Pathophysiology Flashcards
Definition of GERD
- 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
Disease Burden of GERD
-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???
GERD Imbalance b/w Protective & Causative Factors
Protective: GE reflux barriers, esophageal clearance (back to stomach), mucosal resistance
Causative: gastric acid & pepsin, duodenal contents, inc. gastric volume, inc. abdominal presssure
GERD injury: Gastric Contents
-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)
-
GERD injury: Duodenal Contents
- conjugated bile acids (worse in acid) & typsin & deconjugated bile acids (neutral environment)
- hard to quantify accuracy
GERD protective factors: Anatomic Antireflux Barrier
- 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
Healthy LES
- 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
Hypotensive LES
uncommon: mostly with severe esophagitis
- also occurs with pregnancy (estrogen & progesterone) with systemic disease (scleroderma) and after ablative surgery (Heller myotomy)
Decreased LES pressure with???
- fat
- chocolate
- peppermint
- many meds
Transient LES Relaxation (tLESR)
- 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
Hiatal Hernia: Disruption of Cardial Function
- 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
GERD Protective Factors: Esophageal Clearance & Resistance
-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
GERD: gravity
-worse reflux when supine
GERD: gastric volume
-worse with delayed gastric emptying (anatomic or functional, diabetic gastroparesis)
GERD: abdominal & intragastric pressure
- increase GE pressure gradient
- GERD worse with obesity (& after gastric banding)
Cardinal Symptoms of GERD
- Heartburn: burning behind sternum radiating up to neck, worse after meals and lying flat, eased by antacid sen: 30-76% spec: 62-96%
- Regurgitation: reflux of gastric content into hypopharynx
- Dysphagia: from esophageal dysmotility (active inflammation) or strictures (scarring or cancer)
- reported by over 30% patients with GERD
Associated Symptoms of GERD
- Belching & Hiccups from esophageal irritation
- “water brash” sudden appearance of sour/salty fluid in mouth increased salivary secretion in response to acid reflux
- reflux laryngitis, due to reflux into hypopharynx (hoarseness and globus)
- cough & bronchospasm from intermittent micro-aspiration into airway
GERD Clinical Diagnosis
-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
GERD: Radiologic Evaluation
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
GERD: Endoscopic Evaluation
-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
GERD: pH Monitoring
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
pH Monitoring Methods
- traditional: transnasal probe tip 5cm above LES, portable recorder & event monitor, 24 hr duration
- wireless: probe stapled to the distal esophagus
GERD pH Monitoring Interpretation
Acid Reflux: Esophageal pH < 4.0 for > 5 sec
Pathologic reflux: pH 5% recorded time
No absolute threshold value for GERD
GERD Evaluation: Manometry
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
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
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
GERD Treatment: Acid Suppression
- antacids: Mg2+ (maalox, mylanta) vs. Al3+ (amphogel) only for mild symptoms (doesn’t heal)
- short term buffer of acid, alginic barrier (gaviscon) - 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
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
Prokinetics: GERD Treatment
- Correct GERD related motility disorders
- not effective as single agent; combined w/acid suppression
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
Baclofen: Prokinetics
- vagal inhibitory neurotransmitter which decreases tLESR
- dose should be titrated upwards slowly
- side effects: drowsiness, nausea, lowering of seizure threshold
Bethanecol: Prokinetics
-cholinergic agonist, severe side effect
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
GERD Pre-op
-EGD, UGI, manometry, pH study
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
GERD Medical vs Surgery
-incomplete relief with surgery
Complications of GERD
- Aspiration: vocal cords: laryngitis & hoarseness
airways & lungs: cough/bronchospasm /pneumonia - Inflammation & Scarring: acute inflammation, different degrees of esophagitis
chronic scarring: pelvic strictures - Neoplastic Transformation: interstitial metaplasia (Barrett’s esophagus +/- dysplasia), adenocarcinoma
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
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)
Esophageal Cancer
GERD
- dec. squamous cell CA
- inc. adenocarcinoma (x4)
- low US incident
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
Barrett Esophagus Gross Pathology
-replacement of normal thick greyish squamous mucosa by thin tan glandular mucosa
Barrett Esophagus Microscopic Pathology
-columnar epithelium with goblet cells
GERD is most common in??
-middle-age obese white males
Primary Symptom of GERD?
-heartburn
What are the 2 functional areas of the stomach?
fundus
antrum/body
Function of fundus?
-provide relaxation and accommodation
Function of antrum/body?
-grinding, mixing, and transfer
Where is stomachs pacemaker function?
-greater curvature (mid part)
Fundic Abnormalities
decreased distension
decreased compliance
Antral Abnormalities
low amplitude waves
decreased frequency
arythmia
pylorospasm
Causes of Gastroparesis
- Diabetes (30%-most common)
- Idiopathic (28%)
- VIral induced
- Post surgical
- Scleroderma
- Parkinsons Disease
- Intestinal Pseudo-obstruction
Symptoms of Gastroparesis
- nausea (93%)
- abdominal pain (90%)
- early satiety (86%)
- vomiting (68%)
- features of malnutrition & wasting
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
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
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
Other Diagnostic Tests for Gastroparesis
- gastro duodenal manometry
- Breath Test (13C labeled acetate or octanoic acid)
- wireless motility capsule
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
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
