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🏥 GASTROINTESTINAL TRACT PATHOLOGY

2 MBBS - MUHS Exam Notes (Based on Robbins Pathology)

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TOPIC 1: SALIVARY GLAND TUMOURS

Pleomorphic Adenoma (Mixed Tumour) ⭐⭐ MOST IMPORTANT

• 60% of all salivary gland tumours
• Most common site: Parotid gland (80%)
• Also in submandibular gland, minor salivary glands

• Well-encapsulated, lobulated mass
• Cut section: glistening, pale grey-white
• Rubbery to firm consistency
• Pseudopods may project beyond the capsule

┌─────────────────────────────────────────────────┐
│          PLEOMORPHIC ADENOMA - HISTO             │
│                                                   │
│  Epithelial Component:                            │
│  • Ductal cells (inner lining)                   │
│  • Myoepithelial cells (outer layer)             │
│                                                   │
│  Mesenchymal/Stromal Component:                  │
│  • Myxoid stroma                                 │
│  • Chondroid areas (cartilage-like)              │
│  • Rarely osseous/bony foci                      │
│                                                   │
│  HALLMARK: Epithelial cells embedded in          │
│  chondromyxoid stroma                            │
└─────────────────────────────────────────────────┘

• Slow-growing, painless, mobile mass
• Facial nerve INTACT (unlike malignant)
• Recurs if incompletely excised (pseudopod extension)
• Malignant transformation: Carcinoma ex pleomorphic adenoma (~6%)

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CLASSIFICATION OF SALIVARY GLAND TUMOURS

🟢 BENIGN TUMOURS:

🔴 MALIGNANT TUMOURS:

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TOPIC 2: ORAL SQUAMOUS CELL CARCINOMA ⭐⭐

Etiopathogenesis:

RISK FACTORS:
┌────────────────────────────────────────┐
│  1. Tobacco (smoking + smokeless)      │ ← MOST IMPORTANT
│  2. Alcohol (synergistic with tobacco) │
│  3. HPV 16, 18 (oropharynx)           │
│  4. Betel nut / Pan masala            │ ← Important in India
│  5. Chronic irritation                 │
│  6. Actinic radiation (lip)            │
│  7. Immunosuppression                  │
└────────────────────────────────────────┘

Precancerous Lesions:

• Leukoplakia (white patch) - 5-25% transform
• Erythroplakia (red patch) - higher risk than leukoplakia
• Oral submucous fibrosis
• Lichen planus (erosive)

Sites:

• Most common: Floor of mouth, ventral/lateral tongue
• Oropharynx (tonsil, base of tongue) - HPV related

Gross Features:

• Irregular, indurated ulcer with raised everted edges
• OR exophytic cauliflower-like growth
• Hard on palpation (due to desmoplasia)

Microscopic Features:

┌──────────────────────────────────────────┐
│    ORAL SCC - HISTOLOGY                  │
│                                          │
│  Well differentiated (Grade 1):          │
│  • Keratin pearls / cell nests           │
│  • Intercellular bridges                 │
│  • Low mitoses                           │
│                                          │
│  Moderately diff (Grade 2):              │
│  • Partial keratinization                │
│  • Moderate mitoses                      │
│                                          │
│  Poorly diff (Grade 3):                  │
│  • No keratinization                     │
│  • High mitoses, pleomorphism            │
└──────────────────────────────────────────┘

Spread:

• Direct: Adjacent structures (jaw, palate)
• Lymphatic: Submandibular, deep cervical nodes (common)
• Blood-borne: Lung, liver (late)

Prognosis:

• 5-year survival ~50% (better with early detection)
• HPV-positive oropharyngeal SCC has better prognosis

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TOPIC 3: PEPTIC ULCER DISEASE (PUD) ⭐⭐⭐

Definition:

Risk Factors:

┌─────────────────────────────────────────────┐
│            RISK FACTORS FOR PUD              │
│                                              │
│  MAJOR:                                      │
│  ✦ H. pylori infection (duodenal 100%,       │
│    gastric 70%)                              │
│  ✦ NSAID/aspirin use                         │
│                                              │
│  MINOR:                                      │
│  • Smoking                                   │
│  • Zollinger-Ellison syndrome (gastrinoma)   │
│  • Alcohol                                   │
│  • Corticosteroids                           │
│  • Blood group O (duodenal ulcer)            │
│  • Stress (Cushing's / Curling's ulcers)    │
│  • Genetic predisposition                    │
└─────────────────────────────────────────────┘

Pathogenesis:

Normal mucosal defense vs. Aggressive factors
            ↓
  IMBALANCE → ULCER
  
AGGRESSIVE FACTORS:          DEFENSIVE FACTORS:
• H. pylori                  • Mucus secretion
• Acid (HCl)                 • Bicarbonate secretion
• Pepsin                     • Mucosal blood flow
• NSAIDs                     • Epithelial renewal
• Bile reflux                • Prostaglandins (PGE2)

Role of H. pylori in PUD:

H. pylori
    │
    ├─→ Urease → NH3 → Neutralizes local pH → protects bacteria
    │
    ├─→ Inflammation (antral gastritis)
    │       ↓
    │   Stimulates G-cells → ↑Gastrin → ↑Acid
    │       ↓
    │   Inhibits D-cells → ↓Somatostatin → ↑Gastrin
    │
    ├─→ CagA toxin → IL-8 → Neutrophil infiltration
    │       ↓ (mucosal damage)
    │
    ├─→ Antral Gastritis → Duodenal Ulcer (most common)
    │
    └─→ Pangastritis → Gastric Atrophy → Gastric Ulcer/Cancer

GROSS FEATURES OF PEPTIC ULCER:

┌──────────────────────────────────────────────┐
│         PEPTIC ULCER - GROSS                  │
│                                              │
│  • Size: 2-4 cm (usually < 3 cm)            │
│  • Shape: Round/oval, punched-out            │
│  • Edges: Sharp, straight (perpendicular)    │
│  • Floor/Base: Clean, smooth                 │
│  • Surrounding mucosa: Folds radiate to edge │
│  • Wall: NOT undermined                      │
│  • Single, solitary (usually)                │
│                                              │
│  SITE: Duodenum → 1st part, posterior wall  │
│         Stomach → Lesser curvature           │
└──────────────────────────────────────────────┘

MICROSCOPIC FEATURES (4 Zones - Askanazy):

┌──────────────────────────────────────────────┐
│  ZONE 1 (Surface): Fibrinous exudate +        │
│                     necrotic debris           │
│  ─────────────────────────────────────────── │
│  ZONE 2: Nonspecific inflammatory             │
│           infiltrate (neutrophils)            │
│  ─────────────────────────────────────────── │
│  ZONE 3: Granulation tissue                   │
│           (fibroblasts + new vessels)         │
│  ─────────────────────────────────────────── │
│  ZONE 4 (Deepest): Fibrosis / Collagenous    │
│                     scar tissue               │
└──────────────────────────────────────────────┘

Complications (Mnemonic: HOPE):

• Hemorrhage (most common) - posterior wall → erodes gastroduodenal artery
• Obstruction (pyloric stenosis) - cicatricial scarring
• Perforation (acute) - anterior wall → chemical peritonitis
• Expansion into adjacent organs (penetration) - pancreas most common

---

TOPIC 4: GASTRIC CARCINOMA ⭐⭐⭐

Epidemiology:

• Second most common cancer death worldwide
• Common in Japan, Korea, China, South America
• Male > Female (2:1)

Etiopathogenesis:

┌────────────────────────────────────────────────┐
│           RISK FACTORS - GASTRIC Ca             │
│                                                  │
│  ENVIRONMENTAL:                                  │
│  • H. pylori infection (↑ 3-6x risk)            │
│  • Dietary: smoked fish, nitrites, low vit C    │
│  • Smoking                                       │
│                                                  │
│  PRECANCEROUS LESIONS:                           │
│  • Chronic atrophic gastritis (type A & B)      │
│  • Intestinal metaplasia                         │
│  • Adenomatous polyps                           │
│  • Menetrier's disease (giant hypertrophic)     │
│                                                  │
│  GENETIC:                                        │
│  • CDH1 (E-cadherin) mutation → diffuse type    │
│  • APC gene mutation → intestinal type          │
│  • TP53 mutation                                 │
│  • Blood group A (diffuse type)                  │
│                                                  │
│  OTHER:                                          │
│  • Previous gastric surgery                      │
│  • Pernicious anemia                             │
└────────────────────────────────────────────────┘

Lauren Classification (Most Important):

┌──────────────────┬───────────────────┐
│  INTESTINAL TYPE │   DIFFUSE TYPE    │
├──────────────────┼───────────────────┤
│ Better diff.     │ Poorly diff.      │
│ Gland formation  │ Signet ring cells │
│ Expanding growth │ Infiltrative      │
│ Older age        │ Younger, women    │
│ H. pylori assoc. │ CDH1 mutation     │
│ Better prognosis │ Worse prognosis   │
│ Distal stomach   │ Entire stomach    │
└──────────────────┴───────────────────┘

Gross Features:

TYPES OF GASTRIC CARCINOMA (GROSS):

1. FUNGATING/POLYPOID (Exophytic)
   → Protrudes into lumen
   → Better prognosis

2. ULCERATING
   → Malignant ulcer: irregular edges,
     necrotic floor, nodular base
   → Ulcerative-infiltrating: most common

3. DIFFUSE INFILTRATIVE (Linitis Plastica)
   → "Leather bottle stomach"
   → Entire wall thickened and rigid
   → Diffuse-type histology
   → Worst prognosis

4. SUPERFICIAL SPREADING
   → Early gastric cancer
   → Limited to mucosa/submucosa
   → Best prognosis

Microscopic Features:

• Intestinal type: Glandular structures, columnar cells, resembles colon adenocarcinoma
• Diffuse type: Individual cells, signet ring cells (mucin pushes nucleus to periphery), poor cohesion due to loss of E-cadherin
• Desmoplastic stroma in diffuse type

Spread:

• Direct: Into pancreas, colon, liver
• Peritoneal: Krukenberg tumour (ovarian mets via peritoneum)
• Lymphatic: Virchow's node (left supraclavicular)
• Blood: Liver most common
• Sister Mary Joseph nodule (umbilical peritoneal mets)

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TOPIC 5: INTESTINAL TUBERCULOSIS ⭐⭐

Etiopathogenesis:

• Caused by Mycobacterium tuberculosis (human type) or M. bovis (rare)
• Route: Swallowing of infected sputum, or hematogenous spread from lung TB
• Most common site: Ileocecal region (60-80%) - due to:
  • Abundant lymphoid tissue (Peyer's patches)
  • Relative stasis of contents
  • High fluid absorption

Pathogenesis:

M. tuberculosis ingested
        ↓
Penetrates mucosa → reaches submucosa
        ↓
Engulfed by macrophages
        ↓
Type IV hypersensitivity (CMI)
        ↓
Granuloma formation with central CASEATION
        ↓
Ulceration of overlying mucosa
        ↓
TRANSVERSE ULCERS (perpendicular to long axis)

Morphology:

Gross:

┌──────────────────────────────────────────────┐
│         INTESTINAL TB - GROSS                 │
│                                              │
│  Ulcerative type (most common):              │
│  • Transverse / circumferential ulcers       │
│  • Short axis of bowel                       │
│  • Multiple, irregular with undermined edges │
│  • Surrounding mucosa congested              │
│                                              │
│  Hypertrophic type:                          │
│  • Fibrosis + thickening of bowel wall       │
│  • Resembles carcinoma (can mimic!)          │
│  • Stricture formation                       │
│                                              │
│  Mixed type: Combined features               │
│                                              │
│  Serosal surface: Caseous nodules,           │
│  fibrous adhesions, matted mesenteric LN     │
└──────────────────────────────────────────────┘

Microscopic:

• Epithelioid cell granulomas with Langhans giant cells
• Caseating necrosis (pathognomonic)
• Granulomas in all layers (transmural) - submucosal > mucosal
• Mesenteric lymph nodes show caseating granulomas
• Acid-fast bacilli on ZN stain (sparse)

Differentiation: Tubercular vs Typhoid Ulcers

┌────────────────┬──────────────────────┬───────────────────────┐
│  FEATURE       │  TUBERCULAR ULCER    │  TYPHOID ULCER        │
├────────────────┼──────────────────────┼───────────────────────┤
│ Cause          │ M. tuberculosis      │ Salmonella typhi      │
│ Site           │ Ileocecal junction   │ Terminal ileum (PP)   │
│ Orientation    │ TRANSVERSE/          │ LONGITUDINAL/         │
│                │ circumferential      │ oval (along axis)     │
│ Edges          │ Undermined, ragged   │ Clean-cut, thin       │
│ Distribution   │ Multiple, scattered  │ Multiple, Peyer's     │
│                │                      │ patches only          │
│ Perforation    │ Less common          │ Common (2nd-3rd week) │
│ Histology      │ Caseating granuloma  │ Mononuclear           │
│                │ Langhans giant cells │ infiltrate; No        │
│                │                      │ granulomas            │
│ Mesenteric LN  │ Caseous (matted)     │ Hyperplastic          │
│ Serology       │ Mantoux +ve          │ Widal test +ve        │
│ Complications  │ Stricture, fistula   │ Perforation,          │
│                │                      │ hemorrhage            │
└────────────────┴──────────────────────┴───────────────────────┘

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TOPIC 6: ULCERATIVE LESIONS OF BOWEL + UC vs CD ⭐⭐⭐

List of Ulcerative Lesions of Bowel:

1. Peptic ulcer (stomach, duodenum)
2. Intestinal tuberculosis
3. Typhoid (Salmonella)
4. Ulcerative Colitis (IBD)
5. Crohn's Disease (IBD)
6. Amoebic colitis (E. histolytica)
7. Ischemic colitis
8. Radiation enterocolitis
9. Necrotizing enterocolitis (neonates)
10. Carcinoma (ulcerated)
11. Solitary rectal ulcer
12. Drug-induced (NSAIDs)

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Ulcerative Colitis (UC) vs Crohn's Disease (CD) ⭐⭐⭐

╔══════════════════╦══════════════════════╦═════════════════════╗
║ FEATURE          ║ ULCERATIVE COLITIS   ║ CROHN'S DISEASE     ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ EXTENT           ║ Colon only           ║ Any part of GIT     ║
║                  ║ (rectum always)      ║ (mouth to anus)     ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ DISTRIBUTION     ║ Continuous           ║ Discontinuous       ║
║                  ║ (no skip areas)      ║ (SKIP LESIONS)      ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ ILEUM INVOLVED   ║ No (backwash ileitis)║ YES (terminal)      ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ RECTUM           ║ Always involved      ║ Typically spared    ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ DEPTH            ║ MUCOSAL only         ║ TRANSMURAL          ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ GROSS            ║ Diffuse, continuous  ║ Cobblestone         ║
║                  ║ pseudopolyps         ║ appearance          ║
║                  ║ "collar-stud" ulcers ║ Linear ulcers       ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ WALL             ║ Thin (no thickening) ║ Thickened, rigid    ║
║                  ║                      ║ "hose pipe" bowel   ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ FISTULAE         ║ Rare                 ║ COMMON              ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ GRANULOMAS       ║ ABSENT               ║ PRESENT (50-60%)    ║
║                  ║                      ║ Non-caseating       ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ HISTOLOGY        ║ Crypt abscesses      ║ Transmural lymphoid ║
║                  ║ Goblet cell depletion║ aggregates          ║
║                  ║ Mucosal only         ║ Sarcoid-like        ║
║                  ║                      ║ granulomas          ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ MALIGNANCY RISK  ║ HIGH (colitis-Ca)    ║ Lower               ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ COMPLICATIONS    ║ Toxic megacolon      ║ Abscess, fistulae   ║
║                  ║ Hemorrhage           ║ Obstruction         ║
║                  ║ Carcinoma            ║ Malabsorption       ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ SURGERY          ║ CURATIVE             ║ Not curative        ║
╠══════════════════╬══════════════════════╬═════════════════════╣
║ SEROLOGY         ║ p-ANCA positive      ║ ASCA positive       ║
╚══════════════════╩══════════════════════╩═════════════════════╝

UC Gross Diagram:

     ULCERATIVE COLITIS (Colon)
     ┌──────────────────────────┐
     │  Rectum ←─ STARTS HERE  │
     │  ███████████████████████│ ← Continuous mucosal ulceration
     │  Pseudopolyps (islands   │
     │  of surviving mucosa)    │
     │  No skip areas           │
     │  DOES NOT involve ileum  │
     └──────────────────────────┘
     
     CROHN'S DISEASE
     ┌────────────────────────────────┐
     │ Normal │■■■■│ Normal │■■│ Norm │
     │  Skip   Skip   Skip lesions   │
     │ ↑ Terminal ileum most common  │
     │ Cobblestone mucosa            │
     │ Transmural → fistulae         │
     └────────────────────────────────┘

---

TOPIC 7: CARCINOMA COLON ⭐⭐⭐

Etiopathogenesis:

Risk Factors:

HIGH RISK:
• FAP (Familial Adenomatous Polyposis) - APC mutation → 100% risk
• HNPCC/Lynch syndrome - Mismatch repair genes (MLH1, MSH2)
• Ulcerative colitis (long-standing)
• Previous adenoma/colorectal cancer
• Family history

MODERATE RISK:
• Adenomatous polyps (villous > tubular)
• Diet: high fat, low fiber, red/processed meat
• Obesity, physical inactivity
• Smoking, alcohol
• Crohn's disease

Molecular Pathogenesis (Vogelstein Sequence):

NORMAL COLON EPITHELIUM
         ↓ APC mutation (chromosome 5q)
ABERRANT CRYPT FOCUS / SMALL ADENOMA
         ↓ K-RAS mutation
INTERMEDIATE ADENOMA
         ↓ SMAD2/SMAD4 loss (18q)
LARGE ADENOMA WITH DYSPLASIA
         ↓ TP53 mutation (17p)
CARCINOMA
         ↓ DCC, other changes
METASTATIC CARCINOMA

Gross Features:

RIGHT COLON (Cecum, Ascending):
┌─────────────────────────────────┐
│  • POLYPOID/FUNGATING mass     │
│  • Exophytic, cauliflower-like  │
│  • Fills lumen but RARELY       │
│    obstructs (large caliber)    │
│  • Presents: Iron-deficiency    │
│    anemia, occult blood         │
└─────────────────────────────────┘

LEFT COLON (Descending, Sigmoid, Rectum):
┌─────────────────────────────────┐
│  • ANNULAR/"NAPKIN RING" type  │
│  • Encircles bowel wall         │
│  • OBSTRUCTS lumen (narrow)    │
│  • "Apple core" on barium enema │
│  • Presents: change in bowel    │
│    habit, obstruction           │
└─────────────────────────────────┘

Microscopic Features:

• Adenocarcinoma (most common ~90%)
• Glandular structures with columnar cells
• Variable mucin production
• Signet ring cell variant (rare, worse prognosis)
• Mucinous adenocarcinoma (>50% extracellular mucin)
• Dirty/necrotic luminal contents in glands ("dirty necrosis") - characteristic

Spread:

• Direct: Into mesorectal fat, adjacent organs
• Lymphatic: Paracolic → intermediate → central nodes
• Blood: Liver (most common) → lungs → bone/brain
• Peritoneal: Carcinomatosis

Staging (Duke's / TNM):

┌──────────────┬────────────────────────────┬──────────────┐
│ DUKE'S STAGE │ EXTENT                     │ 5-yr SURVIVAL│
├──────────────┼────────────────────────────┼──────────────┤
│ A            │ Mucosa/submucosa (T1-T2N0) │ 90-95%       │
│ B            │ Muscularis → serosa (T3N0) │ 60-75%       │
│ C            │ Lymph node involvement     │ 30-40%       │
│ D (Astler)   │ Distant metastasis         │ < 5%         │
└──────────────┴────────────────────────────┴──────────────┘

---

TOPIC 8: CARCINOMA OF RECTUM

Key Differences from Colon Ca:

┌─────────────────────────────────────────────────┐
│             RECTAL CARCINOMA - KEY POINTS        │
│                                                   │
│  • 20-30% of all colorectal cancers              │
│  • Sites: Upper rectum (rectosigmoid junction),   │
│    middle, lower rectum                           │
│                                                   │
│  • Gross: Annular (napkin ring) or polypoid       │
│                                                   │
│  • Histo: Adenocarcinoma, same as colon          │
│                                                   │
│  SPREAD:                                          │
│  • Circumferential spread in bowel wall          │
│  • Lymphatics: Follow superior rectal artery     │
│    (internal iliac + para-aortic nodes)          │
│  • Direct: Prostate, seminal vesicles (M),       │
│    uterus, vagina, bladder (F)                   │
│  • Blood: Portal → LIVER most common             │
│                                                   │
│  CLINICAL FEATURES:                              │
│  • Rectal bleeding (fresh blood mixed with stool)│
│  • Tenesmus (feeling of incomplete evacuation)   │
│  • Change in bowel habits                        │
│  • Rectal mass on DRE                            │
│                                                   │
│  TREATMENT: Abdominoperineal resection (APR) /   │
│  Low anterior resection (LAR)                     │
└─────────────────────────────────────────────────┘

---

TOPIC 9: BENIGN vs MALIGNANT GASTRIC ULCERS ⭐⭐

╔═══════════════════╦════════════════════════╦═════════════════════╗
║ FEATURE           ║ BENIGN PEPTIC ULCER    ║ MALIGNANT ULCER     ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ SITE              ║ Lesser curvature,      ║ Lesser curvature,   ║
║                   ║ anterior wall          ║ fundus, greater     ║
║                   ║                        ║ curvature also      ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ SIZE              ║ Usually < 2 cm         ║ Usually > 2-3 cm    ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ SHAPE             ║ Round/oval, regular    ║ Irregular, variable ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ EDGES             ║ Smooth, punched-out,   ║ Raised, nodular,    ║
║                   ║ STRAIGHT walls         ║ EVERTED/heaped-up   ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ BASE/FLOOR        ║ Clean, smooth, grey    ║ Necrotic, shaggy,   ║
║                   ║                        ║ hemorrhagic         ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ MUCOSAL FOLDS     ║ Converge (radiate)     ║ Do NOT radiate;     ║
║                   ║ toward ulcer edge      ║ clubbed/fused       ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ SURROUNDING       ║ Edematous, soft        ║ Hard, indurated     ║
║ TISSUE            ║                        ║ (nodular)           ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ GASTRIC WALL      ║ NOT thickened          ║ Thickened, rigid    ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ ENDOSCOPY         ║ H. pylori, heals with  ║ Does NOT heal with  ║
║                   ║ PPI + antibiotics      ║ treatment           ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ HISTOLOGY         ║ 4 Askanazy zones       ║ Malignant cells,    ║
║                   ║ (see above)            ║ invasion, no true   ║
║                   ║                        ║ zoning              ║
╠═══════════════════╬════════════════════════╬═════════════════════╣
║ BARIUM MEAL       ║ Ulcer projects OUTSIDE ║ Ulcer within the    ║
║                   ║ lumen (Hampton line)   ║ lumen/tumour mass   ║
╚═══════════════════╩════════════════════════╩═════════════════════╝

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TOPIC 10: GASTRITIS ⭐⭐

Classification:

A. Acute Gastritis:

Etiological Agents:

CAUSES OF ACUTE GASTRITIS:
┌────────────────────────────────────────────┐
│  1. NSAIDs (aspirin, ibuprofen)            │ ← Most common drug cause
│     - Inhibit COX → ↓PGE2 → ↓mucus       │
│     - ↓Bicarbonate, ↓mucosal blood flow   │
│                                            │
│  2. Alcohol                                │
│  3. Smoking                                │
│  4. Chemotherapy agents                    │
│  5. Uremia (ammonia effect)               │
│  6. Systemic infections (CMV, etc.)       │
│  7. Severe stress (Cushing's, Curling's)  │
│  8. Corticosteroids                        │
│  9. Bile reflux                            │
│  10. Trauma (nasogastric tube)             │
└────────────────────────────────────────────┘

• Edema, hyperemia
• Neutrophilic infiltrate in lamina propria
• Surface erosions ± hemorrhage
• Acute erosive hemorrhagic gastritis if both erosions + hemorrhage

---

B. Chronic Gastritis - Classification:

CHRONIC GASTRITIS
│
├── TYPE A (Autoimmune / Fundal):
│   • Autoantibodies against parietal cells
│   • Anti-intrinsic factor antibodies
│   • Affects BODY & FUNDUS
│   • ↓Intrinsic factor → Pernicious anemia (B12 def)
│   • ↓Acid → Hypochlorhydria
│   • ↑Gastrin (G cells active, trying to stimulate)
│   • Risk: Gastric adenocarcinoma, Carcinoid tumour
│
└── TYPE B (H. pylori / Antral / Environmental):
    • MOST COMMON (90%)
    • H. pylori infection
    • Affects ANTRUM first
    • Progresses to pangastritis
    • Risk: Peptic ulcer, Gastric adenocarcinoma

---

H. pylori Gastritis - Detailed:

Organism Features:

H. pylori - Characteristics:
• Gram-negative, spiral bacillus
• Microaerophilic
• Found beneath mucous layer, above epithelium
• Concentrated in antrum

VIRULENCE FACTORS:
┌────────────────────────────────────────┐
│ 1. FLAGELLA → motility in viscous      │
│              mucus                     │
│ 2. UREASE → NH3 → local alkalization  │
│             (buffers acid around bug)  │
│ 3. ADHESINS → stick to foveolar cells │
│ 4. CagA toxin → stimulates IL-8       │
│                → neutrophil chemoattr │
│ 5. VacA toxin → vacuolation of cells  │
└────────────────────────────────────────┘

Morphology (from Robbins):

• H. pylori visible on H&E or Giemsa stain (comma/S-shaped, in mucus overlying surface epithelium)
• Neutrophils in lamina propria and epithelium
• Pit abscesses (neutrophils in gastric pit lumina)
• Lymphoid follicles in submucosa (H. pylori = major cause of gastric MALT lymphoma)
• Plasma cells and lymphocytes (chronic inflammation)
• Goblet cell metaplasia → Intestinal metaplasia (with long-standing infection)

Sequelae of H. pylori:

H. pylori Infection
         │
   ┌─────┴──────────────┐
   ↓                    ↓
ANTRAL GASTRITIS    PANGASTRITIS
(majority)          (minority)
   ↓                    ↓
Duodenal ulcer      Gastric atrophy
   ↓                    ↓
H. pylori PUD       Intestinal meta
                        ↓
                  Gastric adenoCa
                        +
                  MALT Lymphoma

Diagnosis of H. pylori:

NON-INVASIVE:
• Urea breath test (C13 or C14) ← Gold standard non-invasive
• Stool antigen test
• Serology (IgG antibody - stays positive after treatment)

INVASIVE (Endoscopy + Biopsy):
• Rapid urease test (CLO test) ← Quick, highly specific
• Histology (Giemsa/Warthin-Starry stain)
• Culture (gold standard, rarely done)

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DIAGRAMS FOR EXAM 🎨

Diagram 1: H. pylori in Gastric Mucosa

        GASTRIC LUMEN
    ══════════════════════════
    H.pylori ↓↓↓ (comma shapes in mucus)
    ┌─────────────────────────┐
    │  MUCUS LAYER            │
    │ ~H.p~ ~H.p~ ~H.p~      │
    ├─────────────────────────┤
    │  SURFACE EPITHELIUM     │ ← Adhesins attach here
    │  (foveolar cells)       │
    ├─────────────────────────┤
    │  LAMINA PROPRIA         │ ← PMNs + lymphocytes
    │  [PMN][PMN] ●●●●       │
    ├─────────────────────────┤
    │  MUSCULARIS MUCOSAE     │
    ├─────────────────────────┤
    │  SUBMUCOSA              │ ← Lymphoid follicles
    └─────────────────────────┘

Diagram 2: Peptic Ulcer - 4 Zones

         GASTRIC LUMEN
         ↓
    ═══════╔══════════╗═══════
           ║  ZONE 1  ║  ← Necrotic slough
           ║  ZONE 2  ║  ← Active inflammation (PMN)
           ║  ZONE 3  ║  ← Granulation tissue
           ║  ZONE 4  ║  ← Fibrous/scar tissue
           ╚══════════╝
         ↑                  ↑
    Converging          Sharp, punched-
    mucosal folds        out edges

Diagram 3: Gastric Carcinoma Types

INTESTINAL TYPE                DIFFUSE TYPE (Linitis Plastica)
                               
    ┌──────────┐               ┌──────────────────────┐
    │  GLANDS  │               │ • • • • • • • • • •  │
    │  ┌────┐  │               │ • • SIGNET RING • •  │
    │  │    │  │               │ • • CELLS • • • • •  │
    │  └────┘  │               │ • • everywhere • • • │
    │  ┌────┐  │               │ THICK RIGID WALL     │
    │  │    │  │               │ "Leather bottle"     │
    └──────────┘               └──────────────────────┘
    Columnar cells             Individual signet ring
    Gland formation            cells in desmoplastic
    H.pylori related           stroma; CDH1 mutation

Diagram 4: UC vs Crohn's (Bowel diagram)

UC:
Colon: [RECTUM]■■■■■■■■■■■[CECUM]  (Continuous)
       ↑ Always starts    ↑
       at rectum          May stop anywhere
       
CD:
[Mouth]...[SI]■■■[skip]■■[skip]■■[Colon]...[Anus]
              ↑           ↑
         Skip lesions; any segment; TRANSMURAL

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QUICK REVISION TABLE - ALL TOPICS

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Source: Robbins & Kumar Basic Pathology (Robbins Pathology), 10th Edition - GI Chapter; confirmed sections from library database (ISBN: 9780323790185).

MUHS Exam Tips: Topics marked ⭐⭐⭐ appear almost every year. Always write a comparison table for UC vs CD, and the 4 zones of peptic ulcer in exams. For diagrams, draw simple labeled sketches - color is bonus, accuracy is key.