A 28-year-old man comes to the physician because of a 6-month history of progressive fatigue and intermittent diarrhea. During this time, he has had a 6-kg (13-lb) weight loss. Physical examination shows pale conjunctivae. Abdominal examination shows tenderness to palpation in the lower quadrants. An image from a colonoscopy of the descending colon is shown. Further evaluation is most likely to show which of the following findings?

PAS-positive cytoplasmic granules

Anti-Saccharomyces cerevisiae antibodies

Positive lactose hydrogen breath test

Anti-tissue transglutaminase antibodies

A 23-year-old female presents with a seven-day history of abdominal pain, and now bloody diarrhea that brings her to her primary care physician. Review of systems is notable for a 12-pound unintentional weight loss and intermittent loose stools. She has a family history notable for a father with CAD and a mother with primary sclerosing cholangitis. Upon further workup, she is found to have the following on colonoscopy and biopsy, Figures A and B respectively. Serum perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) is positive. This patient's disease is likely to also include which of the following features?

Continuous progression beginning in the rectum

Worse disease severity near the ileocecal valve

Fistulae and stricture formation

A 31-year-old woman comes to the emergency department because of a 4-day history of fever and diarrhea. She has abdominal cramps and frequent bowel movements of small quantities of stool with blood and mucus. She has had multiple similar episodes over the past 8 months. Her temperature is 38.1°C (100.6°F), pulse is 75/min, and blood pressure is 130/80 mm Hg. Bowel sounds are normal. The abdomen is soft. There is tenderness to palpation in the left lower quadrant with guarding and no rebound. She receives appropriate treatment and recovers. Two weeks later, colonoscopy shows polypoid growths flanked by linear ulcers. A colonic biopsy specimen shows mucosal edema with distorted crypts and inflammatory cells in the lamina propria. Which of the following is the most appropriate recommendation for this patient?

Start annual colonoscopy starting in 8 years

Obtain barium follow-through radiography in 1 year

Obtain glutamate dehydrogenase antigen immunoassay now

Start annual magnetic resonance cholangiopancreatography screening in 10 years

A 22-year-old man presents to the emergency department with abdominal pain. The patient states that he has had right lower quadrant abdominal pain for "a while now". The pain comes and goes, and today it is particularly painful. The patient is a college student studying philosophy. He drinks alcohol occasionally and is currently sexually active. He states that sometimes he feels anxious about school. The patient's father died of colon cancer at the age of 55, and his mother died of breast cancer when she was 57. The patient has a past medical history of anxiety and depression which is not currently treated. Review of systems is positive for bloody diarrhea. His temperature is 99.5°F (37.5°C), blood pressure is 100/58 mmHg, pulse is 120/min, respirations are 17/min, and oxygen saturation is 98% on room air. Cardiopulmonary exam is within normal limits. Abdominal exam reveals diffuse tenderness. A fecal occult blood test is positive. Which of the following is the most likely diagnosis?

Inflammatory bowel disease (IBD)

Ulcerative colitis pathophysiology for USMLE Step 2 CK: High-Yield Internal Medicine Lessons

UC Pathophysiology - Guts Under Siege

Immune-Mediated: Genetic predisposition (e.g., HLA-B27) + environmental triggers disrupt gut homeostasis.
Barrier Dysfunction: Defective colonic epithelial barrier allows luminal antigens to penetrate the mucosa.
Aberrant Immune Response: Predominantly a Th2-mediated response.
- Key cytokines: IL-5 and IL-13.
- IL-13 ↑ epithelial permeability and induces apoptosis.

Ulcerative Colitis: Crypt Abscesses and Mucosal Inflammation

⭐ High-Yield: Approximately 60-70% of individuals with UC are positive for perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA), suggesting an autoimmune component.

The Blame Game - UC's Triggers

Multifactorial Hit: UC arises from a perfect storm of genetic susceptibility, a dysregulated immune response, and environmental insults targeting the colonic mucosa.
Genetic Blueprint:
- Polygenic; strong family association.
- Key loci involved in mucosal barrier function and immune recognition (e.g., HLA-B27).
Immune System on Overdrive:
- Aberrant, exaggerated response to gut microbiota.
- Primarily a Th2-mediated response.
- Key cytokines: ↑ IL-5, ↑ IL-13, leading to mucosal inflammation and damage.
Environmental Triggers:
- Infections (e.g., Salmonella, Campylobacter).
- Medications (NSAIDs can exacerbate).
- Diet: Western diet (↑ fats/sugars, ↓ fiber) implicated.

⭐ Smoking Paradox: Unlike in Crohn's disease, smoking is paradoxically protective in ulcerative colitis and cessation can trigger a flare.

Ulcerative Colitis Pathophysiology: Healthy vs. IBD Colon

Immune Mayhem - The Attack Within

Genetic Predisposition: Strong link to HLA-B27 and other susceptibility genes, leading to a dysfunctional immune response to gut microbiota.
Barrier Dysfunction: Compromised epithelial tight junctions allow luminal bacteria to penetrate the mucosa, triggering inflammation.
Atypical T-Cell Response: A key feature is a dominant Th2-mediated response (unlike Th1/Th17 in Crohn's).
- Produces cytokines like IL-5 and IL-13.
- IL-5 recruits eosinophils.
- IL-13 increases epithelial permeability and induces apoptosis.

Ulcerative Colitis: Crypt Abscess & Mucosal Inflammation

⭐ High-Yield: Positive Perinuclear Anti-Neutrophil Cytoplasmic Antibodies (p-ANCA) are found in ~70% of UC patients, contrasting with their lower prevalence in Crohn's disease.

Under the Scope - A Closer Look

Immune Profile: Predominantly a Th2-mediated response with atypical T-cells.
Key Mediator: ↑ production of IL-13, which compromises epithelial barrier integrity.
Antibody Association: Often positive for perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA).

Ulcerative Colitis: Crypt Abscesses and Distorted Crypts

Histological Hallmarks:
- Inflammation limited to mucosa & submucosa.
- Distorted crypt architecture & branching.
- Goblet cell depletion.

⭐ Exam Favorite: Unlike Crohn's, granulomas are absent. The presence of p-ANCA is seen in up to 70% of UC patients and is strongly associated with co-existing Primary Sclerosing Cholangitis (PSC).

High‑Yield Points - ⚡ Biggest Takeaways

Ulcerative colitis is a diffuse mucosal and submucosal inflammation limited to the colon.

It invariably involves the rectum and extends proximally in a continuous, circumferential pattern.

Hallmark pathology includes crypt abscesses, distorted crypts, and depleted goblet cells.

This is primarily a Th2-mediated immune response with atypical T-cells.

Pseudopolyps form as islands of regenerating mucosa.

Strongly associated with p-ANCA and Primary Sclerosing Cholangitis (PSC).

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