Nichols + ??? Flashcards
Cells in Gastric Glands
- Parietal Cells - make HCL
- Chief Cells - secrete pepsinogen
- Mucus Cells - bicarbonate rich mucus
- G Cells - only in antrum, secrete gastrin
Cephalic Phase of Acid Secretion
-taste, smell, chewing food stimulates acetylcholine release via the vagal nerve
Gastric Phase of Acid Secretion
-chemical effects of food and distention of stomach causes release of gastrin by the G cells
Intestinal Phase of Acid Secretion
-food & acid in small bowel cause release of CCK and secretin which inhibit acid production
What does the Mucous-bicarbonate Layer in the Stomach do?
-causes a pH gradient, secreted by mucus cells, prevent autodigestion
Peptic Ulcer Disease (PUD)
- defect in GI mucosa extending though muscularis mucosae
- costs $5.65 billion
- annual incidence is 0.1-0.3% in US
- decrease over decades
Symptoms of Peptic Ulcer
- Abdominal Pain (80%), epigastric burning, nocturnal or relieved by food
- nausea, anorexia
- asymptomatic & present with complication (more common in elderly or patients taking NSAIDs)
Risk factors for PUD
- Helicobacter pylori gastritis
- Meds: ASA, NSAIDs, clopidogrel
- Smoking
- Genetic factors
- Acid must be present for PUD to occur
- additive risk factors*
PUD associated with Chronic Disease
- stress ulcers in ICU patients on vents
- Cirrhosis
- Organ transplantation
- COPD
- normally get prophylactic PPI while in ICU to prevent ulcers
Helicobacter pylori and PUD
- present in 70% of patients with PUD
- only 10-15% of patients with H.pylori get PUD
- associated with both duodenal and gastric ulcers
- produces urease-makes organism resistant to gastric acid
Morphology of Helicobacter pylori?
- spiral-shaped, gram -, 4-6 unipolar shethed flagella
- stomach and duodenum
- infections seen in healthy patients and patients with GI disease
- can move through mucus layer
H. Pylori & mucosal inflammation?
- resides in mucus layer overlying gastric epithelium
- in lamina propria-always associated inflammatory infiltrate
- epithelial layer is intact: evoke mucosal inflammatory cells
- secretes peptide and LPS (chemotactic for neutrophils & monocytes)
- peptide is heat, acid, alkali stable (MW 3000)
- inflammatory cells: oxygen radicals, prostaglandins, IL-1, TNF
High risk factors for NSAID GI toxicity?
- history of previous complicated ulcer
- multiple >2 risk factors
Moderate risk factors for NSAID GI toxicity?
- age > 65
- high-dose NSAID
- previous history of uncomplicated ulcer
- concurrent use of aspirin, glucocorticoids, or anticoagulants
Diagnosis of PUD
- UGI-barium X-ray of stomach
- Upper endoscopy (allows biopsy for H. pylori)
Complications of PUD
-bleeding-hematemesis, melena, anemia
-perforation (surgery)
-penetration-may penetrate into adjacent organs-pancreas, colon, liver
-gastric outlet obstruction (blocks pylorus or duodenum, may be caused by active ulcer or healing of prior ulcer)
Poorer outcomes in older patients or co-morbid illness with complicated PUD
Treatment of PUD
- anti-secretory agents-H2 blockers or PPI (treat 6-8 weeks)
- Treat H. pylori if present (abx), eradication decreases recurrent PUD
- avoid smoking, NSAIDS, ASA if possible
- select patients may use maintenance medicine
- surgery (complications)
Tests for H. Pylori treatment
- urea breath test (no bismuth, PPI, abx)
- Fecal antigen test using monoclonal ab
- Serological test, not good for evaluating successful treatment
- Biopsy of antrum- urease based tests, no bismuth, PPI or antibioticts, histological evaluation
Gastritis
- pathological diagnosis of gastric inflammation of mucosa (not submucosa)
- may be acute or chornic
- may be caused by NSAIDS, H. pylori, alcohol, ischemia or extreme stress
Acute Hemorrhagic Gastritis
- associated with alcohol, NSAID, bile reflux, trauma, burns, sepsis, shock
- present with abdominal discomfort or pain, heartburn, nausea, vomiting, hematemesis (massive)
- typically have numerous petechiae, erosions, +/- ulcers, +/- bigger hemorrhages
- heals rapidly
Chronic Gastritis leads to??
-atrophy, intestinal metaplasia, dysplasia, or neoplasia or combo
Causes: H. pylori, autoimmune, bile reflux
Helicobacter Pylori Gastritis
-common (inc. with age)
-chronic active gastritis, more sever in antrum, lymphocytic inflammation, germinal centers and neutrophils (active), spiral bacteria in superficial mucus layer
Diagnosis: gastric biopsy or serology & other non-invasive
-leads to gastric adenocarcinoma (1-3%) or low grade lymphoma (0.1%)
Helicobacter Pylori Gastritis: Pathology
- neutrophils infiltration gland in center
- favors neck of gastric glands (lined by mucous cells)
- Giemsa stain: easier to see H. pylori, also immuno stain
- lymphoid follicles (germinal centers) common
Helicobacter Pylori toxins
- Cytotoxin-associated gene A (CagA) protein
- causes degradation of p53
- activates pathways to cell proliferation (via RAS, MEK, ERK, NF-kappaB, beta-catenin)
- messes up cell polarization
-injected into cells by syringe-like type IV secretion systems (T4SS) pilus structrue
Autoimmune Atrophic Gastritis
<10% of chronic gastritis with Ab to parietal cells (achlorhydria) and intrinsic factor (pernicious anemia)
- can have intestinal metaplasia like w/H. pylori
- can get G-cell hyperplasia
Gross Pathology: PUD
- ulcers are small, round, deep and “punched out”
- duodenum, stomach, GE junction (GERD), margins of gastrojejunostomy
- ZE patients: near Meckel diverticulum containing epigastric mucosa
Layers of Chronic Peptic Ulcer
- necrosis
- inflammation
- granulation tissue
- scar
Gastric Benign Ulcer
- round-oval
- flat or overhanging margins
- deeper, punched out
- perpendicular walls or flask shaped
- smooth clean base
- smaller (<2cm)
- radiating rugal folds
Gastric Malignant Ulcer
- irregular shape
- heaped-up or nodular margins
- shallower, sloping
- ulcerated mass or bowl shape
- necrotic shaggy base
- bigger (ofter >3cm)
Stress Ulcers
- occur with brain injury (Cushing ulcer) or burns (Curling ulcer)
- typically 3 to 7 days after the stressful event
- deep, single, hemorrhagic and small (<1cm) but associated with numerous petechiae or larger hemorrhages
Factors Associated with Squamous Cell Carcinoma
- alcohol, smoking, urban & lower SEC populations
- dietary & environmental factors that cause chronic esophageal irritation-lye ingestion, achalasia, high red meat consumption, vit or trace mineral deficiency, head and neck cancer
- rare: Tylosis, Plummer-Vinson syndrome, HPV infection
Adeoncarcinoma of Esophagus: Risk Factors
- Barrett’s Esophagus (intestinal metaplasia)
- GERD
- Truncal Obesity
rare: scleroderma, ZE syndrome
Symptoms of Esophageal Carcinoma
- result from narrowing or ulceration of esophagus
1. dysphagia
2. weight loss
3. odynophagia
4. aspiration
5. anemia
Esophageal Carcinoma Epidemiology (SSC)
male (4:1) black (6:1) mid-esophagus age: 60-70 risk factors: smoking, ETOH
Esophageal Carcinoma Epidemiology (adeno)
male (7:1) white (4:1) distal esophagus age: 50 risk: barrett's esophagus
Is adeno or SCC of Esophagus more common?
equal (50/50)
Diagnosis of Esophageal Cancer
- barium x-rays will show asymmetrical narrowing or mass
- endoscopic: shows mass or stricture for advanced lesions, early lesion: ulcer, nodule, plaque, allows biopsy
Staging of Esophageal Cancer
- CT of chest (look for spread)
- EUS helps determine depth of penetration into wall of esophagus & presence of lymph mets
- decreases survival if lymph node metastases is present
Treatment of Esophageal Cancer
- curative: surgery with or w/o radiation
- 50-60% present incurable locally advanced/mets
- surgery & XRT for palliation
- endoscopic prosthesis may help for dysphagia
- 5 year survival is 5%
Hyperplastic Gastric Polyps
-seen with chronic inflammation, H. pylori, and atrophic gastritis
-usually asx; may cause microscopic blood loss or intermittent prolapse if large
-rarely become malignant-ususally if >2cm
-treatment: remove endoscopically if >1cm
75% of gastric polyps
Fundic Gland Gastric Polyps
- occur in gastric corpus
- usually 1cm
Adenomatous Gastric Polyps
- 10% of gastric polyps
- most are in antrum and associated with atrophic gastritis
- sessile or pedunculated, precursor of some gastric lesions
- treatment: endoscopic removal or surgery
- risk of malignancy increases with size, villous lesions, or high grade dysplasia
Gastric Cancer
- more common in lower SEC and dev. countries
- male (2:1)
- peaks in 7th decade
- declining in US (of distal gastric cancers)
Risk Factors for Distal Gastric Cancer
- chronic atrophic gastritis
- pernicious anemia
- prior gastric surgery
- high dietary nitrates
- adenomatous gastric polyps
- H. pylori infection(3-6X inc)
Types of Gastric Neoplasia
75% adenocarcinoma
25% lymphoma - better prognosis
Symptoms of Gastric Cancer
- diaphragmatic invasion: hiccupps
- weightloss, early satiety
- bleeding, ulceration
- pain, nausea, melena
Clinical course of gastric cancer?
- may metastasize to liver, peritoneum, or distal lymph nodes
- Virchow’s node - left supraclavicular node
- Sister Mary Joseph node - periumbilical nodule
Linitis Plastic
- aggressive diffuse gastric cancer
- 5% of gastric cancers
- gastric wall is infiltrated by malignancy
Treatment of Gastric Cancer
- CT used for staging before surgery
- Surgery is only change for cure (rarely curative)
- May also be used for palliation for obstruction of bleeding
- chemo may improve survival in patients who have surgery
Chronic Inflammation & Neoplasia in Esophagus & Stomach
- Chronic Inflammation
- Cell Death
- Accelerated Regeneration
- Mistake in Replication
(normal to metaplasia/dysplasia to neoplasia)
What makes malignant tumor malignant?
- Invasion
2. Metastasis
Squamous Cell Carcinoma of the Esophagus
- p53 point mutation are common early in pathogenesis
- K-RAS and APC gene mutations are not present in squamous cell carcinoma of esophagus
- HPV DNA is sometimes present in tumors from high incidence areas q
SSC of Esophagus: location
- 20% upper 1/3
- 30% mid 1/3
- 30% lower 1/3
SSC of Esophagus: gross pathology
early: small grey-white plaque-like thickening
late: months to years after early: 60% protruding
15% flat, 25% excavated
Molecular Pathogenesis of Adenocarcinoma of Esophagus
- early: p53 mutation or overexpression in metaplastic intestinal type Barrett’s epithelium
- allelic loss of epigenetic silencing by hypermethylation of p16/INK4a cyclin-dependent kinase inhibitor
- mutation in retinoblastoma (RB) tumor suppressor
- amplification of cERB-B2, cyclin D1 or cyclin E
Hyperplastic Gastric Polyp: Pathology
- hyperplastic mucosal epithelium
- inflamed edematous stroma
Fundic Gland Polyp: Pathology
-dilated corpus (body) oxyntic type glands
Adenomatous Polyp: Pathology
closely packed, disturbed glandular architecture
-stratified columnar epithelium
Intestinal Type: Gastric Carcinoma
- typically masses
- intestinal metaplasia = precursor
Diffuse Type: Gastric Carcinoma
-nasty
-typically linitis plastica
-infiltration by single cells resembling signet rings
(individual cells)
