Chapter 17: The GI Tract - Congenital Abnormalities and Esophagus Flashcards
What is the most common form of esophageal atresia?
- Blind upper segment of esophagus
- Fistula b/w lower segment and trachea, most commonly at or near tracheal bifurcation
*Figure B is most common
What is the most common form of congenital intestinal atresia
A result of what embryologically?
- Imperforate anus
- Failure of cloacal diaphragm to involute
Developmental abnormalities of the the esophagus are associated with what other defects?
- Congenital heart defects
- Genitourinary malformation
- Neurologic disease
What is the most frequent site of ectopic gastric mucosa and what is it referred to here?
May result in what problems?
- Upper 1/3 of esophagus = Inlet patch
- Dysphagia, esophagitis, Barrett esophagus, or rarely, adenocarcinoma
What are examples of ectopia seen within the GI tract?
- Inlet patch: ectopic gastric mucosa in upper 1/3 of esophagus
- Ectopic pancreatic tissue: in stomach or esophagus
- Gastric heterotropia: patches of ectopic gastric mucosa in the small bowel or colon
Gastric heterotropia may present with what signs/symptoms?
Occult blood loss due to peptic ulceration of adjancent mucosa
Differentiate Omphalocele from Gastroschisis.
- Omphalocele = incomplete closure of abdominal ms. and abdominal viscera herniate INTO a ventral membranous sac
- Gastroschisis = similar to omphalocele, BUT involves ALL layers of abdominal wall from peritoneum to the skin - organs are exposed!
What is the most common true diverticulum and where does it occur?
- Meckel diverticulum
- Ileum
Cause of Meckel Diverticulum?
Failed involution of vitelline duct
What is the rule of 2’s in regards to Meckel Diverticulum?
- 2% of population
- Present within 2 feet of ileocecal valve
- 2 in. long
- 2x more common in males
- Symptomatic by age 2 (only 4% are ever symptomatic!)
What may be present in a Meckel Diverticulum that causes symptoms and what are these symptoms?
- Ectopic pancreatic or gastric tissue
- Peptic ulceration of adjancent SI tissue –> occult blood or abdominal pain resembling appendicitis or obstruction
Which sex is most commonly affected by congenital hypertrophic pyloric stenosis?
3-5x more likely in males
Which genetic disorders are associated with an increased risk of Pyloric Stenosis?
- Turner syndrome
- Trisomy 18
Which enviornmental factors have been linked to an increased risk of developing pyloric stenosis?
Erythromycin or azithromycin exposure, orally or via mother’s milk in first 2 weeks of life
When and how does congenital hypertrophic pyloric stenosis typically present?
- Between 3rd and 6th weeks of life
- New onset regurgitation w/ projectile, NON-bilious vomiting after feeding w/ frequent demands of re-feeding
What is palpated on PE with a congenital hypertrophic pyrloric stenosis?
What is tx?
- Firm, ovoid, 1-2 cm abdominal mass
- Tx = myotomy = curative
Which genetic disorder predisposes a child to Hirschsprung disease?
Down syndrome
What is the pathogenesis of Hirschsprung Disease (congenital megacolon)?
Produces a distal intestinal segment lacking what?
- Normal migration of NCC from cecum to rectum is arrested prematurely
- OR when ganglion cells undergo premature death
- Lacking both the Meissner submucosal and Auerbach myenteric plexus, dilation proximal to affected segment
Which genetic abnormality can account for the majority of familial cases of Hirschsprung disease?
Loss-of-function mutation in RET (receptor tyrosine kinase)
How does Hirschsprung disease typically present?
- Failure to pass meconium
- Obstruction or constipation
- Abdominal distention —> bilious vomiting
What are the major threats to life in regards to Hirschsprung disease?
- Enterocolitis
- Fluid/electrolye imbalance
- Perforation
- Peritonitis
Diagnosis of Hirschsprung disease requires what?
Which stain can be used?
- Documenting absence of ganglion cells within affected segment
- Immunohistochemical stains for acetylcholinesterase for ganglion cells
Which part of the colon is ALWAYS affected in Hirschsprung Disease?
Rectum
What are some causes of acquired megacolon?
Which is associated with loss of ganglion cells and which aren’t?
- Chagas disease —> Trypanosoma cruzi(Reduviid bug) = loss of ganglion cells
- Obstruction by neoplasm, inflammatory stricture, or Ulcerative Colitis = NOT associated w/ loss of ganglion cells
How does achalasia differ from hypertensive LES abnormalities?
Achalasia also has reduced esophageal peristaltic contractions
Larger Zenker Diverticulum may produce what signs and symptoms?
A mass and symptoms including regurgitation and halitosis (bad breath)
Idiopathic ledge-like protrusions of mucosa that may cause obstruction in the esophagus are known as?
Esophageal mucosal webs
Esophageal mucosal webs most often occur in whom?
Associated with what other diseases?
- Woman >40 yo
- GERD, chronic GVHD, or blistering skin diseases
What are the characteristic findings in Plummer-Vinson syndrome?
- Esophageal mucosal webs of the upper esophagus
- Iron-deficiency anemia
- Glossitis (beefy red tongue)
- Cheilosis (cracking of corners of mouth)
What is the main symptom of esophageal webs?
Non-progressive dysphagia associated w/ incompletely chewed food
How do Schatzki rings differ from esophageal webs?
Are circumferential, thicker, and include mucosa AND submucosa w/ occasional hypertrophic muscularis propria
What is the triad of Achalasia?
1) Incomplete LES relaxation
2) Increased LES tone
3) Aperistalsis of esophagus
Primary achalasia is the result of what?
What nerve/nucleus may be affected?
- Degeneration of the distal esophageal inhibitory neuronal (ganglion cells)
- Extraesophageal vagus n. and dorsal motor nucleus may also undergo degenerative changes
Secondary achalasia may arise in relation to infection by what bug?
What are the characteristics of this type of achalasia?
- Chagas disease (Trypanosoma cruzi)
- Destruction of myenteric plexus
- Failure of peristalsis
- Esophageal dilation
Achalasia-like disease may result from what other systemic disorders?
- Diabetic autonomic neuropathy
- Malignancy
- Amyloidosis or Sarcoidosis
- Lesions of dorsal motor nuclei (polio or surgical ablation)
- Down syndrome
- Allgrove (triple A) syndrome
What is the inheritance pattern and triad associated with Allgrove (triple A) syndrome?
- Autosomal recessive
- Achalasia
- Alacrima
- Adrenocorticotrophic hormone-resistant adrenal insufficiency
Linkage of achalsia to which immune disorders suggest that achalasia may also be driven by immune-mediated destruction of inhibitory esophageal neurons?
- HSV1 infection
- Immunoregulatory gene polymorphisms
- Sjorgen syndrome
- Autoimmune thyroid disease
What are 3 treatment options for both primary and secondary achalasia?
1) Laparoscopic myotomy
2) Pneumatic balloon dilation
3) BOTOX injection, to inhibit LES cholinergic neurons
When do Zenker Diverticulae most commonly develop (age)?
After age 50
Mallory-Weiss tears are what?
Longitudinal mucosal tears near the gastroesophageal jct.
Mallory-Weiss tears are most commonly associated/caused by what?
- Severe retching (i.e., bulimia)
- Vomiting secondary to acute alcohol intoxication
What is Boerhaave syndrome and how does it compare to Mallory-Weiss tears?
- Much less common, but MORE severe
- Transmural tearing and rupture of the distal esophagus
What occurs in patients suffering from Boerhaave Syndrome and how do they present?
The pt presentation often includes what other differential dx?
- Severe mediastinitis (air in mediastinum 2’ to perf. Esophagus)
- Pt presents w/ severe chest pain, tachypnea, and shock
- Initial diff dx usually includes an MI
Esophagitis caused by what organism is characterized morphologically by gray-white, pseudomembranes composed of densely matted fungal hyphae and inflammatory cells covering the esophageal mucosa?
Candidiasis
Viral esophagitis caused by Herpes virus is distinguished by what morphological characteristics?
- Punched-out ulcers
- Nuclear viral inclusions
Viral esophagitis caused by CMV is distinguished by what morphological characteristics?
- Shallow ulcers
- Nuclear and cytoplasmic inclusions (characteristic)
Which fungi are the most common causes of esophagitis?
- Candidiasis (most common)
- Mucormycosis
- Aspergillosis
What is the most common viral cause of esophagitis?
Herpes simplex
Recruitment of which immune cells are often seen morphologically with more severe injury as a result of GERD?
- Eosinophils recruited into squamous mucosa
- Followed by neutrophils
Basal zone hyperplasia and elongation of lamina propria papillae extending into the upper 1/3 of the epithelium is associated with the pathogenesis of which cause of esophagitis?
GERD
What are some of the complications that may result from reflux esophagitis?
- Ulceration
- Hematemesis
- Melena (dark sticky feces)
- Stricture development (ulcer -> loss of mucosal layer –> fibrosis)
- Barrett esophagus
What are the symptoms of Eosinophilic Esophagitis in both adults and children?
- Adults - food impaction and dysphagia
- Children - feeding intolerance and GERD-like sx’s
What is the cardinal histological feature of eosinophilic esophagitis?
i.e., large #’s of which cells and where
Large #’s of intraepithelial eosinophils, particularly superficially
How is eosinophilic esophagitis different from GERD?
- Acid reflux is NOT prominent
- PPI’s usually do NOT provide relief
The majority of patients with eosinophilic esophagitis are also what?
Many have what underlying disorders?
- Atopic
- May have: atopic dermatitis, allergic rhinitis, asthma, or modest peripheral eosinophilia
What are 2 major causes of Esophageal Varices?
Normal route of blood flow?
1) Portal HTN (cirrhosis - alcoholic liver disease) –> collateral channels –> congested subepithelial and submucosal venous plexi within distal esophagus and prox. stomach
- Left gastric vein —> Portal V.
2) Hepatic schistosomiasis - parasitic disease -> flukes (trematodes)
Variceal hemorrhage is a medical emergency that can be treated how?
- Inducing splanchnic vasoCONSTRICTION
- Endoscopic sclerotherapy (inject thrombotic agents)
- Balloon tamponade
- Variceal ligation
What are the signs/symptoms of esophaeal varices?
- Esophageal bleeding
- PAINLESS hematemesis
Patients with risk factors for variceal hemorrhage, including large varices, elevated hepatic venous pressure gradients, previous bleeding, and advanced liver disease may by treated prophylactically with what?
Beta-blockers
What is the prognosis of someone treated for a variceal hemorrhage?
- 30% or more pts die as consequence of hemorrhage –> hypovolemic shock, hepatic coma, etc..
- 50% of pts who survive 1st bleed have recurrent hemorrhage within 1 year
Cirrhosis patients with small varices that have never bled are at (low/high) risk for bleeding or death?
Low risk
What occurs in the vasculature as a result of Portal HTN and leads to formation of varices?
- Left gastric V. backs up into the esophageal V., resulting in dilation (varices)
- Distal esophageal v. usually drains into the portal v. via the left gastric v.
The greatest concern in Barrett esophagus is that it confers an increased risk of developing?
Esophageal adenocarcinoma
What morphological change is seen with Barrett Esophagus?
- Metaplasia of lower esophageal mucosa
- Stratified squamous epi —> nonciliated columnar epithelium w/ goblet cells
Which type of esophageal cancer is most common worldwide; which is becoming more prevalent?
- Squamous cell carcinoma = more common worldwide
- Adenocarcinoma is becoming more prevalent in the US and Western society
What is the most likely factor contributing to the increasing rates of esophageal adenocarcinoma, especially in the US?
Increased incidence of obesity-related GERD and Barrett Esophagus
Which organism is associated w/ decreased risk of esophageal adenocarcinoma?
- Some serotypes of H. pylroi
- Cause gastric atrophy –> decreased acid secretion and reflux
Which ethnicity and sex is most commonly affected by esophageal adenocarcinoma?
Recent increased incidence in which populations?
- Caucasians
- Men 7x more likely
- Recent increased rates in: Hispanic men and White women
Progression from Barrett Esophagus to Adenocarcinoma occurs over a period of time in a stepwise acquisition of genetic changes, which are seen early on and later in this progression?
- Early: mutations of TP53 and downregulation of CDKN2A
- Later: amplification of EGFR, ERBB2, MET, cyclin D1 and cyclin E
Where in the esophagus does adenocarcinoma typically occur and where may it invade?
Major morphological characteristics?
- Distal 1/3 of esophagus and may invade adjacent gastric cardia
- Initially flat/raised patches —> large masses 5cm or >
- Tumor produces mucin and forms glands
How does a patient with an esophageal adenocarcinoma typically present (signs/symptoms)?
- Pain or difficulty swallowing
- Progressive weight loss
- Hematemesis
- Chest pain
- Vomiting
By the time a patient presents with symptoms of esophageal adenocarcinoma, what has the cancer likely done?
How does this affect prognosis?
- Spread to submucosal lymphatic vessels
- Overall 5-year survival is <25%
- If cancer is limited to the mucosa or submucosa the 5-year survival is closer to 80%
Which gender has the greatest risk for SCC of the esophagus and what is the typical age?
Which race of people are at the greatest risk?
- > 45 yo
- M:F = 4:1 w/
- African Americans 8x more affected!!!
What is the major risk factor and some of the other risk factors for the development of Squamous Cell Carcinoma of the esophagus?
- Alcohol and Tobacco use (major factor)
- Achalasia –> rotting food –> irritation
- Tylosis = thickening of palms and soles + white patches in mouth
- Plummer-Vinson syndrome –> rotting food on ledge of web
- Frequent consumption of hot beverages
- Hx of Radiation to Mediastinum
- HPV infection –> p16 + E6 + E7
There is a pocket of extremely high esophageal squamous cell carcinoma incidence in western Kenya, including patients <30 yo, due to what?
Consumption of traditional fermented milk, which contains the carcinogen acetaldehyde
Which genetic mutations play a role in the development of squamous cell carcinoma of the esophagus?
- Amplification of SOX2
- Over-expression of cyclin D1
- Loss-of-function mutations in TP53, E-cadherin, and NOTCH1
Which part of the esophagus do the majority of squamous cell carcinomas begin?
Middle 1/3 of the esophagus
How does esophageal SCC begin?
Early appearane?
Late appearance?
- Begins as in situ lesion (squamous dysplasia)
- Early: small grey-white plaque thickenings
- Late: exophytic tumor masses –> obstruct lumen
Which 3 structures surrounding the esophagus do SCC’s sometimes invade and what does this lead to in each?
1) Respiratory tree –> pneumonia
2) Aorta –> catastrophic exsanguination
3) Mediastinum/Pericardium
Differentiate the esophageal cancer on the top from that on the bottom; what are the distinguishing morphological features?
- Top: adenocarcinoma; often organized w/ glands
- Bottom: SCC of the esophagus; moderately to well-differentiated w/o presence of glands
HY: the presence of cancers in the upper, middle, and lower 1/3 of the esophagus will have different sites of metastasis, what are they?
- Upper 1/3: cervical LN’s
- Middle 1/3: mediastinal/paratracheal/tracheobronchial LN’s
- Lower 1/3: gastric and celiac nodes
What are the common signs and symptoms of someone presenting with SCC of the esophagus?
What is seen if the tumor ulcerates?
- Progressive dysphagia (solids –> liquids)
- Odynophagia (painful swallowing)
- Pt’s alter diet so have impaired nutrition and prominent wt. loss
- Tumor may ulcerate producing hemorrhage or sepsis w/ sx’s of iron deficiency anemia
What is the association of TE fistula and SCC of the esophagus?
Occasionally the 1st sx’s of SCC are caused by aspiration of food via a TE fistula
How has endoscopic screening impacted the prognosis of esophageal SCC?
What is the overall prognosis in the US?
- 5-year survival of 75% if caught early while still superficial
- Overall in the US 5-year survival remains <20%
Which type of esophagitis is strongly associated with food allergy, allergic rhinitis, and asthma?
Eosinophilic esophagitis
SCC of the esophagus has a very high incidence in which 5 geographic locations?
- Iran
- Central China
- Hong Kong
- Brazil
- South Africa
