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189 Cards in this Set
- Front
- Back
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What is the main physiological function of the digestive tract?
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Process acquired food and water to meet the nutritional needs of the multi-cellular organism
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What is the primary ingestive behavior that develops in utero for all mammalian species?
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Swallowing
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What is the function of the esophagus?
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Transport the bolus (food/water) from the pharynx into the gastric reservoir
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What are the two phases of swallowing?
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1. Initial - voluntary as bolus is pushed backward by tongue to the hypopharynx
2. Later - involuntary as swallow reflex is triggered |
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How many and what muscles are involved in coordinating the act of swallowing?
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> 50 oral, pharyngeal, laryngeal, esophageal, and diaphragmatic muscles
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What happens to the larynx during swallowing?
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Larynx elevates at least 1 inch so that the food goes into the digestive tract and not the trachea
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How long is the esophagus? What compartments does it traverse?
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18-26 cm - traverses the cervical, thoracic, and abdominal compartments
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What is the state of the esophageal lumen normally? How big can it become?
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- Normally is collapsed
- Can expand up to 2-3 cm in diameter during distention |
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What are the layers of the esophageal wall?
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- Mucosa
- Submucosa - Muscularis propria - Adventitia |
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How thick is the esophageal wall?
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2-4 mm in thickness
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What are the two sphincters in the esophagus? Function?
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- Upper and Lower Esophageal Sphincters (UES and LES)
- High-pressure zones at either end of the esophagus that control esophageal inflow and outflow |
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What part of the esophagus is made of striated muscle?
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- Upper 1/4
- UES |
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What part of the esophagus is made of smooth muscle?
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- Lower half
- Intrinsic LES |
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What is the location of the UES? Shape? Function
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- Behind the cricoid cartilage (right below Adam's apple)
- U-shaped muscle - Usually keeps passageway closed because you don't want air to go into stomach when you are breathing |
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What are the components of the esophagogastric junction?
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- LES
- Crural diaphragm |
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How does the esophagus propel food through it?
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Peristalsis - coordinated and propulsive sequential contraction
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What are the two types of esophageal peristalsis? How do you differentiate them?
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- Primary peristalsis - triggered by swallow
- Secondary peristalsis - triggered by esophageal distention |
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What triggers primary peristalsis of the esophagus? What happens?
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- Triggered
- Pharyngeal contraction and appropriately timed relaxation of the UES and LES |
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What happens to the UES when you swallow?
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UES relaxes, which decreases the pressure, allowing bolus to pass through
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What triggers secondary peristalsis of the esophagus? What happens?
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- Triggered by esophageal distention (eg, food stuck in your throat)
- Contraction starts proximal to distal |
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What generates peristalsis in the esophagus?
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- Intrinsic - enteric neural plexus
- Extrinsic - vagus nerve |
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What provides intrinsic innervation to the esophagus, leading to peristalsis when activated?
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Enteric Neural Plexus (found within the muscularis propria and submucosal layers)
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What provides extrinsic innervation to the esophagus, leading to peristalsis when activated?
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Vagus nerve (found on outside of entire length of esophagus)
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What happens when you initiate a swallow?
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(a) Peristaltic wave of contraction migrates smoothly from striated to smooth muscle in esophagus
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What happens if you stimulated the vagus nerve?
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(b)
- Simultaneous contraction of the striated muscle in the esophagus (based on direct innervation of muscle) - Smooth muscle segment has a peristaltic wave because the intrinsic neurons activated by the vagal efferent nerve are capable of evoking a peristaltic contraction |
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In a normal swallowing reflex, what provides the coordinated skeletal muscle contraction as shown in (a)?
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Nucleus Ambiguus (Central Pattern Generator in Brainstem) controls the activation to make a sequential, coordinated peristaltic movement
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What is the mechanism of skeletal muscle contraction in esophagus?
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- Nerve endings at motor end plate release Ca2+ after receiving AP
- Ca2+ released mainly from SR via T-tubules |
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What is the mechanism of smooth muscle contraction in esophagus?
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- Varicose nerve endings innervate smooth muscle
- Gap junctions connect muscle cells - Ca2+ influx from outside - Wave of inhibition followed by a wave of excitation is mediated by a "latency gradient" and "dual peripheral innervation" |
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What chemicals mediate the wave of inhibition and wave of excitation in the smooth muscle of the esophagus?
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- Inhibition: NO
- Excitation: ACh (here the superior area has less NO and more ACh than inferior area so it contracts a bit sooner than the inferior area) |
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How does the vagus mediate the contraction in the smooth muscle of the esophagus?
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- Vagal efferents synapse both on inhibitory and excitatory myenteric neurons (ACh nicotinergic synapse)
- Excitatory motor neurons - predominantly ACh → Ca2+ release → depolarization → 2nd messengers (eg, Substance P) - Inhibitory motor neurons - predominantly NO → cGMP dependent pathway → inhibition of Ca2+ entry → hyperpolarization → VIP (vasoactive intestinal peptide) |
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Where does contraction occur relative to the food bolus in the esophagus? How does contraction push the food to the stomach??
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- Contraction is behind the bolus
- Longitudinal and circular muscles contract simultaneously generating a high pressure of contraction - This contraction gradually moves down pushing the food bolus with it - Muscles relax at the end of the peristaltic wave |
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What is the most specific esophageal symptom?
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Dysphagia
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What does dysphagia mean?
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Difficulty to eat or drink (during swallow)
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Dysphagia is most likely to occur as a result of which of the following?
a) prolonged and coordinated relaxation of LES b) early and synchronized relaxation of UES c) relaxation of esophageal body d) delayed ands short relaxation of LES e) peristaltic and timely contraction of esophageal body |
D - delayed and short relaxation of LES
(a is normal because LES is made of smooth muscle so takes longer time to relax; b is normal because UES is made of skeletal muscle so comparatively it takes less time to relax; c is normal because this happens once the bolus passes into stomach; e is normal as this is how the bolus moves) |
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What is the difference between dysphagia and globus sensation?
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- Dysphagia - sensation occurs at time of swallowing, during eating/drinking
- Globus sensation - always a lump in the throat unrelated to swallowing |
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What do patients complain of that have dysphagia?
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- Food "sticks" in throat
- Food is "caught" in throat - Food is "hung up" in throat |
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What kind of questions should you ask a patient you suspect has dysphagia?
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- What kind of food causes the dysphagia? Solids? Liquids?
- Is it intermittent (only some times) or progressive (always)? - Are other symptoms present: heartburn, regurgitation, odynophagia, chest pain? |
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What symptom causes a burning feeling to feel like it is radiating upward in the chest?
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Heartburn
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What symptom causes effortless return of gastric contents to move up towards the throat (sometimes giving a sour or bitter taste)?
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Regurgitation (sour is from acid and bitter is from bile)
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What symptom causes pain during swallow and bolus transit?
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Odynophagia
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What are the types of dysphagia based on location? How do the symptoms differ?
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- Esophageal - food sticks or hangs up after swallow, they may have chest pain when it is stuck
- Pharyngeal - difficulty initiating swallow, coughing, choking, and nasal regurgitation |
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What would cause food to stick or hang up after swallow and may cause chest pain when the food is stuck?
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Esophageal Dysphagia
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What would cause difficulty initiating a swallow, coughing, choking, and possibly nasal regurgitation?
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Pharyngeal Dysphagia
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What are the more common causes of dysphagia?
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Mechanical causes:
* Peptic stricture - Esophageal ring - Cancer Neuromuscular causes: * Achalasia - Esophageal spasm - Dysmotility - Eosinophilic Esophagitis may be mechanical or neuromuscular in etiology |
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What types of food are a problem for mechanical dysphagia? What are the most common causes of mechanical dysphagia?
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- Solid food (liquids can fit through remaining space usually)
* Peptic stricture - Esophageal ring - Cancer - Eosinophilic esophagitis |
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What types of food are a problem for neuromuscular dysphagia? What are the most common causes of mechanical dysphagia?
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- Liquids (and solids)
* Achalasia - Esophageal spasm - Dysmotility - Eosinophilic esophagitis |
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What are some less common causes of mechanical dysphagia?
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- Web
- Diverticulum - Benign tumors - Foregin body - Extrinsic (tumor) |
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What are some less common causes of neuromuscular dysphagia?
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- Scleroderma
- Chagas disease - Collagen vascular disorders |
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Which causes of dysphagia are usually intermittent?
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- Esophageal ring (mechanical)
- Esophageal spasm (neuromuscular) |
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Which causes of dysphagia are usually progressive?
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- Cancer (mechanical)
- Achalasia (neuromuscular) |
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If a patient has dysphagia associated with solid foods only, what features can help you determine the most likely cause?
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Mechanical obstruction (since it is solid):
- If progressive and age >50 → consider cancer - If chronic heartburn → consider peptic stricture - If intermittent → consider esophageal ring |
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If a patient has dysphagia associated with solid or liquid food, what features can help you determine the most likely cause?
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Neuromuscular (since it is also caused by liquids)
- If progressive w/ heartburn or regurgitation → consider scleroderma or achalasia - If intermittent w/ chest pain → consider esophageal spasm |
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What are the diagnostic approaches to understanding esophageal disorders?
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- Upper GI endoscopy
- Esophageal manometry - Radiography (esophagram) |
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What kind of test gets this data? What do these images show?
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Upper GI Endoscopy
- Left shows hypopharynx during inhalation, esophagus is closed at bottom - Right shows closed airway and opening of esophagus to swallow |
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What is different about these two endoscopies focusing on the body of the esophagus?
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- Left: LES slightly open and gastroesophageal junction (Z line) visible
- Right: LES closed and GEJ (Z line) not visible |
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What is the best test for diagnosing esophageal motor disorders?
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Esophageal Manometry
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What does esophageal manometry measure?
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- Measures esophageal intra-luminal pressures
- Gold standard for diagnosis of esophageal motor disorders - UES is top yellow bar showing high pressure at all times except for slight moment when it relaxes to let food in - LES is bottom green bar that shows increased pressure and longer opening / relaxation (because it is smooth muscle) |
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What is the time course of primary peristalsis?
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- UES relaxes for 1/2 sec to allow bolus passage
- Primary peristaltic wave duration is 3-7 sec - LES relaxes for 3-8 sec to allow bolus into stomach |
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How does the time the UES is open compare to the time the LES is open?
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- UES: half a second
- LES: 3-8 seconds |
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How fast and strong is the primary peristaltic wave through the esophagus?
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- 30-150 mmHg of pressure
- Duration 3-7 seconds - Speed of 3-5 cm/sec |
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What is the definition of Achalasia?
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- Impaired relaxation of the LES (increased LES tone)
- Loss of peristalsis in body of esophagus |
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What is Achalasia also known as?
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- Mega-esophagus
- Cardiospasm - Idiopathic esophageal dilation |
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Which of the following are characteristics of achalasia?
a) spasm of LES b) lack of coordinated esophageal contraction c) no esophageal contraction d) impaired LES relaxation during swallow |
B (lack of coordinated esophageal contraction = no peristalsis)
D (impaired LES relaxation during swallow) |
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What does this image of the esophagus show?
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Achalasia - disorganized non-peristaltic contractions of esophageal body
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What is the pathophysiological reason for abnormal function in the LES in Achalasia?
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Impaired and then loss of inhibitory NO activity
- Normal: excitatory ACh maintains LES tone and inhibitory NO releases to relax LES and allow bolus passage - Achalasia w/ loss of inhibitory NO activity: elevates LES pressure and inability to induce relaxation of LES - Achalasia w/ loss of all neurons: LES pressure is low d/t no excitatory ACh neurons and swallow-induced relaxation is absent = esophageal aperistalsis |
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What is the histological/morphological appearance in Achalasia?
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- Degeneration of ganglion cells in the myenteric plexus (either intrinsic to esophagus or within the vagus nerve)
- Inflammatory lymphocytic infiltration (disappears by end-stage achalasia) |
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When is Achalasia most common?
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- Peaks in 7th decade (60s)
- Also from 20-30 |
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What are the common symptoms of Achalasia?
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* Dysphagia (>90%) for both solids and liquids
- Chest pain, heart burn, regurgitation, and weight loss (although some may be obese) in 60% of patients - Subtle symptom development d/t slow progression and accommodative behavior |
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What causes esophagitis and heart burn in patients with Achalasia?
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- Food stasis and bacterial fermentation
- Acidity |
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What stereotypical accommodative behaviors to patients with Achalasia develop? Why?
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- Slow and stereotypical eating movements
- Avoiding social events with meals - They are able to partially compensate / accommodate because it begins subtly and has a slow progression |
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How do you diagnose Achalasia?
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Two or three modalities:
- Manometry - Radiography - Endoscopy |
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What are the characteristic appearances of Achalasia on a barium esophagram?
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- Bird beak
- Sigmoid shape |
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What are the characteristic appearances of Achalasia on manometry?
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Lack of coordinated peristaltic change in pressure after UES relaxes
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What else should you consider when you suspect a diagnosis of primary Achalasia?
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Secondary Achalasia:
- Chagas disease - Autonomic nerve damage - Infiltrative disorders (amyloidosis or sarcoidosis) - Malignancy - Para-neoplastic syndromes |
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What is Chagas disease caused by? What does it cause?
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- Caused by infection of Trypanosoma cruzi
- Leads to diffuse enteric myenteric destruction, megacolon, heart disease, and neurologic disorders - Type of "secondary achalasia" |
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What does an infection of Trypanosoma cruzi cause?
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Chagas disease
- Leads to diffuse enteric myenteric destruction, megacolon, heart disease, and neurologic disorders - Type of "secondary achalasia" |
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What could cause autonomic nerve damage that leads to secondary achalasia?
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- Diabetic autonomic neuropathy
- Polio - Surgical damage |
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What infiltrative disorders can lead to secondary achalasia?
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- Amyloidosis
- Sarcoidosis |
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What malignancies can lead to secondary achalasia?
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Direct infiltration usually caused by adenocarcinoma (esophageal, gastric, pancreatic, or breast)
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What paraneoplastic syndromes can lead to secondary achalasia?
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Small Cell Carcinoma of the lung
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What are the treatment modalities for Achalasia?
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Focus on disruption of the LES
- Pharm: NO donors or anti-cholinergic agents - Endoscopic therapy: Botox injection (inhibits release of ACh) or pneumatic dilation - Operative therapy |
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What kinds of drugs can be used to treat Achalasia?
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- NO donors
- Anti-cholinergic agents |
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What endoscopic therapies can be used to treat Achalasia?
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- Botulinum toxin injection (inhibits release of ACh)
- Pneumatic dilation |
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What disorder is characterized by discoordinated contraction of the muscularis layer of the esophagus?
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Esophageal spasm
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What happens in esophageal spasm?
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- Discoordinated contraction of the muscularis layer
- Interferes w/ efficient delivery of food and fluids to stomach |
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What does this radiograph show?
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Esophageal spasm - discoordinated contraction of the muscularis layer
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What does this manometry show?
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Esophageal spasm - discoordinated contraction of the muscularis layer, increases wall stress
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What does this manometry show?
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Complete Aperistalsis - eg, Scleroderma esophagus
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What is the most common cause of an esophageal stricture?
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Reflux esophagitis
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What kind of epithelium is found in the esophagus? Function? Weakness?
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Stratified Squamous Epithelium
- Resistant to abrasion from foods - Sensitive to acid |
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What are the protective functions mediated by the pre-epithelium in the esophagus? How does this compare to in the stomach and duodenum?
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Esophagus:
- Sub-mucosal glands of proximal and distal esophagus secrete mucin and bicarbonate - The pre-epithelial barrier has a limited mucus-HCO3 barrier to buffer diffusing H+ Stomach / Duodenum: - H+ ions must cross the mucus-unstirred water layer-bicarbonate barrier before contact can be made with surface epithelium - Mucus blocks diffusion of pepsin, but not H+, but H+ can be neutralized by bicarb found in the water layer |
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What are the protective functions mediated by the epithelium in the esophagus?
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- The apical cell membrane and intercellular junctional complex provide a structural barrier to H+ diffusion
- Intracellular buffering by negatively charged proteins and bicarb - H+ extrusion processes (Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange) regulate intracellular pH |
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What is the most important barrier against reflux into the esophagus?
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- LES tone - LES prevents reflux of acidic gastric contents which are under constant positive abdominal pressure
- The crural diaphragm constitutes the "extrinsic sphincter" - LES and crural diaphragm are anatomically superimposed and anchored to each other by the phrenoesophageal ligament |
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What causes the mucosal injury in GERD?
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- Reflux of gastric juices (specifically acid) is central to the development of mucosal injury
- Duodenal bile reflux may exacerbate damage - Inflammation results from damage and further decreases LES tone (leading to more damage) |
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How does inflammation from gastric juices refluxing into the esophagus exacerbate the pathology?
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- Inflammation induces production of IL-6
- IL-6 leads to increased H2O2 in muscle - H2O2 increases PAF (platelet-activating factor) and PGE2 - PAF and PGE2 reduce ACh release and decrease LES tone - This allows more reflux to occur |
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What can cause an incompetent LES?
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- Transient LES relaxation (most common)
- Strain (eg, during exercise increasing abdominal pressure) - Hypotonic LES |
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What are the injurious gastric contents?
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Acid, pepsin, bile
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What is the term for a separation of the diaphragmatic crura from the LES?
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Hiatal hernia
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What happens in a Hiatal Hernia?
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- Separation of the diaphragmatic crura and LES
- Leads to a protrusion of the stomach into the thorax through the gap |
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What are the two types of Hiatal Hernia?
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- Sliding (type I)
- Para-esophageal (type II) |
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What does this diagram show?
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Type I / Sliding Hiatal Hernia
- Common and asymptomatic in more than 90% of adult cases - Gastroesophageal junction moves above the diaphragm together with some of the stomach |
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What does this diagram show?
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Type II / Para-esophageal Hiatal Hernia
- Less common - A part of the stomach herniates through the esophageal hiatus and lies beside the esophagus, without movement of the gastroesophageal junction |
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What are the morphological features of GERD?
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- Simple hyperemia / redness may be the only sign
- Basal Zone Hyperplasia >20% of the total epithelial thickness, may be present - Elongation of lamina propria papillae that extends into the upper 1/3 of the epithelium, may be present - Erosions (mucosal breaks), may be present with more damage - In more severe cases, a small number of eosinophils are recruited into the squamous mucosa, followed by neutrophils |
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What do these endoscopic views show?
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GERD
- Left (erythemia) is more common now because people have acid inhibitors or change their lifestyles - The erosions used to be the hallmark; they are specific for GERD |
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What is the most common cause of esophagitis?
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Reflux of gastric contents into the lower esophagus
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How common is reflux esophagitis / GERD? Who is most likely to get it?
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- Most common out-patient GI diagnosis in US (10-20% of population)
- Most common in adults >40 yo |
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What are the risk factors for reflux esophagitis / GERD?
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* Obesity (higher intra-abdominal pressure)
- Alcohol and tobacco use - CNS depressants - Pregnancy - Hiatal hernia - Delayed gastric emptying - Increased gastric volume |
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What are the classic symptoms of reflux esophagitis / GERD?
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- Heartburn - burning or sharp epigastric / substernal discomfort radiating retrosternally
- Regurgitation - feeling sour contents of stomach in throat - Dysphagia - Other: atypical chest pain, chronic cough, and hoarseness (posterior laryngitis) may also be seen if acid gets higher up |
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How do you diagnose reflux esophagitis / GERD? Efficiacy?
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- Endoscopy (90% specific but only 50% sensitive)
- Ambulatory reflux monitoring (70% sensitive) - Radiography |
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How does the damage discovered on endoscopy, etc relate to the patients symptoms?
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Symptoms do not necessarily correlate with degree of mucosal damage
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What alarm symptoms should you watch for with GERD? What should you do if they have any of these alarm symptoms?
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Alarm Symptoms:
- Dysphagia - Anemia - Weight loss - Abdominal mass - Vomiting Plan: - Endoscopy with biopsy |
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How do you treat reflux esophagitis / GERD?
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Lifestyle modifications:
- Weight loss for obese - Elevate bed and avoid late meals for patients w/ recumbent or nocturnal symptoms - Avoid trigger foods (eg, EtOH, caffeine, chocolate, greasy food, citrus or carbonated beverages) Pharmacologic: - Anti-secretory drugs - PPIs >> Histamine H2 blockers Operative: - Fundoplication (complete and partial) - Substitute devices to enforce LES |
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What lifestyle modifications can be helpful for patients with reflux esophagitis / GERD?
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- Weight loss for obese
- Elevate bed and avoid late meals for patients w/ recumbent or nocturnal symptoms - Avoid trigger foods (eg, EtOH, caffeine, chocolate, greasy food, citrus or carbonated beverages) |
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What pharmacologic therapies can be helpful for patients with reflux esophagitis / GERD?
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- Anti-secretory drugs are very effective in healing esophagitis and provide symptomatic relief
- Proton Pump Inhibitors >> Histamine H2 blockers |
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What operative therapies can be helpful for patients with reflux esophagitis / GERD?
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- Fundoplication (complete and partial)
- Substitute devices to enforce LES (LINX and stimulator) |
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What are the potential complications of reflux esophagitis / GERD?
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- Esophageal ulcer
- Esophageal stricture (most common cause of this) - Bleeding - Barrett's esophagus |
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What does this endoscopy show?
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Esophageal Ulcer - can be a complication of GERD
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What does this endoscopy show? Cause?
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Esophageal Stricture
- Most often d/t inflammation and scarring caused by chronic GERD, radiation, or caustic injury - Narrowing generally caused by fibrous thickening of submucosa, atrophy of the muscularis propria, and/or secondary epithelial damage |
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What are the symptoms most likely associated with these endoscopic findings?
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Esophageal Stricture
- Stenosis-associated dysphagia usually progressive - Difficulty eating solids well before liquids |
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What is the most common cause of ER visits due to food impaction in the US?
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Eosinophilic Esophagitis
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What are the cardinal features of Eosinophilic Esophagitis?
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Epithelial infiltration by large numbers of eosinophils (usually superficial) and far from GE junction
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How can you distinguish Eosinophilic Esophagitis from GERD and other causes of esophagitis?
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- Abundance of eosinophils
- Far from GE junction - Failure of the acid suppressive treatment and absence of acid reflux - Personal or family history of atopia |
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What are the clinical symptoms of Eosinophilic Esophagitis in ADULTS?
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- Dysphagia
- Most common cause of food impaction - Less commonly, heartburn and nausea |
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what are the clinical symptoms of Eosinophilic Esophagitis in CHILDREN?
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- Nausea
- Burning - Food intolerance |
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What personal or family history is associated with Eosinophilic Esophagitis?
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Atopia (atopic dermatitis, rhinitis, or asthma)
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What is the pathophysiology responsible for Eosinophilic Esophagitis?
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- Allergic immune reaction to ingested or inhaled allergens
- T-cell mediated hypersensitivity reaction - Cascade of cytokine release from eosinophils - Deposition of MBP (major basic protein) and increased IL-5 and IL-13 within epithelium - Tissue remodeling and fibrosis can change the mechanical properties of the esophagus |
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What is deposited and expressed at higher levels in the esophageal epithelium in Eosinophilic Esophagitis?
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- Major basic protein deposited
- Increased expression of IL-5 and IL-13 |
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How do you diagnose Eosinophilic Esophagitis?
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Histologic confirmation of >15 eosinophils / HPF in esophageal mucosa
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What does this slide show?
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Eosinophilic Esophagitis - > 15 eosinophils / HPF in esophageal mucosa
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How does endoscopy contribute to the diagnosis of Eosinophilic Esophagitis?
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- Endoscopic appearance is helpful but not required for diagnosis
- Corrugated esophagus on left - Longitudinal furrows and white abscesses (exudates) on right |
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What does this endoscopy show?
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Eosinophilic Esophagitis
- Corrugated esophagus on left - Longitudinal furrows and white abscesses (exudates) on right |
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How do you treat a patient with Eosinophilic Esophagitis?
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1. Elimination diet (try seafood, wheat, soy, nuts, milk, and eggs)
2. Topical steroids 3. Systemic steroids 4. Endoscopic dilation (remove strictures) |
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What foods could be implicated in causing the allergic reaction in Eosinophilic Esophagitis? How do you determine this?
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1. Seafood
2. Wheat 3. Soy 4. Nuts 5. Milk 6. Eggs - Try an elimination diet where you see if the symptoms relieve when you stop eating that food |
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Besides GERD and Eosinophilic Esophagitis, what are some other causes of esophagitis?
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- Chemical Esophagitis
- Infectious Esophagitis - Iatrogenic Esophagitis (something we did to patient caused this) - Skin disorder associated with Esophagitis |
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What kinds of irritants can cause Chemical Esophagitis?
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- Corrosive acid
- Corrosive alkali (Lye ingestion) - Alcohol - Excessively hot fluids - Heavy smoking - Medicinal pills that lodge and dissolve in esophagus (eg, NSAIDs, doxycycline, forosomax) |
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What are the symptoms of Chemical Esophagitis?
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- Self-limited pain
- Odynophagia (pain w/ swallowing) - Hemorrhage, stricture, or perforation in more severe cases |
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What drugs can cause pill-induced esophagitis?
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- NSAIDs
- Doxycycline - Fosomax - Occurs if they get lodged and dissolve in the esophagus, rather than passing into the stomach |
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Who is most commonly affected by Infectious Esophagitis? What kinds of infections?
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- May occur in healthy people, but more commonly debilitated or immunosuppressed
- Viral, fungal, and bacterial organisms |
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What are the most common causes of Viral Esophagitis?
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- HSV
- CMV |
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What is the appearance of the HSV and CMV in Viral Esophagitis?
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- HSV: punched-out ulcers
- CMV: shallow ulcerations |
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What are the histological appearances of HSV and CMV in Viral Esophagitis?
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- HSV: nuclear inclusions within a rim of degenerating epithelial cells at the ulcer edge
- CMV: cytoplasmic AND nuclear inclusions within capillary endothelium and stroma |
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What are the most common causes of Fungal Esophagitis?
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* Candida
- Mucormycosis - Aspergillosis |
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What is the appearance of Candida Esophagitis?
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- Adherent, grey/white pseudo-membrane
- Densely matted fungal hyphae and inflammatory cells |
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How common is Bacterial Esophagitis? What bacteria are most common?
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- Bacterial esophagitis ~10% of infectious esophagitis cases
- Non-pathogenic oral bacteria frequently found in ulcer beds |
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What happens in Bacterial Esophagitis?
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Bacteria may invade the lamina propria and cause necrosis of the overlying mucosa
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What can cause Iatrogenic Esophagitis?
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- Cytotoxic chemotherapy
- Graft vs Host disease - Radiation |
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What are the findings of Iatrogenic Esophagitis?
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- Non-specific morphologic changes
- Ulceration and accumulation of neutrophils - Irradiation causes blood vessel thickening adding some element of ischemic injury |
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What skin disorders are associated with Esophagitis?
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* Desquamative skin disease (bullous pemphigoid and epidermolysis bullosa)
* Lichen planus - Crohn's disease |
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What desquamating skin diseases are associated with esophagitis?
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- Bullous pemphigoid
- Epidermolysis bullosa |
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What does Barrett's Esophagus put you at increased risk for?
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Esophageal Adenocarcinoma
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What do these slides show?
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Gastro-Esophageal Junction
- Purple mucosa on left is Columnar (as seen in the intestine) - Pink mucosa on the right is Stratified Squamous (as seen in the esophagus) |
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What is the definition of Barrett's Esophagus?
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Normal esophageal squamous epithelium replaced by metaplastic columnar mucosa (specifically intestinal metaplasia)
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What are the signs of Intestinal Metaplasia in Barrett's esophagus?
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Goblets cells (w/ their distinct mucous vacuoles) define intestinal metaplasia (upper right)
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What is happening to the incidence of Barrett's Esophagus, and thus Esophageal Adenocarcinoma which it is associated with?
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They are both increasing in incidence
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What is Barrett's Esophagus a complication of?
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Chronic GERD - ~10% of GERD patients have BE
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How common is epithelial dysplasia in patients with Barrett's Esophagus? Importance?
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- 0.2% - 1.0% of persons with BE get epithelial dysplasia per year
- Epithelial dysplasia is a pre-malignant lesion - Defined as low-grade or high-grade based on morphology |
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What gene is expressed in Barrett's esophagus?
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- Cdx gene expressed in 100% of Barrett's esophagus specimens, but not in normal esophagus or stomach
- Cdx2 expression in normal-appearing squamous epithelium above specialized intestinal metaplasia in BE has been identified |
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What abnormalities are associated with dysplasia in Barrett's esophagus and later carcinogenesis?
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- Abnormalities in p53 and Cyclin D1 expression
- Cancer in BE evolves through a series of genetic mutations that favor cell growth |
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What characterizes intramucosal carcinoma?
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Invasion of neoplastic epithelial cells into the lamina propria
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What is the morphological appearance of Barrett's Esophagus?
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- Tongues or patches of red, velvety mucosa extending upward from the GE junction
- BE metaplastic mucosa alternates w/ residual smooth, pale squamous mucosa proximally |
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What is the clinical presentation of Barrett's Esophagus?
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Usually completely asymptomatic (other than the GERD symptoms)
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How do you diagnose Barrett's Esophagus?
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- Endoscopic evidence of abnormal mucosa above the GE junction
- Histologically documented metaplasia |
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Who is most likely to get Barrett's Esophagus?
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White adult male between 40-60 years with long-term reflux symptoms
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What should you do for a patient with Barrett's Esophagus?
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Periodic endoscopy, with biopsy, for detection of dysplasia is reasonable (but no guidelines on how frequently this should be done)
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Which of the following cause dysphagia?
a) Reflux related esophageal dysmotility b) Mediastinal or esophageal cancer c) Barrett's esophagus d) Esophageal peptic stricture e) Eosinophilic esophagitis |
Barrett's esophagus - does not cause dysphagia because it is asymptomatic (aside from GERD symptoms which also do not cause dysphagia)
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What are the two types of cancer that occur in the esophagus?
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- Squamous Cell Carcinoma
- Adenocarcinoma |
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In whom is esophageal adenocarcinoma most common?
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- White middle age male
- Highest incidence in developed Western countries (US, UK, Canada, etc) |
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What are the well-known risk factors for esophageal adenocarcinoma?
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- Dysplasia in Barrett's esophagus
- Tobacco use - Obesity - Radiation therapy |
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What is the relationship between genetic changes and developing esophageal adenocarcinoma?
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- Progression of Barrett's esophagus to esophageal adenocarcinoma occurs via stepwise acquisition of genetic and epigenetic changes
- Chromosomal abnormalities and p53 mutations are often present at early stages - Other genetic changes include amplification of c-ERB-B2, cyclin D1, and cyclin E genes |
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Which genes can be amplified in esophageal adenocarcinoma?
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- c-ERB-B2
- Cyclin D1 - Cyclin E |
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Besides genetic changes, what other process can contribute to neoplastic progression of esophageal adenocarcinoma?
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Inflammation - increased epithelial expression of TNF and NF-κB-dependent genes
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What are the morphologic characteristics of esophageal adenocarcinoma?
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- Barrett's esophagus is present adjacent to tumor
- Early lesions: flat or raised patches w/ otherwise intact mucosa - Distal 1/3 of esophagus - May develop large exophytic masses, infiltrate diffusely, invade adjacent gastric cardia, or ulcerate and invade deeply |
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What part of the stomach can be affected by esophageal adenocarcinoma? Why does this make sense?
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- Gastric cardia
- Esophageal adenocarcinoma affects the distal 1/3 of the esophagus |
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On microscopic examination of esophageal adenocarcinoma, what is noted?
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Tumors typically produce mucin and form dense glands
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In whom is esophageal squamous cell carcinoma (SCC) most common?
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- African Americans (x6)
- Males (x4) - >45 years old - Most common in Asia (Iran, Turkmenistan, China, and Hong Kong), Argentina, Brazil, and S. Africa |
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What are the risk factors for esophageal squamous cell carcinoma (SCC)?
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- Alcohol and tobacco
- Poverty (more common in rural and under-developed areas) - History of caustic esophageal injury - Achalasia and Plummer-Vinson syndrome - Frequent consumption of very hot beverages - Previous radiation therapy |
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How does esophageal squamous cell carcinoma (SCC) compare to esophageal adenocarcinoma in terms of who is affected?
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- SCC: African American male adults > 45 years, more common in non-Western countries (eg, Iran, Turkmenistan, China, Hong Kong, etc)
- AC: White middle aged males, more common in western countries |
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How does esophageal squamous cell carcinoma (SCC) compare to esophageal adenocarcinoma in terms of the risk factors?
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SCC: alcohol, poverty, caustic esophageal injury, achalasia, Plummer-Vinson syndrome, very hot beverages
AC: dysplasia in Barrett's esophagus, obesity Both: tobacco, radiation therapy |
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When esophageal squamous cell carcinoma (SCC) does occur in the Western world, what is most commonly attributable to the development?
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Alcohol and tobacco
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What risk factors are proposed for esophageal squamous cell carcinoma (SCC) in endemic areas?
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- Nutritional deficiencies
- Mutagenic compounds such as though in fungus-contaminated foods (polycyclic hydrocarbons, nitrosamines) - HPV infection |
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What are the morphologic characteristics of esophageal squamous cell carcinoma (SCC)?
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- Half occur in middle 1/3 of esophagus
- Early lesions are small, gray-white plaque like thickenings - Grow into tumor masses that protrude and obstruct lumen - May spread within esophageal wall and invade surrounding structures like respiratory tree or aorta |
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How does esophageal squamous cell carcinoma (SCC) compare to esophageal adenocarcinoma in terms of morphology?
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SCC:
- Middle 1/3 - Early: small, gray-white plaque - Later: tumor masses AC: - Distal 1/3 - Early: flat or raised patches - Later: large exophytic masses, ulcerate, or infiltrate |
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How does esophageal squamous cell carcinoma (SCC) compare to esophageal adenocarcinoma in terms of where they spread?
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- SCC: respiratory tree or aorta
- AC: gastric cardia |
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What are the symptoms of esophageal squamous cell carcinoma (SCC)?
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- Dysphagia
- Odynophagia (pain on swallowing) - Obstruction - Patients may adjust their diet from solid to liquid - Extreme weight loss and debilitation from impaired nutrition and effects of tumor - Aspiration of food through a tracheo-esophageal fistula |
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What is the prognosis for esophageal carcinoma?
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- 5 year survival in superficial esophageal carcinoma is 75% (30% of cases are superficial in adenocarcinoma)
- Lymph node metastases associated w/ poor prognosis - Overall 5 year survival rte is only 9% (d/t late diagnosis) |
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When carcinoma affects the proximal 1/3 of the esophagus, what lymph nodes may be affected?
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Cervical lymph nodes
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When carcinoma affects the middle 1/3 of the esophagus, what lymph nodes may be affected?
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Mediastinal, paratracheal, and tracheobronchial lymph nodes
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When carcinoma affects the distal 1/3 of the esophagus, what lymph nodes may be affected?
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Gastric and celiac lymph nodes
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What are the symptoms of esophageal adenocarcinoma?
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- Dysphagia
- Odynophagia (pain with swallowing) - Progressive weight loss - Vomiting |
