel apart from backwash ileitis, in which the distal ileum shows inflammatory changes from the adjacent cecum — so "UC never touches the ileum" is an oversimplification.

Because the injured surface is a friable, bleeding mucosa, the cardinal symptom is bloody diarrhea with or without mucus (> 90% of patients), with tenesmus (a constant urge to defecate) and fecal urgency in more than 70%. Under the endoscope the mucosa has lost its vascular pattern and is granular, friable, and ulcerated "in a symmetric, continuous, and circumferential pattern" from the distal rectum upward, with islands of surviving mucosa standing up as pseudopolyps. Biopsy shows crypt abscesses, cryptitis, distorted crypt architecture, goblet-cell (mucin) depletion, and diffuse inflammation — and no granulomas. Roughly 15–30% of colonic IBD cannot be labeled UC or CD at first and is called indeterminate colitis.

The lethal turn happens when inflammation stops respecting the depth rule. If a severe flare reaches the muscularis propria, "it may damage the nerves resulting in dilatation, aperistalsis, and ischemia" — toxic megacolon, a nonobstructive dilation of the colon with systemic toxicity, the most common cause of death in UC, complicating about 5% of acute severe UC (and about 2.3% of CD). Inducible nitric oxide synthase floods the wall with nitric oxide and the smooth muscle stops contracting; the colon balloons past 6 cm, loses its haustral markings, and — once the wall thins — perforates. The precipitants are the nursing lesson: antimotility agents, opioids, anticholinergics, antidepressants, hypokalemia, C. difficile and other enteric infections, and colonoscopy, bowel prep, or barium enema performed in an inflamed colon.

CD is "transmural inflammation that can involve any segment of the gastrointestinal tract" — from the mouth to the anus — with skip lesions: diseased segments separated by normal mucosa. The favored real estate is the terminal ileum and right colon, and the rectum may be spared — the mirror image of UC. Endoscopically the mucosa is segmental and cobblestoned; biopsy shows focal, patchy inflammation and, in up to 33% of patients, the most discriminating finding of all — the noncaseating granuloma. Its absence does not exclude the diagnosis, which is why multiple biopsies are taken.

Depth is the whole story of CD’s complications. Ulceration begins in the superficial mucosa, then fissuring ulcers extend through the entire wall. Chronic transmural injury heals by fibrosis, and fibrosis narrows the lumen into strictures — about 60% of CD patients develop them, and roughly half develop fistulae, phlegmons, strictures, or abscesses within 20 years. When the fissure crosses the wall instead, it forms a fistula into whatever lies next door (bladder, skin, vagina, another loop of bowel) or walls off as an abscess. UC, by contrast, rarely strictures and does not fistulize — perianal fistulae are common in Crohn’s and absent in UC.

Location drives the nutritional picture. Jejunoileal disease causes malabsorption and steatorrhea, bleeding iron, albumin, calcium, magnesium, the fat-soluble vitamins A, D, E, and K, folate, zinc, selenium, and copper. Terminal-ileum disease or resection removes the only site that absorbs vitamin B12, spills bile salts (→ gallstones), and lets unabsorbed fat bind calcium so that oxalate is absorbed instead (→ calcium-oxalate kidney stones). Since CD often produces nonbloody chronic diarrhea and vague abdominal pain, the tell-tale symptom is frequently weight loss, and in children growth failure.

Cell by cell: Location — UC colon only, always beginning at the rectum; CD anywhere from mouth to anus, favoring the terminal ileum and right colon, often sparing the rectum. Depth — UC mucosa and submucosa; CD transmural. Pattern — UC continuous, circumferential, pseudopolyps, crypt abscesses, no granulomas; CD skip lesions, cobblestoning, fissures, noncaseating granulomas (up to 33%). Stools — UC frequent bloody, mucoid diarrhea with tenesmus (rectal bleeding in 52–97%); CD diarrhea often nonbloody (bleeding 14–60%), with steatorrhea when the small bowel is involved. Pain — UC cramping, typically left lower quadrant in distal disease (typical, not diagnostic — pancolitis hurts everywhere); CD right lower quadrant, colicky, often relieved by defecation, and able to mimic appendicitis. Perianal disease — fistulae, abscesses, fissures, and skin tags in about 25% of CD, essentially none in UC. Malabsorption and B12 deficiency — a CD feature from ileal disease. Cancer — colorectal risk rises in both when the colon is involved; in UC it climbs with duration and extent, while CD small-bowel cancer risk stays low.

Smoking is the paradox that trips students. In CD smoking is unambiguously harmful — it may double the chance of developing the disease, precipitates flares, and raises recurrence after surgery — so every CD patient is urged to stop. In UC, epidemiology shows the reverse association: the disease is more prevalent in nonsmokers and recent quitters, smokers tend to have milder disease, and smoking cessation is a recognized flare trigger. The correct teaching is the paradox itself, plus vigilance around a UC patient who has just quit — never smoking as therapy. NSAIDs are the other shared trigger: they are linked to onset and relapse in both diseases, so pain gets acetaminophen.

Surgery completes the chart with its own nuance. Because UC lives only in the colon, colectomy "is curative in patients with ulcerative colitis" — but curative of the colitis: pouchitis and other pouch complications follow the J-pouch, EIMs that run independently (PSC, uveitis, ankylosing spondylitis) persist, and colorectal-cancer risk is realizable before and after restorative surgery. In CD surgery is not curative: disease recurs, "frequently at the anastomosis site," with endoscopic recurrence near 90%, so operations are bowel-sparing. Finally, extraintestinal manifestations (EIMs) touch 10–30% of UC patients and up to half of all IBD patients over a lifetime; some (peripheral arthritis, erythema nodosum, episcleritis, aphthous ulcers) parallel bowel activity and settle when the colitis is treated, while others (ankylosing spondylitis, uveitis, primary sclerosing cholangitis, thromboembolism) run their own course.