4. Stomach Flashcards
Diseases of the stomach
- Congenital anomalities
- Diaphragmatic Hernia
- Pyloric Stenosis - Acute gastritis
- Chronic gastritis
- Helicobacter pylori gastritis
- Autoimmune gastritis
- Eosinophilic gastritis
- Lymphocytic gastritis (Varioliform gastritis)
- Tuberculous gastritis - Peptic ulcer disease
- Hypertrophic gastropathies
- Ménétrier Disease
- Zollinger-Ellison Syndrome - Neoplasms
- Gastric adenocarcinoma
- Gastric neuroendocrine tumours (Carcinoids)
- Gastric lymphoma
- Gastrointestinal Stromal Tumours (GIST)
Diaphragmatic Hernia
- Due to incomplete closure of pleuroperitoneal canals
- Leads to herniation of abdominal viscera into thoracic cavity
- May lead to pulmonary hypoplasia due to space-filling effect of the displaced viscera
Pyloric stenosis
- Congenital pyloric stenosis
- More common in males
- Genetic associations: trisomy 18, Turner syndrome
- Presents in 2nd-3rd week of life as persistent projectile vomiting
- Can be corrected surgically with myotomy - Acquired pyloric stenosis
- Due to antral gastritis or peptic ulcers near pylorus
Definition of acute gastritis
Acute, transient gastric mucosal inflammatory process
Causes of acute gastritis
- Drugs
- Non-steroidal anti-inflammatory drugs
- Corticosteroids
- Cigarette smoking - Direct-acting luminal chemicals
- Alcohol
- Bile salts (in bile reflux, e.g. post-gastrectomy)
- Corrosives - Stress
- Severe burn or trauma (gives rise to Curling’s ulcers)
- Intracranial lesions (gives rise to Cushing’s ulcers)
- Post-myocardial infarction - Ischemia
- Shock
- Portal hypertension
- High altitudes - Chemotherapy
Pathogenesis of acute gastritis
- Increased acid secretion with back-diffusion
- Decreased bicarbonate buffer production
- By NH4+ produced due to action of Helicobacter pylori urease activity on urea - Reduced blood flow
- Decreased gastric perfusion (e.g. in shock)
- Decreased production of cytoprotective prostaglandins (by NSAIDs & corticosteroids) - Disruption of adherent mucus layer
- Direct damage to gastric epithelium
- By direct-acting luminal agents (alcohol, bile salts)
- Chemotherapy reduces epithelial regeneration
Pathological Effects & Complications of acute gastritis
- Erosions (loss of superficial epithelium, generating a defect limited to the lamina propria)
- Ulcers (extension of erosion beyond lamina propria)
- Epigastric pain, indigestion
- Bleeding, which may present as:
- Hematemesis, with coffee grounds (gastric-digested blood seen in the esophagus during endoscopy)
- Melena (tarry foul-smelling stools)
Definition of chronic gastritis
Chronic gastric mucosal inflammation leading to mucosal atrophy & intestinal metaplasia of gastric epithelium; has several types but by far, the most important & common type is Helicobacter pylori gastritis
Most common form of chronic gastritis
Helicobacter pylori gastritis
Cause of Helicobacter pylori Gastritis
Due to H. pylori colonization of the gastric mucosa
- H. pylori found within mucous layer on surface
- H. pylori has tropism for gastric-type mucosa
- Colonization increases with age
Helicobacter pylori gastritis typically affects
The antrum (antral gastritis)
Histology of Helicobacter pylori gastritis
- Active inflammation (intraepithelial neutrophils which may accumulate in gastric pits to form crypt abscesses, subepithelial macrophages, plasma cells & lymphocytes which in severe cases may form lymphoid follicles with germinal centres)
- Regenerative changes (mitoses in epithelium, loss of mucous vacuoles)
- Intestinal metaplasia (appearance of goblet cells)
- Mucosal atrophy (loss in glandular structures &
specialized cells) - Potentially: hyperplasia → dysplasia → carcinoma-
in-situ → carcinoma
Endoscopy of Helicobacter pylori gastritis
Erythematous antral mucosa with coarse/nodular appearance
Diagnosis of H. pylori infection for Helicobacter pylori gastritis
- Urea breath test (drink radioactively labeled urea, if
H. pylori present, urease activity on urea will released
radioactive CO2 that can be detected in the breath) - Serology (H. pylori antibodies in serum)
- Histology (detection of spiral organisms within
surface mucous with special stains – e.g. Warthin-
Starry silver stain) - Culture (microaerophilic conditions)
Pathological effects & complications of Helicobacter pylori gastritis
- Mostly asymptomatic
- Peptic ulcer disease
- Chronic atrophic gastritis
- Malignancies (gastric carcinoma, gastric lymphoma)
Autoimmune Gastritis
Due to autoantibodies produced against gastric
components:
1. Gastric parietal cells (90%)
2. Intrinsic factor (60%)
Association of autoimmune gastritis
Associated with other autoimmune disorders:
- Graves disease
- Diabetes mellitus
- Hashimoto’s thyroiditis
Autoimmune gastritis typically affects
The body of the stomach
Pathological effects & complications of autoimmune gastritis
- Hypochlorhydria & secondary hypergastrinemia
- Vitamin B12 deficiency (due to decrease in intrinsic factor production by parietal cells) with resultant megaloblastic (pernicious) anemia
- Increased risk of adenocarcinoma
Causes of reactive gastritis
- Chemical injury
- NSAID use
- Bile reflux
Histology of reactive gastritis
- Foveolar hyperplasia
- Glandular regenerative changes
- Mucosal edema
Endoscopy of reactive gastritis
Endoscopically: Watermelon stomach
- Longitudinal stripes of edematous erythematous mucosa alternating with less severely injured mucosa
Eosinophilic gastritis
Due to allergies & parasites
- May co-exist with eosinophilic (gastro)enteritis
Lymphocytic gastritis (Varioliform Gastritis)
- Idiopathic
- Associated with celiac disease - Histologically:
- Marked increase in intraepithelial CD8+ T cells - Endoscopy:
- Thickened folds covered by small nodules with central aphthous ulcerations
Tuberculous Gastritis
Due to chronic granulomatous inflammatory conditions
- Idiopathic
- Tuberculosis
- Crohn disease
- Sarcoidosis
Definition of peptic ulcer disease
Breach in mucosa of alimentary tract which penetrates the muscularis mucosae & beyond, typically associated with chronic H. pylori gastritis
Causes of peptic ulcer disease
- Helicobacter pylori infection
- Drugs
- Analgesics
- Anti-inflammatory drugs (NSAIDs, corticosteroids) - Smoking & alcohol
- Psychological stress
Site of peptic ulcers
- Duodenum – 1st part (75%)
- Stomach – lesser curve, antrum (20%)
- Lower esophagus
- In the setting of gastroesophageal reflux disease - Stomal ulcer
- At the stoma of a gastroenterostomy - Meckel diverticulum – specifically when it possess ectopic gastric mucosa
- Distal duodenum + jejunum
- In addition to stomach & 1st part of duodenum in Zollinger-Ellison syndrome
Pathogenesis of peptic ulcer disease
- Peptic ulcers form as a result of imbalances between mucosal defences & damaging forces
- Mechanisms of peptic ulceration in H. pylori infection
- H. pylori urease: generates free NH3 from endogenous urea, elevating gastric pH
- H. pylori proteases: breaks down glycoproteins in gastric mucous
- H. pylori phospholipases: damages epithelial cells to allow leakage of nutrients into surface microenvironment for bacterial sustenance; may release bioactive leukotrienes
- H. pylori platelet activating factor: promotes thrombotic occlusion of mucosal capillaries
- Neutrophil myeloperoxidase: involved in neutrophil respiratory burst to release cytotoxic free radicals
- Chronically inflamed mucosa (with perpetually recruitment of inflammatory cells by bacterial antigens) more susceptible to acid injury - Main mechanisms involved in gastric ulcers
- Motility defects
- Mucosal ischemia
- Mucosal inflammation - Main mechanisms involved in duodenal ulcers
- Excessive acid-pepsin secretion that overwhelms (impaired) mucosal defences (hence epigastric pain experienced when hungry, which is relieved by food)
Morphology of peptic ulcer
- [Grossly]
- Round to oval, sharply demarcated, punched-out defect (in contrast to tumours with central cavitating necrosis which will appear as an ulcer with raised, heaped-up edges)
- Mucosal margin may overhang base slightly
- Variable depth
- Base is smooth & clean
- Stellate appearance due to scarring & puckering of wall - [Histologically]
- Surface zone of fibrinopurulent exudate
- Acidophilic layer of necrotic tissue
- Zone of granulation tissue
- Zone of dense scar tissue
- Interruption of muscularis propria
- Proximation of muscularis propria & mucosae
- Endarteritis obliterans
(eroded thickened artery which is stiff, unable to undergo vasospasm, hence can cause massive bleeding)
Pathological effects & complications of peptic ulcer disease
- Epigastric burning pain
- Occurs when hungry (for duodenal ulcers) & at night (nocturnal acid secretion)
- Relieved by food & ingestion of alkali (e.g. antacids) - Bleeding
- If mild & chronic: iron deficiency anemia
- If severe & acute: hematemesis - Perforation
- With consequent acute peritonitis - Scarring & strictures
- Can result in obstruction (e.g. in stomach where ulcers are mostly found in the antrum, may lead to acquired pyloric stenosis) - Gastric adenocarcinoma
Definition of hypertrophic gastropathies
Uncommon diseases characterized by giant cerebriform enlargement of gastric rugal folds due to epithelial hyperplasia without inflammation, linked to excessive release of growth factors
Types of hypertrophic gastropathies
- Ménétrier Disease
2. Zollinger-Ellison Syndrome
Ménétrier Disease
- Rare disorder due to excessive secretion of TGF-alpha
2. Diffuse hyperplasia of foveolar epithelium of gastric body & fundus
Morphology of Ménétrier Disease
- Grossly: irregular enlargement of rugae in body & fundus with antral sparing
- Histologically: foveolar mucous cell hyperplasia, parietal & chief cell hypoplasia
Pathological effects & complications of Ménétrier Disease
- Hypoproteinemia due to resultant protein-losing enteropathy
- Increased risk of gastric adenocarcinoma
Zollinger-Ellison Syndrome
Gastrin-secreting tumour (gastrinoma) of pancreas or duodenum
Histology of Zollinger-Ellison Syndrome
- Proliferation of parietal cells, mucous neck cells & endocrine cells
- Hence increasing oxyntic mucosal thickness
Pathological effects & complications of Zollinger-Ellison Syndrome
- Peptic ulcers (gastric, duodenal, jejunal)
2. Chronic diarrhoea
Neoplasms of the stomach
- Gastric adenocarcinoma
- Gastric Neuroendocrine Tumours (Carcinoids)
- Gastric Lymphoma
- Gastrointestinal Stromal Tumours (GIST)
Gastric adenocarcinoma
Derived from columnar epithelial cell in gastric mucosa
Etiologies & associations of gastric adenocarcinoma
- Helicobacter pylori chronic gastritis (intestinal metaplasia as a precursor lesion)
- Diet (nitrites, smoked food, lack of vegetables)
- Cigarette smoking
- Partial gastrectomy (allows reflux of bile, induces chronic gastritis)
- Barrett esophagus (increased risk of gastroesophageal junction tumours)
Location of gastric adenocarcinoma
Typically at gastric antrum & lesser curvature
Histological types of gastric adenocarcinoma
- Intestinal types (papillary, tubular, mucinous)
- Intestinal histological morphology
- Typically arise from precursor lesion of
intestinal metaplasia (as in chronic gastritis) - Diffuse types (signet-ring cell, undifferentiated)
- Signet-ring cells have large cytoplasmic mucin vacuoles & peripherally displaced crescent- shaped nuclei
- Involves CDH1 mutation (encodes E-cadherin), which is also seen in lobular carcinomas of the breast (some of which have signet-ring cells too)
3 macroscopic growth patterns of gastric adenocarcinoma
- Exophytic growth (typical of intestinal types)
- Excavated growth (typical of intestinal types)
- Flat/depressed growth (typical of diffuse types)
***Note: extensive infiltration of a broad region of the stomach in advanced flat growth patterns creates a rigid, thickened leather bottle appearance of the stomach termed linitis plastica (metastatic lung & breast cancers to the stomach can also give a similar appearance)
Clinical features of gastric adenocarcinoma
- Insidious clinical course, remains asymptomatic until late in its course
- Non-specific symptoms: weight loss, abdominal pain, anorexia, vomiting, altered bowel habits,
dysphagia, anemia, hematemesis - Prognostic factors: depth of invasion, nodal & distant metastases, HER-2/neu (allows treatment with trastuzumab)
- Treatment: surgical resection with or without adjuvant chemotherapy & radiotherapy
- Prognosis: 5-year survival rate for surgically treated early gastric cancer = 90-95%; that for advanced gastric cancer < 15%
Gastric neuroendocrine tumours (carcinoids)
Derived from enterochromaffin-like (ECL) cells in gastric
mucosa
- Carcinoids can also be derived from the scattered
endocrine cells found elsewhere in the GIT
Etiologies & associations of gastric neuroendocrine tumours (carcinoids)
- Setting of chronic atrophic gastritis with secondary hypergastrinemia
- Multiple endocrine neoplasia type I
- Zollinger-Ellison syndrome
***Note: all of them essentially result in a hypergastrinemic state which causes ECL cell hyperplasia, a presumed precursor lesion
Morphology of gastric neuroendocrine tumours (carcinoids)
- Grossly: intramural or submucosal masses that create small polypoid lesions; may ulcerate through epithelial or serosal surfaces
- Histologically: islands or uniform cells with scant, pink granular cytoplasm & a round stippled nucleus; positive immunohistochemical staining for endocrine granule markers (chromogranin A, synaptophysin)
Clinical features of gastric neuroendocrine tumours (carcinoids)
- Carcinoid syndrome: due to release of vasoactive
substances into systemic circulation; characterized by cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, right-sided cardiac valvular fibrosis
(note: carcinoids confined to the GIT typically do not cause carcinoid syndrome as vasoactive substances produce undergo ‘first-pass’ effect in liver, hence carcinoid syndrome is strongly associated with metastatic disease)
- Prognostic factors: location (gastric carcinoids –
good prognosis; midgut carcinoids – very aggressive)
Gastric lymphoma
Derived from lymphocytes in gastric mucosa
1. Almost all gastric lymphomas are B-cell lymphomas of the extranodal mucosa-associated lymphoid tissue (MALT) type
- Gastric lymphomas constitute 5% of all gastric tumours & 20% of all extranodal lymphomas
Etiologies & associations of gastric lymphoma
- Helicobacter pylori chronic gastritis
2. Trisomy 3 & t(11;18) translocation
Morphology of gastric lymphoma
- [Grossly]
- May grow as discrete nodules or infiltrate gastric wall diffusely - [Histologically]
- Dense lymphocytic infiltrate in lamina propria
- Inset shows lymphoepithelial lesions (neoplastic lymphocytes surrounding & infiltrating gastric glands)
- Reactive-appearing B-cell follicles may be present
Gastrointestinal stromal tumours (GIST)
Derived from the interstitial cells of Cajal
- GIST can also be found elsewhere in the GIT
Etiologies & associations of gastrointestinal stromal tumours (GIST)
- c-KIT (a receptor tyrosine kinase, receptor for stem cell factor) gain-of-function mutation (75-80%)
- PDGFRA (platelet-derived growth factor receptor alpha) gene mutation (8%)
- May rarely be part of a tumour syndrome: Carney’s triad (gastric GIST, paraganglioma, pulmonary chondroma), neurofibromatosis type I
Morphology of gastrointestinal stromal tumours (GIST)
- Grossly: can grow up to 30cm in diameter, usually
forms a solitary, fleshy, well-circumscribed mass - Histologically: spindle cells &/or epithelioid cells
- Positive immunohistochemical staining for c-KIT
Clinical features of gastrointestinal stromal tumours (GIST)
c-KIT positive tumours can be treated with imatinib
