II-1. GI system: diseases of the stomach and small intestine

消化管：胃と小腸の疾患

Peptic Ulcer Disease

Defects in GI mucosa extending through the muscular layer; chronic bleeding → iron-deficiency anemia.
Etiology: H. pylori, NSAIDs (even low-dose aspirin), viral, gastrinoma (Zollinger-Ellison), idiopathic.

H. pylori

Tests false-negative in ≥10% (antibiotics/PPIs; OTC PPIs mask symptoms). Ulcer incidence 6–10× higher than uninfected.
Colonizes the antrum: produces NH₃ (buffers acid → favorable environment) → irritates mucosa → more acid; ongoing immune response damages mucosa → hyperacidity.
Diagnosis (urease activity): urease breath test (¹³C-urea → labeled CO₂ in breath), direct urease test/histology of biopsy. Suspected infection/reflux → gastroscopy.

Chronic NSAID Use

Common cause of refractory/complicated ulcers; low-dose aspirin ↑GI bleeding risk 60%; PPIs reduce risk. NSAIDs inhibit all COX → ↓prostaglandins (which normally inhibit acid) → ↑acid production.

Symptoms & Complications

Dyspepsia (epigastric pain) most prominent; ~70% asymptomatic.
Complications: GERD (40–50%), GI bleeding (anemia, rarely hematemesis), perforation (2–10%) → peritonitis → shock → death, rarely gastric cancer.

Intestinal Disease — Leading Symptoms

Abdominal pain, malabsorption, diarrhea (±blood). High intestinal flow → minor mucosal change → large fluid loss (diarrhea).

Lactose Intolerance

Intolerance to lactose; most common intestinal disease worldwide (>70%); prevalence ↑ with age. Adaptation via colonic bacterial conversion to short-chain fatty acids.
Symptoms: abdominal pain, diarrhea, flatulence after dairy (>75% unabsorbed → fermented to SCFAs + H₂).
Etiology:
- Primary: acquired (age-related) lactase deficiency (most common); congenital (rare AR, Finnish); developmental (prematurity).
- Secondary: SIBO, infectious enteritis (rotavirus), mucosal injury (celiac, IBD/Crohn’s, drug/radiation enteritis).
Diagnosis: presumptive (symptoms resolve with avoidance); hydrogen breath test (80% sens, 98% spec); stool pH <6 (infants); lactose tolerance test (↓blood glucose rise <1.1 mmol/L + symptoms).
Management: dietary restriction + Ca²⁺/vitamin D supplementation; oral beta-galactosidase (variable). DDx: cow’s milk allergy.

Celiac Disease

Autoimmune (prevalence ~1:70–1:300); whites of Northern European ancestry; first-degree relatives 10–15% risk. HLA-DQ2 > DQ8 + high gluten intake (± infectious cofactors).
Serum autoantibodies: IgA anti-gliadin; IgA anti-tTG (100% specific).
Classification: classic (villous atrophy, malabsorption/steatorrhea, antibody+, resolves off gluten); atypical (minor GI, anemia/osteoporosis/arthritis); silent (incidental); latent (normal mucosa, prior childhood disease).
Pathomechanism: gluten peptides enter mucosa → tTG deaminates them → antigens to dendritic cells → CD4⁺ response → Th1 (↑IFN-γ → FasL → kills mucosal cells) + fibroblast activation → villous destruction. Possible inducers: rotavirus, enterotoxic E. coli, Campylobacter jejuni; duodenal dysbacteriosis.
Clinical (onset 10–40 yrs): diarrhea (non-bloody), abdominal pain, growth failure/weight loss, severe anemia, B-vitamin neuro disorders, osteopenia (vitamin D/Ca²⁺). Non-GI: arthritis, iron-deficiency anemia, metabolic bone disease, kidney (IgA deposition 33%).
Associations: dermatitis herpetiformis (anti-epidermal transglutaminase), selective IgA deficiency, Down syndrome (20×), T1DM (shared HLA-DQ), liver disease, autoimmune thyroiditis (Hashimoto), IBD (10×).
Consequences: ↑mortality, ↑risk of lymphoma + GI cancer.

一問一答

▶What defines a peptic ulcer?

A defect in the GI mucosa extending through the muscular layer; chronic bleeding can cause iron-deficiency anemia.

▶What are the main causes of peptic ulcer disease?

H. pylori, NSAIDs (even low-dose aspirin), viral causes, gastrinoma (Zollinger-Ellison), and idiopathic.

▶How do NSAIDs cause peptic ulcers?

They inhibit all COX → ↓prostaglandins (which normally inhibit acid) → ↑acid production; low-dose aspirin raises GI bleeding risk by 60%.

▶How does H. pylori cause ulcers?

It colonizes the antrum and produces NH₃ (buffering acid for a favorable environment), irritating the mucosa → more acid; the ongoing immune response damages mucosa → hyperacidity (ulcer incidence 6–10× higher).

▶How is H. pylori diagnosed?

By urease activity: urease breath test (¹³C-urea → labeled CO₂), direct urease test/histology of biopsy; gastroscopy is used for suspected infection/reflux.

▶What are the symptoms and complications of peptic ulcer disease?

Dyspepsia (epigastric pain) is most prominent (~70% asymptomatic); complications include GERD, GI bleeding (anemia, rarely hematemesis), perforation (→ peritonitis → shock → death), and rarely gastric cancer.

▶Why do small intestinal diseases cause large fluid loss?

The high intestinal flow means even a minor mucosal change leads to large fluid loss (diarrhea); leading symptoms are abdominal pain, malabsorption, and diarrhea (±blood).

▶What is lactose intolerance and how common is it?

Intolerance to lactose — the most common intestinal disease worldwide (>70%), with prevalence increasing with age; colonic bacteria adapt by converting lactose to short-chain fatty acids.

▶What causes the symptoms of lactose intolerance?

>75% of unabsorbed lactose is fermented to SCFAs + H₂, causing abdominal pain, diarrhea, and flatulence after dairy.

▶What are the primary and secondary causes of lactose intolerance?

Primary: acquired (age-related) lactase deficiency (most common), congenital (rare AR), developmental (prematurity). Secondary: SIBO, infectious enteritis (rotavirus), mucosal injury (celiac, IBD/Crohn's, drug/radiation enteritis).

▶How is lactose intolerance diagnosed?

Presumptively (symptoms resolve with avoidance), hydrogen breath test (80% sens, 98% spec), stool pH <6 (infants), and the lactose tolerance test (blood glucose rise <1.1 mmol/L + symptoms).

▶What is celiac disease and its key genetic/environmental requirement?

An autoimmune disease (~1:70–1:300) needing HLA-DQ2 > DQ8 plus high gluten intake (± infectious cofactors); first-degree relatives have 10–15% risk.

▶Which autoantibodies are found in celiac disease?

IgA anti-gliadin and IgA anti-tissue transglutaminase (anti-tTG, 100% specific).

▶What is the pathomechanism of celiac disease?

Gluten peptides enter the mucosa → tTG deaminates them → presented to dendritic cells → CD4⁺ Th1 response (↑IFN-γ → FasL kills mucosal cells) + fibroblast activation → villous destruction.

▶What are the four classifications of celiac disease?

Classic (villous atrophy, malabsorption, antibody+, resolves off gluten), atypical (minor GI, anemia/osteoporosis/arthritis), silent (incidental), and latent (normal mucosa, prior childhood disease).

▶What are the clinical features of celiac disease?

Onset 10–40 yrs: non-bloody diarrhea, abdominal pain, growth failure/weight loss, severe anemia, B-vitamin neuro disorders, and osteopenia (vitamin D/Ca²⁺ deficiency).

▶What are the long-term consequences of celiac disease?

Increased mortality and increased risk of lymphoma and GI cancer.

▶What conditions are associated with celiac disease?

Dermatitis herpetiformis, selective IgA deficiency, Down syndrome (20×), T1DM (shared HLA-DQ), liver disease, autoimmune thyroiditis (Hashimoto), and IBD (10×).

▶How is lactose intolerance managed?

Dietary restriction plus Ca²⁺/vitamin D supplementation, and oral beta-galactosidase (variable effect); differential diagnosis is cow's milk allergy.

▶Why can H. pylori tests be false-negative?

In ≥10% of cases due to antibiotics/PPIs (OTC PPIs also mask symptoms).