A 27-year-old female has a history of periodic bloody diarrhea over several years. Colonoscopy shows sigmoid colon inflammation, and the patient complains of joint pain in her knees and ankles. You suspect inflammatory bowel disease. Which of the following would suggest a diagnosis of Crohn disease:

Mucosal and submucosal ulcerations

A 33-year-old man has a history of intermittent bloody diarrhea, tenesmus, fever, fatigue, and lower abdominal cramps for the past 2 weeks. On physical examination, he is lethargic and appears lean and pale. He has aphthous stomatitis, red congested conjunctiva, and tender swollen joints. At the doctor’s office, his pulse is 114/min, blood pressure is 102/76 mm Hg, respirations are 20/min, and his temperature is 39.4°C (102.9°F). There is vague lower abdominal tenderness and frank blood on rectal examination. Laboratory studies show: Hemoglobin 7.6 g/dL Hematocrit 33% Total leucocyte count 22,000/mm3 Stool assay for C.difficile is negative Abdominal X-ray shows no significant abnormality He is symptomatically managed and referred to a gastroenterologist, who suggests a colonoscopy and contrast (barium) study for the diagnosis. Which of the following is the most likely combination of findings in his colonoscopy and barium study?

Colonoscopy: Continuous ulcerated lesions involving the mucosa and submucosa, granular mucosa, crypt abscess, and pseudopolyps, Barium study: Lead pipe colon appearance

Colonoscopy: Multiple vascular malformations that resemble telangiectasias on the colon wall, Barium study: Normal

Colonoscopy: Patches of mucosal erosions with pseudomembrane formation, Barium study: Cobblestone appearance with strictures

Colonoscopy: Discontinuous transmural ‘skip lesions’ with aphthoid linear ulcers and transverse fissures, non-caseating granulomas, and strictures, Barium study: Cobblestone appearance with strictures

Colonoscopy: Normal, Barium study: Lead pipe colon appearance

A 22-year-old man comes to the physician because of a 3-week history of abdominal pain, loose, non-bloody stools, and intermittent nausea. He also reports intermittent fever. He has not had vomiting, tenesmus, or rectal pain. He has no history of serious illness and takes no medications. His vital signs are within normal limits. Rectal exam is unremarkable. Laboratory studies show a leukocyte count of 15,200/mm3 and an erythrocyte sedimentation rate of 44 mm/h. Test of the stool for occult blood and stool studies for infection are negative. A CT scan of the abdomen shows mural thickening and surrounding fat stranding of discrete regions of the terminal ileum and transverse colon. A colonoscopy is performed and biopsy specimens of the affected areas of the colon are taken. Which of the following findings is most specific for this patient's most likely diagnosis?

Intranuclear and cytoplasmic inclusion bodies

Neutrophil-rich pseudomembranes

Neutrophilic inflammation of the crypts

Inflammation of the terminal ileum

A 22-year-old woman presents to the emergency department with a 3-day history of fever and abdominal pain. She says that the pain is located in the left lower quadrant of the abdomen and feels crampy in nature. The pain has been associated with bloody diarrhea and joint tenderness. She has no past medical history but says that she returned 2 weeks ago from vacation in Asia where she tried many new foods. Her family history is significant for multiple cancers in close relatives. Physical exam reveals swollen ulcers on her legs, and colonoscopy reveals contiguous ulcerations from the rectum through the descending colon. Which of the following is associated with the most likely cause of this patient's symptoms?

Perinuclear anti-neutrophil cytoplasmic 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 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)

A 25-year-old man presents to the emergency department for severe abdominal pain. The patient states that for the past week he has felt fatigued and had a fever. He states that he has had crampy lower abdominal pain and has experienced several bouts of diarrhea. The patient states that his pain is somewhat relieved by defecation. The patient returned from a camping trip 2 weeks ago in the Rocky Mountains. He is concerned that consuming undercooked meats on his trip may have caused this. He admits to consuming beef and chicken cooked over a fire pit. The patient is started on IV fluids and morphine. His temperature is 99.5°F (37.5°C), blood pressure is 130/77 mmHg, pulse is 90/min, respirations are 12/min, and oxygen saturation is 98% on room air. Laboratory studies are ordered and are seen below. Hemoglobin: 10 g/dL Hematocrit: 28% Leukocyte count: 11,500 cells/mm^3 with normal differential Platelet count: 445,000/mm^3 Serum: Na+: 140 mEq/L Cl-: 102 mEq/L K+: 4.1 mEq/L HCO3-: 24 mEq/L BUN: 24 mg/dL Glucose: 145 mg/dL Creatinine: 1.4 mg/dL Ca2+: 9.6 mg/dL Erythrocyte sedimentation rate (ESR): 75 mm/hour Physical exam is notable for a patient who appears to be uncomfortable. Gastrointestinal (GI) exam is notable for abdominal pain upon palpation. Ear, nose, and throat exam is notable for multiple painful shallow ulcers in the patient's mouth. Inspection of the patient's lower extremities reveals a pruritic ring-like lesion. Cardiac and pulmonary exams are within normal limits. Which of the following best describes this patient's underlying condition?

Transmural granulomas in the bowel

p-ANCA positive autoimmune bowel disease

Gram-negative microaerophilic organism

Crohn's disease pathophysiology for USMLE Step 1: High-Yield Internal Medicine Lessons

Crohn's Overview - The Patchy Attacker

A chronic, relapsing inflammatory bowel disease (IBD) defined by transmural inflammation.
Can affect any segment of the GI tract ("gum to bum"), but most commonly involves the terminal ileum.
Hallmark features include discontinuous inflammation (skip lesions) and a "cobblestone" mucosal appearance.
- In contrast, Ulcerative Colitis is mucosal and continuous.

📌 Mnemonic: An old Crone is skipping down a cobblestone street (Crohn's, skip lesions, cobblestone mucosa).

Crohn's disease gross pathology: stricture & creeping fat

⭐ Non-caseating granulomas are pathognomonic but found in only about 30% of biopsies.

Pathogenesis - A Gut Reaction

Genetic Susceptibility: Key association with NOD2/CARD15 gene mutations, which impair the ability of Paneth cells to sense and clear intracellular bacteria.
Immune Dysregulation: An unchecked, exaggerated adaptive immune response driven by Th1 and Th17 cells.
- Leads to overproduction of pro-inflammatory cytokines, including TNF-α, IL-12, IL-23, and IFN-γ.
Environmental Factors:
- Smoking is the strongest environmental risk factor, significantly increasing disease risk and severity.
- Likely involves gut microbiome dysbiosis.

⭐ Defective NOD2 in Paneth cells impairs their secretion of antimicrobial α-defensins, crippling the innate defense against gut microbes and initiating the inflammatory cascade.

Pathological Hallmarks - Cobblestones & Granulomas

Gross Pathology: Characterized by segmental "skip lesions."
- Appearance: Deep, linear, serpentine ulcers create a classic cobblestone pattern.
- Bowel Wall: Thickened and rubbery due to edema, inflammation, and fibrosis.
- Mesentery: Creeping fat (mesenteric fat wrapping the serosa) is a hallmark.
- Complications: Strictures, fistulas, and abscesses.

Endoscopy of Crohn's disease: cobblestone mucosa, ulcers

Microscopic Pathology:
- Inflammation: Transmural, involving all layers from mucosa to serosa.
- Granulomas: Non-caseating granulomas are pathognomonic but found in only ~30-50% of cases.

⭐ The presence of non-caseating granulomas on biopsy is highly specific for Crohn's disease, but their absence does not rule it out.

Feature	Crohn's Disease	Ulcerative Colitis
Inflammation Depth	Transmural	Mucosal & Submucosal
Distribution	Skip Lesions	Continuous, ascending
Granulomas	Yes (non-caseating)	No
Gross Appearance	Cobblestones, creeping fat	Friable mucosa, pseudopolyps

High‑Yield Points - ⚡ Biggest Takeaways

Crohn's is defined by transmural inflammation, affecting the entire bowel wall, which can lead to fistulas and strictures.

It classically presents with skip lesions-discontinuous segments of inflammation-anywhere from the mouth to the anus.

The terminal ileum and colon are the most common sites of involvement.

Histology reveals non-caseating granulomas and lymphoid aggregates in about 50% of cases.

The pathophysiology is driven by a Th1 and Th17-mediated immune response against gut flora.

Continue reading on Oncourse

CONTINUE READING — FREE

or get the app

App Store|Google Play