Part 14 - GIT Flashcards
Disruption of the mucosal integrity of the stomach leading to a local defect or excavation due to active inflammation
Ulcer
p. 1911
Pyloric glands are found where?
Antrum
p. 1911
The parietal cell is also known as?
oxyntic cell
p. 1911
The parietal cell is usually found where?
Neck / isthmus / oxyntic gland
p. 1911
The gastric epithelial lining consists of rugae that contain what?
Gastric pits
p. 1911
Where specifically does acid secretion occur?
Apical canalicular surface
p. 1912
First line of defense in the mucosal defense system?
Mucus-bicarbonate-phospholipid layer
p. 1912
Mucus is composed of what?
Water (95%) and mixture of phospholipids and glycoproteins (mucin)
(p. 1912)
Function of mucus
Impedes diffusion of ions and molecules (e.g. Pepsin)
p. 1912
Forms a pH gradient ranging from 1 to 2 at the gastric luminal surface and reaching 6 to 7 along the epithelial cell surface
Bicarbonate
p. 1912
What are the functions of the surface epithelial cells in the mucosal defense system?
1) Generate heat shock proteins that prevent protein denaturation
2) Generate trefoil factor family peptides and cathelicidins
3) Restitution
(p. 1912)
What is restitution?
When gastric epithelial cells bordering a site of injury can migrate to restore a damaged region
(p. 1912)
Which growth factors modulate the process of restitution?
Epidermal growth factor (EGF)
Transforming growth factor a (TGF-a)
Fibroblast growth factor (FGF)
(p. 1912)
Which growth factors are important in regulating angiogenesis in the mucosal defense system?
Fibroblast Growth factor (FGF)
Vascular endothelial growth factor (VEGF)
(p. 1912)
What is/are the function/s of prostaglandins in the mucosal defense system?
1) Regulate the release of mucosal bicarbonate and mucus
2) Inhibit parietal cell secretion
3) Maintain mucosal blood flow and epithelial cell restitution
(p. 1912)
COX-1 is expressed what tissues?
Stomach, platelets, kidneys, endothelial cells
p. 1912
COX-2 is expressed in what cells?
Macrophages, leukocytes, fibroblasts, synovial cells
p. 1912
Selective COX-2 inhibitors with adverse effect of myocardial infarction, therefore was removed from the market?
Valdecoxib and Rofecoxib
p. 1912
What are the two principal gastric secretory products capable of inducing mucosal injury?
Hydrochloric acid and pepsinogen
p. 1912
HCl and pepsinogen play a role in the absorption of what nutrients/vitamins?
Iron, calcium, magnesium, vitamin B12
p. 1912
Basal acid production occurs in a circadian pattern with the highest levels occurring during the _____.
Night
p. 1912
What are the principal contributors to basal acid secretion?
Cholinergic input (via vagus nerve) Histaminergic input (from local gastric sources) (p. 1912)
Stimulated gastric secretion occurs primarily in three phases, namely:
Cephalic
Gastric
Intestinal
(p. 1912)
The GI hormone somatostatin is release from what cells?
Endocrine cells found in the gastric mucosa (D cells)
p. 1912
Somatostatin is released in response to?
HCl
p. 1912
How can somatostatin inhibit acid production directly and indirectly?
Directly via the parietal cell
Indirectly by decreased histamine release from ECL cells and gastrin release from G cells
(p. 1912)
Hormone that may increase gastric acid secretion through stimulation of histamine release from ECL cells
Ghrelin
Pp. 1912-1913
Ghrelin is expressed in what cell?
Gr cells in the stomach
p. 1912
Which cell secretes intrinsic factor (IF) and IL-11?
Parietal cell
p. 1913
The parietal cell expresses receptors for several stimulants of acid secretion, which includes:
Histamine (H2)
Gastrin (cholecystokinin B / gastrin receptor)
Acetylcholine (muscarinic, M3)
(p. 1913)
Histamine stimulates gastric acid secretion indirectly by?
Activating the histamine H3 receptor on D cells –> inhibits somatostatin release
(p. 1913)
Active catalytic site of the enzyme H+K+-ATPase is found within the ___ subunit
Alpha
p. 1913
Where are chief cells located?
Primarily in the gastric fundus
p. 1914
What cell synthesizes and secretes pepsinogen and where is it found?
Chief cell - gastric fundus
p. 1914
Pepsin activity is significantly diminished at a pH of?
4
p. 1914
Pepsin activity is irreversibly inactivated and denatured at a pH of?
Greater than or equal to 7
p. 1914
Ulcers are defined as?
Breaks in the mucosal surface >5 mm in size, with depth to the submucosa
(p. 1914)
What are the two most common risk factors for PUD?
Helicobacter pylori
NSAIDs
(p. 1914)
___ ulcers tend to occur later in life with a peak incidence in the sixth decade of life.
Gastric
p. 1914
Duodenal ulcers occur most often in which part of the duodenum?
First part (>95%) (p. 1914)
Which type of ulcer should be biopsies upon discovery?
Gastric ulcers
p. 1915
Where are benign gastric ulcers most often found?
Distal to the junction between the antrum and the acid secretory mucosa
(p. 1915)
How many types of gastric ulcer are there?
4
p. 1915
Which type of gastric ulcer occur in the gastric body and tend to be associated with low gastric acid production?
Type I
p. 1915
Which type of gastric ulcer occur in the antrum and gastric acid can vary from low to normal?
Type II
p. 1915
Which type of gastric ulcer occur within 3 cm of the pyloric and are commonly accompanied by DUs and normal or high gastric acid production?
Type III
p. 1915
Which gastric ulcer is found in the cardio and is associated with low gastric acid production?
Type IV
p. 1915
Where is a Type I gastric ulcer located?
Gastric body
p. 1915
Where is a Type II gastric ulcer located?
Antrum
p. 1915
Where is a Type III gastric ulcer located?
Within 3 cm of the pylorus
p. 1915
Where is a Type IV gastric ulcer located?
Cardia
p. 1915
Which type of gastric ulcer is the only one associated with high gastric acid secretion?
Type III
p. 1915
H. Pylori plays a role in the development of which conditions?
Peptic Ulcer Disease (PUD)
Gastric mucosa-associated lymphoid tissue (MALT) lymphoma
Gastric adenocarcinoma
(p. 1915)
H. Pylori was initially called?
Campylobacter pyloridis
p. 1915
Two factors that predispose to higher colonization rates of H. Pylori
Poor socioeconomic status
Less education
(p. 1915)
Risk factors for H. Pylori infection
Birth or residence in a developing country
Domestic crowding
Unsanitary living conditions
Unclean food or water
Exposure to gastric contents of an infected individual
(p. 1915)
Transmission of H. Pylori
Oral-oral
Fecal-oral
(p. 1915)
H. Pylori is present in how many % of individuals with gastric ulcers?
30-60%
p. 1915
H. Pylori is present in how many % of individuals with duodenal ulcers?
50-70%
p. 1915
Which specific region of the bacterial genome encodes the virulence factors Cag A and pic B?
cag-PAI
p. 1915
Which virulence factor targets human CD4 T cells, inhibits their proliferation and disrupts normal function of B cells, CD8 T cells, macrophages, and mast cells?
Vac A
p. 1915
H. Pylori strains that are ____ positive are associated with higher risk of PUD, premalignant gastric lesions, and gastric cancer
Cag-PAI
p. 1915
Which enzyme allows the H. Pylori bacteria to reside in the acidic stomach?
Urease
p. 1916
How does urease allow the H. Pylori bacteria to reside in the stomach?
It generates NH3, which can damage epithelial cells
p. 1916
Elevated concentrations of multiple cytokines are found in the gastric epithelium of H. Pylori-infected individuals, namely:
IL-1a/B IL-2 IL-6 IL-8 TNF-a IFN-Y (p. 1916)
The presence of antral-predominant gastritis is associated with ___ ulcer.
Duodenal
p. 1916
Gastritis involving the corpus predisposes to development of ___ ulcer.
Gastric
p. 1916
Risk factors for NSAID-induced ulcer
Advanced age History of ulcer Use of glucocorticoids, high-dose NSAIDs, multiple NSAIDs Use of anticoagulants/clopidogrel Serious multi system disease (p. 1917)
Chronic disorders shown to have a STRONG association with PUD
Advanced age Chronic pulmonary disease Chronic renal failure Cirrhosis Nephrolithiasis A1-antitrypsin deficiency Systemic mastectomies (p. 1917)
Disorders with a POSSIBLE association with PUD
Hyperparathyroidism Coronary artery disease Polycythemia vera Chronic pancreatitis Former alcohol use Obesity African-American race 3 or more doctor visits in a year (p. 1917)
Typical abdominal pain pattern of duodenal ulcer
Occurs 90 minutes to 3 hours after a meal
Frequently relieved by antacids or food
Pain that awakens the patient from sleep (between 12 mn-3am)
(p. 1918)
Most discriminating symptom of duodenal ulcer
Pain that awakens the patient from sleep (between 12mn-3am)
p. 1918
In PUD, elderly patients are less likely to have abdominal pain and may instead present as?
Bleeding or perforation
p. 1918
What is the most frequent PE finding in patients with gastric/duodenal ulcers?
Epigastric tenderness
p. 1918
PE of patient with gastric/duodenal ulcer: A severely tender, board-like abdomen suggests?
Perforation
Presence of succussion splash suggests?
Gastric outlet obstruction
p. 1918
What is the most common complication observed in PUD?
GI Bleeding
p. 1918
GI bleeding as a complication of PUD occurs in how many percent of individuals?
15%
p. 1918
What is the second most common complication of PUD?
Perforation
p. 1918
Perforation as a complication of PUD occurs in how many percent of individuals?
6-7%
p. 1918
___ is a form of perforation in which the ulcer bed tunnels into an adjacent organ.
Penetration
p. 1918
Duodenal ulcers tend to penetrate where?
Posteriorly into the pancreas
p. 1918
Gastric ulcers tend to penetrate where?
Left hepatic lobe
p. 1918
What is the least common PUD-related complication?
Gastric outlet obstruction
p. 1918
Gastric outlet obstruction as a complication of PUD occur in how many percent of individuals?
1-2%
p. 1918
This refers to a group of heterogenous disorders typified by upper abdominal pain without the presence of an ulcer
NUD / functional dyspepsia / essential dyspepsia
p. 1918
Appearance of a duodenal ulcer
Well-demarcated crater, most often seen in the bulb
p. 1919
Appearance of a benign gastric ulcer
Discrete crater with radiating mucosal folds originating from the ulcer margin
(p. 1919)
Ulcers ___ in size or associated with a mass are more often malignant.
> 3 cm
p. 1919
What is the most sensitive and specific approach for examining the upper GI tract (for PUD)
Endoscopy
p. 1919
Specialized testing may be needed to be done in individuals with complicated or refractory PUD. Examples of which are:
Serum gastrin
Gastric acid analysis
Sham feeding
(p. 1919)
Infectious causes of ulcers not caused by H.pylori or NSAIDs
Cytomegalovirus
Herpes simplex virus
Helicobacter heilmannii
(p. 1918, Table 348-1)
Drug/toxic causes of ulcers not caused by H.pylori and NSAIDs
Bisphosphonates Chemotherapy Clopidogrel Crack cocaine Glucocorticoids (when combined with NSAIDs) Mycophenolate mofetil Potassium chloride (p. 1918, Table 348-1)
Invasive tests for detection of H.pylori
Rapid urease
Histology
Culture
(p. 1920)
Non-invasive tests for detection of H.pylori
Serology
Urea breath test
Stool antigen
(p. 1920, Table 348-2)
Mainstay of treatment of PUD (non-pharmacological)
Eradication of H.pylori
Prevention of NSIAID-induced disease
(p. 1919)
Side effect of aluminum hydroxide
Constipation
Phosphate depletion
(p. 1920)
Side effect of magnesium hydroxide
Loose stools
p. 1920
Magnesium-containing preparation (antacid) should not be used in chronic renal failure patients because?
Possible hypermagnesemia
Chronic neurotoxicity (due to aluminum)
(p. 1920)
Milk-alkali syndrome is caused by?
Long term use of calcium carbonate
p. 1920
What is milk-alkali syndrome?
Hypercalcemia Hyperphosphatemia Possible renal calcinosis Progression to renal insufficiency (p. 1920)
First H2 receptor antagonist used for treatment of acid peptic disorders
Cimetidine
p. 1920
Which H2 receptor antagonist has a weak antiandrogenic effect resulting in reversible gynecomastia and impotence?
Cimetidine
p. 1920
Which H2 receptor antagonists can bind to hepatic cytochrome P450?
Cimetidine
Ranitidine
(p. 1920)
Substituted benzimidazole derivatives that covalently bind and irreversibly inhibit H+,K+-ATPase
Proton pump inhibitors
Purposes of sodium bicarbonate in combination with PPIs:
1) Protect the Omeprazole from acid degradation
2) Promote rapid gastric alkalinization and subsequent proton pump activation
(p. 1920)
Half-life of PPIs
~18 hours
p. 1921
Mechanism for rebound gastric hypersecretion after discontinuation of PPIs
Gastrin-induced hyperplasia and hyper trophy of histamine-secreting ECL cells
(p. 1921)
Long term acid suppression (esp. with PPIs) has been associated with a higher incidence of what conditions?
Community-acquired pneumonia
Community and hospital acquired Clostridium difficile-associated disease
(p. 1921)
PPI containing an imidazopyridine ring instead of a benzimidazole ring, which promotes irreversible proton pump inhibition
Tenatoprazole
p. 1921
PPI that has a longer half-life and may be beneficial for inhibiting nocturnal acid secretion
Tenatoprazole
p. 1921
Pharmacologic: complex sucrose salt in which the hydroxyl groups have been substituted by aluminum hydroxide and sulfate
Sucralfate
p. 1921
Adverse effects of short term use of bismuth-containing compounds
Black stools
Constipation
Darkening of the tongue
(p. 1921)
Adverse effect of long term use of bismuth-containing compounds
Neurotoxicity
p. 1921
The Maastricht IV/Florence Concensus Report recommends that eradication of H.pylori should be considered in the ff:
1) First degree relatives of family members with gastric cancer
2) Patients with previous gastric neoplasm treated by endoscopic or subtotal resection
3) Patients with risk of gastritis or severe atrophy
4) On gastric acid inhibition for more than a year
5) Strong environmental risk factors for gastric cancer
6) H. Pylori positive with fear of gastric cancer
(p. 1922)
Risk factors for gastric cancer
Heavy smoking
High exposure to dust, coal, quartz, cement
Work in the quarries
(p. 1922)
First triple regimen found effective against H.pylori
Bismuth, metronidazole, and tetracycline
p. 1922
Failure of H.pylori eradication with triple therapy in a compliant patient is usually due to what?
Infection with a resistant organism
p. 1923
What pharmacologic agent can heal gastric/duodenal ulcers independent of whether NSAIDs are discontinued?
PPIs
p. 1923
This study demonstrated that the advantage of Celecoxib in preventing GI complications was offset when low-dose aspirin was used simultaneously
CLASS study
p. 1923
Treatment for gastric/duodenal ulcer caused by H.pylori?
Triple therapy for 14 days followed by continued acid-suppressing drugs (H2 blocker or PPI) for a total of 4-6 weeks
(p. 1924)
Test of choice for documenting eradication of H.pylori
Stool antigen test OR urea breath test
p. 1924
For gastric ulcer negative for neoplasm on initial endoscopy/biopsy, when should repeat endoscopy be done?
8-12 weeks
p. 1924
When is a gastric ulcer considered to be refractory to therapy?
If it fails to heal after 12 weeks of therapy
p. 1924
When is a duodenal ulcer considered to be refractory to therapy?
If it fails to heal after 8 weeks of therapy
p. 1924
Signs and symptoms of EARLY dumping syndrome is due to what?
Rapid emptying of hyperosmolar gastric contents into the small intestine –> Fluid shift into the gut lumen –> plasma volume contraction and acute intestinal distention
(p. 1924)
LATE phase of dumping syndrome is due to what?
Hypoglycemia from excessive insulin release
p. 1926
Dumping syndrome is most noticeable after meals rich in ___.
Simple carbohydrates (especially sucrose) and high osmolarity (p. 1926)
Cornerstone of therapy for patients with dumping syndrome
Dietary modification
p. 1926