patoloji-ders-notlari

Title

Serdar Balcı

Pathology of the Stomach

Serdar BALCI, MD

Stomach

Cardia
- Lined mainly by mucin-secreting foveolar cells that form small glands
Antrum
- Similar to cardia
- Contain endocrine cells
- G cells release gastrin to stimulate luminal acid secretion by parietal cells within the gastric fundus and body
Body, funds
- Glands contain chief cells
- Produce and secrete digestive enzymes, pepsin

ACUTE GASTRITIS

Autopsy Pathology: A Manual and Atlas

Acute Gastritis

Transient mucosal inflammatory process

May be asymptomatic

Cause variable degrees of epigastric pain, nausea, and vomiting

In severe cases mucosal erosion, ulceration, hemorrhage, hematemesis, melena, massive blood loss

Robbins Basic Pathology

Protective mechanisms of gastric epithelium

Gastric lumen is strongly acidic, pH ~1
- potential to damage the mucosa
Mechanisms protect the gastric mucosa
- Mucin secreted by surface foveolar cells
- A thin layer of mucus
  - prevents large food particles from directly touching the epithelium
- Neutral pH as a result of bicarbonate ion secretion by surface epithelial cells
- Rich vascular supply to the gastric mucosa
  - oxygen, bicarbonate, and nutrients
  - washing away acid that has back-diffused into the lamina propria

Disruption of protective mechanisms result in gastritis

Reduced mucin synthesis in elderly
Nonsteroidal anti-inflammatory drugs (NSAIDs)
- decrease prostaglandins and reduce bicarbonate secretion
Ingestion of harsh chemicals
- Accidentally, suicide attempt
Direct cellular injury
- Excessive alcohol consumption, NSAIDs, radiation therapy, chemotherapy

Morphology of gastritis

Mild acute gastritis
- moderate edema
- slight vascular congestion
- surface epithelium intact
- scattered neutrophils
- Lamina propria lymphocytes and plasma cells not prominent
Severe mucosal damage
- Erosion
- Loss of the superficial epithelium
- Mucosal neutrophilic infiltrates
- Purulent exudates
- Hemorrhage
Acute erosive hemorrhagic gastritis

ACUTE PEPTIC ULCERATION

Acute Peptic Ulceration

Focal, acute peptic injury
- complication of NSAIDs
- severe physiologic stress
Stress ulcers
- shock, sepsis, severe trauma
Curling ulcers
- proximal duodenum
- severe burns or trauma
Cushing ulcers
- stomach, duodenum, esophagus
- intracranial disease
- high incidence of perforation

Pathogenesis

NSAID-induced ulcers
- direct chemical irritation
- cyclooxygenase inhibition, prevents prostaglandin
  - decreased bicarbonate secretion
  - decreased vascular perfusion
Intracranial injury
- direct stimulation of vagal nuclei
Systemic acidosis
- Decreased intracellular pH of mucosal cells
Stress
- splanchnic vasoconstriction
- Hypoxia
- reduced blood flow

Morphology of ulcer

Acute ulcers
- rounded
- less than 1 cm in diameter
- Ulcer base stained brown to black
  - acid-digested extravasated red cells
- associated with transmural inflammation and local serositis
- Healing with complete reepithelialization
- days or weeks after the injurious factors are removed.
Chronic peptic ulcers
- Scarring and thickening of blood vessels

Erosions superficial epithelial damage

Ulcers deeper lesions penetrate the mucosa

Robbins Basic Pathology

CHRONIC GASTRITIS

Chronic Gastritis

Less severe but more persistent than acute gastritis
Helicobacter pylori
- Most common cause
Autoimmune gastritis
- the most common cause of atrophic gastritis
- <10% of cases of chronic gastritis
- most common form of chronic gastritis in patients without H. pylori infection
Radiation injury
Chronic bile reflux

H. pylori

Helicobacter pylori Gastritis

H. pylori
- spiral-shaped or curved bacilli
- present in 90% of patients with chronic gastritis affecting the antrum
- increased acid secretion result in peptic ulcer disease of the stomach or duodenum
- increased risk of gastric cancer.
poverty, household crowding, limited education
Colonization rates exceed 70% in some groups
- 10% to more than 80% worldwide
In high-prevalence areas, infection often is acquired in childhood and then persists for decades

H. pylori virulence

Flagella
- allow the bacteria to be motile in viscous mucus
Urease
- generates ammonia from endogenous urea
- elevate local gastric pH around the organisms
- protect bacteria from the acidic pH of the stomach
Adhesins
- enhance bacterial adherence to surface foveolar cells
Toxins
- cytotoxin-associated gene A ( CagA )
- may be involved in ulcer or cancer development

H. pylori

Predominantly antral gastritis
- high acid production
- Hypogastrinemia
Progress to pangastritis
- multifocal atrophic gastritis
- reduced acid secretion
- intestinal metaplasia
- increased risk of gastric adenocarcinoma

H. pylori shows tropism for gastric foveolar epitheleum

Generally not found in areas of intestinal metaplasia, acid-producing mucosa of the gastric body, or duodenal epithelium

Antral biopsy is preferred for evaluation of H. pylori gastritis

Robbins Basic Pathology

concentrated within the superficial mucus overlying epithelial cells in the surface and neck regions

Robbins Basic Pathology

neutrophils within the lamina propria

Some cross the basement membrane

intraepithelial location

accumulate in the lumen of gastric pits to create pit abscesses

Robbins Basic Pathology

superficial lamina propria includes large numbers of plasma cells, often in clusters or sheets

increased numbers of lymphocytes and macrophages

inflammatory infiltrates may create thickened rugal folds, mimicking infiltrative lesions

Lymphoid aggregates, some with germinal centers

Induced form of mucosa-associated lymphoid tissue (MALT) -potential to transform into lymphoma

Robbins Basic Pathology

Intestinal metaplasia

Goblet cells and columnar absorptive cells

Associated with increased risk of gastric adenocarcinoma

Robbins Basic Pathology

Diagnostic methods for H.pylori

Histopathology
Serologic test for anti-H. pylori antibodies
Fecal bacterial detection
Urea breath test
Biopsy can be used for
- Rapid urease test
- Bacterial culture
- PCR, bacterial DNA

H.pylori vs Autoimmune Gastritis

Robbins Basic Pathology

Autoimmune gastritis

Antibodies against parietal cells

Loss of glands

Decreased acid, decreased intrinsic factor

Increased gastrin production by Neuroendocrine cells

Hypergastrinemia and hyperplasia of antral gastrin-producing G cells

No intrinsic factor, no ileal vitamin B 12 absorption, B12 deficiency, megaloblastic anemia (pernicious anemia)

Reduced serum concentration of pepsinogen reflects chief cell loss

Diffuse damage of the oxyntic mucosa within the body and fundus
Damage to the antrum and cardia typically is absent or mild
Diffuse atrophy
- the oxyntic mucosa of the body and fundus appears markedly thinned, and rugal folds are lost
Inflammatory infiltrate more commonly is composed of lymphocytes, macrophages, and plasma cells
- Inflammatory reaction most often is deep and centered on the gastric glands
Intestinal metaplasia may develop

Netter’s Illustrated Human Pathology, Second Edition

PEPTIC ULCER DISEASE

Peptic ulcers develop anywhere in the gastrointestinal tract in contact with acid-pepsin secretion. Majority are found in the duodenum or stomach.

Autopsy Pathology: A Manual and Atlas

Netter’s Illustrated Human Pathology, Second Edition

Peptic Ulcer Disease

Most often associated with H. pylori infection or NSAID use
May occur in any portion of the gastrointestinal tract exposed to acidic gastric juices
- Most common in the gastric antrum and first portion of the duodenum
- Esophagus
  - Result of GERD
  - Acid secretion by ectopic gastric mucosa
- Small intestine
  - Secondary to gastric heteropia within a Meckel diverticulum
Imbalances of mucosal defenses and damaging forces that cause chronic gastritis
Generally develops on a background of chronic gastritis
70% of PUD cases are associated with H. pylori infection
- only 5% to 10% of H. pylori –infected persons develop ulcers

Cofactors in peptic ulcerogenesis

Chronic NSAID use
Cigarette smoking
- impairs mucosal blood flow and healing
High-dose corticosteroids
- Suppress prostaglandin synthesis and impair healing
Alcoholic cirrhosis
Chronic obstructive pulmonary disease
Chronic renal failure, and hyperparathyroidism
- hypercalcemia stimulates gastrin production
Psychologic stress

Gastric hyperacidity

H. pylori infection

Parietal cell hyperplasia

Excessive secretory responses

Impaired inhibition of stimulatory mechanisms

Zollinger-Ellison syndrome

Uncontrolled release of gastrin by a neuroendocrine tumor

Massive acid production

Multiple peptic ulcerations in the stomach, duodenum, jejunum

Peptic ulcers

4x more common in the proximal duodenum than in the stomach
Duodenal ulcers
- Within a few centimeters of the pyloric valve
- Involve the anterior duodenal wall
Gastric peptic ulcers
- Located near the interface of the body and antrum
Solitary in more than 80% of patients