L12- patho (peptic ulcer, gastritis and gastric cancer) Flashcards
Stomach essential recap
Functions:
- A ‘mixing’ reservoir for food
- Digestion of proteins
Mucosal products:
HCl and pepsin – two main products of gastric mucosa
Sections:
- Cardia
- Body
- Antrum
- Pre-pyloric area (i.e. Pylorus)
Peptic Ulcer nature
Ulcers (loss of mucosa) developing along the upper GI tract due to peptic / gastric juice action
(No acid or gastric juice, no peptic ulcer)
Peptic Ulcer sites (In descending order of frequency)
(In descending order of frequency)
- Duodenum - mostly first part of duodenum (immediate post-pyloric region).
- Stomach - non-acid secreting pyloric gland mucosa (pyloric antrum and the lesser curve - where HCl production is low)
- Oesophagus - in reflux esophagitis.
- Gastroenterostomy stroma (anastomotic ulcer) - jejunal side.
- Others: e.g. Jejunum (in conditions with pathological secretion of gastrin or hypersecretion
of gastric acid).
Gastroenterostomy
Surgical creation of a connection between the stomach and the jejunum. At the jejunal side, gastroenterostomy stoma (anastomotic ulcer) is often found (4th common form of peptic ulceration)
Epidemiology of peptic ulcer
Marked decrease in incidence in Hong Kong and developed countries (because of treatment against Helicobacter pylori).
Pathogenesis of peptic ulcer
Pathogenesis of peptic ulcer:
Virulent factor(s) + hypergastrinaemia + hyperacidity
Normally, gastric acid and pepsin from gastric juice constantly attacks; which is met by the equal defence force from mucosa in the form of mucus and normal epithelial turnover
Any excessice attack force, or inadequae mucosal defence, will lead to imbalance and the formation of peptic ulcer, such as:
- Weakening of mucosal defence in Gastric ulcer
- Increased acid and pepsin production in Duodenal ulcer
Peptic ulcers etiology
Multifactorial Risk Factors:
1. Helicobacter pylori infection
- High incidence in PU
- DU (95%); GU (75%)
- Eradication of HP leads to remission & decreasing incidence of PU
2. Environmental factors:
- Smoking (Nicotine stimulates HCl production; reduces mucus)
- Alcohol (organic solvent that dissolves epithelial mucus surface)
- Drugs (e.g. analgesic, NSAIDS -> inhibits prostaglandin)
- Organic stress (e.g. stroke, burns)
**3. Hormonal factor **
- Male preponderance
- rare in pregnant women
4. Hypercalcemia
- stimulates gastrin production and therefore acid secretion
5. Excess production of (?)
- Pepsin
- Acid
- Gastrin
- Histamine
Why may we consider peptic ulcer as infective disease
Because Helicobacter pylori infection is one of the most important risk factors of peptic ulcer:
- Duodenal Ulcer (95%)
- Gastric Ulcer (75%);
Eradication of HP by antibiotics leads to remission & decreasing incidence of PU
Helicobacter Pylori
Characteristics:
- gram-negative
- microaerophilic
- spiral shape
- flagella
- Stained black by Silver stain (Warthin-Starry stain)
- resides in the Interface between mucus and gastric epithelial surface (gastric metaplasia in duodenum)
Virulent factors:
Produces enzymes and exotoxin - urease, phospholipase, catalase, mucinase and toxic chemicals.
Epidemiology:
- Overall prevalence in Hong Kong is 55% (increasing with age)
- 95% of the DU are HP positive
- 75% of the GU are HP positive
Notes:
HP → chronic gastritis → damage to gastric mucosa → impaired mucosal resistance → GU
HP → chronic antral gastritis → increased acid production → gastric metaplasia in duodenum →
infect of metaplastic epithelium in duodenum → active chronic duodenitis → impaired mucosal resistance → DU
Eradication of HP provides long term remission of Peptic Ulcer and GU diseases.
H. Pylori and Gastric Ulcers
HP → chronic gastritis → damage to gastric mucosa → impaired mucosal resistance → GU
(mucosal damage caused by virulent factors of HP: enzymes and exotoxin e.g. urease, phospholipase, catalase, mucinase and toxic chemicals)
H. Pylori and Duodenal Ulcers
HP → chronic antral gastritis → increased acid production → gastric metaplasia in duodenum →
infect of metaplastic epithelium in duodenum → active chronic duodenitis → impaired mucosal resistance → DU
(Inflammation damage caused by virulent factors of HP: enzymes and exotoxin e.g. urease, phospholipase, catalase, mucinase and toxic chemicals)
Erosions versus Ulcers
Erosions
- Loss of less than the full thickness of mucosa.
- Healing without scarring likely.
Ulcers
- Loss of the full thickness of the mucosa with a variable degree of penetration into underlying coats
- Healing with scarring more common in chronic ulcers.
Acute & Chronic peptic ulcer differences
Mainly depends on the depth of ulceration
Acute Peptic ulcer:
1) Shallow penetration; affecting mucosa only
2) Smaller (sometimes may reach as large as 2 cm in diameter which perforates and bleeds heavily)
3) Multiple
4) Microscopically without granulation tissue and fibrosis.
Chronic Peptic Ulcer
1) Deep penetration (deeper than mucosa); fibrotic base extending to serosa
2) Larger
3) Usually solitary
4) granulation tissue and fibrosis.
The above features apply to both gastric and duodenal ulcers alike
Acute peptic ulcer macroscopic appearance
Acute Peptic ulcer:
1) Shallow penetration; affecting mucosa only
2) Smaller (sometimes may reach as large as 2 cm in diameter which perforates and bleeds heavily)
3) Multiple
4) Can occur anywhere in the stomach. Rare in duodenum.
Chronic peptic ulcer macroscopic appearance
Chronic Peptic Ulcer
1) Deep penetration (deeper than mucosa); fibrotic base extending to serosa
2) Larger
3) Usually solitary
4) Round or oval
5) Usually have sharp margins (punched-out edge)
6) Oedematous surrounding mucosa
7) With or without fibrous adhesion to adjacent organs.
8) Healing takes place by proliferation of epithelium from ulcer edge, forming a thin layer over the ulcer floor - a stellate scar grossly.
Acute peptic ulcer microscopic appearance
- Polymorphs proliferation
- Necrotic cellular debris (from gastric juice digested cells)
- The histological appearance of the ulcer resembles that of the chronic type, but without granulation tissue and fibrosis.
Chronic peptic ulcer microscopic appearance
Ulcer floor has several layers histologically:
(1) an uppermost layer of polymorphs and necrotic debris,
(2) a middle zone of granulation tissue (fibroblasts and young capillaries), and
(3) a lower fibrous scarring zone completely interrupting the muscular coat.
Healing of Chronic peptic ulcer
Healing takes place by proliferation of epithelium from ulcer edge, forming a thin layer over the ulcer floor. This will lead to loss of rugae and the formation of the characteristic Stellar Scar
Haemorrhage due to PU
Affects Small blood vessels, Veins, artery. Ranges from occult blood in stool, melena, hematemesis or massive bleeding.
1. Hematemesis:
- Vomiting of coffee ground material (small amt of blood)
- Vomiting of fresh blood (large amt of blood)
2. Bleeding into intestine
- melena
Perforation due to PU
Pathophysiology:
- Duodenal ulcer > gastric ulcer
- Anterior ulcer > posterior ulcer
- male > female
- chronic > acute
Complications:
- Will lead to peritonitis; firstly chemical peritonitis, then secondary bacterial peritonitis.
- Localised peritonitis -> pelvic/subphrenic abscess.
Penetration due to PU
Penetration into adjacent organs:
- E.g. penetration into pancreas (posterior gastric ulcer), production of gastro-colic fistula.
- Penetration into pancreas will be extremely painful due to the abundance of nerve plexus
Fibrosis & Stenosis due to PU
- causing pyloric stenosis in chronic duodenal or pyloric ulcers
- Hourglass deformity in chronic gastric ulcer (rare)
Acute gastritis (morphology, presentation, etiology)
Morphology: The increased mucosal inflammatory infiltrates being predominately Acute inflammatory cells (polymorphs - neutrophils)
Presentation:
- Transient
- Abdominal pain; can give rise to bleeding
Etiology:
- NSAID
- heavy alcohol consumption, heavy smoking, severe stress (burn, stroke), etc

Chronic gastritis (morphology, subclasses, Etiology)
Morphology:
- Chronic inflammatory cells (lymphocytes & plasma cells) within the lamina propria.
- An infiltrate of neutrophils may accompany chronic gastritis, and the density of this infiltrate is referred to as activity and graded accordingly (“Active” chronic gastritis)
Subclasses:
A. Superficial (inflammatory cells present in the superficial part of mucosa)
B. Diffuse (in the whole depth of mucosa)
C. Atrophic (with shortening of glands)
Etiology: Helicobacter pylori, autoimmune
Gastric adenocarcinoma epidemiology and prognosis
Epidemiology:
- Incidence falling world-wide but still a common fatal tumour
- Higher incidence in Eurasia and South America; highest in Japan
- For Hong Kong:*
- 9.1/100,000 population (Department of Health)
- 4 th leading fatal cancer (after lung, colorectal and liver cancers)
Prognosis:
The prognosis is poor (5-year survival < 25%).
Gastric adenocarcinoma etiology
1. Helicobacter pylori infection
- HP is classified as class 1 carcinogen by WHO
2. Dietary and environmental factors
- smoking (tobacco tar)
- high salt
- nitrosamines (from nitrites and nitrates), e.g. smoked food and salted fish
- decreased intake of fresh vegetables and fruit esp. citrous fruits (antioxidants e.g. vitamin A & C are protective)
3. Premalignant conditions and lesions
- gastric adenoma
- chronic type A autoimmune gastritis, pernicious anaemia
- intestinal metaplasia and dysplasia in chronic atrophic gastritis (H.pylori related)
- Others
Macroscopical appearance of gastric adenocarcinoma
i) Polypoid or fungating
ii) Ulcerative (after upper part of polypoid became ischemic and then necrotic) -> heaped up and everted edges
- Irregular border
- Dirty base/floor
- Greater than 5 cm
iii) Diffuse scirrhous (very firm, leather-bottle stomach or linitis plastica; diffuse type of carcinoma)
- thickened mucosa
Microscopic appearance of adenocarcinoma
In general:
- Mitotic figures
- Larger nuclei
Two main types (Lauren classification):
a. Intestinal type
- formation of glandular structures.
b. Diffuse type
- malignant cells singly or in sheets (small cluster) with minimal gland formation
- diffuse infiltrative pattern
- Signet-ring cells with large mucin vacuoles distending cytoplasm and compressing the nucleus (peripherally located), may be present.
Early gastric cancer classification
Classified morphologically into 3 types:
Type I: polypoid
Type II: superficial
IIa: elevated
IIb: flat
IIc: depressed
Type III: excavated
Their relative incidence varies in different geographical areas and this may have epidemiological significance.
Differentiation between benign peptic ulcer and ulcerative carcinomas of stomach
Always make a histological confirmation (with endoscopic examination and biopsy) of a gastric ulcer to differentiate between gastric peptic ulcer and gastric malignancy - this is rarely needed for duodenal ulcer, except in odd cases
COMPARISON
(Peptic Ulcer vs Malignant ulcer of carcinoma)
1) Size: [Smaller] vs [Larger]
2) Number: [single or multiple] vs [single]
3) Margin: [oedematous, not raised] vs [Irregular, heaped up, raised (everted)]
4) Edge: [sharp] vs [shape, irregular, undetermined]
5) Floor: [Clean] vs [Dirty, necrotic]
6) Base (light microscopy): [typically consists of ulcer slough and granulation tissue with complete destruction of muscular layer] vs [Carcinoma cells intermixed with the muscular layer]
7) Location: [Lesser curvature of antrum and pylorus] vs [Greater & Lesser curvature of cardia, body, antrum & pylorus]
