COMMON UPPER GIT DISEASES

Acute Erosive Gastropathy/Acute Erosive Gastritis It is a self-limited inflammation of the gastric mucosa. Aspirin and NSAIDs Alcohol Acid and alkali (e.g., suicidal ingestion) Stress Shock-related mucosal ischemia (e.g., in burns, brain trauma and surgery) Sepsis How to remember? 3A + 3S Acute gastritis occurs when one or more of the mechanisms that protect gastric mucosa from the acidic environment is defective. Refer next page. Pathogenesis depends on the aetiology: Chronic Gastritis It is characterized by ongoing mucosal inflammation with mucosal atrophy, it provides a substrate in which dysplasia (and carcinoma) can arise. Helicobacter pylori infection (most common Chronic Type B) Alcohol Cigarette smoking Psychological stress Caffeine Autoimmune gastritis (10% of cases Chronic Type A) Pathogenesis depends on the aetiology. Virulence factors in H. pylori infections include: Flagella Motility Urease production Buffering gastric acid Bacterial adhesins Bind to surface epithelial cells Toxins (e.g., cagA and vacA cytotoxins) H. pylori induces predominantly antral gastritis, characterized by increased acid production and disruption of the normal mucosal protection mechanism. Over time, the initial antral gastritis progresses to multifocal atrophic gastritis (i.e., mucosal atrophy with reduced acid production) and intestinal metaplasia.

Aetiology

Pathogenesis Chronic use of NSAIDs reduce HCO3- secretion into mucus and
reduce prostaglandin which is necessary to inhibit acid production, promote mucin synthesis and increase vascular perfusion. Direct effect of a potentially toxic substances such as alcohol and heavy smoking.

Grossly: Moderate edema and hyperemia, occasionally with haemorrhage (acute hemorrhagic erosive gastritis)

Grossly: Infected mucosa is erythematous and coarse to nodular. Microscopically: H. pylori are typically found in the antrum. Gastric biopsy shows organisms concentrated in the superficial mucus overlying surface and neck epithelium.

Morphology
Microscopically: Neutrophils invade the epithelium, with superficial epithelial sloughing (erosion) and a fibrinous luminal exudates.

There are variable numbers of intraepithelial and luminal neutrophils (forming pit abscess) and lamina propria contains abundant plasma cells, macrophages and lymphocytes.

COMMON UPPER GIT DISEASES

Long standing gastritis is a/w diffuse mucosal atrophy, with prominent lymphoid aggregates occasionally with germinal centers.

Clinically, it presents with; epigastric burning, pain, nausea and vomiting. Severe cases exhibit ulceration with hemorrhage presenting as hematemesis or melena.

Symptoms are less severe as compared to acute gastritis, but they are more persistent. Dysphagia Dyspepsia Nausea H. pylori can be diagnosed by antibody serologic test, urea breath test, bacterial culture, direct bacterial visualization in gastric biopsy and DNAbased test. H. pylori infection is a risk factor for peptic ulcer disease (PUD), gastric adenocarcinoma and gastric lymphoma.

Clinical Features

10 15%: Have bleeding 1 4%: Have blood loss that need blood transfusion 5%: Ulcers perforated. Usually, after removal of the injurious factors, healing will occur with complete re-epitheliazation.

NORMAL Damaging Forces: Gastric aciditiy Peptic enzymes

NORMAL Defensive Forces: Surface mucus secretion HCO3- secretion into mucus Mucosal blood flow Apical surface membrane transport Epithelial regenerative capacity Elaboration of prostaglandins

COMMON UPPER GIT DISEASES

Peptic Ulcer Disease (PUD) PUD is a multifactorial disease, and several causes are involved: Infection: H. pylori in 90% of duodenal and 65% of gastric ulcer patients. Neuroendocrine factors: Stress and nervous tension (type A personality) and endocrine disorders. Local mucosal factors: NSAIDs, alcohol, spicy food, cigarette smoking, substances that stimulate acid secretion. Gastric Carcinoma H. pylori infection (WHO designated this bacterium as Grade I carcinogen) Chronic atrophic gastritis with intestinal metaplasia Postgastrectomy states (3% of people undergoing gastrectomy develop cancer over a period of 20 years) Gastric adenomatous polyps (these are rare tumours may undergo malignant transformation. Tumors >2cm give rise to adenocarcinoma in 50% of cases) Consumption of carcinogens (e.g., food preservation) Low intake of antioxidants in fruits and green leafy vegetables Adenocarcinomas constitute >90% of gastric malignancies; they are divided into intestinal and diffuse forms with different risk factors, genetic perturbations (perturbation is anxiety or mental uneasiness) and clinical and pathologic presentations. In diffuse gastric cancer: Mutation in CDHI gene encoding for E-cadherin leads to loss of intercellular adhesion. Also a/w familial gastric carcinoma and also occur in 50% of sporadic lesions. In intestinal-type gastric cancer: A/w FAP, mutation in protein that associate with E-cadherin. In both types of gastric cancer a/w H. pylori infections, immune response gene polymorphisms influence risk, p53 mutations are also present in majority of sporadic cancers of both. Gastric cancers involve the antrum more than the lesser curvature more than the greater curvature. In diffuse gastric cancer: Grossly: Tumors is rigid, thickened gastric wall termed linitus plastic (leather bottle). In intestinal-type gastric cancer: Grossly: Tumors tend to form bulky exophytic composed of glandular structures.

Aetiology

PUD results from imbalances in mucosal damage and defenses. Hyperacidity in PUD can be caused by infection, parietal cell hyperplasia, excessive secretory response or increased gastrin production (e.g., secondary to hypercalcemia or produced by a tumor). NSAIDs and steroids block the normal prostaglandin cytoprotective effects (as mentioned earlier). Cigarette smoking impairs mucosal blood flow and healing.

Pathogenesis

Morphology

Grossly: There is sharply punched-out defect with overhanging mucosal borders and smooth, clean ulcer bases.

COMMON UPPER GIT DISEASES

In diffuse gastric cancer: Microscopically: Diffuse infiltrative pattern of growth tend to be composed of signet-ring cells (intracellular mucin vacuoles push the nucleus to the periphery) that are discohesive and do not form glands. These also tend to induce a fibrous desmoplastic response. There are no identified precursor lesions. In intestinal-type gastric cancer: Microscopically: Tumors develop from precursor lesions including flat dysplasia and adenomas. Clinically, it presents with; epigastric gnawing, burning or aching pain, worse at night and 1 to 3 hours after meals. Nausea, vomiting, belching and weight loss can also occur. Severe cases exhibit ulceration with hemorrhage presenting as hematemesis or melena. Complication: Anemia, hemorrhage, perforation and obstruction. Malignant transformation is rare and is related to underlying gastritis. Treatment is focused on H. pylori eradication, as well as neutralization or reduced production of gastric acid. Gastric carcinoma is an insidious disease; early symptoms resemble those for chronic gastritis (e.g., dysphagia, dyspepsia, nausea). Advance stages present with weight loss, anorexia, altered bowel habits, anemia and haemorrhage. Prognosis: Depends on depth of invasion and the extent of nodal or distant metastases. After surgical resection, the 5-year survival of early gastric cancer is more than 90% even with nodal spread.

Microscopically: There are thin layers of fibrinoid debris with underlying inflammation merging into granulation tissue and deep scarring. The surrounding mucosa usually exhibits chronic gastritis.

Clinical Features