Transcript esophageal adenocarcinoma

Pathophysiology
of
Gastrointestinal Tract
1:Esophagus
D:\Photos\Voyage\North1204\Road
By: Amir A. Ashrafian, MD.
Goals: learning
1. Esophageal Structure and Function
2. Symptoms of Esophageal Disease
3. Esophageal Disorders:
Structural Disorders
Hiatal Hernia
Rings and Webs
Diverticula
Tumors
Esophageal Motility Disorders
Achalasia
Diffuse Esophageal Spasm (Des)
Gastroesophageal Reflux Disease (GERD)
Pathophysiology
Symptoms
Complications
Treatment
Congenital Anomalies
Introduction: Gastrointestinal tract Function
GIT serves two functions—assimilating nutrients and eliminating waste.
Mouth: Chewing & Mixing with salivary amylase
Esophagus propels the bolus into the stomach.
The esophageal mucosa squamous, does not permit significant diffusion or
absorption.
Stomach mixing the bolus with pepsin and acid. Gastric acid sterilizes the
upper gut. Proximal stomach has a storage function. Distal stomach exhibits
phasic contractions that propel solid food residue against the pylorus. Stomach
secretes intrinsic factor for vitamin B12 absorption.
The small intestine serves most of the nutrient absorptive function of the gut.
The intestinal mucosa exhibits villus architecture to provide maximal surface
area for absorption and is endowed with specialized enzymes and transporters.
Introduction: Gastrointestinal tract Function
Triturated food from the stomach mixes with pancreatic juice and bile in the
duodenum to facilitate digestion. Pancreatic juice contains the main enzymes
for carbohydrate, protein, and fat digestion as well as bicarbonate to optimize
the pH for activation of these enzymes.
Bile secreted by the liver and stored in the gallbladder is essential for intestinal
lipid digestion.
The proximal intestine is optimized for rapid absorption of nutrient breakdown
products and most minerals, while the ileum is better suited for absorption of
vitamin B12 and bile acids. The small intestine also aids in waste elimination.
The small intestine terminates in the ileocecal junction, a sphincteric structure
that prevents coloileal reflux and maintains small-intestinal sterility.
Introduction: Gastrointestinal tract Function
The colonic mucosa dehydrates the stool, decreasing daily fecal volumes from
1000–1500 mL delivered from the ileum to 100–200 mL expelled from the
rectum.
The colonic lumen possesses a dense bacterial colonization that ferments
undigested carbohydrates and short-chain fatty acids.
Whereas transit times in the esophagus are on the order of seconds and times
in the stomach and small intestine range from minutes to a few hours,
propagation through the colon takes more than one day in most individuals.
The proximal colon serves to mix and absorb fluid, while the distal colon
exhibits peristaltic contractions and mass actions that function to expel the
stool.
The colon terminates in the anus.
Esophageal Structure and Function
The esophagus is a hollow muscular tube coursing through the
posterior mediastinum joining the hypopharynx to the stomach
with a sphincter at each end.
It functions to transport food and fluid between these ends,
otherwise remaining empty.
Esophageal diseases can be manifested by impaired function or
pain. Key functional impairments are swallowing disorders and
excessive gastroesophageal reflux.
Pain, sometimes indistinguishable from cardiac chest pain, can
result from inflammation, infection, dysmotility, or neoplasm.
Symptoms of Esophageal Disease
The clinical history remains central to the evaluation of esophageal symptoms.
Important details include weight gain or loss, gastrointestinal bleeding, dietary
habits including the timing of meals, smoking, and alcohol consumption. The
major esophageal symptoms are heartburn, regurgitation, chest pain,
dysphagia, odynophagia, and globus sensation.
Heartburn (pyrosis), the most common esophageal symptom, is characterized
by a discomfort or burning sensation behind the sternum that arises from the
epigastrium and may radiate toward the neck. Heartburn is an intermittent
symptom, most commonly experienced after eating, during exercise, and while
lying recumbent. The discomfort is relieved with drinking water or antacid but
can occur frequently and interfere with normal activities including sleep.
Regurgitation is the effortless return of food or fluid into the pharynx without
nausea or retching. Patients report a sour or burning fluid in the throat or
mouth that may also contain undigested food particles. Bending, belching, or
maneuvers that increase intraabdominal pressure can provoke regurgitation.
Symptoms of Esophageal Disease
Chest pain is a common esophageal symptom with characteristics similar to
cardiac pain, sometimes making this distinction difficult. Esophageal pain is
usually experienced as a pressure type sensation in the mid chest, radiating to
the mid back, arms, or jaws. The similarity to cardiac pain is likely because the
two organs share a nerve plexus and the nerve endings in the esophageal wall
have poor discriminative ability among stimuli. Gastroesophageal reflux is the
most common cause of esophageal chest pain.
Esophageal dysphagia is often described as a feeling of food "sticking”.
Important distinctions are between uniquely solid food dysphagia as opposed
to liquid and solid, episodic versus constant dysphagia, and progressive versus
static dysphagia. If the dysphagia is for liquids as well as solid food, it
suggests a motility disorder such as achalasia. Conversely, uniquely solid food
dysphagia is suggestive of a stricture, ring, or tumor.
Symptoms of Esophageal Disease
Odynophagia is pain either caused by or exacerbated by swallowing.
Odynophagia is more common with pill or infectious esophagitis than with
reflux esophagitis and should prompt a search for these entities. When
odynophagia does occur in GERD, it is likely related to an esophageal ulcer or
deep erosion.
Globus sensation, alternatively labeled "globus hystericus," is the perception
of a lump or fullness in the throat that is felt irrespective of swallowing.
Although such patients are frequently referred for an evaluation of dysphagia,
globus sensation is often relieved by the act of swallowing. As implied by its
alternative name (globus hystericus), globus sensation often occurs in the
setting of anxiety or obsessive-compulsive disorders.
Water brash is excessive salivation resulting from a vagal reflex triggered by
acidification of the esophageal mucosa. This is not a common symptom.
Esophageal Disorders
Structural Disorders
Hiatal Hernia
Hiatus hernia is a herniation of viscera, most commonly the stomach, into the
mediastinum through the esophageal hiatus of the diaphragm. Four types of
hiatus hernia are distinguished with type I, or sliding hiatal hernia comprising
at least 95% of the overall total. A sliding hiatal hernia is one in which the
gastroesophageal junction and gastric cardia slide upward as a result of
weakening of the phrenoesophageal ligament attaching the gastroesophageal
junction to the diaphragm at the hiatus. True to its name, sliding hernias
enlarge with increased intraabdominal pressure, swallowing, and respiration.
The incidence of sliding hernias increases with age and conceptually, results
from wear and tear: increased intraabdominal pressure from abdominal
obesity, pregnancy, etc., and hereditary factors predisposing to the condition.
The main significance of sliding hernias is the propensity of affected
individuals to have GERD.
Esophageal Disorders
Structural Disorders
Rings and Webs
A lower esophageal mucosal ring, also called a B ring, is a thin membranous
narrowing at the squamocolumnar mucosal junction. Its origin is unknown but B
rings are demonstrable in about 15% of people and are usually asymptomatic.
When the lumen diameter is less than 13 mm, distal rings are usually associated
with episodic solid food dysphagia and are called Schatzki rings. Schatzki ring is
one of the most common causes of intermittent food impaction. Symptomatic rings
are easily treated by dilatation.
Esophageal Disorders
Structural Disorders
Diverticula
Esophageal diverticula are categorized by location with the most common being
epiphrenic, hypopharyngeal (Zenker's), and mid esophageal. Epiphrenic and
Zenker's diverticula are false diverticula involving herniation of the mucosa and
submucosa through the muscular layer of the esophagus. These lesions result from
increased intraluminal pressure associated with distal obstruction. Small Zenker's
diverticula are usually asymptomatic but when they enlarge sufficiently to retain
food and saliva they can be associated with dysphagia, halitosis, and aspiration.
Treatment is by surgical diverticulectomy.
Mid-esophageal diverticula may be caused by traction from adjacent inflammation
(classically tuberculosis) in which case they are true diverticula involving all
layers of the esophageal wall, or by pulsion associated with esophageal motor
disorders.
Esophageal Disorders
Structural Disorders
Tumors
Esophageal cancer occurs in about 4.5:100,000 people in the United States with
the associated mortality being only slightly less at 4.4:100,000. One notable trend
is the shift of dominant esophageal cancer type from squamous cell to
adenocarcinoma, strongly linked to reflux disease and Barrett's metaplasia.
The typical presentation of esophageal cancer is of progressive solid food
dysphagia and weight loss. Associated symptoms may include odynophagia, iron
deficiency, and, with mid-esophageal tumors, hoarseness from left recurrent
laryngeal nerve injury. Even when detected as a small lesion, esophageal cancer
has poor survival because of the abundant esophageal lymphatics leading to
regional lymph node metastases.
Benign esophageal tumors are uncommon and usually discovered incidentally. In
decreasing frequency of occurrence, cell types include leiomyomas, fibrovascular
polyps, squamous papillomas, granular cell, lipomas, neurofibromas, and
inflammatory fibroid polyps.
Esophageal Disorders
Congenital Anomalies
The most common congenital esophageal anomaly is esophageal atresia,
occurring in about 1 in 5,000 live births. Esophageal atresia is usually recognized
and corrected surgically within the first few days of life. Later life complications
include dysphagia from anastomotic strictures or absent peristalsis and reflux,
which can be severe.
Less common developmental anomalies include congenital esophageal stenosis,
webs, and duplications.
Esophageal Disorders
Esophageal Motility Disorders
Esophageal motility disorders are diseases attributable to esophageal
neuromuscular dysfunction commonly associated with dysphagia, chest pain, or
heartburn.
Achalasia
Achalasia is a rare disease caused by loss of ganglion cells within the esophageal
myenteric plexus with a population incidence of about 1:100,000 and usually
presenting between age 25 and 60.
Functionally, inhibitory neurons mediate deglutitive lower esophageal sphincter
(LES) relaxation and the sequential propagation of peristalsis. Their absence leads
to impaired deglutitive LES relaxation and absent peristalsis.
Esophageal Disorders
Esophageal Motility Disorders
Achalasia (continued)
Long-standing achalasia is characterized by progressive dilatation and sigmoid
deformity of the esophagus with hypertrophy of the LES.
Clinical manifestations may include dysphagia, regurgitation, chest pain, and
weight loss. Most patients report solid and liquid food dysphagia. Regurgitation
occurs when food, fluid, and secretions are retained in the dilated esophagus.
Patients describe a squeezing, pressure-like retrosternal pain, sometimes radiating
to the neck, arms, jaw, and back.
Therapy is directed at reducing LES pressure so that gravity and esophageal
pressurization promote esophageal emptying. Peristalsis rarely, if ever, returns.
Esophageal Disorders
Esophageal Motility Disorders
Achalasia (continued)
LES pressure can be reduced by pharmacologicals therapy, forceful dilatation, or
surgical myotomy.
Nitrates or calcium channel blockers are administered before eating, advising
caution because of their effects on blood pressure.
Botulinum toxin, injected into the LES under endoscopic guidance, inhibits
acetylcholine release from nerve endings and improves dysphagia in about 66% of
cases for at least 6 months.
The only durable therapies for achalasia are pneumatic dilatation and Heller
myotomy. Pneumatic dilatation, with a reported efficacy ranging from 32–98%, is
an endoscopic technique using a noncompliant, cylindrical balloon dilator
positioned across the LES and inflated to a diameter of 3–4 cm.
Esophageal Disorders
Gastroesophageal Reflux Disease (GERD)
It is estimated that 15% of adults in the United States are affected by GERD. With
respect to the esophagus, the spectrum of injury includes esophagitis, stricture,
Barrett's esophagus, and adenocarcinoma.
Of particular concern is the rising incidence of esophageal adenocarcinoma, an
epidemiologic trend that parallels the increasing incidence of GERD.
Esophageal Disorders
Gastroesophageal Reflux Disease (GERD)
Pathophysiology
The best defined subset of GERD patients, albeit a minority overall, have
esophagitis. Esophagitis occurs when refluxed gastric acid and pepsin cause
necrosis of the esophageal mucosa causing erosions and ulcers.
Three dominant mechanisms of esophagogastric junction incompetence are
recognized: (1) transient LES relaxations, (2) LES hypotension, or (3) anatomic
distortion of the esophagogastric junction inclusive of hiatus hernia.
Factors tending to exacerbate reflux regardless of mechanism are abdominal
obesity, pregnancy, gastric hypersecretory states, and delayed gastric
emptying.
Inherent in the pathophysiologic model of GERD is that gastric juice is harmful to
the esophageal epithelium.
Esophageal Disorders
Gastroesophageal Reflux Disease (GERD)
Symptoms
Heartburn and regurgitation are the typical symptoms of GERD. Somewhat less
common are dysphagia and chest pain.
With chest pain, cardiac disease must be carefully considered.
Extraesophageal syndromes with an established association to GERD include
chronic cough, laryngitis, asthma, and dental erosions.
A multitude of other conditions including pharyngitis, chronic bronchitis,
pulmonary fibrosis, chronic sinusitis, cardiac arrhythmias, sleep apnea, and
recurrent aspiration pneumonia have proposed associations with GERD.
GERD (GORD)
Esophageal Disorders
Gastroesophageal Reflux Disease (GERD)
Complications
The complications of GERD are related to chronic esophagitis (bleeding and
stricture) and the relationship between GERD and esophageal adenocarcinoma.
However, both esophagitis and peptic strictures have become increasingly rare in
the era of potent antisecretory medications.
Conversely, the most severe histologic consequence of GERD is Barrett's
metaplasia with the associated risk of esophageal adenocarcinoma, and the
incidence of these lesions has increased, not decreased in the era of potent acid
suppression.
Esophageal Disorders
Gastroesophageal Reflux Disease (GERD)
Treatment
Lifestyle modifications are routinely advocated as GERD therapy. Broadly
speaking, these fall into three categories:(1) avoidance of foods that reduce lower
esophageal sphincter pressure, making them "refluxogenic" (these commonly
include fatty foods, alcohol, peppermint, tomato-based foods, possibly coffee and
tea); (2) avoidance of acidic foods that are inherently irritating; and (3) adoption of
behaviors to minimize reflux and/or heartburn. In general, minimal evidence
supports the efficacy of these measures.
However, clinical experience dictates that subsets of patients are benefitted by
specific recommendations, based on their unique history and symptom profile.
A patient with sleep disturbance from nighttime heartburn is likely to benefit from
elevation of the head of the bed and avoidance of eating before retiring, but those
recommendations are superfluous for a patient without nighttime symptoms.
Esophageal Disorders
Gastroesophageal Reflux Disease (GERD)
Treatment (continued)
The most broadly applicable recommendation is for weight reduction. Even
though the benefit with respect to reflux cannot be assured, the strong
epidemiologic association between obesity and GERD and the secondary health
gains of weight reduction are beyond dispute.
The dominant pharmacologic approach to GERD management is with inhibitors of
gastric acid secretion. Pharmacologically reducing the acidity of gastric juice does
not prevent reflux, but it ameliorates reflux symptoms and allows esophagitis to
heal.
Proton pump inhibitors (PPIs) are more efficacious than histamine2 receptor
antagonists (H2RAs).