1
Q
What does GERD stand for?
A
Gastroesophageal reflux disease
2
Q
What is the neurotransmitter responsible for regulating tone of the lower esophageal sphincter?
A
Ach
(therefore we do not want to use anti-cholinergics)
(this could cause a problem for people who also suffer from asthma-> atrovent)
3
Q
normal physiology of acid in the esophagus
A
1) acid and food reflux into the esophagus
2) peristalsis returns most acid reflux to the stomach
3) after peristalsis, a small amount of acid remains in the esophagus
4) saliva neutralizes the remaining acid in the esophagus
4
Q
what are the normal defenses mechanisms against acid in the esophagus
A
1) peristalsis
2) saliva that contains bicarbonate in it to neutralize the stomach acid
5
Q
lower esophageal sphincter (LES)
A
- 3-4cm of tonically contracted smooth muscle situated at the gastroesophageal junction
- main function is to protect the esophagus from noxious stomach contents
- dynamic to protect against reflux in a variety of situations such as swallowing, recumbency, and abdominal straining
- tone is maintained by Ach
- pressure is 15-30mmHg above intragastric pressure and varies from person to person-> this downward pressure forces the flap down
6
Q
Explain how the LES pressure exhibits diurnal variation
A
- highest at night (otherwise all our stomach contents would come back up)
- lowest at daytime and postprandially (after you eat)
- therefore it is weakest right after you eat-> why the flap is slightly delayed in closing- why you experience heartburn after you eat
7
Q
what else is the LES pressure affected by?
A
-various drugs, foods, and hormones
8
Q
pyloric sphincter
A
-controls emptying of stomach contents into the duodenum
9
Q
How does the pyloric sphincter contribute to GERD
A
- by delaying gastric emptying and therefore increasing intra-abdominal pressure that opens LES
- as soon as food backs up it creates the intra-abdominal pressure that opens LES
10
Q
what is the best non-pharm to prevent GERD
A
- get ACTIVE!
- will increase transport of GI motility (and therefore reduce the intra-abdominal pressure)
11
Q
duodenum
A
- first portion of the small intestine
- continues digestion of chyme
- pH around 6.5
12
Q
main components of the stomach
A
-fundus, body, antrum, pyloric sphincter, and stomach lining
13
Q
what is the pH of the stomach’s gastric juices?
A
1
14
Q
what does the gastric juices contain
A
-Hcl, electrolytes (Na, K, sulfates, phosphates, Ca, bicarbonate), water, ezymes (pepsin), and organic substances (mucus and proteins)
15
Q
what protects the stomach walls from the gastric juices?
A
-lipoprotein rich membrane
16
Q
what influences the ability of the mucosa membrane to withstand injury
A
-age and nutritional status
17
Q
How can gastric juices contribute to GERD?
A
by too much acid being produced
18
Q
how can excess acid production be stopped?
A
- work directly on the parietal cells that produce the acid
- proton pump inhibitors- by inhibiting you reduce the output of acid (this blocks the ultimate effect of histamine)
19
Q
Gastric acid production
A
- done by gastric glands deep within stomach lining
- parietal cells, G cells, and Enterochromaffin-like cells all lead to acid production
- controlled by 3 regulatory pathways that overlap and are stimulated by the vagus nerve by food (all 3 of these bind to receptors on the parietal cell to increase acid production
1) Ach- sight, smell, and taste of food; stomach distension
2) Gastrin- dietary aa stimulate G cells; Ach via stomach distension; elevated pH (lower pH is inhibitory via release of somatostatin from antral D cells)
3) Histamine (H2)- via Ach and gastrin (HENCE H2 blockers)
20
Q
which cells within the stomach lining do not contribute to acid production
A
-mucous cells (aka superficial epithelial lining)-> mucus
chief cells-> pepsinogen (chymotrypsin, gastric lipase)-> aka digestive enzymes (while these are not acid, if the mucosal lining is gone these can still do damage)
21
Q
what does the parietal cells secrete
A
-HCl and intrinsic factor (B12)
22
Q
what does G cells in the antrum secrete
A
gastrin
23
Q
what does the Enterochromaffin-like cells secrete?
A
Histamine
24
Q
how does histamine contribute to acid production?
A
receptors located on the parietal cells and when stimulated by histamine, gastric acid (HCL) secretion occurs. It is the most important gastric acid secretion stimulant and is released from enterochromaffin-like cells by gastric and cholinergic activity.
25
How does gastrin contribute to acid production?
- is a peptide hormone that is the most potent in stimulating secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility
- Gastrin binds to cholecystokinin B receptors to stimulate the release of histamines in enterochromaffin-like cells, and it induces the insertion of K+/H+ ATPase pumps into the apical membrane of parietal cells (which in turn increases H+ release into the stomach cavity). Its release is stimulated by peptides in the lumen of the stomach.
- May impact lower esophageal sphincter (LES) tone, causing it to contract
26
What is so dangerous about gastric acid?
- Has HCl pH 1-2: denatures and hydrolyze protein, TG, and carbohydrates
- Has pepsin and other proteases rapidly hydrolyzes protein
- If there is an imbalance between gastric acid and mucosal defenses can result in inflammation, and damage to stomach lining leading to ulcerations
27
how many acid pumps do each parietal cell have
-1 million (hence the use of proton pump inhibitors)
28
H-K-ATPase proton
- exchange H ions from the cytosol for K in the canaliculi using energy from ATP
- there is passive movement of K and Cl ions into the canaliculus
- when H ins are transported out they meet up with Cl ions to form HCl
- by acting on these pumps we can decrease acid production (and also help prevent stomach cancers in people with hyper-active parietal cells)
29
Is there a standard definition for GERD
- no
| - it is about the clinical presentation and clinical history
30
What is GERD
-chronic disorder related to the retrograde flow of gastro-duodenal contents into the esophagus and/or adjacent organs, resulting in a spectrum of symptoms, with or without tissue damage
31
How long is GERD a chronic disorder until?
-until you do something to change it (i.e. change your lifestyle- diet, exercise, quit smoking, etc)
32
Why is it important to have both symptoms and pathophysiological changes in the definition?
- because most people experience some reflux every hour without symptoms or changes
- pathological reflux (i.e. the damaging of tissues) results in the true definition of GERD vs heartburn which is an unpleasant/ burning sensation below sternum
- these changes can lead to a host of other issues
- pathological reflux is also more frequent and in longer duration occurring both day and night disrupting patient's life
33
Epidemiology
- 44% of american pop suffer GERD symptoms monthly and 20% weekly
- prevalence is higher in Western countries and increases with adults over 40
- no real gender differences (except in pregnancy-> this increases intra-abdominal pressure)
- mortality rate is 1 in 100000 (but the repeated wearing away of the esophageal lining can turn into ulcer/tumor)
- true incidence is hard to know (b/c many don't seek medical treatment and there is no standard definition for diagnosis)
34
What are the areas of the body in which signs/ symptoms of GERD can occur?
- chest
- pulmonary
- oral
- throat
- ear
35
What symptoms occur in the chest area?
- heartburn
- regurgitation
- chest pain
- dysphagia/ odynophagia
- belching
36
what symptoms occur in the pulmonary area?
- non-allergic asthma
- cough
- aspiration
- hoarseness
37
What symptoms occur in the oral area?
- tooth decay
| - gingivitis
38
What symptoms occur in throat area?
- globus sensation
- hoarseness
- laryngitis
39
what symptom can eventually occur in the ear?
- ear ache
| - by the time it gets here that means the condition has gotten a lot worse (symptoms becoming more symptomatic)
40
What is the hallmark symptom of GERD?
heartburn-> most common sign
41
At what time does heartburn usually occur?
- usually after a meal
- aggravated by bending over
- >2x per week suggests GERD
42
What is almost certain if heartburn occurs with regurgitation
90% certainty of GERD diagnosis
43
extraesophageal symptoms
-laryngitis, pharyngitis, chronic sinusitis, dental erosions, asthma, and chronic cough
44
difference between heartburn, regurgitation, and dyspepsia
heartburn- burning pain that can move up from stomach to the middle of the chest and maybe into thought (can include regurgitation)
regurgitation- symptom of acid reflux; contents of stomach move into the esophagus and maybe into throat (sour taste in mouth)
dyspepsia- aka indigestion; mostly stomach discomfort (burping, nausea, bloating, upper abdominal pain)
-all are used to describe symptoms of GERD, but each can happen independently of GERD too
45
true or false: there is only one cause of GERD
```
false- it is multifactorial and hard to know what is the exact mech sometimes
when things go wrong:
-decreased salivation
-impaired esophageal acid clearance
-impaired tissue resistance
-transient LES relaxation
-decreased resting tone of LES
-delayed gastric emptying
-hiatus hernia
-too much acid prouced
```
46
what is the key factor in the causation of GERD
-the retrograde movement of acid or duodenal contents from the stomach into the esophagus
47
what characteristics of the reflux are important
the content and the volume
- these substances> protective mechs of the esophagus
- it comes down to the aggressive mechs that are harmful to the esophagus that overwhelm protective mechs such as peristalsis, mucous production and salivation
48
What can the content of the reflux include?
acid, pepsin, bile, and pancreatic enzymes
49
dysfunction in the LES pressure
1) spontaneous LES relaxation
2) increases in intra-abdominal pressure
3) sphincter is atonic
- exact mech is not known- lasts 10-35 seconds, but esophageal distension, vomiting, belching, and retching can cause a lower LESP
- while these things happen to everyone, it comes down to the protective measures
- may occur with straining, bending over, eating or coughing
- allos gastric contents to move freely between sphincter and esophagus- usually associated with severe esophagitis
50
spontaneous LES relaxation
- not associated with swallowing= transient LES relaxation (TLESR)
- most common causative mech
- unrelated to swallowing or peristalsis
51
what are some causes of increases of intra-abdominal pressure
-thigh clothing, obesity, pregnancy
52
spincter is atonic
- no tone-> may need surgical intervention
| - factors that can lower LES tone include endogenous hormones, meds, and food
53
true or false: TLSER can occur in anyone- some may have it and not lead to GERD
true- all depends on their protective mechs, as well as the potency and time exposed to the gastric contents
54
mechanisms of GERD in normal volunteers vs patients with GERD (% comparisons)
Tone LES: 94% vs 65%
Transient increase in intra-ab pressure: 5% vs 17%
atonic sphincter: 1% vs 18%
55
Food that increases LES pressure
protein (good!!!)
56
food that decreases LES pressure
fat, chocolate, ethanol, peppermint, garlic, onions
57
hormones that increases LES pressure
gastrin, motilin, Sub P
58
hormones that decrease LES pressure
glucagon, progesterone, estrogen (therefore be careful with females on birth control)
59
What process do medications that increase LES pressure undergo?
speed up GI mobility (aka they are GI mobility agonists)
60
What is a major medication that can decrease LES pressure?
-anticholinergics (also nicotine, caffeine, nitrates, DA, narcs,)
61
esophagus is cleared mainly by:
1) primary peristalsis due to swallowing (secondary peristalsis due to esophageal distension or gravity)
2) swallowing increases salivary flow (contains bicarbonate that buffers acidic content)
62
impaired acid clearance
-decreased peristalsis, decreased salivation, and increased frequency of reflux leads to increased time the mucosa is exposed to gastric contents
63
true or false: production of saliva naturally decreases as we age
true (especially if they have Sjorgen's)
64
true or false saliva production increases as we sleep
false- decreases therefore making nocturnal GERD an issue for many patients
65
whats an easy non-pharm to help patients with GERD, especially elderly
-suck on a sugarless candy to increase salivation
66
what does severity of GERD depend on?
- duration of acid exposure
- composition of the reflux
- delay of gastric emptying
67
what is the primary cause of symptoms and tissue damage
- the duration of acid exposure -threshold seems to be a pH of 4
- the more time exposed to reflux under pH of 4 the more severe symptoms and longer recovery (only so many defence mechanisms)
- a pH of 4 is the threshold between erosive and non-erosive reflux in a 24 hour period and improved healing rates after 8 weeks (if pH can be maintained above 4, most patients will remain symptom free and eventually lead to healing
68
what are the most notable compositions of the reflux
- pH of 2, pepsin, and acid (at pH 2, pepsinogen is activated)
- bile or alkaline pancreatic secretions (bile acids are also a direct irritant)
69
what does the delay of gastric emptying lead to
-increase in gastric volume= increased frequency and volume to be refluxed (fatty meals and smoking contribute)
70
true or false: the most important thing to try and prevent is regurgitation of the stomach
true-> it is more acidic
71
true or false: more pain is felt at lower pH levels
true (eventually weans off at pH 4)
72
is there a gold standard to diagnosing GERD?
no
73
what are some tests that are included?
- endoscopy
- 24 hour pH monitoring
- proton pump administering
- manometry
74
what is the most important tool
-looking at clinical history
75
endoscopy
-looks at scar tissue in lower esophageal tissue-> look at and possibly biopsy the condition of the mucosa (esophagitis and Barrett's esophagitis)
76
24 hour pH monitoring
- involves having patient write diary of symptoms and at the same time a pH probe is placed 5cm above the LES and measurements are compared to diary
- in addition, probe monitors the % of time the pH was low, the frequency and severity of reflux
77
Proton pump admin
- useful, especially hen endoscopy has ruled out other complications such as Barrett's esophagus, ulcers, or cancer
- no standard treatment regiment (aka no specific dose with set timeline)
78
Manometry
-looks at motility issues by measuring the pressure differences across the stomach, LES, esophagus and pharynx
79
differential diagnosis: heartburn vs cardiac chest pain
heartburn- burning substernal pain
- may spread to neck or throat
- pain doesn't change upon exertion (except bending)
- increasing symptoms when lying down or eating
cardiac chest pain- crushing chest pain (elephant)
- radiating pain into left arm, neck, back and shoulder
- pain increases with exertion
- increasing symptoms till treatment or death
80
clinical complications of GERD
- esophagitis
- bleeding (can lead to death)
- esophageal erosions and ulcerations
- stricture formaton (scar tissue)
- barrett's esophagus (normal tissue lining of esophagus change to tissue that resembles lining of intestine- becomes darker in colour)
- adenocarcinoma of the esophagus
* THEREFORE NEED TO TREAT/ CHANGE LIFESTYLE ASAP*
81
esophagitis
inflammation of esophagus- usually the first sign leading towards GERD
82
what can injury to tissue result in?
tissue destruction and the development of erosions and ulcerations
83
how does stricture formation occur?
-protective mechs against ulcerations involving the deposition of fibrous tissue leads to stricture formation
84
what does stricture formation cause
- this leads to dysphagia as it always feels like there is something stuck in the throat
- weight loss in uncommon as most patients will change their diet to suit their needs and avoid pain
85
how does barrett's esophagus form
-when all the other complication s occur and then intestinal-type columnar epithelium cells replace normal but ulcerated squamous epithelial cells, Barrett's esophagus develops-> severe complication indicating a long-term assault of reflux on the esophagus and is linked to developing cancer
86
factors that trigger GERD
-certain foods, obesity, pregnancy, medications, smoking, hiatial hernia
87
explain how food can trigger GERD
- large meals induce TLESRs
- meals within 2-3 hours of bedtime or with alcohol increase acid production and increase nocturnal GERD (remember that LESP decreases at night)
- high fatty meals impairs gastric emptying
- aggravating foods include: raw onions, caffeine, chocolate, alcohol, tomato products, spicy foods, citrus, peppermint, carbonated drinks, coffee, and tea
88
explain how obesity can trigger GERD
- there are conflicting results, but generally recognized that exercise and weight loss with decrease symptoms
- thought to increase intra-abdominal pressure thereby opening LES
- weightloss is generally recommended as a first line therapy for treating GERD
89
Explain how pregnancy can trigger GERD
- most typically have heartburn symptoms and usually subside after delivery
- thought to increase intra-abdominal pressure thereby opening up LES
- also from the excess estrogen and progesterone
90
explain how some meds can trigger GERD
- anticholinergic meds that affect LESP and LES tone and reduces salivation and slow intestinal mobility causing delays in gastric emptying
- increased risk for NSAID users
91
explain how smoking can trigger GERD
- the nicotene decreases LESP
- promotes the movement of bile from the intestine to the stomach which changes the content of the reflux
- smoking also inhibits saliva secretion thereby stopping a natural defence mech
92
hiatal hernia
- the proximal stomach is dislocatedthrough the hiatus of the diaphragm into the chest and the crural diaphragm becomes separated from the LES
- pulls open LES-> it stretches and opens the sphincter and leaves the esophagus exposed
- these are found in more than 90% of patients with severe erosive esophagitis; most often found in patients with Barrett's esophagus and may contribute to its development
93
what are some recommendations that we can give to treat GERD
-eat smaller meals, less fatty meals, at least 3-6 hours before sleeping, sleep on an incline, lose weight, exercise, decrease alcohol and coffee consumption
94
hallmark clinical characteristics of GERD (aka red flags)
- chest pain typical of cardiac event
- recurring vomiting
- blood loss in vomit or stool
- dysphagia (difficulty swallowing); especially with solids like rice
- odynophagia (pain on swallowing)
- unexplained weight loss >5%
- family history of gastric cancer/ tumour
- unexplained cough, hoarseness, or dyspnea
HINT: VBAD
- persistent Vomiting
- Bleeding
- Abdominal weight loss
- Dyphagia
95
what are the typical ages of GERD
under 18 or over 50
96
within lifestyle modifications, what should patients avoid?
- foods that trigger
- lying down right after meals
- smoking
- excessive bending
- tight fitting clothes
97
within lifestyle modifications what should patients do
- exercise
- maintain healthy body weight
- reduce alcohol intake
- reduce caffeine intake
- eat smaller, more frequent meals
- reduce stress
- sleep with the head elevated higher than pelvis
98
what is the first line treatment for non-complicated mild to mod GERD
-lifestyle modifications with or without addition of antacids or H2 blockers
99
OTC options
- antacids (Tums)
| - alginic acid (gaviscon)
100
antacids
- lack efficacy data over placebo
- provide symptomatic relief by raising by raising pH over 4 which decreases conversion of pepsinogen to pepsin
- neutralizes acidic contents
- contains Ca, Mg, and Al
101
Alginic acid
- creates a viscous barrier at the top of the stomach contents
- decreases reflux episodes
- efficacy is lacking on healing
102
Rx treatment options
- H2 receptor antagonists
- proton pump inhibitors
- prokinetics
- mucosal protectants
103
explain H2 receptor antagonists
- block the action of histamine at the histamine H2 receptors of the parietal cells in the stomach-> decreases production of stomach acid
- provide immediate relief of symptoms (12 week therapy at BID)
- all options have similar efficacy-> choice based on kinetic profie and side effects
- common adverse effects include diarrhea, headache, dizziness, rash and tiredness
104
Proton pump inhibitors
- superior to all other pharm treatments for all types of patients (esp daytime)- most potent inhibitors of acid production
- newer agents have fewer drug interactions
- maintains pH above 4 for grater period of time allowing healing
- best to take 30 mins before breakfast b/c they only work on actively secreting pump
- side effects are mild and reversible (headache, diarrhea, nausea, abdominal pain, constipation, dizziness, and rash)
- if symptoms are greater than 2 times a week, these are considered first line
105
prokinetics
- help move contents of stomach faster therefore reducing intra-abdominal pressure
- signigicant drug interactions and side effects
106
mucosal protectants
- only used in minor GERD; or if patient is at risk and becomes hospitalized (therefore sedentary)
- protects stomach and esophageal tisue lining (chalk-like coating)
- not used often
107
alternative off-label treatment options
- baclofen (improves tone of LES and increases gastric emptying- works at antrum)
- surgical (laparoscopal sphuncter augmentation-device comprised of string of magnetized beads)
- trazodone and SSRIs (improve esophageal pain on swallowing- analgesics)
- cholestyramine (from patients who fail PPI therapy and have bile reflux; binds fats and cholesterol and through to increase speed of gastric emptying- evidence is lacking)
- acupuncture (helps control regurgitation and heartburn- evidence is lacking)
108
overall cause of GERD
- lower esophageal flap loosening
- slow motility of GI
- overproduction of acid
- hiatal hernia
