2-Esophageal disorders.pdf

2-Esophageal disorders Subject Pathology Anki First Study Second Study Revision Second Revision Week Week 1 Congenital conditions of the esophagus...

2-Esophageal disorders Subject Pathology Anki First Study Second Study Revision Second Revision Week Week 1 Congenital conditions of the esophagus Esophageal atresia Absence, or agenesis, of the esophagus is extremely rare Atresia is more common than agenesis Here the development is incomplete In esophageal atresia a thin, noncanalized cord replaces a segment of esophagus, causing a mechanical obstruction Esophageal fistula Fistula is generally a communication between 2 epithelialized hollow spaces Tracheoesopphageal fistulas can lead to aspiration, suffocation, and pneumonia. Ectopic tissues (developmental rests) are common in the GI tract. The most frequent site of ectopic gastric mucosa is the upper third of the esophagus, where it is referred to as an inlet patch. While generally asymptomatic, acid released by gastric mucosa within the esophagus can result in dysphagia Acquired conditions of the esophagus Acquired diseases of the esophagus ranges from highly lethal cancers to the persistent “heartburn” of gastroesophageal reflux that may be chronic and incapacitating or merely an occasional annoyance. Esophageal Obstruction (functional and mechanical) The esophagus is, essentially, a tube that delivers ingested solid food and fluids to the stomach. This can be impeded by structural, i.e. (mechanical) obstruction or functional obstruction. Types: 1-Functional obstruction 2-Esophageal disorders 1  Functional obstruction results from disruption of the coordinated waves of peristaltic contractions that follow swallowing. Causes : Nutcracker esophagus Diffuse esophageal spasm Hypertensive lower esophageal sphincter. 2-Mechanical obstruction Mechanical obstruction can be caused by stenosis, webs, rings, strictures or cancer It presents as progressive dysphagia that begins with inability to swallow solids. With progression ingestion of liquids is also affected. What is Paterson-Brown-Kelly or Plummer-Vinson syndrome.? Please go and read about it Achalasia Achalasia is a condition characterized by the triad of incomplete LES relaxation, increased LES tone, and aperistalsis of the esophagus. Increased tone of the lower esophageal sphincter (LES) occurs as a result of impaired smooth muscle relaxation This leads to dysphagia for BOTH solids and liquids from the start Types: 1-Primary achalasia Primary achalasia is the result of distal esophageal inhibitory neuronal, that is, ganglion cell, degeneration. This leads to increased tone, an inability to relax of the lower esophageal sphincter, and esophageal aperistalsis. The cause is unknown 2-Secondary achalasia Secondary achalasia may arise in Chagas disease, in which Trypanosoma cruzi infection causes destruction of the myenteric plexus, failure of peristalsis, and esophageal dilatation. Lacerations Normally, a reflex relaxation of the gastroesophageal musculature precedes the antiperistaltic contractile wave associated with vomiting. This relaxation fails during prolonged vomiting, with the result that refluxing gastric contents overwhelm the gastric inlet and cause the esophageal wall to stretch and tear. What is Mallory Weiss tear? What is Boerhaave syndrome? Please go and read about them Esophagitis 1-Chemical and Infectious Esophagitis The stratified squamous mucosa of the esophagus may be damaged by a variety of irritants including alcohol, corrosive acids or alkalis, excessively hot fluids, and heavy smoking. Symptoms range from self-limited pain, particularly on swallowing, that is, odynophagia, to hemorrhage, stricture, or perforation in severe cases. Causes of chemical esophagitis : Accidental ingestion of household cleaning products in children Suicide attempts in adults. Pill-induced esophagitis frequently at the site of strictures. Iatrogenic by cytotoxic chemotherapy, radiation therapy, or graft-versus- host disease. Esophageal infections 2-Esophageal disorders 2  Esophageal infections in healthy individuals are uncommon and most often due to herpes simplex virus. Infections in patients who are debilitated or immunosuppressed, is more common and can be caused by herpes simplex virus, cytomegalovirus (CMV), or fungal organisms. Among fungi, candidiasis is most common, although mucormycosis and aspergillosis are also seen. Candidiasis, appears as, gray-white pseudomembranes Under the microscope fungal hyphae are seen Herpes viruses typically cause punched-out ulcers Under the microscope, nuclear viral inclusions are seen Herpes viruses typically cause punched-out ulcers Biopsy specimens demonstrate nuclear viral inclusions CMV causes shallow ulcerations Under the microscope, CMV causes characteristic nuclear and cytoplasmic inclusions 2-Reflux Esophagitis Normally, the stratified squamous epithelium of the esophagus is resistant to abrasion from foods but is sensitive to acid. Submucosal glands, which are most abundant in the proximal and distal esophagus, contribute to mucosal protection by secreting mucin and bicarbonate. More importantly, the tone of the lower esophageal sphincter prevents reflux of acidic gastric contents, which are under positive pressure and would otherwise enter the esophagus. Reflux of gastric contents into the lower esophagus is the most frequent cause of esophagitis and the most common outpatient GI The associated clinical condition is termed gastroesophageal reflux disease (GERD). Aetiology: The most common cause of gastroesophageal reflux is transient lower esophageal sphincter relaxation +/_ increase abdominal pressure. This is thought to be mediated via vagal pathways, and can be triggered by: Gastric distention, by gas or food Stress. Forceful opening of a relatively hypotensive lower esophageal sphincter by an abrupt increase in intraabdominal pressure, such as that due to coughing, straining, or bending. Other contributory factors are: Alcohol Tobacco use Obesity Pregnancy Hiatal hernia In many cases, no definitive cause is identified. Pathogenesis: Aetiologic agents cause transient lower esophageal sphincter relaxation +/_ increase abdominal pressure. Reflux of gastric juices is central to the development of mucosal injury in GERD. Morphology : Simple hyperemia/ redness 2-Esophageal disorders 3  Clinical features: GERD is most common in individuals older than age 40 The most frequent clinical symptoms are heartburn, dysphagia, and regurgitation of sour-tasting gastric contents. Treatment & Course Proton pump inhibitors (PPIs) that reduce gastric acidity typically provides symptomatic relief. Complications of reflux esophagitis include ulceration, hematemesis, melena, stricture development, and Barrett esophagus. 3-Eosinophilic Esophagitis This is clinicopathologic entity that is characterized clinically by symptoms related to esophageal dysfunction and histologically by an eosinophil-rich inflammation that is limited to the esophagus. The incidence of eosinophilic esophagitis is increasing markedly. The majority of individuals with eosinophilic esophagitis are atopic and many have atopic dermatitis, allergic rhinitis, asthma, or modest peripheral eosinophilia. Symptoms include food impaction and dysphagia in adults and feeding intolerance or GERD-like symptoms in children. Morphology: The cardinal histologic feature is large numbers of intraepithelial eosinophils. Barrett Esophagus Barrett esophagus is a complication of chronic GERD that is characterized by intestinal metaplasia within the esophageal squamous mucosa. The incidence of Barrett esophagus is rising, and it is estimated to occur in as many as 10% of individuals with symptomatic GERD. Barrett esophagus is most common in white males and typically presents between 40 and 60 years of age. The greatest concern in Barrett esophagus is that it confers an increased risk of esophageal adenocarcinoma. The vast majority of esophageal adenocarcinomas are associated with Barrett esophagus Minority of Barret's esophagus progresses to esophageal adenocarcinoma Morphology: Grossly, tongues or patches of red, velvety mucosa extending upward from the gastroesophageal junction. Microscopically, intestinal-type metaplasia with goblet cells is seen replacing the squamous esophageal epithelium Dysplasia can be seen Metaplasia in Barret's esophagus Clinical features: Barrett esophagus can only be identified thorough endoscopy and biopsy, which are usually prompted by GERD symptoms. Treatment: Once diagnosed periodic endoscopy with biopsy, for dysplasia surveillance is recommended, then manage accordingly. Disease progression : Esophageal Tumors: Benign tumors of the esophagus are generally mesenchymal, and arise within the esophageal wall, with leiomyomas being most common. The vast majority of esophageal cancers fall into one of two types; adenocarcinoma and squamous cell carcinoma. 2-Esophageal disorders 4  Squamous cell carcinoma is more common worldwide, but adenocarcinoma is on the rise. 1-Adenocarcinoma Most esophageal adenocarcinomas arise from Barrett esophagus. Additional risk factors include tobacco use and exposure to radiation. Conversely, risk is reduced by diets rich in fresh fruits and vegetables and some serotypes of Helicobacter pylori The incidence varies widely worldwide, Esophageal adenocarcinoma occurs most frequently in Caucasians and shows a strong gender bias, being sevenfold more common in men. Pathogenesis: Molecular studies suggest that the progression of Barrett esophagus to adenocarcinoma occurs over an extended period through the stepwise acquisition of genetic and epigenetic changes. Chromosomal abnormalities, mutation of TP53 are detected at early stages. Later during progression there is amplification of protoncogens loke EGFR Morphology: Esophageal adenocarcinoma usually occurs in the distal third of the esophagus and may invade the adjacent gastric cardia The can form masses (exophytic) or can be flat or ulcerative (endophytic) Microscopically, Barrett esophagus is frequently present adjacent to the tumor. Invasive glands showing cytological features of malignancy. What are the cytological features of malignancy? Clinical features: Pain on swallowing (odynophagia) Difficulty in swallowing (dysphagia to solid then to liquid and solid), progressive weight loss Hematemesis or vomiting. Course and prognosis: By the time symptoms appear, the tumor has usually spread to submucosal lymphatic vessels. As a result of the advanced stage at diagnosis, overall 5-year survival is less than 25%. 2-Squamous Cell Carcinoma Esophageal squamous cell carcinoma occurs in adults older than age 45 and affects males four times more frequently than females. Esophageal squamous cell carcinoma is nearly eight-fold more common in African Americans than Caucasians Risk factors and aetiology: These include alcohol and tobacco use, Plummer-Vinson syndrome, diets that are deficient in fruits or vegetables, frequent consumption of very hot beverages and previous radiation to the mediastinum Pathogenesis: The molecular pathogenesis of esophageal squamous cell carcinoma remains incompletely defined, but recurrent abnormalities include”: Amplification of the transcription factor gene SOX2 Overexpression of the cell cycle regulator cyclin D1 Loss-of-function mutations in the tumor suppressors TP53 Squamous cell carcinoma begins as an in situ lesion termed squamous dysplasia Over months to years they grow as exophytic masses or endocytic ulcerative lesions or as wall thickening causing rigidity and luminal narrowing. The tumor may invade surrounding structures with fistulae formation including the respiratory tree, causing pneumonia; the aorta, causing catastrophic exsanguination; or the mediastinum and pericardium. The rich lymphatic network promotes tumor spread 2-Esophageal disorders 5  Impaired nutrition and effects of the tumor can cause weight loss and debilitation Hemorrhage may accompany tumor ulceration with subsequent iron deficiency Sepsis may accompany tumor ulceration Morphology : Half of squamous cell carcinomas occur in the middle third of the esophagus Grossly, they appear as exophytic mass, or ulcerative lesion (endophytic), or wall thickening/ rigidity with lumen narrowing Microscopically: invasive sheets and nests of malignant squamous cells Clinical features: Symptomatic tumors are generally very large at diagnosis and have already invaded the esophageal wall. The onset of esophageal squamous cell carcinoma is insidious and it most commonly presents with dysphagia (firstly to solid food, later to solid and liquid foods), odynophagia (pain on swallowing), or obstruction. Others: Prominent weight loss and debilitation Hematemesis Symptoms of iron deficiency anemia Sepsis Prognosis: The overall 5-year survival rate varies by tumor stage and patient age, race, and gender. 5-year survival rates are 75% in individuals with superficial esophageal squamous cell carcinoma but much lower in patients with more advanced tumors. Lymph node metastases, which are common, are associated with poor prognosis. Hematemesis Hematemesis is vomiting of blood It has many aetiologies including varices, ulcer, Mallory Weiss tear and cancers with esophageal-aortic fistula Esophageal Varices Normally, venous blood from the GI tract passes through the liver, via the portal vein, before returning to the heart. Diseases that impede this flow cause portal hypertension and can lead to the development of esophageal varices, which are important cause of esophageal bleeding. Diseases that impede this flow include liver cirrhosis and hepatic schistosomiasis Pathogenesis: Portal hypertension results in the development of collateral channels at sites where the portal and caval systems communicate. These collateral veins allow some drainage to occur, but at the same time they lead to development of congested subepithelial and submucosal venous plexi within the distal esophagus and proximal stomach. These vessels are termed varices And Variceal rupture results in hemorrhage into the lumen or the esophageal wall Morphology: Varices are tortuous dilated veins lying primarily within the submucosa of the distal esophagus and proximal stomach Clinical features: Asymptomatic Bleeding (hematemesis) Prognosis: 2-Esophageal disorders 6  Despite these interventions, 30% or more of patients with variceal hemorrhage die as a direct consequence of hemorrhage such as hypovolemic shock, hepatic coma, or other complications. Hiatal hernia A hiatal hernia occurs when a portion of the stomach prolapses through the diaphragmatic esophageal hiatus It is characterized by separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the resulting gap. Congenital hiatal hernias are recognized in infants and children, but many are acquired in later life. Clinical features: Asymptomatic Symptomatic: heartburn and regurgitation of gastric juices (similar to GERD.) 2-Esophageal disorders 7