Peptic Ulcer Disease and Related Disorders Flashcards
(157 cards)
1
Q
Describe PUD in terms of its relationship to fasting vs meal intake
A
2
Q
term for this symptom complex: burning epigastric pain exacerbated by fasting and improved with meals
A
3
Q
parietal cell, also known as the ______
A
oxyntic cell
3
Q
H+,K+-adenosine triphosphatase (ATPase) is expressed in what part of what cell
A
tubulovesicle membrane of parietal/oxyntic cell
4
Q
first line of defense of gastric mucosa
A
mucus-bicarbonatephospholipid layer,
5
Q
The ____ functions as a nonstirred water layer impeding diffusion of ions and molecules such as pepsin.
A
mucous gel
6
Q
Bicarbonate forms a pH gradient ranging from ____ at the gastric luminal surface and reaching ____along the epithelial cell surface.
A
Bicarbonate forms a pH gradient ranging from 1 to 2 at the gastric luminal surface and reaching 6–7 along the epithelial cell surface.
7
Q
The mucosal defense system can be envisioned as a three-level barrier, composed of …. (3)
A
- preepithelial
- epithelial
- subepithelial elements
7
Q
Surface epithelial cells generate____ that prevent protein denaturation and protect cells from certain factors such as increased temperature, cytotoxic agents, or oxidative stress
A
heat shock proteins
8
Q
If the preepithelial barrier were breached, gastric epithelial cells bordering a site of injury can migrate to restore a damaged region. This process is termed…
A
restitution
9
Q
____ is the key component of the subepithelial defense/repair system, providing HCO3 − , which neutralizes the acid generated by the parietal cell.
A
An elaborate microvascular system within the gastric submucosal layer
10
Q
Prostaglandins are derived from what substance/chemical
A
esterified arachidonic acid
11
Q
A key enzyme that controls the rate-limiting step in prostaglandin synthesis is ____
A
cyclooxygenase (COX)
12
Q
This COX isoform is expressed in a host of tissues, including the stomach, platelets, kidneys, and endothelial cells
vs
this COX isoform is expressed in macrophages, leukocytes, fibroblasts, and synovial cells.
A
COX-1
vs
COX-2
13
Q
the expression of THIS COX ISOFORM is inducible by inflammatory stimuli
A
COX-2
14
Q
The beneficial effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on tissue inflammation are due to inhibition of what COX isoform….
A
COX-2
15
Q
the toxicity of NSAIDS (e.g., GI mucosal ulceration and renal dysfunction) is related to inhibition of WHAT COX ISOFORM
A
COX-1
16
Q
Selective COX-2 inhibitors have had adverse effects on the cardiovascular (CV) system, leading to increased risk of myocardial infarction. Therefore, the U.S. Food and Drug Administration (FDA) has removed TWO OF THESE AGENTS from the markeT
A
- valdecoxib
- rofecoxib
17
Q
What are the two principal gastric secretory products capable of inducing mucosal injury.
A
- HCl
- pepsinogen
18
Q
Acid secretion should be viewed as occurring under basal and stimulated conditions. Basal acid production highest levels occurring during the ____and lowest levels during the ____ hours.
A
Basal acid production highest levels occurring during the NIGHT and lowest levels during the MORNING hours.
19
Q
2 principal contributors to basal acid secretion
A
- Cholinergic input via the vagus nerve
- histaminergic input from local gastric sources
20
Q
Stimulated gastric acid secretion occurs primarily what three phases based on the site where the signal originates
A
- cephalic
- gastric
- intestinal
21
Q
cephalic phase stimulates gastric secretion via the WHAT nerve.
A
via the vagus nerve
22
Q
When is the gastric phase activated
A
. The gastric phase is activated once food enters the stomach
23
The last phase of gastric acid secretion (intestial )is initiated WHEN...
as food enters the intestine
24
The last phase of gastric acid secretion (intestial )is mediated by (2)
mediated by luminal distention and nutrient assimilation.
25
This substance is released from endocrine cells found in the gastric mucosa (D cells) in response to HCl. This substance can inhibit acid production by both direct (parietal cell) and indirect mechanisms
somatostatin
26
the appetite-regulating hormone
Ghrelin
27
Ghrelin is expressed in what cells....
Gr cells in the stomach
28
acid-secreting parietal cell is located in what gland
oxyntic gland
29
Give at least 3 substances that are stimulants of acid secretion together with their receptors...
* histamine (H2)
* gastrin (cholecystokinin 2/gastrin receptor)
* acetylcholine (muscarinic, M3 )
30
Binding of histamine to the H 2 receptor leads to activation of ____ and ____ pathways in turn resulting in an increase in cyclic adenosine monophosphate (AMP) and intracellular calcium respectively
Binding of histamine to the H 2 receptor leads to activation of **adenylate cyclase and the phosphoinositol pathway**s in turn resulting in an increase in cyclic adenosine monophosphate (AMP) and intracellular calcium respectively.
Activation of the gastrin and muscarinic receptors results in activation of the **protein kinase C/phosphoinositide** signaling pathway.
31
Activation of the gastrin and muscarinic receptors results in activation of the ____ signaling pathway.
Binding of histamine to the H 2 receptor leads to activation of **adenylate cyclase and the phosphoinositol pathway**s in turn resulting in an increase in cyclic adenosine monophosphate (AMP) and intracellular calcium respectively.
Activation of the gastrin and muscarinic receptors results in activation of the **protein kinase C/phosphoinositide** signaling pathway.
32
Parietal cells also express receptors for ligands that inhibit acid production . Give 4 examples....
Parietal cells also express receptors for ligands that inhibit acid production
* glucagon-like peptide-1
* prostaglandins
* somatostatin
* EGF
33
This enzyme is responsible for generating the large concentration of H+
H+ ,K+ -ATPase
34
This cell, found primarily in the gastric fundus, synthesizes and secretes pepsinogen
Chief cell
35
the inactive precursor of the proteolytic enzyme pepsin.
Pepsinogen
36
The ____ leads to cleavage of the inactive precursor pepsinogen to pepsin
**The acid environment within the stomach** leads to cleavage of the inactive precursor to pepsin
37
* Level of pH required for pepsin activity
* Pepsin activity is significantly diminished at a pH of ____
* and irreversibly inactivated and denatured at a pH of ____
* pH < 2
* pH 4
* pH 7 or more
38
Ulcers are defined as breaks in the mucosal surface ____mm in size, with depth to the ____.
Ulcers are defined as breaks in the **mucosal surface >5 mm in size,** with depth to the **submucosa**.
39
most common risk factors for PUD (2)
H. pylori and NSAIDs
40
peak incidence of Gastri ulcer is reported in the WHAT decade
GUs tend to occur later in life than duodenal lesions,
with a peak incidence reported in the **sixth decade**
41
DUs occur most often in the WHAT PART of the duodenum
DUs occur most often in the **first portion** of the duodenum
42
The base of the duodenal ulcer often consists of a zone of ____
eosinophilic necrosis with surrounding fibrosis
43
Malignant DUs are common. True or False
False.
**Malignant DUs are extremely rare**
44
GUs can represent a malignancy
and should be biopsied WHEN
GUs can represent a malignancy
and should be biopsied **upon discovery.**
45
Benign GUs are most often found AT WHAT PART OF THE STOMACH
Benign GUs are most often found **distal to the junction between the antrum and the acid secretory mucosa**
46
Differentiate gastric output in GU vs DU
GU - normal or decreased
DU - increased
47
Location of Types I to IV of GU
* Type I - gastric body
* Type II - antrum
* Type III - within 3 cm of the pylorus
* Type IV - cardia
48
Different the 4 types of GU in terms of gastric acid output production
* Type I - low gastric acid production
* Type II - low to normal
* Type III - normal or high gastric acid prod
* Type IV - low gastric acid prod
49
Type of GU that is commonly accompanied by DU
type III
50
The first step in infection by H. pylori is dependent on the bacteria’s motility and its ability to produce ____
urease
51
Two factors that p pose to higher colonization rates of H pylori
* poor socioeconomic status
* less education
52
Mode of Transmission of H. pylori
oral-oral or fecal-oral route
53
H. pylori infection is virtually always associated with a
chronic active gastritis, but only 10–15% of infected individuals develop frank peptic ulceration
true or false
True
54
This substacne allows the bacteria to reside in the acidic stomach
urease
55
Urease, which allows the bacteria to reside in the acidic stomach, generates ____ , which can damage epithelial cells.
NH3
56
H. pylori makes ____ and ____ that break down the glycoprotein lipid complex of the mucous gel, thus reducing the efficacy of this first line of mucosal defense.
H. pylori makes **proteases and phospholipases** that break down the glycoprotein lipid complex of the mucous gel, thus reducing the efficacy of this first line of mucosal defense.
57
H. pylori expresses ____, which facilitate attachment of the bacteria to gastric epithelial cells.
H. pylori expresses **adhesins (OMPs like BabA)**, which facilitate attachment of the bacteria to gastric epithelial cells.
58
GUs are associated with H. pylori–induced **pangastritis**
| True or False
True
59
First-degree relatives of DU patients are three times as likely to develop an ulce
| True or False
True
60
personality traits associated with PUD
neuroticism
61
Pain in DU occurs how many minutes after a meal
The typical pain pattern in DU occurs 90 min to 3 h after a meal
62
most discriminating symptom of DU
Pain that awakes the patient from sleep (between midnight and 3 a.m.)
63
# o
differentiate pain in DU vs GU in terms of response to food
DU - relieved by food intake
GU - pain aggravated by food intake
64
the most frequent sign in patients with GU or DU
Epigastric tenderness
65
the most common complication observed in PUD.
GI bleeding
66
The second most common ulcer-related complication is ....
perforation
67
form of perforation in which the ulcer bed tunnels into an adjacent organ
Penetration
68
DUs tend to penetrate posteriorly into the ____, whereas GUs tend to penetrate into the _____
DUs tend to penetrate posteriorly into the **pancreas** leading to pancreatitis, whereas GUs tend to penetrate into the **left hepatic lobe**
69
The most commonly encountered diagnosis among patients seen for upper abdominal discomfort is_____
functional dyspepsia (FD) or essential dyspepsia
70
Ulcers ____ cm in size or those associated with a mass are more often malignant.
Ulcers ** .>3 cm ** in size or those associated with a mass are more often malignant.
71
provides the most sensitive and specific approach for examining the upper GI tract
Endoscopy
72
____the mainstay of treatment in PUD
eradication of H. pylori and therapy/prevention of NSAID-induced disease
73
This test is for H pylori is useful for early followup
74
Examples of INVASIVE tests for H pylori
75
most commonly used antacids in PUD
mixtures of aluminum hydroxide and magnesium hydroxide
76
what component of antacid causes :
* constipation
* phosphate depletion
* loose stools
* **Aluminum hydroxide** can produce constipation and phosphate depletion
* **magnesium hydroxide** may cause loose stools.
77
Side effect magnesium hydroxide vs aluminum hydroxide if used in patients with chronic renal failure (kaya avoid use of these agents in CRF)
.
* magnesium OH - hypermagnesemia,
* aluminum OH - chronic neurotoxicity
78
long term use of calcium carbonate (converts to calcium chloride in the stomach) can cause what synrome
milk-alkali syndrome (hypercalcemia, hyperphosphatemia with possible renal calcinosis and progression to renal insufficiency).
79
80
This H2 receptor antagonist may have weak antiandrogenic side effects resulting in reversible gynecomastia and impotence
Cimetidine
81
This H2 receptor antagonit has the ability to inhibit cytochrome P450, careful monitoring of drugs such as warfarin, phenytoin, and theophylline is indicated with long-term usage
Cimetidine
82
PPis reversibly inhibit H+,K+-ATPase
| True or False
FALSE...
PPis IRREVERSIBLY inhibit H+,K+-ATPase
83
PPIS potently inhibit all phases of gastric acid secretion.
| TRUE OR FALSE
TRUE
84
Onset of action of PPI is rapid, with a maximum acid inhibitory effect between ________ and ______ hrs after administration
between 2 and 6 hrs
85
duration of inhibition of acid inhibition of PPI lasting up to how many hrs
72–96 hrs
85
Mild to moderate hypergastrinemia has been observed in patients taking these drugs. Serum gastrin levels return to normal levels within HOW MANY weeks after drug cessation.
1-2 weeks
86
What is the mechanism behind the rebound gastric acid hypersecretion seen in patients using PPI
involves gastrin-induced hyperplasia and hypertrophy of histamine-secreting ECL cells
87
How to prevent occurrence of rebound gastric acid hypersecretion
Gradual tapering of the PPI and switching to an H 2receptor antagonist may prevent this from occurring.
88
Why does rebound gastric acid hypersecretion in px using PPI does not occur in patients who are H pylori positive
H. pylorii-nduced inflammation and concomitant decrease in acid production may explain why this does not occur in H. pylori–positive patients.
89
PPIs that can inhibit cyp450
Hepatic cytochrome P450 can be inhibited by the earlier PPIs
* omeprazole
* lansoprazole
90
Long-term acid suppression, especially with PPIs, has been associated with a higher incidence of community-acquired pneumonia as well as community and hospital acquired Clostridium difficileassociated disease.
| True or false
True
91
PPIs may exert a negative effect on the antiplatelet let effect of aspirin. True or False
False....
Clopidogrel....
92
Mechanism behind the decrease in antiplatelet effect of clopidogrel when used with PPI
The mechanism involves the competition of the PPI and clopidogrel with the same cytochrome P450 (CYP2C19)
93
PPIs may exert a negative effect on the a let effect of clopidogrel. Whether this is a class effect of PPIs is unclear; there appears to be at least a theoretical advantage of WHAT PPI over the other PPIs
Pantoprazole
94
If PPIs are to be given with Clopidogrel, some have recommended that there be a ____ hour separation between administration of the PPI and clopidogrel to minimize competition of the two agents with the involved cytochrome P450.
If PPIs are to be given, some have recommended that there be a **12-h separation** between administration of the PPI and clopidogrel to minimize competition of the two agents with the involved cytochrome P450. One option is to g**ive the PPI 30 min before breakfast and the clopidogrel at bedtime.**
95
These compounds inhibit gastric acid secretion via potassium competitive binding of the H+,K+-ATPase
potassium-competitive acid pump antagonists (P-CABs)
96
Examples of potassium-competitive acid pump antagonists (P-CABs)
Revaprazan
Venoprazan
97
This compound is insoluble in water and becomes a viscous paste within the stomach and duodenum, binding primarily to sites of active ulceration.
Sucralfate
98
Most common side effect of sucralfate
constipation
99
Standard dosing of sucralfate
Sucralfate 1 gram QID
100
Sucralfate should be avoided in patients with chronic renal insufficiency to prevent WHAT COMPLICATION
aluminum-induced neurotoxicity
101
The resurgence in the use of Bismuth-contaning compounds is due to what effect
their effect against H. pylori
101
Adverse effects of this drug for PUD are black stools and darkening of the tongue.
Bismuth containing compounds
102
MOA of prostaglandin in PUDs
The mechanism by which this rapidly absorbed drug provides its therapeutic effect is through e**nhancement of mucosal defense and repair.**
103
most common toxicity noted with prostaglandin
Diarrhea
104
H pylori regimen with FDA approval
105
Drugs (+dose) included in Clarithromycin triple
106
Drugs (+dose) included in Bismuth quadruple
107
The most feared complication with ampicillin
pseudomembranous colitis
108
most common cause for treatment failure in compliant patients with PUD
Antibiotic-resistant strains
109
If recurrent infection occurs within the first 6 months after completing therapy, the most likely explanation is reinfection.
| true or false
False....
If recurrent infection occurs within the first 6 months after completing therapy, the most likely explanation is **recrudescence** as opposed to reinfection.
110
H pylori regimen for patients with penicillin allergey and prior macrolide exposure
110
H pylori regimen for patients with penicillin allergey and BUT NO prior macrolide exposure
111
Guide to NSAID therapy for patients with NO CV risk and NO GI risk
112
Guide to NSAID therapy for patients with NO CV risk and HIGH GI risk
113
Guide to NSAID therapy for patients with (+) CV risk and NO GI risk
114
Guide to NSAID therapy for patients with (+) CV risk and (+) GI risk
114
Any patient, regardless of risk status, who is being considered for long-term traditional NSAID therapy, should also be considered for H. pylori testing and treatment if positive.
| True or False
True
115
With H. pylori present, independent of the NSAID status, WHAT H pylori REGIMEN is recommended for 14 days
With H. pylori present, independent of the NSAID status, t**riple therapy** is recommended for 14 days
116
Timing of documentation of H pylori eradication
H. pylori eradication should be documented **4 weeks after completing antibiotics**
117
The test of choice for documenting eradication of H pylori is
the laboratory-based validated monoclonal stool antigen test or a urea breath test (UBT)
118
timinig of repeat endoscopy in patients treated for GU
repeat endoscopy to document healing at **8–12 weeks s**hould be performed,
119
Tests used to rule out ZES
* fasting gastrin
* secretin stimulation test
120
most common ulcer-related complication
hemorrhage
121
classic presentation of a perforated viscous
Sudden onset of severe abdominal pain with peritoneal signs and evidence of pneumoperitoneum on abdominal imaging
122
Conservative management of functional gastric outlet obstruction (3)
Conservative management for 7- 10 days with the hope that a functional obstruction will reverse
* nasogastric suction
* intravenous hydration/nutrition
* and antisecretory agents is indicated for 7–10 days
123
Specific operations for duodenal ulcer (3)
* vagotomy and drainage (by pyloroplasty, gastroduodenostomy, or gastrojejunostomy)
* highly selective vagotomy (which does not require a drainage procedure)
* vagotomy with antrectomy.
124
____is a component of each of these surgical procedures for DU and is aimed at decreasing acid secretion through ablating cholinergic input to the stomach.
Vagotomy
125
both truncal and selective vagotomy (preserves the celiac and hepatic branches) result in ____ despite successful reduction of both basal acid output and maximal acid output
both truncal and selective v tomy (preserves the celiac and hepatic branches) result in **gastric atony** despite successful reduction of both basal acid output (BAO; decreased by 85%) and maximal acid output
126
____ is required in an effort to compensate for the vagotomy-induced gastric motility disorder.
**Drainage through pyloroplasty or gastroduodenostomy** is required in an effort to compensate for the vagotomy-induced gastric motility disorder.
127
To minimize gastric dysmotility,
____ vagotomy was developed. Only the vagal fibers innervating the portion of the stomach that contains parietal cells is transected, thus leaving fibers important for regulating gastric motility intact.
highly selective vagotomy
(also known as parietal cell, super-selective, or proximal vagotomy)
128
The procedure that provides the lowest rates of ulcer recurrence (1%) but has the highest complication rate is ______.
The procedure that provides the lowest rates of ulcer recurrence (1%) but has the highest complication rate is **vagotomy (truncal or selective) in combination with antrectomy.**
129
This procedure is aimed at eliminating an additional stimulant of gastric acid secretion, gastrin.
**Antrectomy** is aimed at eliminating an additional stimulant of gastric acid secretion, gastrin.
130
Two principal types of reanastomoses are used after antrectomy:
* Billroth I - gastroduodenostomy
* Billroth II - gastrojejunostomy
131
Billroth I is often preferred over II
| True or false
True
132
the treatment of choice for an antral ulcer
Antrectomy (including the ulcer) with a Billroth I anastomosis
133
Vagotomy is performed only if a DU is present.
| True or False
True
134
Ulcers located near the esophagogastric junction may require a more radical approach, a subtotal gastrectomy with a Roux-en-Y esophagogastrojejunostomy also called ....
Csendes’ procedure
135
A less aggresive approach, including antrectomy, intraoperative ulcer biopsy, and vagotomy may be indicated in fragile patients with a high GU.
Kelling-Madlener procedure
136
Ulcers that recur after partial gastric resection tend to develop at what site
at the anastomosis
137
most frequent presenting complaint (>90%) of recurrent ulcerarion
Epigastric abdominal pain
138
Incomplete vagotomy can be ruled out HOW ....
by gastric acid analysis coupled with sham feeding.
In this test, gastric acid output is measured while the patient sees, smells, and chews a meal (without swallowing). The cephalic phase of gastric secretion, which is mediated by the vagus, is being assessed with this study. An increase in gastric acid output in response to sham feeding is evidence that the vagus nerve is intact.
138
This complication is rarely seen today as a result of the decrease in the performance of Billroth II anastomosis
Afferent loop syndrome
139
there are 2 types of afferent loop syndrome. Mechanism of the more common type....
* The more common of the two is **bacterial overgrowth in the afferent limb secondary to stasis**.
* Patients may experience postprandial abdominal pain, bloating, and diarrhea with concomitant malabsorption of fats and vitamin B12.
140
there are 2 types of afferent loop syndrome. Mechanism of the less common type....
* less common afferent loop syndrome can present with severe abdominal pain and bloating that occur 20–60 min after meals.
* The cause of this clinical picture is theorized to be i**ncomplete drainage of bile and pancreatic secretions from an afferent loop that is partially obstructed**
141
timing of occurence of early vs late dumping syndrome
* Early dumping takes place **15–30 min afte**r meals
* Late phase of dumping typically occurs **90 min to 3 h after** meals.
141
Mechanism for signs and symptoms of early dumping
Early dumping takes place 15–30 min after meals and consists of crampy abdominal discomfort, nausea, diarrhea, belching, tachycardia, palpitations, diaphoresis, light-headedness, and, rarely, syncope. These signs and symptoms arise from the r**apid emptying of hyperosmolar gastric contents into the small intestine, resulting in a fluid shift into the gut lumen with plasma volume contraction and acute intestinal distention.**
142
Mechanism for signs and symptoms of LATE dumping
Vasomotor symptoms (light-headedness, diaphoresis, p tations, tachycardia, and syncope) predominate during this phase. This component of dumping is thought to be secondary to **hypoglycemia from excessive insulin release.**
143
Dumping syndrome is most noticeable after meals rich in ......
simple carbohydrates (especially sucrose) and high osmolarity
144
cornerstone of therapy for patients with dumping syndrome.
Dietary modification....
* Small, multiple (six) meals
* devoid of simple carbohydrates
* coupled with elimination of liquids during meals
145
Drug useful in dumping syndrome that is diet-refractor
Octreotide
146
These drugs are often useful in symptom control for postvagotomy diarrhea
Diphenoxylate or loperamide
147
A subset of post–partial gastrectomy patients who present with abdominal pain, early satiety, nausea, and vomiting will have mucosal erythema of the gastric remnant as the only finding. Histologic examination of the gastric mucosa reveals minimal inflammation but the presence of epithelial cell injury. This clinical picture is categorized as....
Bile Reflux Gastropathy
147
# ...
Drugs useful for bile reflux gastropathy (3)
* Prokinetic agents
* cholestyramine
* and sucralfate
148
Mechanism behind reduced Vitamin B12 after partial gastrectomy
* This is usually not due to deficiency of intrinsic factor (IF), since a minimal amount of parietal cells (source of IF) are removed during antrectomy.
Reduced vitamin B 12 may be due to
* competition for the vitamin by bacterial overgrowth or
* inability to split the vitamin from its protein-bound source due to hypochlorhydria.
