Lectures 3,4: Stomach Flashcards
What are the layers of the stomach?
Mucosa (epithelium, lamina propria, muscularis mucosae), submucosa (w/ plexus), muscularis externa (oblique, circular, longitudinal layer), serosa
Parietal cells make
Acid and intrinsic factor
ECL cells make
Histamine
Chief cells make
Pepsinogen
Where are the stem cells in the gastric fundic gland?
Mucous neck cells
Surface mucous cells make
Mucus, trefoil peptide, bicarbonate secretion
Functions of the stomach (3)
Mechanical churning of food; initiation of chemical digestion (acid, pepsin, lipase); produce intrinsic factor (B12 absorption)
Main function of fundus/body
Secretion reservoir
Main function of the antrum
Mixing, grinding
Inhibits gastric emptying…(what goes through intestine and product that does the inhibition; 3 for duodenum and 1 for ileum)
Duodenum: Secretin (via low pH), cholecystokinin (aa and fatty acids), vagal afferents (osmolarity); Ileum: PYY (carbohydrates)
Motilin: where it is made, what it does, action
Duodenum; binds to receptors on smooth muscle and causes motility by increase phase III contractions of migrating motor complex
Erythromycin is a _________ agonist
Motilin
What are the effects of gastric distention (2)? What nerve is involved?
Increased acid, pepsin release and increased gastrin release; vagal nerve also potentiates both of these actions
Three parietal cell receptors…what do they do?
CCK-B (gastrin), H2 (histamine), M3 (ACh) –> translocation of proton pump to cell surface
Describe parietal cell secretion pathways
Secretes H+ via H/K/ATPase and Cl- via chloride channel, also secretes HCO3- basolaterally
What is the effect of gastrin on the parietal cell? On the ECL cell?
Positive; positive
What does ECL do?
ECL produces histamine, which is a paracrine and positively effects the parietal cell
What is the effect of ACh on the parietal cell? On the ECL cell?
Positive; positive
How does the parietal system get turned off?
HCl positively effects the D cell, which releases SST –> inhibition of G, ECL, and parietal cells
What protects the stomach from developing ulcers?
Mucus-bicarbonate layer
Gastritis is defined by…
Superficial erosions
Why does an ulcer bleed?
Eaten into submucosa, which has blood vessels
Three consequences of ulcers
Bleeding, penetration (e.g. into pancreas –> pancreatitis, or colon), perforation
Duodenal ulcers are due to…
Hypersecretion of acid
Gastric ulcers are due to…
Disruption of mucus barriers (NSAIDs, aspirin)
Two most common causes of peptic ulcers…
- H pylori (interaction w/ cigarettes and alcohol); 2. NSAIDs, aspirin
Other causes of peptic ulcers…
Stress (burns, head trauma), gastrinoma (benign, gastrin-secreting tumor), rare causes due to overproduction of histamine (systemic mastocytosis = histamine production by mast cells and basophilic leukemia = histamine production by basophils)
H-pylori colonizes % of US population and what part of stomach?
50%; GASTRIC mucosa alone via burrowing through mucus gel above epithelium
What protective factor does H pylori produce?
Urease (produces ammonia from urea)
Mechanisms of injury via H pylori (4)
- Releasing cytotoxins on epithelium; 2. Disrupting mucous layer via proteases; 3. Stimulating host pro-inflammatory cytokines; 4. Inhibiting somatostatin by antral D cells –> acid hypersecretion
Another name for gastrinoma…treatment?
Zollinger-Ellison; surgery
Presentation of peptic ulcer disease (5)
- Pain (epigastric, boring, relieved by food, may awaken patient in morning); 2. Bleeding (occult or overt); 3. Obstruction; 4. Perforation (free air under diaphragm); 5. Penetration (into adjacent organ)
Peptic ulcer disease: treatment
- Remove inciting agent (treat H pylori; avoid NSAIDs, alcohol, surgical removal of gastrinoma); 2. Pharmacological (antacids, PPIs/H2 blockers, meds that enhance prostaglandin production); 3. Surgical therapy
What are the three surgical treatments for peptic ulcer disease? When indicated?
- Highly selective vagotomy; 2. Antrectomy; 3. Subtotal gastrectomy; rare, only if complicated
What is the Bilroth II procedure?
A form of antrectomy that plugs the stomach later into the SI than the duodenum to protect against bile refux
Causes of hypergastrinemia (3)
- Insufficient amounts of luminal acid (because acid turns off gastrin via D cells, caused by PPIs/H2 blockers OR autoimmune gastritis w/ destruction of parietal cells = pernicious anemia); 2. Overproduction of gastrin (rare, due to antral G-cell hyperplasia OR retained antrum on duodenal stump after surgical antrectomy); 3. Ectopic production of gastrin (rare, gastrinoma)
Describe acute erosive gastritis
Discrete foci of surface necrosis w/ potential for serious bleeding; etiology = NSAIDs or severe stress
Burn-related ulcer
Curling ulcer
Surgery-related or head trauma ulcer
Cushing ulcer
Describe “chemical” gastropathy
Erythema on endoscopy +/- erosive gastritis mostly due to NSAIDs or bile reflux
What does”chemical” gastropathy look like histologically? (3)
Loss of epithelial mucin, dilated capillaries, corkscrew gastric pits
Describe chronic gastritis histologically
Mucosa infiltrated by mononuclear inflammatory cells (plasma cells and lymphocytes) and eosinophils
Chronic gastritis can progress to…
Atrophic gastritis (loss of glands) with intestinal metaplasia (also a cancer risk)
If the body of the stomach is involved, it is…
Autoimmune gastritis
If the antrum of the stomach is involved, it is…
Antra-predominant (H pylori)
If the whole stomach is involved (pangastritis), it is..
Multifocal atrophic gastritis (MAG, H pylori or other environmental factors)
Chronic autoimmune gastritis: key features
LOSS OF PARIETAL CELL MASS –> hypochlorhydria (high pH), malabsorption of B12 (loss of intrinsic factor), G cell hyperplasia –> hypergastrinemia, ECL cell hyperplasia –> carcinoid tumors
Chronic autoimmune gastritis is associated with what increase in gastric cancer?
3-fold
Histological and gross appearance of chronic autoimmune gastritis
Reduced glands, loss of parietal/chief cells, replacement by antral/intestinal epithelium, chronic inflammation; gross = flat, loss of rugae
Lab features of chronic autoimmune gastritis (5)
Anti-parietal cell/ anti-intrinsic factor Abs, elevated gastric pH, elevated serum gastrin, low B12, megaloblastic anemia
Stain to detect G cell hyperplasia
Gastrin immunostain
Stain to detect ECL cell hyperplasia
Chromogranin immunostain
T/F: Carcinoids in the setting of chronic autoimmune gastritis are aggressive
False, they are generally indolent
H. pylori gastritis is associated with what sequelae? Increased cancer risk?
Gastric and duodenum ulcers; 2-5 fold cancer risk
How to test for H pylori?
Test for presence of urease by plating acid juice on urea, will alkalize very quickly
H pylori: virulence factors (3)
- Proteolytic and glycolytic enzymes; 2. Cytotoxins; 3. Breakdown of acid-protective barriers
Describe multifocal atrophic gastritis: define, etiology, and increased cancer risk
Pan-gastritis with large atrophy and reduced acid output; likely related to early H pylori infection and other env’t factrs; 10x increased cancer risk
H. pylori tends to cause ulcers where? What percent of stomach ulcers are caused by H. pylori?
Duodenal bulb (80%); 70% of all ulcers in stomach caused by H. pylori
MAG causes ulcers where?
Gastric only (not much acid produced, only degrades stomach due to weak barrier)
Why does H. pylori cause duodenal ulcers?
In patients that over-secrete acid there is gastric metaplasia in duodenum (to protect against acid), which H pylori can colonize
How long does a treated ulcer take to heal? What does delayed healing suggest?
About 6 weeks; occult gastric cancer
Complications of H pylori (5)
Chronic gastritis, gastric peptic ulcer, duodenal peptic ulcer, gastric cancer, MALT (mucosa associated lymphoid tissue) lymphoma
Gastric cancer risk factors (4)
Dietary (smoked/pickled/grilled), older age, genetic factors, chronic atrophic gastritis (H pylori, autoimmune, env’t)
Two types of adencarcinoma gastric cancers
Intestinal (histologically looks like intestinal epithelium) and diffuse
Intestinal: age/gender
55 yo, M>F
Diffuse: age/gender
45 yo, F>M
Intestinal: incidence/risk factors
Decreasing incidence, environmental, dietary, H pylori
Diffuse: incidence/risk factors
Stable incidence, unknown risk (genetic?), maybe H pylori
Intestinal: surrounding mucosa/gross/histological
Chronic gastritis, intestinal metaplasia, dysplasia w/ a discrete mass, malignant glands and tubules
Diffuse: surrounding mucosa/gross/histologica
Often normal w/ ill-defined mass (hard to remove), poorly cohesive tumor cells
Gross term related to diffuse gastric cancer
Linitis plastica: thick, rigid gastric wall
What does a barium run look like if a patient has diffuse type?
Seriously shrunk, rigid, contracted stomach
Histological cell term related to diffuse gastric cancer
Signet ring cells (look like a half moon)
T/F: Gastric cancers are often fatal
True: very aggressive and metastatic
Survival % for early (submucosal) gastric cancer; survival % for advanced (muscularis propria) gastric cancer
90%; 5%
Krukenberg tumors
Bilateral metastatic disease causing ovarian enlargement
