Term
| What is the basic microscopic anatomical organization of the stomach? |
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Definition
1) Gastric mucosa
2) Submucosa with Meisner's plexus
3) Muscularis propria with circular and longitudinal muscle layers, sandwiching the ENS of the myenteric plexus in between.
4) Adventitia/Serosa |
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Term
| What are the unique properties of the mucosa in each region of the stomach? |
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Definition
Gastric mucosa composed of secretory glands and pits (1:1 is cardiac and antrum regions, and 1:4 and 1:2, respectively, in the fundus and body (approximately).
1) Cardiac mucosa secretes mucous and pespsinogen
2) Proximal mucosa (Oxyntic gland) has mucous, parietal and chief cells, producing mucous, acid and intrinsic factor and pepsinogen 1, respectively.
- Few APUD cells as well (somatostatin or biogenic amines like histamine and serotonin).
3) Distal stomach (Pyloric glands) contains no parietal cells, but there are large numbers of APUD cells, especially G cells (gastrin) and D cells (Somatostatin) |
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Term
What is the basic arterial blood supply of the stomach?
Why is gastric ischemia relatively rare? |
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Definition
1) Less curve (left and right gastric arteries)
Greater curve (left and right gastroepiploic arteries)
Fundus (short gastric arteries from splenic a.)
2) Anastomose and overlap redundantly |
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Term
| Describe the basic venous drainage of the stomach. |
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Definition
Ultimately the portal vein.
In portal hypertension, porto-systemic shunting occurs leading to dilation of thin walled vessels, "varices," which may occur in fondus or stomach. |
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Term
| What is the basic nervous system innervation of the stomach? |
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Definition
1) Intrinsic network (Myenteric and submucosal plexus)
2) Dual extrinsic innervation
a) Parasympathetic from vagal trunks (left V. gets anterior and right V. gets posterior)
- 90% visceral afferents
- 10% visceral efferents that synapse in myenteric plexus
b) Sympathetic fibers from celiac plexus
- sympathetic efferents synapse directly on target vessels/muscle |
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Term
| What are the 3 main mechanisms that stimulate HCl secretion from parietal cells? |
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Definition
Remember, they are found in cardiac and proximal regions.
1) Neurocrine- ACh from vagus binds M3 receptors on parietal cell membrane
- activated by smell alone
2) Endocrine: Gastrin from G cells in antrum enters systemic circulation and binds CCK2 receptor on parietal and APUD cells, leading to histamine release and ultimately acid secretion
**also inhibits somatostatin release from D cells**
3) Paracrine: Histamine from ECL cells binds H2 receptors on parietal cells |
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Term
| How do gastrin, histamine and ACh generate acid secretion from parietal cells? |
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Definition
1) Gastrin and ACh bind CCK and M3 receptors, respectively, leading to PIP2 signaling, increasing Ca2+, up-regulating kinase activity and activating the H+/K+ ATPase
2) Histamine binds H2 receptors , stimulating GPCFR activity, AC and cAMP production, leading to PKA-mediated activation of H+/K+ ATPase. |
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Term
| What 5 mechanisms control gastrin release from G cells? |
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Definition
1) ACh- Neurocrine stimulation via CN X
2) Gastrin Releasing Peptide (GRP)- neurocrine stimulation via CN X
3) Somatostatin (D cells)- Paracrine inhibition via diffusion
4) Luminal acid- Feedback inhibition on G cell
5) Luminal food and AA- Stimulation of G cell |
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Term
| What are the 2 major inhibitory mechanisms that prevent HCl secretion from parietal cells? |
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Definition
1) Somatostatin
- Released from D cell of antrum inhibits HCl secretion -
- Directly: receptor-mediated inhibitory GPCR leading to decreased PKA
-Indirectly by binding somatostatin receptor on G-cell and inhibiting release of gastrin
2) Prostaglandins bind PG receptor on parietal cell inducing production of inhibitory G proteins in a similar way to somatostatin (decreased protein kinase activity). |
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Term
| What is the importance of intrinsic factor (IF)? |
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Definition
Secreted by parietal cells, IF binds dietary B12 and preserves it in the gut to be transported for ileal absorption.
Without it, you get macrocytic PERNICIOUS ANEMIA
Without acid release, you get high gastric pH and hypertrophy of G cells in the antrum, leadng to carcinoids, and perhaps endocrine tumors! |
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Term
| Why do you see carcinoid and endocrine tumors in patients with Pernicious Anemia? |
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Definition
This occurs when these is loss of parietal cells.
1) Lack of IF means that there is no B12 absorption in illeum, and you get macrocytic anemia
2) Lack of acid secretion induces G cells to release a ton of gastrin, leading to hypertrophy/hyperplasia of cells in antrum that can produce tumors |
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Term
Which of the following is the most effective therapeutic method of lowering acid levels in the stomach?
1) Vagotomy
2) Gastric resection
3) H2 blockers
4) Proton pump blockers
5) Atropine |
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Definition
All will work, but H2, histamine blockers are the most effective for treating gastroesophageal disorders.
Without histamine release from D1 ECL cells, you get less parietal stimulation and less HCl secretion. |
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Term
What gastric region accomplishes each of the following elements of gastric motility?
1) Filling
2) Storage and Mixing
3) Trituration
4) Emptying |
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Definition
1) Relaxation of proximal stomach (vagally-mediated) without increase in intra-gastric pressure
2) Corpus and antrum
3) Corpus and antrum (powerful contraction leading to retropulsive jet stream)
**ACh from vagus stimulates M3 receptors and leads to Calcium entry through L-type channels, leading to AP on top of slow waves generated by ICCs**
4a) Liquid- Rapid, because of tonic pressure gradient from stomach to duodenum
4b) Solid- Triturated food (antral contractions) particles are seived through pyloric sphincter into duodenal bulb (larger particles are intermittently emptied by strong, 3-10 minute contractions, though open pylorus during fasting state)
Large-particle "migrating motor complexes" are intestinal house-keepers and occur once every 1.5-2 hours. |
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Term
| What are the typical symptoms associated with symptomatic gastric disorders? |
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Definition
Remember that many gastric disorders cause few or NO symptoms!
1) Dyspepsia- Epigastric or LUQ pain (crampy, sharp or burning)
2) Bloating
3) Distention
4) Early satiety, anorexia, nausea or vomitting |
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Term
An infant presents with projectile vomiting.
How can you confirm the diagnosis? |
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Definition
More common in boys
1) Congenital Hypertrophic pyloric stenosis (outlet obstruction), where there is a loss of inhibitory (nitricergic) neurons in the pylorus).
2) Confirm with Ultrasound/barium swallow |
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Term
| Why might you see gastric outlet obstruction in adults? |
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Definition
Recurrent ulcers or malignancies
May be able to perform endoscopic therapy, rather than surgery to correct. |
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Term
| What is gastric volvulus? |
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Definition
Rare condition where stomach is abnormally rotated.
It presents acutely (obstruction) or chronically (epigastric discomfort and dysphagia) in "Organoaxial" or "Mesenteroaxial" Form.
Treat with surgery |
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Term
| Why does Somatostatin work to diagnose/treat Zollinger Ellison Syndrome? |
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Definition
- Excess gastrin secretion through endocrine tumor in upper abdomen (usually pancreas), leads to hypertrophy of gastric folds and proliferated parietal cells.
- Mucosa injury occurs with difficult-to-treat reflux and/or peptic ulcer disease.
- Somatostatin inhibits acid secretion from parietal cells (directly and indirectly) as well as gastrin secretion from G cells. |
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Term
| What are the major infective etiologies of Gastritis? |
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Definition
1) Bacteria- H. pylori
**Rarely, Mycobacterial and T. pallidum (syphillitic)
2) Viral- HSV and CMV in immunocompromised hosts
3) Fungi- Candida, Aspergillus, Histoplasma, mucormycosis
4) Parasites- Cryptosporidium, Giardia, Nematodes, Strongyloides |
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Term
| How does Heliobacter pylori cause infective gastritis? |
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Definition
Gram-negative, microaerophilic, curved bacillus found only on gastric mucosa that causes 95% of duodenal ulcers and 60% of gastric ulcers.
1) Infection causes inflammatory infiltrate that leads to production of cytokines that directly affect epithelial cells and alter acid secretion through activation of ECL cells
2) ECL-mediated histamine release causes mucosal ulceration.
3) Atrophic gastritis can arise and extend proximally, increasing pH and allowing bacterial colonization and concentration of carcinogens.
**Ongoing stimulation of immune system in chronic infection can cause MAL lymphoma (clonal proliferation of B cells) |
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Term
| How is H. pylori most effectively treated? |
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Definition
Proton-pump inhibitor or H2 blocker with 2 antibiotics (or 1 antibiotic with a bismuth compound).
If low-grade B cell proliferation occurs causing lymphoma, make sure to treat quickly before cancer progresses! |
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Term
| What are the 2 major types of Atrophic gastritis? |
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Definition
Atrophy of gastric mucosa associated with intestinal metaplasia and carcinoid tumors.
1) Type A is autoimmune with anti-parietal antibodies attacking the corpus reducing HCl and IF
- Hypochlorhydria (with elevated gastrin) and pernicious anemia may result.
2) Type B is H. pylori-associated, antral-predominant gastritis with normal gastrin levels. |
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Term
A patient presents with burning pain in the epigastrium at night and a few hours after food intake.
How do you confirm your suspicion and what is the pathogenesis of this condition? |
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Definition
Burning epigastric pain at night and after feeding suggests Peptic Ulcer Disease.
Confirm with Endoscopy or UGI.
Generally, Mucosal lesion result from imbalance between defensive and injurious influences (e.g. increase in acid secretion and decrease in protective HCO3- secretion).
**Ulcers extend into deep muscular layers vs. erosions**
Etiology is most likely NSAID or H. Pylori
1) NSAIDS- COX-1 inhibition decreases protective PGE (should try COX-2 specific if possible)
2) H. pylori |
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Term
| What are the most common etiologies of gastric dysmotility disorders (Gastroparesis)? |
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Definition
Diagnose with Solid-phase gastric emptying study (radio-labeled scrambled eggs)
1) Neuropathic
- Example is congenital pyloric stenosis (absence of inhibitory neurons)
2) Pacemaker cell dysfuction
3) Myopathic |
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Term
| How do you treat Gastric dysmotility (Gastroperesis)? |
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Definition
1) Correct metabolic abnormalities that might be causing it
2) Metoclopramide (central and peripheral dopamine antagonist (antiemetic, but drowsy) and cholinergic agonist via indirect pre-synaptic effects on enteric motor neurons.
**long-term use associated with tardive dyskinesia**
3) Erythromycin- motilin receptor agonist and cholinergic agonist (pro-kinetic agent) for acute treatment. |
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Term
| What diseases include normal or elevated gastric acid secretion in the setting of compromised innate mucosal protective mechanisms or barriers, producing mucosal injury, pain and/or metaplasia/malignancy? |
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Definition
1) GERD (erosive esophagitis and non-erosive reflux)
2) Barrett's esophagus
3) Esophageal (peptic) strictures
4) Esophageal adenocarcinoma
5) Benign peptic ulcers of stomach and duodenum (Peptic ulcer disease, including H. pylori-related)
6) NSAID-induced ulcers
7) Ulcers secondary to Zollinger-Ellison |
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Term
| How do proton-pump inhibitors treat GERD? |
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Definition
The "....prazoles" are coated in "enteric gelatin" that protect them from acid pH (only activated at alkaline pH)
- Rapidly absorbed, highly protein -bound and extensively metabolized in liver (CYP2C19 and CYP3A4)
1) Pro-drugs that enter parietal cells from bloodstream and accumulate in acid secretory canaliculi, where they are activated by proton-catylyzed process, forming thiophilic sufenamde or sulfenic acid.
2) Active form covalently binds sulfhydryl group of cysteines on extracellular domain of H+,K+ ATPase (Position 813)
3) Irreversible binding lowers 95% of acid secretion, and secretion resumes ONLY AFTER new pumps are inserted in membrane. |
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Term
| How is acid produced under normal conditions? |
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Definition
Vagal efferents either
1) Directly stimulate Parietal cells by releasing ACh that binds to M3 receptor on basolateral membrane
2) Indirectly by stimulating G cells (antrum) and ECL cells (body/fundus) to release gastrin and histamine, respectively, which bind to CCK2 and H2 receptors and lead to acid secretion.
**Gastrin actually mostly stimulates acid release indirectly, by binding CCK receptors on ECL cells, which then release histamine that binds to parietal cells** |
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Term
| What innate gastric protective mechanisms prevent acid erosion? |
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Definition
1) Intercellular tight junctions between gastric epithelial cells
2) Mucin layer overlying gastric epithelial cells.
3) Prostaglandins (PGE2 and PGEI2) inhibit parietal cell (bin d EP3 receptor) secretion gastric mucosa and stimulate secretion of mucous and HCO3- ions into that mucin. |
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Term
| Why do proton-pump inhibitors have such long actions, despite short half lives (1-2h)? |
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Definition
Remember, long term use can be problem fro osteoporosis (impaired calcium absorption), hip fractures, CAP and intestinal infections.
PPIs covalently bind and deactivate proton pumps, which must then bee re-synthesized before function returns! |
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Term
| What are the potential side effects of long-term PPI use? |
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Definition
1) Osteoporosis (impaired calcium absorption) with fractures
2) CAP
3) Intestinal infection (C. dif) |
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Term
| How do H2 receptor antagonists suppress gastric acid production? What side effects should you look out for? |
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Definition
The "Idines" like cimetidine, ranitidine, famotidine with IV peak doses between 2-8 h depending on agent.
Prevent histamine-mediated activation of parietal cells at basailar membrane surface.
1) Reversibly compete with histamine for binding (vs. irreversible covalent binding of PPI)
2) Biggest effect on basal acid secretion (during sleep), which may be important for duodenal ulcer healing and to prevent nocturnal-acid breakthrough in patients on PPIs.
3) Small amount is protein-bound, with minimal hepatic metabolism (most metabolism/filtration goes by kidney).
4) Cemetidine inhibits CYP450 system and may alter other drugs. |
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Term
| What are the important differences between Proton Pump Inhibitors and H2 receptor antagonists in terms of reducing gastric acid secretion? |
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Definition
1) PPI is highly protein bound, while H2R-a is minimally protein bound in serum
2) PPI undergoes extensive hepatic metabolism, while H2R-a is mostly renal (watch out in renal disease)
3) PPI generally used for heightened acid secretion, while H2R-a is best to suppress basal secretion during sleep. |
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Term
| Why might you prescribe a drug like Misoprostol to reduce gastric acid production? |
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Definition
Prostaglandin analogues that are rapidly absorbed and undergo extensive first-pass metabolism in liver (peak at 30 min)
1) PGE2 and PGEI2 produced by mucosal cells inhibit acid production by binding EP3 receptor on parietal cells and reducing production of cAMP.
**Both basal and food-induced acid secretion**
2) PGE is also cyto-protective, stimulating mucin and HCO3- secretion.
3) Useful to treat NSAID-mediated mucosal damage, |
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Term
| What are the side effects and contraindications for Misoprostol use? |
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Definition
1) Diarrhea is most common (30%)
2) Can exacerbate IBD
3) Pregnancy because of effects on uterine contractility |
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Term
| Why might you give a drug like Sucralfate? |
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Definition
To prevent acid-induced damage and pepsin-mediated hydrolysis of mucosal proteins
**Activated by acid, so take on empty stomach**
1) Sucrose with an added ammonium hydroxide that undergoes extensive cross-linking to form a viscous gel that adheres to epithelium and ulcer craters to inhibit hydrolysis of mucosal proteins by pepsin.
2) Also cyto-protective (like Misoprostol), stimulating local PGE production and binding bile salts. |
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Term
| Why might you be worried about treating a patient with Sucralfate or an antacid if they are in renal failure? |
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Definition
Aluminum in both compounds relaxes intestinal smooth muscle and may become over-absorbed.
Remember, this causes constipation in Sucralfate, but not antacid (Mg2+ counteracts it) |
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Term
| What is the basic composition/action of antacids and what are their common side effects? |
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Definition
Have become less popular over time due to PPi and H2R-a
1) Various conjugated bases (often with Al3+ and Mg2+) that neutralize stomach acid
2) Don't take with lots of milk, or you may get Milk-Alkali syndrome, where over-alkalinazation causes calcium precipitation in kidney leading to renal insufficiency. |
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Term
| What are the mainstay treatments for GERD? |
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Definition
Goal is to resolve symptoms and heal esophagus.
Try "step-up regimen", where you start an H2RA (less aggressive) and only use a PPi if symptoms fail to respond
1) PPis are better than H2Ras for uncomplicated GERD
**PPis are used to diagnose/treat**
2) IF GERD is complicated or there is Barrett's esophagus, complete acid control and 24h pH monitoring is required (use an H2Ra at bedtime)
**Sucralfate may be useful if bile is an issue**
3) LIFESTYLE MODIFICATIONS |
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Term
| What are the mainstay treatments for Peptic Ulcer Disease? |
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Definition
1) Uncomplicated PUD
- PPis are more rapid, but both PPi and H2Ra are effective
- If H. pylori, use "triple therapy" with 2 Antibiotics (Amoxicillin and Metronidazole) and 1 PPi
2) Complicated PUD (bleeding)
- IV PPi as part of triple therapy |
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Term
What are the mainstay treatments for NSAID-related ulcers?
What about for Zollinger-Ellison? |
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Definition
1) PPI with Misoprostal
2) PPIs for gastrinoma acid secretion |
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Term
| What are the important congenital anomalies of the stomach? |
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Definition
1) Heterotopia
- Pancreatic heterotopia = small nodules of “normal” pancreatic tissue present within the gastric mucosa or wall
- Gastric heterotopia = small patches of “normal” gastric mucosa in duodenum, esophagus and other sites
2) Diaphragmatic Hernia
- Defective closure of the diaphragm results in herniation of abdominal contents into the thorax
May be asymptomatic or life threatening
3) Pyloric Stenosis
- Present with projectile nonbilious vomiting
- Palpable mass (“olive”) near distal stomach
- Acquired: Due to long-term gastritis, malignancy |
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Term
| How can you distinguish between acute and chronic gastritis in terms of symptoms, histology and etiology? |
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Definition
1) Acute
- sudden-onset epigastric pain, nausea and vomiting, with or without mucosal hemorrhage/hematemesis
- See PMNs infiltrating epithelium and erosions with or without hemorrhage
- Caused by NSAIDs, alcohol and toxins, burns, ischemia, or infection.
2) Chronic
- For H. Pylori, see “Band-like” infiltrate of lymphocytes and plasma cells within the superficial lamina propria
- Caused by chronic infection (H. pylori), autoimmune (pernicious anemia), chemical damage, or granulomatous infection. |
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Term
What is the most common cause of chronic active gastritis?
What are the pertinent histological findings and future complications associated? |
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Definition
H. pylori (active because PMNs are seen)
- Mild chronic (inactive) gastritis often of unclear cause
- Multifocal atrophic gastritis = chronic gastritis with gastric atrophy and intestinal metaplasia, is associated with increased risk of gastric cancer development |
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Term
What is the most common cause of "diffuse corporal atrophic gastritis"
What pertinent histological findings and complications are associated? |
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Definition
Autoimmune, chronic gastritis
-Autoantibodies to gastric parietal cells and intrinsic factor
- "Body-prominent" chronic Inflammatory response with loss of parietal cell mass (atrophy):
- Associated with carcinoid tumors, because of G cell proliferation (vs. gastric cancer in H. pylori) |
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Term
| What are the common etiologies of chronic gastritis with granulomatous inflammation? |
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Definition
1) Crohn’s Disease
2) Sarcoidosis
3) Infection:
- Tuberculosis
- Histoplasmosis
4) Vasculitis
5) Foreign body GCR
6) Granulomatous gastritis (IDIOPATHIC) |
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Term
| What are the most common sites to find Peptic ulcers? |
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Definition
Breach in mucosa that extends down into muscularis propria (most often associated with H. pylori)
1) First portion of duodenum
2) Gastrum antrum
3) Gastro-esophageal junction (Barrett's association) |
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Term
| What is Menetrier's disease? |
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Definition
| One cause of hypertrophic gastropathy where over-expression of mucosal growth factor causes massive hyperplasia of surface mucous cells (foveolar hyperplasia), often leading to hemorrhage, epigastric discomfort, weight loss and loss of protein into gastric fluid. |
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Term
| What are the important types of benign gastric tumors? |
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Definition
Hyperplastic polyp, Fundic polyp, Gastric adenoma
1) Hyperplastic polyp
- Found with chronic gastritis
- Prominent pits
2) Fundic gland polyp
- Prominent gland compartment, crowding pits with fundic-type mucosa
3) Gastric adenoma
- Pre-malignant, dysplastic cells found in setting of intestinal metaplasia |
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Term
| What are the most important risk factors associated with gastric carcinoma? |
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Definition
1) Enviormental
- H. pylori
- Diet
- Smoking
- Socioeconomic status
2) Host factors
- chronic gastritis (via hypochlorhydria)
- partial gastrectomy (free reflux of bile and alkaline fluid)
- Barrett's esophagus
3) Genetics
- Blood type A
- family history of gastric cancer, familial gastric carcinoma (E-cadherin mutations) and HNPCC
- atrophy, intestinal metaplasia |
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Term
| How does H. pylori infection increase the risk of gastric cancer? |
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Definition
Depends on virulence of bacteria and on host factors (hypochlorhydria and pepsin secretion)
- Chronic gastritis, followed by atrophy, intestinal metaplasia, dysplasia and Carcinoma |
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Term
| What is the most common location of gastric cancer? What are the 3 macroscopic patterns of growth? |
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Definition
1) Pylorus/antrum (50-60%)
**Like peptic ulcers, which like the antrum**
2a) Exophytic- protrusion into lumen
2b) Flat/depressed- erosive crater in wall of stomach
**Hard to detect by radiology**
2c) Ulcerated (excavated)
- Look like peptic ulcers, with thickened "leather bottle" stomach (Linitus plastica) |
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Term
| What are the 2 microscopic types of gastric carcinomas? |
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Definition
Both tend to be insidious until late in their course, when they presents with weight loss, abdominal pain, nausea, anemia and hemorrhage.
Survival really depends on stage at time of treatment.
1) Intestinal type
- Neoplastic glands that look like colonic adenocarcinoma
2) Diffuse type
- Signet ring of epithelial cells |
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Term
| What is the most common cause of gastric lymphoma and how to you usually treat? |
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Definition
H. pylori infection- MALT tumors
Treat the H. pylori with triple therapy (2Ab and PPi) and cancer usually goes away!
Lymphoid cells usually creep into epithelium of glands and pits ("lymphoepithelial lesions" |
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Term
| What are Gastrointestinal Stromal Tumors (GISTs)? |
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Definition
Mesenchymal origin, derived from ICCs, producing tumors of varying sizes in different locations.
**c-KIT + on IHC, reflecting and activating point mutation that is responsive to certain TK therapies like Gleevec** |
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Term
| What is the most common origin of gastric neuroendocrine tumors? |
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Definition
- ECL (histamine) cells in oxyntic mucosa
- Also arise in Zollinger-Ellison syndrome (hypergastrinemic)
Sporadic tumors have worst prognosis! |
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Term
True or False:
Tumor metastases of the stomach are unusual |
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Definition
True!
Most common are systemic lymphomas. |
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