Stomach Lectures Flashcards
What is the proximal gastric motor function?
Initial receptive relaxation (storage, vagus nerve)
Followed by increase in tonic and phasic contractions (push into antrum)
What is the distal gastric motor function?
Baseline slow wave activity in muscle cell membrane potential – interstitial cells of Cajal
Sweep towards pylorus
How many distal gastric motor functions are there per minute?
about 3
How large of particles does the pyloric sphincter let through?
Liquids and 1-2 mm particles
Larger solids are retropelled back into antrum for more grinding (triturition)
What do receptors in the small intestine pay attention to?
The nutrient delivery – constant 1-4 kcal/minute delivery of energy to small intestine
When is secretin released?
When lipids, amino acids or HCl enters the duodenum – it relaxes gastric tone and inhibits contractions
When is somatostatin released?
In response to acids/peptides
It inhibits gastric emptying
When is Cholecystokinin released?
From the duodenum in response to fat – it inhibits gastric motility (increases small bowel motility)
What is the ileal brake?
The secretion of PYY in response to delivery of nutrients to distal small intestine
When are glucagon-like peptide-1 (GLP-1) and glucose-dependednt insulinotropic peptide (GIP) secreted?
Released into small intestine in response to glucose delivery
GLP-1 is also secreted in response to colonic fermentation of carbohydrates and intraduodenal glutamine, aa, fatty acids
*inhibits gastric motility
What does Ghrelin do?
Increases the rate of gastric emptying –induces migrating motor complex
Does a reduced caloric intake/weight loss cause delayed or sped-up gastric emptying?
Delayed
Also, faster gastric emptying in obese
What is scintigraphy?
Nuclear medicine test to assess emptying non-invasively
Uses a radiolabeled solid or liquid and detects the amount retained at set points in time
When does fasting motor activity occur after a meal?
Onset is delayed one hour for every 200 kcal ingested
Occurs every 90 minutes with fast
Allows for the clearance of large indigestible solids from gut
What is gastroparesis?
Delayed gastric emptying in the absence of mechanical obstruction
Symptoms = early satiety, postprandial fullness, nausea, vomiting, bloating, upper abdominal pain
What must you be sure to exclude with possible gastroparesis?
Exclude obstruction in the foregut
What are some medications that may induce gastric emptying delay?
Anti-cholinergics Opiates NSAIDS Pramlintide (amylin analog) Exenatide (GLP-1 receptor agonist) Cyclosporine
What is the effect of vagal injury on gastric emptying?
Poor accommodation- liquids empty rapidly
Poor antral grinding- solids empty slowly
What is visceral hypersensitivity?
Postprandial pain but no ulcer
Lower threshold for pain (especially with stress)
Associated with anxiety and depression, aging, diabetes, analgesics
Mechanism unclear
What are some gastric dysfunctions seen in diabetes?
Long term Type I or Type II DM
Vagal dysfunction, loss of enteric neurons
Rapid or slow gastric emptying
What are some possible causes of elevated acid secretion?
Elevated gastrin Elevated vagal tone Elevated histamine (mastocytosis, basophilic granulocytic leukemia) Elevated parietal cell mass/idiopathic Paraneoplastic (non-gastrin: rare)
What do you need to interpret elevated gastrin levels?
pH
Hypersecretion of gastric acid due to a gastrin secreting neuroendocrine tumor
Zollinger-Ellison syndrome
What are the two types of ZE
Sporadic: Isolated gastrinoma, localize and remove for cure, usually in duodenum/pancreas
Component of Multiple Endocrine Neoplasia I (MEN I): multifocal, not curable, also associated with hyperparathyroidism, other islet cell tumors, pituitary tumors
What are some diagnostic features of ZE syndrome?
Elevated basal acid secretion (15mEq/hr)
Gastrin > 150 pg/mL (>1000 pg/ml diagnostic with low pH)
Secretin stimulation: gastrin increases > 120 pg/ml
PPI can cause a false negative test
Clinical manifestations of ZE syndrome
Severe ulcer disease – extends to distal duodenum/jejunum, relapsing ulcer, high PPI dose to cure
Diarrhea – large acidic fluid volume, inactivation of pancreatic enzymes, hypokalemia, steatorrhea, weight loss
What are some other causes of gastrin mediated high acid secretion?
H. pylori (via reduced somatostatin) Antral G-cell hyperplasia Gastric outlet obstruction Retained antrum (gastric surgery) Cysteamine treatment Short bowel syndrome Renal failure (rare)
Conditions that cause low acid secretion.
Medications: PPI, H2RA, anticholinergic Inflammatory destruction of parietal cells (gastritis) Acute H. pylori infection Vagal injury/transection VIP producing tumors
How does low acid secretion commonly present?
Overall well tolerated with modern diet, impaired protein digestion Impaired absorption of Fe, Ca, B12 Gastric bacterial overgrowth Enteric infections/TB Small bowel bacteria overgrowth Impaired delivery of certain drugs
Describe the Schilling Test for vitamin B12
4 steps:
- Replace B12 parenterally, do 24 hour collection of radiolabelled vitamin B12 orally – checks to see if you are absorbing it
- If low, repeat while giving IF – checks to see if you have IF deficiency
- If low, repeat after empiric antibiotic treatment for small bowel bacteria overgrowth – check to see if bacteria are not allowing you to create IF
- If still low, give pancreatic enzymes to test for pancreatic insufficiency or terminal ileal disease
What is one main cause of decreased secretion of bicarb/mucous?
Overuse of NSAIDS
Describe the bacteria H. pylori
Spiral shaped, microaerophilic, gram negative bacteria
Exclusively colonizes gastric type epithelium
What is the hallmark of H. pylori infection?
Neutrophilic infiltration, along with lymphocytes, plasma cells, macrophages (chronic active gastritis)
What is the virulence factor that is present in some strains of H. pylori and may cause more intense damage?
Cytotoxin-associated gene A [CagA]
Describe the early stage of H. pylori.
Confined to the antrum
Inhibited D cell somatostatin secretion – increased gastrin secretion
Acid secretion increased
Duodenal ulcers
Describe the late stage of H. pylori.
Colonization and inflammation expand to corpus/fundus
Destruction of parietal cells – acid decreased, gastrin increased
Gastric ulceration
If H. pylori eradication –> neutrophilic infiltration resolves, lymphocytic infiltration may persist
Where is H. pylori infection most likely?
Developing countries
Crowding, poverty
Increased with age
When do you acquire an H. pylori infection?
In infancy/childhood – fecal/oral, oral/oral transmission
How do you diagnose an H. pylori infection?
Serology (persists even after eradication)
Endoscopic gastric mucosa biopsy
Urea breath testing
Stool antigen testing
False negative with recent antibiotics or PPI therapy
What are some adverse effects of H. pylori infection?
Peptic ulcer
Enteric infections
Malnutrition/iron & B12deficiency
Gastric neoplasia –> Adenocarcinoma, MALToma, carcinoid
What are some adverse effects of eliminating H. pylori?
GERD/adenocarinoma of esophagus
Weight gain
Atopic diseases
Inherited form associated with immune response in the oxyntic mucosa against parietal cells and IF
Autoimmune gastritis
What is associated with Autoimmune gastritis?
Lymphocytic inflammation with destruction of parietal cells
Associated with other autoimmune disease (thyroid, celiac, type I DM)
More common in women
Inflammatory destruction of normal mucosa with replacement by metaplastic elements (commonly intestinal type with goblet cells)
Atrophic metaplastic gastritis
Type A chronic gastritis
Autoimmune, first part of stomach, body and funds
Type B chronic gastritis
H. pylori bacteria, second part of stomach, antrum
What are some findings in atrophic metaplastic gastritis?
Achlorhydia–increased gastrin
Reduced/absent intrinsic factor
What are some consequences of atrophic metaplastic gastritis?
Reduced acid secretion
Pernicious anemia
Gastric cancer
Gastric carcinoid
What is the difference between gastritis and gastropathy?
Gastritis is an inflammation associated mucosal injury – infectious, autoimmune
Gastropathy is epithelial cell damage and regeneration with minimal or no associated inflammation (bile, alcohol, aspiring, NSAIDs, ischemia)
What are some toxic gastric effects of NSAIDs?
Trapped in epithelial cells
Uncouple oxidative phosphorylation
Reduced energy production
Increased cell permeability
Rapid cell death and superficial mucosal injury
Inhibit COX-1 prostaglandin synthesis causing reduced blood flow and oxygen delivery, decreased mucin, bicarb and phospholipid secretion and decreased epithelial cell proliferation and migration
What is the difference between an ulcer and an erosion?
Ulcer extends below muscularis mucosa
Erosion superficial to muscularis mucosa
What are some risk factors for peptic ulcer disease?
Increasing age and smoking
H. pylori associated decreasing
NSAID/aspirin
What is the breakdown of PUD in NSAID/aspirin users?
50% develop erosions
25% develop PUD
2-4% have complications resulting in hospitalizations
90% of PUD is associated with what 3 things.
- Aspirin/NSAIDs
- Helicobacter pylori
- Surreptitious/unaware NSAID use
What are some complications from PUD?
Acute GI hemorrhage Chronic GI blood loss/iron deficiency anemia Perforation/peritonitis/pancreatitis Gastric outlet obstruction GI fistula Malabsorption/malnutrition/weight loss Iatrogenic complications
What are some symptoms of PUD?
Hematemesis (loss of 25% of total blood volume)
Melena, red blood per rectum (loss of 33% blood volume)
Recurrent post-prandial vomiting (obstruction)
Diarrhea (fistula)
May have no symptoms
What do signet ring cells look like and what are they indicative of?
Munin-Filled vacuole with displaced nucleus
Diffuse type gastric adenocarcinoma
How is the hereditary diffuse type of gastric adenocarcinoma inherited?
Autosomal dominant with high penetrance (80% of carriers will develop disease)
Associated with mutations in E-cadehere gene (CDH1)-tumor suppressor gene that affects cellular adhesion/motility
What are the two types of gastric adenocarcinoma?
Intestinal type (most common) - in distal stomach, H. pylori is the main risk factor, older men Diffuse type -- younger age, associated with blood group A, signet ring cell histology, more aggressive
What is the average age of onset of hereditary diffuse type gastric adenocarcinoma?
38 years
Increased risk of breast cancer
What are some other heritable associations of gastric adenocarcinoma?
Familial adenomatous polyposis (FAP)
Lynch Syndrome
Peutz-Jeghers syndrome
Li-Fraumeni syndrome
What is diffuse type EBV associated adenocarcinoma?
Male predominant
No age predilection
Higher proportion in developed countries
Less aggressive behavior
What is adenocarcinoma of the cardia?
Incidence is rising
Risk factors = lack of H. pylori, male gender, obesity, smoking
What are some common clinical presentations?
Abdominal pain Early satiety and nausea (linitis plastica) Weight loss Dysphagia Vomiting GI bleeding/perforation
What are MALToma’s strongly associated with?
H. pylori – 80% regression with eradication
What are some risk factors for gastric lymphoma?
Immunodeficiency/immunosuppresion
Celiac disease
Autoimmune disorders
What is the common clinical presentation of gastric lymphoma?
Epigastric pain Anorexia Weight loss Nausea and/or vomiting Occult GI bleeding B symptoms Rarely perforation
What is the endoscopic appearance of gastric lymphoma?
Mucosal erythema
