Built from GI Lecture 19–20 (LOs 1–8). Close notes. Fill from memory. Reveal only after a genuine attempt.

LO 1

ON EXAM — Meckel's rule of 2's, true vs pseudo diverticula, ectopic tissue complications, Hirschsprung RET mutations

Diverticula classification (LO1)

Feature	True Diverticulum	Pseudo (False) Diverticulum
Wall layers	All 3 (mucosa + submucosa + muscularis)	Mucosa + submucosa only
Origin	Congenital (developmental failure)	Acquired (increased intraluminal pressure)
Example	Meckel diverticulum	Colonic diverticulosis
Can contain ectopic tissue?	Yes	No

Meckel diverticulum — rule of 2's (LO1)

EXAM CLASSIC: Everything about Meckel comes in 2's — memorize this mnemonic cold.

Population & Size

% of population affected

Length of diverticulum

2 inches

Distance from ileocecal valve

2 feet

Ectopic Tissue & Presentation

Number of ectopic tissue types

Name 2 types of ectopic tissue present

Gastric mucosa and pancreatic tissue

Age of symptom onset (years)

2 (or before age 2)

Embryology

What embryologic structure fails to regress?

Vitelline duct (omphalomesenteric duct)

When should this regress (gestation week)?

Week 7

Meckel scan detects what tissue?

Ectopic gastric mucosa

Meckel diverticulum complications (LO1)

Complication	Mechanism / Key Feature	Most Common in Which Age?
GI bleeding	Ectopic gastric mucosa secretes acid → ulcerates adjacent ileal mucosa → painless bleeding	Children <2 years
Obstruction	Diverticulum acts as lead point for volvulus, intussusception, or adhesion	Any age
Volvulus	Intestines wrap around the diverticulum → twisting obstruction	Adults
Diverticulitis	Inflammation of the diverticulum → RLQ pain (mimics appendicitis)	Any age

Hirschsprung disease — pathogenesis & diagnosis (LO1)

Embryologic defect (what fails)?

Neural crest cells fail to migrate into distal colon

Gene mutation classically implicated

RET gene (proto-oncogene)

Name the missing cell population

Ganglion cells (enteric neurons)

Histology of affected segment — what's absent?

Ganglion cells in myenteric and submucosal plexuses (aganglionosis)

Biopsy shows ↑ what nerve fiber marker (acetylcholinesterase staining)?

Hypertrophic nerve trunks with increased acetylcholinesterase staining

Classic presentation — age at diagnosis

Newborn fails to pass meconium within first 48 hours

Location of most common defect (how far proximal)?

Usually rectosigmoid junction; can extend more proximally (long-segment disease)

Association with Down syndrome — increased risk how many-fold?

10–20 fold increased risk

LO 2

ON EXAM — Types of hernia, strangulation vs simple obstruction, adhesions, volvulus, intussusception lead points, imaging clues

Hernia classification & anatomy (LO2)

Hernia Type	Anatomic Location	Risk Factors / Pathogenesis	Strangulation Risk?
Hiatal hernia	Esophageal hiatus of diaphragm	Increased intra-abdominal pressure, age-related muscle laxity, smoking, obesity	No
Umbilical hernia	Umbilical ring (congenital weakness)	Patent umbilical opening, increased abdominal pressure	Rare
Ventral/incisional	Surgical incision site	Post-surgical, obesity, wound infection, poor healing	Moderate
Inguinal hernia	Inguinal canal (above inguinal ligament)	Congenital weakness (patent processus vaginalis) or acquired (straining, heavy lifting)	High (~10%)
Femoral hernia	Femoral ring (below inguinal ligament, medial to femoral vessels)	Femoral ring weakness; rare; females >> males	HIGHEST (~20%)

Obstruction types — mechanisms (LO2)

KEY: Simple obstruction = reduced lumen. Strangulation = compromised blood supply. Strangulation is surgical emergency (necrosis within 6–8 hrs).

Obstruction Type	Mechanism	Leads to Strangulation?	Surgical Emergency?
Adhesions (most common)	Fibrous bands from previous surgery, peritonitis bind bowel	No (low risk)	No (managed conservatively)
Volvulus	Bowel twists on mesentery → lumen obstructed + blood supply compromised	Yes (high risk)	Yes
Intussusception	Proximal bowel segment invaginates into distal segment	Yes (if not reduced promptly)	Yes (if >24–48 hrs or failed reduction)
Hernia (incarcerated)	Hernia contents trapped in defect → lumen narrowed	Yes (depends on neck width)	Yes (risk of strangulation)

Comparison of obstruction presentations (LO2)

Feature	Adhesions	Volvulus	Intussusception
Most common location	Small bowel (jejunum/ileum)	Sigmoid colon (most common)	Ileocolic junction
Classic imaging finding	Transition point; no distinctive sign	Bird's beak sign (twisted mesentery)	Target or doughnut sign
Age of presentation	Any age (post-surgery)	Sigmoid: elderly; cecal: adults	6 months–3 years (peak 1–2 yrs)
Bloody stool ("current jelly")?	No	Late finding if necrosis	Yes (classic)

Volvulus pathophysiology (LO2)

Sigmoid volvulus — classic presentation (age, risk factors)

Institutionalized elderly (mean age ~65); cognitive impairment, immobility, chronic constipation, neuropsychiatric drugs

Cecal volvulus — mechanism vs sigmoid difference

More mobile cecal wall; twists on mesentery; higher perforation risk; less responsive to non-operative reduction

AXR finding: "bird's beak" sign — what does it indicate?

Twisted mesentery at the point of torsion (rectosigmoid junction in sigmoid volvulus)

Barium/air enema therapeutic mechanism for sigmoid volvulus

Hydrostatic pressure straightens the twist; resolves obstruction in ~70% without surgery

Why cecal volvulus often requires surgery while sigmoid can be non-surgical

Sigmoid enema decompression successful in most; cecal volvulus less amenable to non-operative reduction; higher risk of perforation

Intussusception clinical pearls (LO2)

Classic age of presentation

6 months to 3 years (peak 1–2 years)

Lead point in adults (3 common causes)

Malignancy (lymphoma, adenocarcinoma), Meckel diverticulum, polyp

Classic symptom triad

Colicky pain + palpable abdominal mass + currant jelly stools (blood-stained)

Ultrasound finding: "target sign" or "doughnut sign" represents what?

Cross-section of invaginated mesentery with blood vessels surrounded by bowel wall

Non-operative reduction approach + contraindications

Air enema or barium enema (70% success); contraindicated if perforation, peritonitis, or >24–48 hrs symptoms

LO 3 · LO 4

ON EXAM — Watershed zones, SMA embolism pain out of proportion, acute vs chronic ischemia, malabsorption causes, fat-soluble vitamin deficiency pattern

Ischemic bowel disease — arterial territories (LO3)

Artery	Embryologic Origin	Structures Supplied	Watershed Zone Vulnerability
Celiac	Foregut	Distal esophagus, stomach, duodenum (proximal 2 parts), liver, gallbladder, spleen, pancreatic head	None (sole supply)
SMA (Midgut)	Midgut	Duodenum (distal 3rd & 4th), jejunum, ileum, cecum, ascending colon, proximal 2/3 transverse colon	Splenic flexure (SMA/IMA border) — MOST VULNERABLE
IMA (Hindgut)	Hindgut	Distal 1/3 transverse colon, descending colon, sigmoid, upper rectum	Rectosigmoid junction (IMA/pudendal border) — second vulnerable

Acute mesenteric ischemia — types & clues (LO3)

CLASSIC STEP 1 CLUE: Severe periumbilical pain OUT OF PROPORTION to soft abdominal exam. This is the pathognomonic presentation before peritoneal signs develop.

Type	Cause	Vascular Pathology	Risk Factors
Arterial embolism (most common)	SMA occlusion by thrombus from heart	Embolic obstruction; sudden onset	Atrial fibrillation, cardiac thrombus, endocarditis
Arterial thrombosis	SMA occlusion at site of atherosclerotic lesion	Stenotic plaque progression to complete thrombosis	Atherosclerosis (smoking, hyperlipidemia); may have chronic ischemia history
Venous thrombosis	Mesenteric vein thrombosis	Portal or SMV thrombosis	Hypercoagulable states, portal hypertension, pancreatitis, malignancy
Non-occlusive (vasoconstriction)	Splanchnic vasoconstriction without vessel blockage	Functional ischemia from hypotension, medications	Severe shock, diuretics, vasoconstrictors, dehydration

Chronic mesenteric ischemia (LO3)

"Intestinal angina" mechanism — why does eating trigger pain?

Postprandial increased blood flow demand cannot be met by stenosed mesenteric vessels → visceral ischemia during meal digestion

Classic triad of symptoms

Postprandial abdominal pain + weight loss (food fear/malabsorption) + diarrhea

Why weight loss is pronounced despite adequate intake

Chronic mucosal ischemia → intestinal mucosal damage (malabsorption) + food avoidance due to pain

Diagnostic test of choice + findings

CT angiography or MR angiography (shows stenosis/occlusion of mesenteric vessels)

Malabsorption — causes & classification (LO4)

Malabsorption = inadequate absorption due to mucosal disease, pancreatic insufficiency, or luminal problems (e.g., bile salt deficiency).

Category	Mechanism	Example Conditions (2)
Mucosal disease	Epithelial damage reduces surface area and nutrient transport	Celiac disease, tropical sprue, Whipple disease
Pancreatic insufficiency	Reduced pancreatic enzyme secretion into lumen	Chronic pancreatitis, cystic fibrosis
Luminal / bile problems	Reduced bile salts or impaired micelle formation	Biliary cirrhosis, bile acid sequestrant use, ileal resection

Fat-soluble vitamin (ADEK) deficiency patterns (LO4)

Vitamin A

Deficiency → manifestation

Night blindness, Bitot spots, squamous metaplasia (corneal xerosis)

Vitamin D

Deficiency → manifestation

Osteomalacia (bone pain, muscle weakness), hypocalcemia, secondary hyperparathyroidism

Vitamin E

Deficiency → manifestation

Neurologic: ataxia, neuropathy, spinocerebellar degeneration

Vitamin K

Deficiency → manifestation

Coagulopathy (prolonged PT/INR, easy bruising, bleeding)

B12 Absorption

Where absorbed (segment)

Terminal ileum (ileocecal region)

Cofactor requirement

Intrinsic factor (from gastric parietal cells)

Bile Salt Circulation

Where reabsorbed (segment)

Terminal ileum (enterohepatic circulation)

Loss of reabsorption → effect

More bile salts lost in stool → steatorrhea (increased fecal fat) + diarrhea

LO 4 · LO 5

ON EXAM — Celiac serology (tTG-IgA, EMA, anti-endomysial), villous atrophy histology, HLA-DQ2/DQ8, IBD vs IBS, extraintestinal manifestations

Celiac disease — pathogenesis (LO4)

Trigger antigen (protein in gluten)

Gliadin (prolamin protein in wheat gluten)

Genetic predisposition — HLA types required

HLA-DQ2 (~95% of patients) or HLA-DQ8 (~5%)

Autoantigen that forms immune complexes

Tissue transglutaminase (tTG); deamidation of gliadin peptides creates epitope recognized by autoreactive T cells

Pathophysiology: which intestinal cells are damaged?

Villous atrophy (flattening of villi) → reduced absorptive surface

Celiac disease — serology & histology (LO4)

Test	Marker	Sensitivity / Specificity	What It Detects
First-line serology	tTG-IgA (tissue transglutaminase IgA antibody)	~98% sensitivity, ~95% specificity	Auto-antibodies against tissue transglutaminase
Endomysial antibody	Anti-endomysial IgA (EMA)	Very specific but less sensitive than tTG	Auto-antibodies against endomysium
Gold standard biopsy	Duodenal biopsy showing villous atrophy (Marsh stage 3 or higher)	Definitive diagnosis	Histologic evidence of mucosal damage

Celiac histologic stages (Marsh classification) (LO4)

Stage 0 (Normal)

Intact villi, normal crypt-to-villous ratio

Stage 1 (Infiltration only)

Increased intraepithelial lymphocytes, normal villous architecture

Stage 3 (Partial villous atrophy) — what % villous height lost?

25–75% loss of villous height

Stage 3c (Total villous atrophy) — appearance + crypt hyperplasia

Flattened villi + crypt height >1:1 to villous height (completely atrophic)

IBD overview — ulcerative colitis vs Crohn disease (LO5)

KEY: Both are chronic relapsing-remitting inflammatory bowel diseases, but location, depth, and extraintestinal manifestations differ dramatically.

Feature	Ulcerative Colitis	Crohn Disease
Location(s)	Colon and rectum only (may have backwash ileitis)	ANY part of GI tract from mouth to anus; commonly terminal ileum + cecum
Depth of inflammation	Mucosa and submucosa only	Transmural (full thickness)
Continuous vs patchy	Continuous (no skip lesions)	Patchy with skip lesions
Rectal involvement	ALWAYS involved (continuous from rectum proximally)	Often spared (may have isolated ileocolic disease)
Bloody diarrhea?	Yes, classically bloody (mucosal ulcers)	Less common (no mucosal ulceration typically)

IBD complications — extraintestinal manifestations (LO5)

Ocular

3 ocular complications

Anterior uveitis, posterior uveitis, episcleritis

Rheumatologic

Arthritis types + HLA association

Large joint peripheral arthritis (non-erosive) + HLA-B27 association in some

Hepatic

2 hepatic complications

Primary sclerosing cholangitis (PSC) + primary biliary cholangitis (PBC)

Skin

2 dermatologic manifestations

Erythema nodosum + pyoderma gangrenosum

Vascular

Thrombotic risk — mechanism

Hypercoagulable state (increased pro-coagulants, endothelial activation) → DVT/PE/mesenteric thrombosis

Renal

Kidney stone composition in IBD

Calcium oxalate (hyperoxaluria from fat malabsorption)

LO 5 · LO 6

ON EXAM — Crohn pathognomonic findings (fissuring ulcers, fistulas, strictures), UC cancer risk, toxic megacolon, diverticulitis imaging & complications

Crohn disease — distinctive pathologic features (LO5)

PATHOGNOMONIC: Crohn has skip lesions, fissuring ulcers, fistulas, and can affect any part of GI tract from mouth to anus. Full-thickness inflammation.

Characteristic histology pattern (non-continuous)

Skip lesions with patchy inflammation separated by normal mucosa

Ulcer morphology — "fissuring" or "knife-like"?

Fissuring (knife-like) ulcers penetrating into submucosa and muscularis

Cobblestone appearance — what causes it?

Intersecting linear ulcers with residual mucosa creating irregular mucosal pattern

Fistula formation — why only in Crohn (transmural) + 3 types

Transmural (full-thickness) inflammation allows penetration → enteroenteric, enterovesical, enterocutaneous, rectovaginal fistulas

Stricture formation — pathophysiology

Fibrosis from chronic transmural inflammation → luminal narrowing; "string sign" on barium study

UC vs Crohn — complications (LO5)

Complication	UC Only	Crohn Only	Both
Toxic megacolon	YES (primarily)	Rare (transmural)	Both but more UC
Colorectal cancer risk (magnitude)	Higher (~2–4% after 10 yrs)	Lower (~0.5–1% per 10 yrs)	Both elevated
Perforation	Yes (severe inflammation)	Yes (transmural)	Both
Fistulas	No (mucosal only)	YES (pathognomonic)	Crohn only
Abdominal abscess	Rare	Common (perforating ulcers)	Both but more Crohn

Diverticular disease — pathogenesis & epidemiology (LO6)

Definition: pseudo-diverticula contain which layers?

Mucosa + submucosa only (lack muscularis propria)

Pathophysiology — ↑intraluminal pressure herniates at what sites?

Penetrate at points where blood vessels enter muscularis ("natural weak points")

Western diet risk factors — 3 mechanisms

Low fiber (↑colonic pressure to move hard stool) + refined carbs (dysbiosis, abnormal pressure) + reduced fluid (dehydration)

Asian populations — different location pattern, why?

Right-sided diverticula more common (genetic differences in colonic muscle architecture)

Diverticulitis — clinical presentation & imaging (LO6)

Feature	Uncomplicated Diverticulitis	Complicated (Perforation/Abscess/Fistula)
Location of pain (sigmoid typical)	LLQ pain	LLQ pain + peritoneal signs
Classic imaging (CT)	Diverticula + pericolic fat stranding	Diverticula + abscess/free fluid/fistula ± free air
Associated peritoneal signs	Minimal or none	Present (if perforation/peritonitis)
Management approach	Bowel rest, clear liquids, antibiotics (outpatient if mild)	NPO, IV antibiotics, possibly abscess drainage or colectomy

Diverticulitis complications (LO6)

Fistula

Colovesical fistula → symptoms

Pneumaturia (air in urine) + fecaluria (feces in urine) + recurrent UTI

Why female patients spared colovesical fistula

Uterus interposes between sigmoid colon and bladder; women more prone to colovaginal fistula if hysterectomy done

Recurrence & Management

% recurrence after 1st episode (uncomplicated)

~20% (many can be managed conservatively)

Elective colectomy after how many episodes?

After 2–3 episodes of uncomplicated or 1 episode of complicated diverticulitis

Right-sided Diverticulitis

Why mimics appendicitis

RLQ pain, fever, elevated WBC; can be indistinguishable at diagnosis

Epidemiology — which populations more common?

More common in Asian populations; rare in Western populations

LO 7 · LO 8

ON EXAM — Polyp histology & malignant potential, adenoma-carcinoma sequence, Lynch syndrome vs FAP, CRC staging (TNM), high-grade dysplasia management

Colonic polyps — classification & risk (LO7)

Polyp Type	Histology	Malignant Potential	Management
Hyperplastic polyp	Elongated crypts with sawtooth outline; superficial only	Very low (<1%)	Not removed if <5 mm; resect if >5 mm for confirmation
Sessile serrated polyp (SSP)	Irregular crypts, sessile morphology; extends deeper than hyperplastic	Moderate to high (30–50%)	Always resect; surveillance 3–5 years
Tubular adenoma	Tubular glands with adenomatous epithelium	5–10% if <1 cm; increases with size	Resect completely; surveillance 5–10 years
Villous adenoma	Frond-like villous projections (>75% villous)	HIGHEST (~40%); cancer focus in 10–15%	Resect completely; often requires surgery if large; surveillance 3 years
Tubulovillous adenoma	Mixed tubular and villous (25–75% villous)	Intermediate (10–30%)	Resect completely; surveillance 3–5 years

Adenoma-carcinoma sequence — genetics (LO8)

The canonical multi-hit hypothesis: APC loss → KRAS activation → TP53 loss → invasive carcinoma. Takes ~10 years average.

Hit #	Gene	% of Adenomas with Mutation	Functional Change
Hit 1 (Early)	APC (adenomatous polyposis coli)	~80%	Loss of tumor suppressor → initiates adenoma formation
Hit 2 (Intermediate)	KRAS	~40%	Activating mutation → promotes cell proliferation
Hit 3 (Late)	TP53	~50% of cancers	Loss of p53 (guardian of genome) → genomic instability + invasion

Familial CRC syndromes (LO8)

Syndrome	Gene(s)	Inheritance	Polyp Burden & Cancer Risk	Extraintestinal Features
Familial Adenomatous Polyposis (FAP)	APC	Autosomal dominant	Hundreds to thousands of polyps; near 100% cancer risk if untreated	Osteomas, epidermoid cysts, desmoids, fundic gland polyps, CHRPE
Lynch syndrome (HNPCC)	MLH1, MSH2, MSH6, PMS2 (mismatch repair)	Autosomal dominant	Few polyps but accelerated progression; ~70% lifetime CRC risk	Endometrial cancer (often before CRC), ovarian cancer
PTEN Hamartoma Syndrome (Cowden)	PTEN	Autosomal dominant	Hamartomatous polyps throughout GI; increased CRC risk	Macrocephaly, trichilemmomas, breast/thyroid/endometrial cancers
Peutz-Jeghers Syndrome	STK11 (LKB1)	Autosomal dominant	Hamartomatous polyps; GI cancer increased (not adenomatous)	Perioral pigmentation (dark lips/buccal), breast/pancreatic/lung cancers

Colorectal cancer — TNM staging (LO8)

T = depth of tumor penetration, N = lymph node involvement, M = distant metastases. Stage I (T1–T2 N0) has ~90% 5-yr survival; Stage IV has ~10%.

TNM Component	Depth / Extent
T1	Invasion into submucosa (but not muscularis propria)
T2	Invasion through muscularis propria into subserosa/pericolorectal fat
T3	Invasion through entire bowel wall into pericolorectal fat (beyond visceral peritoneum)
T4a	Invasion through visceral peritoneum to reach peritoneal surface
T4b	Direct invasion of adjacent structures (bladder, prostate, small bowel)
N0, N1, N2	N0 = no regional nodes \| N1 = 1–3 nodes involved \| N2 = 4+ nodes involved
M0 vs M1	M0 = no distant mets \| M1 = distant metastases present

CRC metastatic patterns & prognosis (LO8)

Most common site of hematogenous mets

Liver (portal circulation drains to liver)

Lymphatic spread — typical progression

Progresses along lymphatic vessels to regional nodes; N2 worsens prognosis (~25% 5-yr survival with N2 vs ~70% with N0)

Mucinous adenocarcinoma — prognosis vs typical

Worse prognosis; mucin-producing → worse cell differentiation

Microsatellite instability (MSI-H) — Lynch vs sporadic prevalence

Lynch: ~15% of CRC (MLH1, MSH2, MSH6, PMS2 deficiency) | Sporadic: ~5% (usually MLH1 methylation)

LO 1–8 · USMLE Step 1 Style

8 questions — cover all 8 LOs. High-yield vignettes and pathophysiology.

Q1. A 5-year-old boy presents with painless rectal bleeding for 3 weeks. Colonoscopy is unremarkable, and the bleeding has decreased. A technetium-99m pertechnetate scan is ordered. What ectopic tissue is the scan designed to identify, and where is it located?

A. Ectopic pancreatic tissue in the ileum at Meckel's diverticulum
B. Ectopic gastric mucosa in the ileum at Meckel's diverticulum
C. Heterotopic colonic mucosa in the upper jejunum
D. Ectopic stomach wall in the antimesenteric border of ileum
E. Adenomatous polyp in the terminal ileum

B — Ectopic gastric mucosa in the ileum at Meckel's diverticulum
Meckel's diverticulum is a remnant of the vitelline duct and frequently contains ectopic gastric mucosa, which secretes acid and can ulcerate adjacent ileal mucosa → painless GI bleeding (most common complication in children). The scan uses Tc-99m pertechnetate, which localizes to gastric mucosa. Located on the antimesenteric border, typically within 2 feet of the ileocecal valve (Rule of 2's: 2%, 2 feet, 2 inches, age 2).

Q2. A 68-year-old man with cognitive impairment and severe chronic constipation presents with acute abdominal distension, vomiting, and abdominal pain localized to the left lower quadrant. Abdominal X-ray shows a massively dilated sigmoid colon with a "bird's beak" appearance at the rectosigmoid junction. What is the diagnosis, and why is this patient at particularly high risk?

A. Cecal volvulus; risk factors include chronic laxative abuse and institutionalization
B. Sigmoid volvulus; risk factors include cognitive impairment, institutionalization, and chronic constipation
C. Adhesive small bowel obstruction; previous abdominal surgery is the major risk
D. Diverticulitis with perforation; elderly age and male gender increase risk
E. Intussusception in adults; malignancy as a lead point in the elderly

B — Sigmoid volvulus; risk factors include cognitive impairment, institutionalization, and chronic constipation
Sigmoid volvulus = axial twist of the sigmoid colon, classically in institutionalized elderly with cognitive impairment and chronic constipation. The "bird's beak" is pathognomonic (twist at rectosigmoid junction). Risk: immobility, laxative abuse, neuropsychiatric conditions. Can be decompressed non-operatively with endoscopic reduction or barium enema in many cases, but surgery may be needed if blood supply is compromised (strangulation).

Q3. A 2-year-old girl presents with colicky abdominal pain, palpable abdominal mass, and "currant jelly" stools. Abdominal ultrasound demonstrates a target (doughnut) sign. Which of the following BEST describes the pathophysiology of this condition?

A. Adhesions between bowel loops cause partial luminal obstruction
B. One segment of bowel telescopes into an adjacent segment, compromising blood supply
C. A congenital diverticulum acts as a lead point, twisting the intestine
D. Increased intraluminal pressure herniates the mucosa through the muscularis
E. Bacterial infection causes villous necrosis and hemorrhagic diarrhea

B — One segment of bowel telescopes into an adjacent segment, compromising blood supply
Intussusception = invagination of proximal bowel into distal bowel (most commonly ileocolic). Classic in children 6 months–3 years (peak 1–2 yrs). Presents with colicky pain, palpable mass, and "currant jelly" (blood-stained) stools. Ultrasound target sign = cross-section of invaginated mesentery + blood vessels surrounded by bowel wall. Non-operative reduction via air enema is successful in >70% if performed early; surgery if perforation or failed reduction.

Q4. A 45-year-old man with a history of atrial fibrillation presents with acute-onset severe periumbilical pain. Physical examination reveals a soft abdomen with minimal peritoneal signs. CT angiography shows an embolus occluding the superior mesenteric artery. Which segment of bowel is at GREATEST risk, and why is the "pain out of proportion" sign clinically significant?

A. Gastric antrum; early ulceration causes severe visceral pain
B. Terminal ileum; mesenteric ischemia causes loss of absorptive capacity
C. Jejunum, ileum, and right colon; visceral afferents signal ischemia before peritoneal signs develop
D. Descending and sigmoid colon; the IMA is collateral-dependent
E. Entire small intestine; SMA supplies all segments equally and is the primary blood supply

C — Jejunum, ileum, and right colon; visceral afferents signal ischemia before peritoneal signs develop
SMA supplies jejunum, ileum, cecum, ascending colon, and proximal 2/3 of transverse colon (midgut). SMA embolism is a surgical emergency with high mortality if diagnosis is delayed. The pathognomonic clue is severe pain OUT OF PROPORTION to exam — visceral afferents detect ischemia before transmural necrosis and perforation occur, before peritoneal signs manifest. Elevated lactate, bloody diarrhea, and shock are late findings. Diagnosis: CT angiography. Treatment: immediate surgical revascularization or thrombectomy.

Q5. A 28-year-old woman presents with chronic diarrhea, weight loss, and iron-deficiency anemia. Serologic testing shows elevated tissue transglutaminase (tTG) IgA and positive endomysial antibodies. Small bowel biopsy demonstrates villous atrophy with increased intraepithelial lymphocytes and crypt hyperplasia. Which of the following HLA types is she MOST likely to carry, and what dietary component triggers this pathology?

A. HLA-B27; bacterial lipopolysaccharide
B. HLA-DQ2 or HLA-DQ8; gliadin (a wheat gluten protein)
C. HLA-DR3; gliadin and related cereal proteins
D. No specific HLA type required; IgE-mediated hypersensitivity to milk proteins
E. HLA-A2; tissue damage from molecular mimicry against commensal bacteria

B — HLA-DQ2 or HLA-DQ8; gliadin (a wheat gluten protein)
Celiac disease is an autoimmune enteropathy triggered by gluten (specifically gliadin) in genetically predisposed individuals (HLA-DQ2 ~95%, HLA-DQ8 ~5%). Gliadin peptides are deamidated by tissue transglutaminase (tTG) → recognized by autoreactive T cells → mucosal inflammation → villous atrophy. Serology: tTG-IgA (most sensitive/specific) and endomysial antibodies. Biopsy is gold standard. HLA-DQ2/DQ8 is necessary but not sufficient (~3% of population carry it; only ~3% of carriers develop disease). Dietary trigger is gluten elimination (wheat, barley, rye).

Q6. A 35-year-old man with a 10-year history of crampy abdominal pain, diarrhea, and weight loss undergoes colonoscopy. Multiple areas of inflammation are noted with intervening normal-appearing mucosa (skip lesions). Biopsy reveals transmural inflammation with granulomas. Which complication is he at GREATEST risk for developing, and how does it differ pathophysiologically from ulcerative colitis?

A. Toxic megacolon; occurs exclusively in inflammatory bowel disease with continuous inflammation
B. Colorectal cancer; both UC and Crohn carry equal cancer risk after 10 years of disease
C. Fistula and stricture formation; transmural inflammation in Crohn allows penetration to involve adjacent structures
D. Massive hemorrhage; loss of colonic vasculature is more extensive in Crohn than UC
E. Fulminant colitis; mucosa-limited disease in Crohn allows rapid progression to perforation

C — Fistula and stricture formation; transmural inflammation in Crohn allows penetration to involve adjacent structures
Crohn disease is characterized by TRANSMURAL (full-thickness) inflammation with skip lesions, fissuring ulcers, and penetrating inflammation. This leads to fistulas (to other bowel loops, skin, or bladder), strictures (from fibrosis), and abscesses — unique to Crohn. Ulcerative colitis is LIMITED TO THE MUCOSA AND SUBMUCOSA → continuous inflammation in colon only → bloody diarrhea without fistulas. Toxic megacolon and CRC risk are seen in both, but fistulization is Crohn-specific. Granulomas on biopsy are pathognomonic for Crohn (~40% of cases).

Q7. A 64-year-old man with a history of chronic constipation and diverticulosis presents with acute left lower quadrant pain, fever, and leukocytosis. CT imaging reveals diverticula with pericolic fat stranding and a small fluid collection. He is treated conservatively with bowel rest and antibiotics. At follow-up 6 months later, he reports recurrent episodes of abdominal pain and has noticed pneumaturia (air in urine). What complication has developed, and why is it more common in men?

A. Colovesical fistula; more common in men because the bladder is directly anterior to the sigmoid colon without the uterus interposing
B. Chronic diverticulitis with abscess formation; men have more extensive diverticula than women
C. Colorectal cancer arising from long-standing inflammation; older age is the predominant risk factor
D. Adhesions from recurrent inflammation causing small bowel obstruction; men have more visceral adhesions
E. Pericolic abscess with rupture into peritoneum; severe sepsis in men but not women

A — Colovesical fistula; more common in men because the bladder is directly anterior to the sigmoid colon without the uterus interposing
Diverticulitis complicated by fistulization most commonly involves colovesical fistula (sigmoid → bladder) due to anatomic proximity. Pneumaturia (air in urine) and fecaluria are pathognomonic. More common in men because women have the uterus between sigmoid and bladder, protecting against fistula formation (women more prone to colovaginal fistula if hysterectomy has been performed). Colovaginal fistula presents with feculent vaginal discharge. Other fistulas: coloenteric, colocutaneous. Fistulous diverticulitis often requires elective colectomy after acute phase resolves.

Q8. A 42-year-old woman is found to have a 1.2 cm tubular adenoma during routine colonoscopy with no other polyps noted. The adenoma is removed completely with clear margins. What is the recommended surveillance interval for the next colonoscopy, and what molecular event is she at risk of NOT having prevented through polypectomy?

A. Return in 1 year; adenomatous polyps that are not removed progress to carcinoma within 2–3 years
B. Return in 5 years; even small adenomas contain both KRAS and TP53 mutations
C. Return in 10 years; small adenomas have not yet acquired the TP53 mutation necessary for malignant transformation
D. Return in 3 years; all adenomas progress to cancer if given sufficient time (adenoma-carcinoma sequence)
E. Return in 2 years; the small size suggests aggressive biology and early acquisition of KRAS mutation

C — Return in 10 years; small adenomas have not yet acquired the TP53 mutation necessary for malignant transformation
The adenoma-carcinoma sequence is a multi-hit process: APC loss (early) → KRAS activation (intermediate) → TP53 loss (late) → invasion. Small adenomas (<1 cm) typically have NOT yet acquired the TP53 mutation, so polypectomy effectively prevents cancer development. Surveillance: 1 adenoma <1 cm → 10 years; 2–3 adenomas or 1 adenoma ≥1 cm → 5 years; ≥4 adenomas or any with high-grade dysplasia → 3 years. The process takes ~10 years average from adenoma to cancer, giving a window for screening and surveillance to prevent CRC.

GI Lecture 19–20: Intestinal Pathology — Answer Key