W11 Upper GI Flashcards
(164 cards)
1
Q
What are the 4 basic GI processes ?
A
Motility
Secretion
Digestion
Absorption
2
Q
What actions are mixing movements involved with ?
A
Redistributing luminal contents locally
Enhancing the exposure to digestive secretions
Exposing luminal contents to GI tract absorbing surfaces
3
Q
What is the purpose of propulsive movements in the GI tract ?
A
Move luminal contents forward
Rate of propulsion varies with specific function of region
4
Q
What actions do the inner circular layer and outer longitudinal layer of the muscularis externa have ?
A
Inner: contraction—> constriction of lumen
Outer: contraction —> shortening of the GI tract
5
Q
Where does the myenteric plexus lie and what is its purpose?
A
Between 2 layers of muscularis externa
Coordinates muscularis externa contractions
6
Q
What initiates contraction of smooth muscle ?
A
Increased cytoplasmic calcium
7
Q
Where does the sarcoplasmic reticulum associate with the plasma membrane ?
A
At indentations known as cavaeoli
8
Q
How are contractile acto-myosin filaments arranged ?
A
Obliquely
9
Q
Where are cytoskeleton filaments anchored ?
A
Dense body junctions
10
Q
Where are smooth muscle cells physically and electrically coupled?
A
Gap junctions
11
Q
What activates myosin light chain kinase (MLCK)
A
Calcium binding to calmodulin when there is increased intracellular calcium concentration
12
Q
What occurs when MLCK phosphorylates myosin light Chain
A
Myosin can bind to actin and begin the shortening process
13
Q
What terminates the contraction of smooth muscle
A
Myosin light chain phosphatase
14
Q
How does a voltage change in smooth muscle lead to a release of Ca2+ ?
A
Depolarization of SM membrane —> activate voltage gated calcium channel
—> Ca2+ influx —> SR calcium channel release —> calcium induced calcium release in SM cell
15
Q
Outline pharmacy-mechanical coupling for the release of Ca2+
A
Compound triggers production of IP3 at sarcolemma —> diffuse through cytosol —> activate IP3 receptor to open —> Ca2+ diffuses out of SR into cytosol —> initiate contraction
no change in membrane potential
16
Q
What 4 factors regulate GI motility ?
A
Intrinsic electrical properties of smooth muscle cells
Enteric nervous system
Autonomic nervous system
Other systems (eg. Brain, immune, hormones)
17
Q
What are the pacemaker cells in smooth muscle ?
A
Interstitial cells of Cajal (ICC)
18
Q
What are slow waves ?
A
Depolarising potentials
19
Q
Where do slow waves propagate ?
A
From pacemaker cells into adjacent SM cells through gap junctions —> electrical signals flow between cells
20
Q
What helps modulate the duration and amplitude of slow waves ?
A
Neurotransmitters/agonists that are released by enteric motor neurons
21
Q
If slow wave depolarizations reach AP threshold what is the result ?
A
A burst of action potentials
22
Q
What is the number of APs stimulated by a slow wave proportional to ?
A
The duration the slow wave remains above the AP threshold
23
Q
How does the speed at which [Ca2+] increases in myoplasm of SM when it is depolarizer compared to skeletal and cardiac muscle ?
How do the kinetics of the contraction compare?
A
Very slow
Equally slow
24
Q
What comprises the enteric nervous system ?
A
The submucosal and myenteric plexuses
25
Why is the enteric nervous system considered reflexive ?
It can operate entirely within the GI wall w/o external input
26
What are the 3 main components of the enteric nervous system?
Sensory neurons (mechanoreceptors, osmoreceptors, chemoreceptors)
Interneurons (excitatory and inhibitory)
Secretomotor cells
27
What do secretomotor cells influence ?
Smooth muscle
Epithelial cells that secrete or absorb fluid/electrolytes
Enteric endocrine cells
28
What can the intrinsic reflex arc for motility respond to and what actions does it have ?
Mucosa can sense mechanical, chemical or thermal change —> activate reflex arc which can inhibit or contract SM cells
29
How does the ANS influence GI motility ?
Influences ongoing ENS activity
Directly affects SM and glands
Alters GI hormone levels
30
How does parasympathetic input affect GI tract in general ?
Increases motility and GI secretions
31
How does sympathetic drive affect the GI system ?
Decreased motility and decreased volume of secretions
32
How is swallowing coordinated ?
Initiation is voluntary —> reflexive and is coordinated by swallowing center of medulla oblongata
33
Describe the oral phase of swallowing
Push food bolus toward back of oral cavity and up against palate by using the tongue —> activate sensory receptors in the back of the throat
34
Describe the pharyngeal phase of swallowing ?
Touch and pressure receptors in the pharyngeal palate are activated by food bolus —> info sent to medulla via trigeminal nerve (CN V) —>
Initiate reflexive component of swallowing —> contraction of pharyngeal wall behind bolus pushes food toward esophagus
- tongue prevents food from travelling back to mouth
- uvula elevates to seal nasal passages
- epiglottis closes over trachea
35
Describe the esophageal phase of swallowing
Swallowing centre relaxes pharyngoesophageal sphincter
Swallowing center initiates primary peristaltic waves by enteracting with the ENS
Gastroesophageal sphincter opens when food bolus is against this region
(Reflexive relaxation mediated by vagus nerve)
36
Describe primary peristalsis
Inner circular muscle contacts —> pinching ring
Outer longitudinal muscle contracts in front of pinched ring —> decrease length of tube
Sequence propagates along length of esophagus
Takes 5-9 seconds
37
Describe secondary peristalsis
Reflexive
Activated when luminal contents become lodged
- distension of GI walls —> stretch receptors —> stimulate ENS —> coordinate strong peristaltic wave to dislodge contents
38
What are the 2 dominant motility paradigms in the small intestine
Segmentation
- ensures thorough mixing
Migrating mobility complex
- moves luminal contents along
39
Describe small intestine segmentation
During meal
| Alternating contractions and relaxations of adjacent sections of small intestine
40
What initiates segmentation in small intestine ?
Distension of lumen
Presence of enterogastrone gastrin
Parasympathetic input
41
Describe the action of migrating mobility complex in small intestine
- following absorption of meal
- begins at duodenal-gastric junction
- weak parastaltic contractions
- second wave begins slightly more distally —> travel slightly further
~2 hours from stomach to large intestine
42
Acid neutralizing/lower drugs
Antacids
Histamine H2 receptor antagonists
Proton pump inhibitors
43
Antacids and their mechanism of action
Hydroxide and/or carbonate salts
Direct neutralization of stomach acid
—> increase gastric pH
44
How might antacids affect the absorption of other drugs ?
Counter ions are poorly absorbed and may chelate other drugs and effect their absorption
Increased pH may also affect absorption of other drugs
45
Indications for antacids
Heartburn/ mild GERD
| Dyspepsia
46
Side effects of antacids
Carbonate based salts —> belching
Ca2+ containing: hypercalcemia
Al3+ containing: constipation, hypophosphatemia —> impaired absorption
Mg 2+ containing : diarrhea
47
Suffix of H2 receptor agonists
Tidine
48
Mechanism of action of H2 receptor antagonists
Competitive, selective block of histamine H2 receptors —> reduced (60-70%) acid secretion
Most effective in nocturnal acid secretion
49
Pharmacokinetics of H2 receptor antagonists
Oral, IM and IV formulations
| Oral: bioavailability ~50%, peak absorption in 1-3 hours, twice daily administration
50
Indications for H2 receptor antagonists
GERD
Peptic ulcer disease
Dyspepsia
Prevention of bleeding from stress related gastritis
51
Common Side effects of H2 receptor antagonists
Diarrhea or constipation
Headache
Drowsiness/fatigue
Muscle pain
52
Rare side effects of H2 receptor antagonists
```
Confusion/agitation
Delirium/hallucinations
Slurred speech
Gynecomastia
Blood dyscrasias
```
53
Suffix of PPIs
Prazole
54
Mechanism of action of PPIs
Irreversible inactivation of Proton pump common to all triggers of gastric acid secretion
55
Indications for proton pump inhibitors
Gastric and duodenal ulcers
GERD
Prevention of bleeding from stress related gastritis
Gastric hypersecretory conditions
56
Common side effects of PPIs
Nausea
Diarrhea (or constipation)
Abdominal pain
Flatulence
57
What are up to 80% of peptic ulcers correlated with ?
Presence of H.pylori in GI tract
58
What is the standard triple therapy for peptic ulcer disease with H. Pylori infection ?
- PPI + two antibiotics for 2 weeks
- clarithromycin and amoxicillin or metronidazole
- PPI alone for 6 weeks
59
What is misoprostol
Prostaglandin E1 analogue
60
Mechanism of action of misoprostol
Direct parietal cell inhibition and mucus cell stimulation
61
Pharmacokinetics of misoprostol
Short half life —> frequent dosing
| No impact on cytochrome P450 enzymes
62
Indications for misoprostol
NSAID- induced ulcers
63
Contraindications for misoprostol
Pregnancy
64
Side effects of misoprostol
Diarrhea
Abdominal cramping
Uterine contraction
65
Composition of sucralfate
Al(OH)3-sucrose surface complex
66
Mechanism of action of sucralfate
Acid interaction —> anionic surfaced sucrose —> bind to charged ulcer proteins —> viscous, sticky, protective barrier
- indirect stimulation of PGE2 production
67
Pharmacokinetics of sucralfate
Localized action
Short affect ~6 hours
Take on empty stomach
68
Indications for sucralfate
Gastric and duodenal ulcers
69
Side effects of sucralfate
Al3+ induced constipation
| May reduce absorption of some other drugs
70
Bismuth subsalicylate (pesto-bismo) mechanism of action
Coat ulcers —> protective barrier
Increased PGE2, HCO3- and mucus production
Antimicrobial against H. Pylori
Reduces stool frequency
71
Pharmacokinetics of Bismuth subsalicylate
Dissociates in stomach —> acts locallly
| Only salicylate substantially absorbed
72
Indications for bismuth subsalicylate
Adjuvant to triple therapy for H.pylori- induced ulcers
| Acute diarrhea
73
Contraindications for bismuth subsalicylate
Children with viral infections —> Reye’s syndrome
| Allergies to ASA
74
Side effects of bismuth subsalicylate
Black stool
Blackening of tongue
Constipation
75
Examples of pro kinetic drugs
Metoclopramide and domperidone
76
Mechanism of action of pro kinetic drugs
Dopamine D2 receptor antagonists
Metoclopromide has activity as agonist of serotonin (5-HT) receptors
Relieve basal dopamine inhibition of upper GI tract, stimulating peristalsis and facilitating gastric emptying
77
Pharmacokinetics of pro kinetic drugs
Metoclopromide: PO and parenteral formulations
Domperidone: greater fast pass metabolism
Short (1-2 hour) duration of action
Hepatic metabolism
78
Indications for prokinetic drugs
GERD
Impaired gastric emptying (gastroparesis)
Nausea and vomiting
Postpartum lactation stimulation
79
Contraindications for prokinetic drugs
Situations where GI motility is harmful
80
Side effects of prokinetic drugs
GI cramping
Diarrhea
Hyperprolactinemia
Metoclopromide crosses blood brain barrier
- dystonias, Parkinson’s-like syndromes, tardive dyskinesia
- drowsiness, restlessness, insomnia, anxiety
81
What does anti-emetic pharmacology target ?
Gastric stimuli
| Motion sickness
82
Basis for gastric stimuli
Based on vagal afferents activating brain stem “vomiting centre” and/or chemoreceptor trigger zone
83
Anti emetic drug that targets gastric stimuli
Ondansetron
84
Drugs used to target motion sickness
Dimenhydrinate
| Scopolamine
85
Ondansetron mechanism of action
Agonist of serotonin 5-HT3 receptors
| —> vagal afferents, chemoreceptor trigger zone, and vomiting centre
86
Indications for ondansetron
Chemo induced nausea and vomiting
| Post-op and post radiation nausea and vomiting
87
Side effects of ondansetron
Headache
Dizziness
Constipation
88
Dimenhydrinate mechanism of action
Antagonist of histamine H1 receptors
- some anticholinergic activity
Relatively weak anti-emetic activity
89
Indications for dimenhydrinate
Motion sickness
90
Side effects of dimenhydrinate
Dizziness
Sedation/drowsiness
Dry mouth
Urinary retention
91
Scopolamine mechanism of action
Antagonist of muscarinic receptors
92
Indications of scopolamine
Motion sickness
93
Side effects of scopolamine
Anti muscarinic when given orally or parenterally
94
3 primary functions of the stomach
Mixing and mechanical breakdown of stomach contents
Storage of ingested food and regulated delivery of processed stomach contents to the duodenum
Secretion of HCl and enzymes involved in protein digestion
95
What lines the fundus and body of the stomach ?
Oxyntic mucosa
96
What lines the antrum of the stomach ?
Pyloric gland area (PGA)
97
Exocrine glands of the stomach
Mucous cells
Chief cells
Parietal cells
98
What do mucous cells secrete ? What stimulates this ? What is the function ?
Alkaline mucous
Mechanical stimulation by contents
Protects mucosa against mechanical, pepsin and acid injury
99
What do Chief cells secrete ? What stimulates this ? What is the function of the secreted product ?
Pepsinogen
Ach, gastrin
When activated begins protein digestion
100
What do parietal cells secrete ? What stimulates this ? What is the function of the secreted product ?
HCl
ACh, gastrin, histamine
Activates pepsinogen, breaks down CT, denatures proteins, kills microorganisms
Intrinsic factor —> facilitates absorption of vitamin B12
101
What are the endocrine/pans rinse cells
Enterochromaffin- like (ECL) cells
G cells
D cells
102
What do ECL cells secrete ? What stimulates this? What is the function of the secreted product ?
Histamine
Ach, Gastrin
Stimulates parietal cells
103
What do G cells secrete ? What stimulates this ? What is the function of the secreted product ?
Gastrin
Protein products, ACh
Stimulates parietal, chief and ECL cells
104
What do D cells secrete ? What stimulates this ? What is the function of the secreted product ?
Somatostatin
Acid
Inhibits parietal, G and ECL cells
105
Where are mucous cells, parietal cells and chief cells located ?
All gastric pits
Oxyntic mucosa
Oxyntic mucosa
106
Where are ECL cells, G cells and D cells located ?
Gastric glands of:
- oxyntic mucosa
- PGA
- PGA
107
How do parietal cells secrete HCl ?
Actively
| - ionic pumps move H+ and Cl- ions against their concentration gradients into the lumen
108
What 4 functions does HCl perform that assist in GI activity ?
1. Converts pepsinogen into active pepsin
2. Breaks down CT and muscle fibres of ingested food
3. Breaks the tertiary structure of proteins
4. Protection: kills some ingested microorganisms
109
What activates pepsin
HCl
110
What is the function of Pepsin?
Cleaves peptide bonds between certain amino acids
111
Where is pepsinogen stored
In inactive form in zymogen granules within chief cells
112
What 3 main components of the gastric mucosal barrier protect the epithelial layer from acid injury ?
1. Acid cannot penetrate hydrophobic epithelial membrane
2. Tight junctions: prevent acid from diffusing out of lumen
3. Mucous from mucous cells lining gastric pits is protective.
- lubrication of luminal contents —> decreased friction
- inhibits pepsin to protect against auto-digestion of stomach wall
- neutralizes gastric acid at the epithelial surface
113
Mechanism of H.pylori induced peptic ulcers
H.pylori and its toxins —> weaken mucosal barrier —>
Acid and pepsin penetrate mucosal barrier —> histamine is released from damaged epithelium —> enhance gastric acid and pepsin production
Chronic alcohol use, NSAIDs and stress can also contribute
114
What is B12 needed for ?
DNA replication (mitosis) in RBC formation
115
What 4 chemical messengers regulate the secretion of gastric juices ?
Acetylcholine
Gastrin
Histamine
Somatostatin
116
What does acetylcholine stimulate ?
Parietal, chief, ECL, and G cell secretions
117
What does gastrin stimulate ?
Parietal, chief and ECL cell secretions
118
What is the primary factor responsible for increasing gastric secretions during the ingestion of a meal ?
Gastrin
119
What does gastrin promote the growth of ?
The gastric and duodenal mucosa
120
What type of substance is histamine ?
Paracrine
121
What does histamine stimulate ?
Parietal cell H+ production
122
What is the function of somatostatin ?
Acts in a negative feedback manner to turn off gastric H+, pepsinogen and histamine production
123
What are the 3 phases of secretion of gastric juice during the ingestion of a meal
Cephalic
Gastric
Intestinal
124
What happens during the cephalic phase of gastric secretions ?
Secretion of pepsinogen and H+ in response to sight, smell or thought of food and the process of swallowing
Initiated in the hypothalamus and mediated by vagal efferents
Vagal input —> G cell production of gastrin
125
Describe the gastric phase of gastric secretions
Begins when food enters the stomach
Proteins and peptides within lumen are most potent stimuli
Receptors in ENS —> short reflexes —> gastrin release from G cells
Long reflexive loop —> activate H+ and gastrin secretion via vagal and ENS activity
Histamine release is also stimulated —> H+ secretion
Distension/caffeine/alcohol can also stimulate gastric juice production
126
Describe the intestinal phase of gastric secretion
Inhibitory
Begins when chyme empties into duodenum
As protein is removed from stomach —> stop secretions in gastric pits and glands
Somatostatin is released from D cells in PGA gastric glands in response to drop in pH —> inhibit parietal, chief and HCl cell activity
127
What happens during the intestinal phase of gastric secretions when there is fat, acid, hypertonic chyme and distension in the duodenum ?
Negative feedback:
Influence on gastric secretions via enterogastric reflexes and the enterogastrones CCK and secretin
These factors decrease gastric emptying
128
Typical history of presenting illness for patient with heartburn
Character: vague discomfort vs burning vs pain
Onset: often post-prandial
Location: retrosternal
Intensity: variable
Duration: minutes to hours
Aggrevating: supine position, foods which relax lower esophageal sphincter or delay gastric emptying
Relieving: antacids
129
Associated symptoms with heartburn
Sour taste
Water brash
Odynophagia
Dysphagia
130
Historical clues for heartburn
```
Meds
- opioids
Social history
- smoking
- alcohol
```
131
Red flags with heartburn
```
Vomiting
Weight loss
Bleeding
Anorexia
Dysphagia
```
132
What is reflux esophagitis and what are the possible causes ?
Acid damage to esophagus
- increased abdominal pressure
- increased volume of regurgitant
- decreased esophageal clearance
133
Describe the stepwise treatment of reflux esophagitis
Correct the underlying cause
- reduce or stop meds that drop LES pressure
Lifestyle changes
- smoking cessation
- alcohol cessation
- weight reduction
Medications
Surgery
134
Medications for treating reflux esophagitis
Antacids
Sucralfate
H2RAs
PPIs
135
Complications of esophagitis
```
Pain
Bleeding
Stricture
Barrett’s esophagus
Adenocarcinoma
```
136
GI causes of retrosternal burning
GERD
Esophagitis
Esophageal spasm
Esophageal cancer
137
Cardiac causes of retrosternal burning
MI
Pericarditis
Aortic dissection
138
Different types of esophagitis
Infectious: herpes, cytomegalovirus, candida
Inflammatory: eosinophilic
Trauma: pill
139
Presentation in patients with herpes and CMV esophagitis
Odynophagia - typically very painful
| Often immunosuppressed
140
Candida esophagitis presentation
```
Dysphagia
May or may not have thrush
Usually Immunosupressed
- diabetic
- HIV
-chemo
```
141
Presentation of eosinophilic esophagitis
Dysphagia
History of atopy
Furrows, rings, exudates
Often in younger population
142
Treatment for eosinophilic esophagitis
Viscous budesonide and PPI
| Six food elimination diet (wheat, milk, eggs, soy, nuts, shellfish)
143
Common causes of pill esophagitis
NSAIDs
K+
Alendronate
Antibiotics such as tetracycline and doxycycline
144
Rome iii definition of dyspepsia
One or more of:
- post prandial fullness
- epigastric pain or burning
- early satiety
145
Associated symptoms of dyspepsia
Nausea
Bloating
Anorexia
146
Causes of dyspepsia
```
Functional (60%): no obvious cause
- non-ulcer dyspepsia
- ulcer-like symptoms
- dysmotility-like symptoms
Organic (40%) - detectable etiology
```
147
Etiology of functional dyspepsia
Impaired gastric motor function
Visceral sensitivity
Psychosocial factors
148
Gastritis vs gastropathy
Gastritis- inflammation of gastric mucosa associated with injury
Gastropathy- epithelial cell damage and regeneration without inflammation
149
Two main patterns of gastritis
Antral based
| Corpus predominant
150
Describe antral based gastritis
Infection increases gastrin secretion —> increased parietal acid production —> duodenal damage —> gastric metaplasia in duodenum —> +/- H. Pylori moves into duodenum —> duodenal ulcers
Low pH —> H.pylori don’t move into body as readily
151
Describe corpus-predominant atrophic gastritis or pangastritis
Genetically lower acid production —> easier for H.pylori to move into body —> pangastritis —> risk factor for gastric ulcers as well as intestinal metaplasia —> dysplasia —> gastric carcinoma
152
What is peptic ulcer disease
Damage to the mucosal lining of the intestinal surface where acid is implicated in pathogenesis
Ulcer: damage extends into the muscularis mucosa
153
Causes of peptic ulcer disease
```
Ischemia
H.pylori
Smoking, alcohol
Zollinger-Ellison syndrome, carcinoid
Chron disease, radiation, chemo
Adenocarcinoma
NSAIDs
ICU
```
154
Complications of peptic ulcer disease
Pain
Penetration / perforation
Bleeding
Obstruction
155
Management of peptic ulcer disease
```
Correct underlying cause
Lifestyle changes
Pharmacological: PPI
Endoscopic
- injection
- coagulation
- clipping
Radio graphic
Surgical
```
156
Possible investigations for patients presenting with dysphagia
Labs: serology, urea breath test, stool studies
Radiology: X-rays, upper GI series, fluoroscopy, CT, MRI
Endoscopy: gastroscopy (esophagogastroduodenoscopy), enteroscopy, ERCP, cholangioscopy, colonoscopy
Endoscopic ultrasound
Manometry
157
What conditions would give an abnormal AXR ?
Ileus, SBO, LBO
Volvulus
Constipation
Severe colitis
158
Pros and cons of UGI series (barium swallow)
```
Pros:
Easy
Cheap
Good test in dysphagia
Cons:
Low sensitivity
Low specificity
```
159
What is the best test for severe abdominal pain ?
CT abdomen
160
What is CT enterography
Same as CT abdomen, but with negative PO contrast and with IV contrast
161
What can be used for distinguishing between motility disorders of esophagus ?
Esophageal manometry
162
What are the major structures of the exocrine pancreas ?
Ductal cells
| Acinar cells
163
What is the function of acinar cells ?
Produce digestive enzymes
| ~15-100 grams of protein secreted per day
164
What is the function of ductal cells ?
Produce basic bicarbonate fluid
| —> about 1.5 L of fluid per day
