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36 Cards in this Set
- Front
- Back
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Anatomy and function of stomach
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Fundus and body
-Parietal cells (acid) -Chief cells (pepsin) Cardia -Mucous cells Antrum -Mucous cells -G cells (gastrin) |
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Oxyntic and pyloric glands
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Oxyntic Glands (gastric body)
-mucous neck cells -parietal cells -chief cells -ECL cells Pyloric Glands (gastric antrum) -mucous cells -G cells |
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Gastric pit
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Surface epithelial cells (HCO3)
Mucous cells Oxyntic cells (parietal/acid) Chief cells (enzymes) |
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Parietal cells: function
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Hydrochloric Acid
-kills microorganisms -cleaves pepsinogen to pepsin -activates pepsin at pH < 4 Intrinsic Factor -binds vitamin B12 which allows absorption in the terminal ileum |
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Parietal cell H/K ATPase
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Pumps H into gastric lumen
Chloride follows to maintain electric neutrality In order to maintain pH neutrality, bicarbonate leaves on basal membrane through bicarbonate/Chloride exchanger. Na/K pump on basal membrane pumps K into cell to hyperpolarize which helps drive H out of lumenal side. |
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Vitamin B12 absorption
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B12 is liberated from dietary proteins (meat/dairy) by pepsin/acid
B12 binds to salivary/gastric R factor B12 is cleaved from R factor by pancreatic proteases B12 binds to Intrinsic Factor B12-IF complex binds to ileal receptor |
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Pernicious anemia
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Autoimmune gastritis
Antibodies directed against: -parietal cells -intrinsic factor Mucosal damage is greatest in body and fundus Gland destruction leads to: -achlorhydria -vitamin B12 deficiency Gastritis - metaplasia - dysplasia - carcinoma |
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Chief cells: function
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Pepsinogens
-cleaved to active form by HCl -pepsin is a proteolytic enzyme |
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ECL cell: function
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Enterochromaffin Like Cell
Histamine -stimulates the parietal cell to secrete HCl Histamine release by ECL cells -stimulated by gastrin, acetylcholine (vagus) -inhibited by somatostatin |
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G cell: function
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Gastrin ("go")
-stimulates ECL cells to release histamine -stimulates oxyntic glands to secrete: --HCl --pepsinogens -trophic effect on --parietal cell mass --ECL cell mass |
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Gastrin stimulation vs inhibition
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Gastrin release stimulated by:
-gastric distention -amino acids Gastrin release inhibited by: -somatostatin -gastric acid |
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D cell: function
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Somatostatin ("don't go")
-inhibits histamine release by ECL cells -inhibits gastrin release by G cells -inhibits HCl secretion by parietal cells Somatostatin release by D cells -stimulated by acid, CCK, gastrin -inhibited by acetylcholine (vagus) |
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HCl secretion agonists and antagonists
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Agonists
-histamine -gastrin -acetylcholine Antagonists -somatostatin -prostaglandins -epidermal growth factor (EGF |
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Cephalic phase of acid secretion
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Elicited by sight, smell, and taste of food
Entirely mediated by the vagus nerve -directly stimulates parietal cell -stimulates ECL cells to release histamine -stimulates antral G cell to release gastrin -inhibits D cell release of somatostatin Feedback inhibition: low gastric pH evokes -direct inhibition of parietal cells and G cells -inhibitory neural reflexes |
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Gastric phase of acid secretion
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Gastric distention
-mechanoreceptors in the gastric wall initiate vagovagal reflexes Amino acids and peptides -stimulate antral G cells to secrete gastrin |
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Intestinal phase of acid secretion
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Stimulation
-duodenal distention initiates vagovagal reflex -peptides and AA stimulate duodenal G cells Inhibition -acid in duodenum --inhibits vagovagal reflex --releases secretin, which inhibits acid secretion through inhibition of g cell gastrin release -sugars and fat in the duodenum --release CCK, which inhibits acid secretion through stimulation of D cell somatostatin release |
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Mucosal protection
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mucus secretion
bicarbonate secretion epithelial barrier mucosal blood flow |
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Pathogenesis of peptic ulcer disease
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Acid and pepsin vs mucus and bicarbonate
Usually pathology occurs due to weakened protective barrier (mucus and bicarbonate) rather than increased acid and pepsin. |
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Helicobacter pylori: overview
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Small gram negative rod with flagella
Colonizes the mucous layer (not invasive) Elaborates urease - produces ammonia and thereby neutralizes acid Strains expressing cagA and vacA genes are the most ulcerogenic and carcinogenic (through chronic gastritis which causes intestinal metaplasia and dysplasia) - induces chronic gastritis through the elaboration of cytotoxins and bacterial lipopolysaccharide - inflamed gastric mucosa produces less mucus and bicarbonate, hindering mucosal protection |
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Helicobacter pylori: gastric malignancy
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The most common cause of gastritis is H. pylori
Chronic inflammation leads to: - intestinal metaplasia then dysplasia then carcinoma H. pylori has been associated with a 6-fold increase in the incidence of gastric cancer. H. pylori may cause up to 40% of all cases of gastric adenocarcinoma. H. pylori may cause up to 90% of all cases of MALT (mucosa-associated lymphoid tissue) lymphoma. |
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Helicobacter pylori: epidemiology
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More common in elderly and AA and Hispanic
-Cohort effect due to sanitation Present in ~75% of people with duodenal and gastric ulcers |
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Helicobacter pylori: diagnostic tests
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serology
urea breath test stool antigen assay biopsy urease test (CLO) histology culture (difficult to culture, not done) |
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Helicobacter pylori: antibiotic regimens
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Favored:
Clarithromycin Amoxacillin Omeprazole Other options: Bismuth subsalicylate Metronidazole Tetracycline Clarithromycin Metronidazole Omeprazole |
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NSAID: mechanism
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NSAIDS act through inhibition of cyclo-oxygenase
COX-1 -constitutive isoform of COX -produces prostacyclin (cytoprotective in gastric mucosa) COX-2 -inducible isoform -induced by inflammation, cytokines |
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Effect of prostaglandins on the gastric mucosa
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increase mucosal blood flow
stimulate the secretion of mucus and bicarbonate increase mucosal cell restitution inhibit acid secretion |
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Effect of NSAIDS on gastric mucosa
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decrease mucosal blood flow
decrease mucus production decrease bicarbonate production may increase secretion of acid and pepsin topical toxicity probably not related to PG |
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COX-2 inhibitors theoretical therapeutic advantages
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Inhibition of COX-2 results in desired effects of decreased inflammation
Inhibition of COX-1 results in undesired effects of gastrointestinal toxicity Therefore, a selective COX-2 inhibitor could theoretically provide all the benefit of an NSAID without the adverse effects |
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COX-2 inhibitor
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Celecoxib (Celebrex)
-Expensive |
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Stress ulceration
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Seen only in extremely sick patients
-trauma -burns -head injuries -ventilator patients Related to alpha-adrenergic mediated decrease in mucosal blood flow |
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Gastrinoma: mechanism
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Zollinger-Ellison syndrome
Endocrine tumors of the duodenum or pancreas (rarely stomach,liver, spleen) 1/3 patients have MEN-1 Dramatic gastrin production - drives acid production by parietal cells - increases parietal cell and ECL cell mass - differentiate from increased gastrin production from pernicious anemia because there is also elevated acid (pernicious anemia will have decreased acid) |
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Gastrinoma: presentation, diagnosis, therapy
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90% of patients have PUD
50% of patients have diarrhea Diagnosis is based on serum gastrin level Tumor localization - endoscopic ultrasound, octreotide scan, CT scan Surgical resection is the only curative therapy > 50% are locally invasive or metastatic at dx PPI therapy provides best symptom palliation |
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Complications of peptic ulcer disease
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pain
bleeding perforation gastric outlet obstruction |
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Acid reduction interventions
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Acetylcholine
-anticholinergics -vagatomy Histamine -H2 receptor antagonists Gastrin -antrectomy Proton pump inhibitors |
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H2 receptor antagonists
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All end in "-tidine"
Tagamet (cimetidine) Zantac (ranitidine) Axid (nizatidine) Pepcid (famotidine) |
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Proton pump inhibitors
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All end in "-prazole"
Prilosec (omeprazole) Zegerid (omeprazole+bicarbonate) Nexium (esomeprazole) Prevacid (lansoprazole) Dexilant (dexlansoprazole) Aciphex (rabeprazole) Protonix (pantoprazole) |
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Mucosal protection interventions
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Misoprostol (Cytotec)
-a synthetic prostaglandin E1 analog -increases mucus and bicarbonate production -also inhibits acid production -don't use in pregnant women Sucralfate (Carafate) -adheres to ulcer base, forming a protective barrier -also inhibits pepsin activity |
