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Pathophysiology Flashcards

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1
Q

Definition of GERD

A
  • condition which develops when reflux of gastric contents causes troublesome symptoms and/or complications
  • chronic related to retrograde flow of gastroduodenal contents into esophagus and/or adjacent organs, resulting in a spectrum of symptoms, with or without tissue damage
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2
Q

Disease Burden of GERD

A

-most common GI outpatient disorder in US
-44% adults have heartburn once/month, 20% weekly
-$12 billion/year
-increasing incidence, postulated causes
H. pylori treatment or obesity???

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3
Q

GERD Imbalance b/w Protective & Causative Factors

A

Protective: GE reflux barriers, esophageal clearance (back to stomach), mucosal resistance

Causative: gastric acid & pepsin, duodenal contents, inc. gastric volume, inc. abdominal presssure

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4
Q

GERD injury: Gastric Contents

A

-acid & pepsin: key toxic elements, synergistic
-basis for acid suppression therapy
-worse with hypergastrinemia (ZE syndrome)
-increased GERD incidence with H. pylori eradication (may dec. acid secretion)
-

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5
Q

GERD injury: Duodenal Contents

A
  • conjugated bile acids (worse in acid) & typsin & deconjugated bile acids (neutral environment)
  • hard to quantify accuracy
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6
Q

GERD protective factors: Anatomic Antireflux Barrier

A
  • diaphragm forms a pinchcock around the entrance of the esophagus into the stomach
    1. costal diaphragm: ventilatory muscle
    2. crural diaphragm: muscle & sphincter-like action around the esophagus, inc. lower esophageal pressure, esp during instances when inc. pressure gradient b/w stomach and esophagus favors gastroesophageal reflux
  • LES is 2-4cm long thickened circular muscle fixed by phreno-esophageal lig to diaphragmatic hiatus, contract to 10-30 mm Hg to prevent reflux
  • angulation created at fundus of stomach meets esophagus (angle of His), forms flap valve that anatomically prevents reflux
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7
Q

Healthy LES

A
  • resting pressure (10-30mm Hg) prevents GE reflux (GE pressure gradient: 5-10 mm Hg)
  • LES relaxes to allow food bolus to enter the stomach
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8
Q

Hypotensive LES

A

uncommon: mostly with severe esophagitis
- also occurs with pregnancy (estrogen & progesterone) with systemic disease (scleroderma) and after ablative surgery (Heller myotomy)

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9
Q

Decreased LES pressure with???

A
  • fat
  • chocolate
  • peppermint
  • many meds
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10
Q

Transient LES Relaxation (tLESR)

A
  • accounts for most reflux episodes in healthy patients
  • Present in 40-80% GERD patients with normal LES
  • Independent of swallowing
  • Longer (>10sec) than swallowing-induced LES relaxation
  • Accompanied by inhibiting of crural diaphragm
  • Mechanism for belching?? stimulated by gastric distention and also stress, fat, pharyngeal stimulation
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11
Q

Hiatal Hernia: Disruption of Cardial Function

A
  • widened diaphragmatic hiatus and relaxed phrenoesophageal ligament allows the proximal stomach to migrate into thorax
  • barrier functions are disrupted
    1. loss of diaphragmatic and abdominal pressure at this location, LES pressure zone is shortened
    2. physical barrier function of GE junction is impaired, as angle of His & valve is lost
    3. increase in tLESR frequency in patients
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12
Q

GERD Protective Factors: Esophageal Clearance & Resistance

A

-peristalsis clears refluxate back into stomach
-bicarb (salivary & esophageal) neutralizes acid
-squamous mucosa resistant to acid injury
Importance of Salivation
-initiates primary peristaisis & neutralizes residual acid
-dec. salvation at night, smoking, anticholinergics
-esophageal dysmotility: both cause and result in GERD
-worse with connective tissue disease

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13
Q

GERD: gravity

A

-worse reflux when supine

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14
Q

GERD: gastric volume

A

-worse with delayed gastric emptying (anatomic or functional, diabetic gastroparesis)

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15
Q

GERD: abdominal & intragastric pressure

A
  • increase GE pressure gradient

- GERD worse with obesity (& after gastric banding)

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16
Q

Cardinal Symptoms of GERD

A
  1. Heartburn: burning behind sternum radiating up to neck, worse after meals and lying flat, eased by antacid sen: 30-76% spec: 62-96%
  2. Regurgitation: reflux of gastric content into hypopharynx
  3. Dysphagia: from esophageal dysmotility (active inflammation) or strictures (scarring or cancer)
    - reported by over 30% patients with GERD
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17
Q

Associated Symptoms of GERD

A
  1. Belching & Hiccups from esophageal irritation
  2. “water brash” sudden appearance of sour/salty fluid in mouth increased salivary secretion in response to acid reflux
  3. reflux laryngitis, due to reflux into hypopharynx (hoarseness and globus)
  4. cough & bronchospasm from intermittent micro-aspiration into airway
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18
Q

GERD Clinical Diagnosis

A

-Symptom Questionnaire: complexity & breadth of symptoms & cross-cultural differences (no gold standard) poor specificity
-Therapeutic Trial: anti-reflux lifestyle modifications
acid suppression: 2 weeks high dose PPI
symptomatic response with Rx & recurrence w/o Rx: sufficient to establish diagnosis of GERD

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19
Q

GERD: Radiologic Evaluation

A

Barium studies: noninvasive, available, cheap
Evidence: GE reflux, specific not sensitive
-esophagitis: mucosal ulvers
Contributory factors for GERD: hiatal hernia-potential for surgical repair
-gastric retention: anatomic & functional
Consequence: obstruction test with 13mm tables, stricture, web, ring
-dysmotility “poor man’s manometry”
-not good for Barrett’s esophagus

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20
Q

GERD: Endoscopic Evaluation

A

-visualization of GERD
-indicated for dysphagia, odynophagia, weigh loss, bleeding
-find: edema & erythema, friability, granularity, red streaks, erosions, ulcers
Los Angeles Classification A to D

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21
Q

GERD: pH Monitoring

A

TEST: atypical symptoms to document acid reflux, refractory symptoms to verify poor control of acid reflux, pre-op assessment to predict efficacy of anti-reflux surgery

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22
Q

pH Monitoring Methods

A
  • traditional: transnasal probe tip 5cm above LES, portable recorder & event monitor, 24 hr duration
  • wireless: probe stapled to the distal esophagus
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23
Q

GERD pH Monitoring Interpretation

A

Acid Reflux: Esophageal pH < 4.0 for > 5 sec
Pathologic reflux: pH 5% recorded time
No absolute threshold value for GERD

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24
Q

GERD Evaluation: Manometry

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A

Method: transnasal catheter positioned with tip at LES, measure LES pressure & relaxation & esophageal contraction (amplitude, duration, peristalsis)

GERD-related indications:

  • locate LES to place tip of pH monitor
  • dysphagia without obstruction: evaulate dysmotility
  • non-cardiac chest pain & normal pH: “nutcracker”
  • Pre-op assessment: evaluate for dysmotility
25
GERD Evaluation: Impedance
-to evaluate non-acid reflux detected as bolus of ion-rich fluid -most common symptoms of non-acid reflux: regurgitation and cough Principle: conductivity of liquid contents refluxed into esophagus
26
Treatment of GERD: Lifestyle Modification
Exploit Gravity: do not lie down after meals, avoid bedtime snacks, elevation of head of bead at night, sleep on left side Modify habits & diet: reduce acid secretion (no smoking, coffee, alcohol) -optimize LES function: no fat, chocolate, mint, citrus, meds (theophyline, narcotics, sedatives, Ca blockers) Eliminate other factors: optimize salivary clearance: avoid anticholinergics, reduce gastric distention: more frequent & smaller meals, reduce abdominal pressure: weight loss, no tight clothes
27
GERD Treatment: Acid Suppression
1. antacids: Mg2+ (maalox, mylanta) vs. Al3+ (amphogel) only for mild symptoms (doesn't heal) - short term buffer of acid, alginic barrier (gaviscon) 2. Histamine-2 Receptor Blockers: inhibits one stimulate for acid secretion by parietal cells (cimetidine, ranitidine, famotidine, nizatidine) -safe & cheap: slower action; not as effective as PPI
28
GERD Treatment: Acid Suppression PPI
Protein Pump Inhibitors (H/K-ATPase) - omeprazole/esomeprazole, lansoprazole/dexlansoprazole, rabeprazole, pantoprazole - inhibit common pathway of acid secretion to superior efficacy - irreversible inactivation by covalent binding to proton pump expressed on parietal cells: take 30 min before meals
29
Prokinetics: GERD Treatment
- Correct GERD related motility disorders | - not effective as single agent; combined w/acid suppression
30
Metoclopramide: Prokinetics
- dopamine-antagonist: increases LES pressure, gastric emptying, and acid clearance - crosses blood-brain barrier and cause neurologic side effects: fatigue, lethargy, anxiety, restlessness, parkinsonism, dystonia, tremors, & tardive dyskinesia
31
Baclofen: Prokinetics
- vagal inhibitory neurotransmitter which decreases tLESR - dose should be titrated upwards slowly - side effects: drowsiness, nausea, lowering of seizure threshold
32
Bethanecol: Prokinetics
-cholinergic agonist, severe side effect
33
GERD Surgical Treatment
- anti-reflex surgery: fundoplication 1. tack down stomach below diaphragm 2. restore flap valve & strengthen LES by wrapping stomach around esophagus - perform if no response to PPI, patient preference, volume reflux, peptic stricture
34
GERD Pre-op
-EGD, UGI, manometry, pH study
35
GERD Post-op
- Dysphagia: initially 20%, usually improves with time - Gas-bloat: cannot belch or vomit, increase flatus - Vagus Nerve injury: impaired gastric emptying - not all patients sustain long-term response - supplemental acid suppression after 5-15 years
36
GERD Medical vs Surgery
-incomplete relief with surgery
37
Complications of GERD
1. Aspiration: vocal cords: laryngitis & hoarseness airways & lungs: cough/bronchospasm /pneumonia 2. Inflammation & Scarring: acute inflammation, different degrees of esophagitis chronic scarring: pelvic strictures 3. Neoplastic Transformation: interstitial metaplasia (Barrett's esophagus +/- dysplasia), adenocarcinoma
38
Barrett's Esophagus
-consequences of chronic GERD -damage to squamous epithelium, healing through metaplastic process, replacement by columnar epithelium DDX: endoscopy: columnar epithelium in distal esophagus -specialized intestinal metaplasia -predisposition to esophageal adenocarcinoma
39
Esophagectomy
- definitive treatment: complete removal of lesion - extensive surgery: significant morbidity & mortality Endoscopic Treatment: eliminate high risk cells, repopulation by squamous cells -current strategies: ablation (thermal or photodynamic treatment), mucosal resection (especially mucosal irregularity)
40
Esophageal Cancer
GERD - dec. squamous cell CA - inc. adenocarcinoma (x4) - low US incident
41
GERD Pathology
- acid-pepsin injury causes increased cell death and desquamation at the surface, with compensatory basal hyperplasia (+ elongated submucosal rete pegs) - inflammation with mucosal and submucosal lymphocytes, neutrophils and eosinophils
42
Barrett Esophagus Gross Pathology
-replacement of normal thick greyish squamous mucosa by thin tan glandular mucosa
43
Barrett Esophagus Microscopic Pathology
-columnar epithelium with goblet cells
44
GERD is most common in??
-middle-age obese white males
45
Primary Symptom of GERD?
-heartburn
46
What are the 2 functional areas of the stomach?
fundus | antrum/body
47
Function of fundus?
-provide relaxation and accommodation
48
Function of antrum/body?
-grinding, mixing, and transfer
49
Where is stomachs pacemaker function?
-greater curvature (mid part)
50
Fundic Abnormalities
decreased distension | decreased compliance
51
Antral Abnormalities
low amplitude waves decreased frequency arythmia pylorospasm
52
Causes of Gastroparesis
1. Diabetes (30%-most common) 2. Idiopathic (28%) 3. VIral induced 4. Post surgical 5. Scleroderma 6. Parkinsons Disease 7. Intestinal Pseudo-obstruction
53
Symptoms of Gastroparesis
- nausea (93%) - abdominal pain (90%) - early satiety (86%) - vomiting (68%) - features of malnutrition & wasting
54
Diagnosis of Gastroparesis
- H & P - labs: blood glucose, CBC, electrolytes, thyroid function, serum cortisol - upper endoscopy to evaulate gastric outlet obstruction - gastric emptying study - rarely electrogastrography
55
Endoscopy
- evaluate mechanical obstruction - retained food in stomach, w/o obstruction - severe cases with gastric bezoar - barium examination can be done as an alternative to endoscopy
56
Gastric Emptying Study
- come fasting, given meal labelled with radioactive isotope - measure of % of gastric emptying after 2-4 hrs - gastric retention of >10% at 4 hrs is indicative of delayed gastric emptying
57
Other Diagnostic Tests for Gastroparesis
- gastro duodenal manometry - Breath Test (13C labeled acetate or octanoic acid) - wireless motility capsule
58
Management of Gastroparesis
- rehydration, correct electrolytes - decrompression: PEG - suppression of bacterial overgrowth - symptomatic treatment of diarrhea or constipation - DIET: low in residue & fat, enteral feeding/jejunostomy, total parental nutrition
59
Gastroparesis: Drugs
- Anti-emetics: phenargan & ondansetron - Metoclopramide: 5-10mg before meals - dopamine receptor blocker - serotonin blocker & pro motility - tradive dyskinesis ***Black Box*** - Macrolide Abx: mimic motilin action - early resistance - colitis - long QT syndrome - Cisapride: stimulates 5HT4 receptors with release of Acetylcholine in myenteric plexus, not in USA b/c high incidence of cardiac arrhythmias - Domperidone: local dopamine blocker, not FDA - Botox Injection: injection in pyloric sphincter, endoscopic treatment, multiple sessions, limited response - Gastric Pacemaker: data not avilable, approved as humanitarian use device, potential candidates are those with refectory disease for 1 year
GI
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