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Peptic Ulcer Disease, Inflammatory Bowel Disease - Comprehensive Notes

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1. Etiologies of Peptic Ulcer Disease (PUD)

Major Causes

• Present in ~50% of the world's population; responsible for >70% of PUD cases
• The bacterium physically burrows through the mucosal barrier and releases urease, which generates ammonia - this liquefies the mucus layer and directly stimulates HCl secretion
• H. pylori secretes proteases and lipases that degrade mucin, impairing the protective function of the mucus layer
• Only 5-10% of infected individuals actually develop ulcers, suggesting additional host factors are required

• The second most common cause; virtually all NSAIDs (including low-dose aspirin) increase PUD risk
• Mechanism: NSAIDs inhibit cyclooxygenase (COX-1 and COX-2) enzymes, blocking prostaglandin synthesis. Prostaglandins are essential for mucosal protection (stimulate mucus, bicarbonate, mucosal blood flow, epithelial restitution)
• Ulcer disease develops in ~25% of regular NSAID users; gastric ulcers are 5x more common than duodenal ulcers with NSAID use
• Risk factors for NSAID-associated PUD: age >65, history of prior PUD, high-dose therapy, concurrent aspirin/corticosteroid/anticoagulant use, concurrent H. pylori infection
• Selective COX-2 inhibitors (e.g., celecoxib) have lower GI toxicity but carry cardiovascular risk

Less Common / Secondary Causes

• Gastrin-secreting tumors (usually in pancreas or duodenum) cause massive, unregulated acid hypersecretion
• Results in multiple ulcers in the stomach, duodenum, and even jejunum
• Should be suspected in ulcers refractory to standard therapy

• Parietal cell hyperplasia
• Excessive secretory responses
• Loss of signals that inhibit acid secretion

• Alcohol-related cirrhosis - increased PUD risk
• Chronic obstructive pulmonary disease (COPD)
• Chronic renal failure - hypercalcemia stimulates gastrin production → increased acid
• Hyperparathyroidism - same mechanism via hypercalcemia

• Cigarette smoking - reduces mucosal blood flow and impairs healing
• Excess alcohol consumption - directly breaks down the mucosal barrier
• High-dose corticosteroids - suppress prostaglandin synthesis, impair mucosal healing
• Stress ulcers (Acute) - critically ill patients (burns/Curling ulcer, head injury/Cushing ulcer, sepsis)

• A subset of ulcers has no identifiable H. pylori infection or NSAID use ("non-H. pylori, non-NSAID ulcers")

Sources: Robbins & Kumar Basic Pathology, p. 3905-3909; Guyton and Hall Medical Physiology, p. 1320-1327; Symptom to Diagnosis, p. 11030-11056; Sabiston Textbook of Surgery, p. 1957-1960

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2. Defense Mechanisms of the Stomach

A. Pre-Epithelial Defense (The Mucus-Bicarbonate Layer)

• Mucus gel layer: A 0.1-0.5 mm thick viscoelastic gel secreted by surface mucous cells and mucous neck cells. Composed of ~85% water and 15% mucin glycoprotein. Acts as a mechanical barrier that is relatively impermeable to pepsin and impedes ion movement from lumen to mucosa
• Bicarbonate secretion: Surface epithelial cells actively secrete HCO3⁻ into the mucus layer, creating a pH gradient - luminal pH is ~2, but the pH at the epithelial cell surface is maintained at ~7
• Mucus secretion is stimulated by: vagal stimulation, cholinergic agonists, prostaglandins
• Mucus secretion is inhibited by: NSAIDs, anticholinergic drugs

B. Epithelial Defense

• Tight junctions between mucosal cells maintain a high transepithelial electrical resistance (-30 to -50 mV), preventing back-diffusion of H⁺ ions into the mucosa
• Rapid cell restitution: After superficial injury, surface mucous cells rapidly migrate along the basement membrane to cover damaged areas within minutes (restitution/reconstitution)
• Surface phospholipids on the apical membrane are hydrophobic and resist acid penetration

C. Prostaglandins (Central Coordinators of Defense)

• Gastric mucosa is rich in prostaglandins (synthesized via COX-1 pathway)
• Prostaglandins protect via:
  1. Stimulating mucus and bicarbonate secretion
  2. Maintaining mucosal blood flow
  3. Inhibiting parietal cell acid secretion
  4. Promoting epithelial cell restitution and proliferation
• NSAIDs disrupt all of these mechanisms by inhibiting COX-1

D. Mucosal Blood Flow

• Adequate blood flow delivers oxygen and nutrients to maintain mucosal integrity
• Marked decreases in blood flow → mucosal injury and ulcer formation, especially in the presence of luminal acid
• Nitric oxide (NO): Constitutively produced by NO synthase in the mucosa; contributes to cytoprotection by stimulating mucus, increasing blood flow, and maintaining epithelial barrier function

E. Duodenal Defense

• Brunner's glands in the first few centimeters of the duodenum secrete alkaline mucus
• Pancreatic bicarbonate (stimulated by secretin) neutralizes gastric acid entering the duodenum
• Bile provides additional bicarbonate

F. Neuroendocrine Feedback

• When excess acid enters the duodenum: nervous reflexes and hormonal feedback inhibit gastric secretion and slow gastric emptying
• Acid in the small intestine releases secretin, which stimulates pancreatic bicarbonate secretion

Sources: Sabiston Textbook of Surgery, p. 1824-1836; Harrison's Principles of Internal Medicine 22e, p. 1949-1952; Guyton and Hall Medical Physiology, p. 1305-1314

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3. Urea Breath Test (UBT) for H. pylori Detection

Principle

Procedure

1. The patient ingests a solution of urea labeled with ¹³C (non-radioactive stable isotope) or ¹⁴C (radioactive, less preferred)
2. If H. pylori urease is present in the stomach, the labeled urea is hydrolyzed
3. Labeled ¹³CO₂ (or ¹⁴CO₂) is absorbed into the bloodstream and excreted in the breath
4. The patient blows into a collection tube 30 minutes later
5. Breath samples are analyzed by mass spectrometry (for ¹³C) or scintillation counting (for ¹⁴C)
6. A rise in labeled CO₂ above baseline confirms active H. pylori infection

Performance

• Sensitivity and specificity: >90-95% - among the most accurate noninvasive tests
• Detects active, ongoing infection (unlike serology, which can remain positive after eradication)

Indications

• Initial diagnosis of H. pylori infection (when endoscopy is not required)
• Confirming eradication after antibiotic therapy - the preferred test for this purpose
• More accurate than serology for monitoring treatment success

Important Limitations and Precautions

• Must NOT be performed within:
  • 4 weeks after antibiotics or bismuth compounds (false negatives due to bacterial suppression)
  • 2 weeks after stopping a proton pump inhibitor (PPI)
• False negatives occur when bacterial load is temporarily reduced
• Serologic tests (IgG antibodies) cannot be used to confirm eradication, as titers remain elevated for >14 weeks after successful treatment

Comparison with Other Tests

Sources: Harrison's Principles of Internal Medicine 22e, p. 1069-1073; Maingot's Abdominal Operations, p. 3992-3996; Sabiston Textbook of Surgery, p. 1947-1951

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4. Complications of PUD

A. Hemorrhage (Bleeding) - Most Common Complication

• Occurs in ~15-20% of PUD patients; most common cause of death from PUD
• Results from erosion of a blood vessel at the ulcer base (most commonly posterior duodenal ulcers eroding the gastroduodenal artery)
• Presentation:
  • Hematemesis (vomiting blood) - fresh blood or "coffee-ground" emesis
  • Melena (dark, tarry stools) from upper GI blood
  • Hematochezia (bright red rectal bleeding) with massive hemorrhage
  • Occult/chronic bleeding presenting as iron deficiency anemia (may be asymptomatic in NSAID users - 60% of NSAID ulcers are asymptomatic)
• Management: Endoscopic hemostasis (injection therapy, thermal coagulation, hemoclips); PPIs; surgery for refractory bleeding

B. Perforation - Second Most Common; Most Dramatic

• Occurs in ~5% of PUD patients; the free perforation usually involves anterior duodenal ulcers
• Presentation:
  • Sudden onset of excruciating, severe diffuse abdominal pain - patients can often pinpoint the exact moment of onset
  • Rigid, board-like abdomen with peritonitis (rebound tenderness, guarding, rigidity)
  • Pneumoperitoneum: Free intraperitoneal air detected under the right hemidiaphragm on upright chest/abdominal X-ray in ~75% of cases
  • CT abdomen (if equivocal): Shows edema around the gastric antrum/duodenum with extraluminal air
• Important notes:
  • Endoscopy is contraindicated when perforation is suspected (gastric insufflation can convert a sealed perforation to a free one)
  • Older/debilitated patients may present with less dramatic symptoms
  • 30-day mortality is approximately 25-30%; 2-year mortality >40%
• Management: Emergency surgery (laparotomy or laparoscopy with Graham patch repair) ± H. pylori eradication and PPI therapy post-operatively

C. Gastric Outlet Obstruction (Pyloric Stenosis) - Least Common

• Results from edema, fibrosis, or scarring of ulcers in the pyloric channel or duodenum
• Acute: Edema and spasm → potentially reversible with medical therapy
• Chronic: Fibrotic scarring → mechanical obstruction requiring intervention
• Presentation:
  • Persistent nausea and non-bilious vomiting (often of food eaten hours earlier)
  • Postprandial fullness, epigastric pain
  • Progressive weight loss, dehydration
  • Succussion splash on abdominal examination
  • Metabolic alkalosis with hypokalemia (loss of HCl through vomiting; compensatory renal H⁺ retention → hypokalemia and paradoxical aciduria)
• Diagnosis: Upper GI endoscopy (gold standard); barium swallow showing dilated stomach with delayed emptying
• Management: Nasogastric decompression, IV fluids, H. pylori eradication, PPIs; endoscopic balloon dilation; surgery (gastrojejunostomy or antrectomy) for refractory cases

D. Malignant Transformation

• Gastric ulcers carry a risk of malignancy (gastric adenocarcinoma); all gastric ulcers must have multiple biopsies taken at endoscopy to exclude malignancy
• Gastric ulcers should be re-endoscoped after 8-12 weeks of treatment to confirm healing and repeat biopsies
• Duodenal ulcers are essentially never malignant

E. Penetration (Contained Perforation)

• The ulcer erodes through the full thickness of the bowel wall but is contained by an adjacent organ (pancreas, liver, biliary tree, colon)
• Presentation: Change in character of pain (back pain in pancreatic penetration), elevated serum amylase/lipase
• May result in fistula formation (e.g., gastrocolic fistula)

Summary of Complications

Sources: Symptom to Diagnosis, p. 11066-11069; Sleisenger & Fordtran's GI and Liver Disease, p. 2709-2720; Bailey and Love's Short Practice of Surgery 28e, p. 8735; Robbins & Kumar Basic Pathology, p. 3909

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5. Crohn's Disease

Definition

Epidemiology

• Peak age of onset: 15-30 years, with a second smaller peak in the 7th decade
• Slight female predominance (F:M = 1.2:1)

Pathology

• Transmural inflammation (involves all layers of the bowel wall) - characteristic
• Skip lesions (discontinuous areas of involvement separated by normal "skip areas")
• Granulomatous inflammation - non-caseating granulomas in ~50% of cases
• Cobblestone appearance of mucosa (submucosal edema with linear ulcers)
• Fissure ulcers and fistula formation due to transmural nature
• Fibrotic scarring → strictures
• "String sign" on barium enema - narrowed terminal ileum

Distribution

• Terminal ileum alone (primary ileal): ~30%
• Ileocolonic: ~40% (most common pattern)
• Colonic alone: ~25%
• Upper GI (esophagus, stomach, duodenum): ~5% (rare; usually with distal disease)

Clinical Features

• Abdominal pain - typically right lower quadrant (terminal ileum involvement); may be colicky
• Diarrhea - often non-bloody (if small bowel only); may be bloody with colonic involvement
• Weight loss, malnutrition, fatigue
• Fever in moderate-severe disease
• Perianal disease (in up to 30%): fissures, skin tags, abscesses, fistulas
• Fistulas (in 20-40%): enterocutaneous, rectovaginal, enterovesicular, enteroenteric
• Obstructive symptoms: pain, distension, nausea (from strictures)
• Malabsorption: B12 deficiency (terminal ileum), fat malabsorption, calcium oxalate renal stones

Disease Activity

• The Crohn's Disease Activity Index (CDAI) is used in clinical trials:
  • Remission: CDAI <150
  • Response: decrease in CDAI ≥100 points

Extraintestinal Manifestations (shared with UC unless noted)

• Arthropathy (most common; 10-20%): peripheral arthritis, ankylosing spondylitis, sacroiliitis
• Skin: erythema nodosum (10-15%), pyoderma gangrenosum (1-2%)
• Ocular: uveitis, episcleritis (5-15%)
• Primary sclerosing cholangitis (PSC)
• Osteoporosis/osteomalacia (CD only - due to malabsorption)
• Vitamin B12 deficiency (CD only)
• Thromboembolic disease
• Secondary amyloidosis (chronic inflammation)

Diagnosis

• Colonoscopy with ileoscopy and biopsy (gold standard)
• MR enterography / CT enterography: mural thickening, hyperenhancement, "comb sign" (engorged peri-enteric vessels), fistulas, abscesses
• Biomarkers: elevated CRP, fecal calprotectin, fecal lactoferrin
• Serology: ASCA (anti-Saccharomyces cerevisiae antibodies) more associated with CD; pANCA with UC

Treatment

• Induction: Corticosteroids, budesonide (for ileal/right colonic disease)
• Maintenance: Azathioprine/6-MP, methotrexate, biologics (anti-TNF-α: infliximab, adalimumab; vedolizumab; ustekinumab)
• Surgery: Indications include intra-abdominal abscess, medically intractable fistula, fibrotic stricture, toxic megacolon; ileocecal resection is the most common procedure. Principle: preserve intestinal length (no wide margins)
• By 20 years from symptom onset, ~75% of CD patients will have undergone surgical resection; risk of recurrence is high

Sources: Goldman-Cecil Medicine, p. 1455-1489; Sleisenger & Fordtran's GI and Liver Disease, blocks 31 & 33

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6. Ulcerative Colitis (UC)

Definition

Epidemiology

• Peak age of onset: 20-40 years, with a second smaller peak beyond the 7th decade
• Equal sex distribution (F:M = 1:1)

Pathology - Key Characteristics

• Mucosal inflammation only (does NOT extend transmurally - unlike Crohn's)
• Always begins in the rectum and extends proximally in a continuous pattern
• Mucosal appearance:
  • Mild: granular, hyperemic, edematous mucosa
  • Severe: mucosal ulceration extending into the lamina propria
  • Chronic: pseudopolyps (inflammatory pseudopolyps) form between ulcers due to epithelial regeneration; colon shortens and loses normal haustral fold pattern
• Histopathology:
  • Acute: epithelial necrosis, acute inflammatory infiltrate in lamina propria, cryptitis and crypt abscesses (pathognomonic)
  • Chronic: lymphocytic infiltrate, crypt architectural distortion (branching, shortening)
• NO granulomas, no skip lesions, no fistulas, no perianal disease

Extent of Disease at Diagnosis

• Proctosigmoiditis: 44-49%
• Disease extending beyond the rectum: 36-41%
• Pancolitis: 14-37%

Clinical Features

• Bloody diarrhea - the hallmark symptom
• Tenesmus (painful urge to defecate with little passage)
• Production of mucus and pus
• Urgency to defecate
• Abdominal pain/cramping
• With extensive/severe disease: weight loss, fever, nausea, fatigue, peripheral edema (hypoalbuminemia)
• In proctitis/proctosigmoiditis: may paradoxically have constipation

Complications

• Toxic megacolon: Life-threatening dilatation of the colon (>6 cm transverse colon); fever, tachycardia, abdominal distension; risk of perforation
• Perforation: Especially in toxic megacolon
• Massive hemorrhage
• Strictures (less common than in CD; raises concern for malignancy)
• Colorectal carcinoma: Major long-term risk; after 10-12 years of disease, cancer risk is ~20% and increases thereafter; colonoscopic surveillance with biopsies every 1-2 years is mandatory
  • Prophylactic proctocolectomy is advocated in those with >10 years of extensive colitis

Diagnosis

• Sigmoidoscopy/Colonoscopy: Friable mucosa, mucus/pus/blood, loss of vascular pattern, continuous involvement from rectum
• Barium enema (double-contrast): Smooth shortened bowel, loss of haustrations, pseudopolyps with "cobblestone" appearance
• Histology: Crypt abscesses, crypt architectural distortion (no granulomas)

Treatment

• Mild-moderate: 5-aminosalicylates (5-ASA; mesalazine) - oral and/or rectal; topical/systemic corticosteroids for acute flares
• Moderate-severe: Systemic corticosteroids, IV hydrocortisone for hospitalized patients
• Maintenance: 5-ASA, azathioprine/6-MP, biologics (infliximab, vedolizumab)
• Fulminating disease: Total bowel rest, parenteral nutrition

• Indications: Failure of medical therapy, toxic megacolon, perforation, severe hemorrhage, dysplasia/malignancy
• Procedure of choice (young fit patients): Total proctocolectomy with ileal pouch-anal anastomosis (IPAA/J-pouch) - avoids permanent ileostomy
• Alternative: Total proctocolectomy with permanent ileostomy
• Emergency: Subtotal colectomy with end ileostomy and mucous fistula

Crohn's Disease vs. Ulcerative Colitis - Key Comparison

Sources: Goldman-Cecil Medicine, p. 1429-1490; Pye's Surgical Handicraft 22e, p. 8628-8665; Rosen's Emergency Medicine, p. 2745-2902

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