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Pathology lec. 8 Gastrointestinal tract Esophagus We'll start talking about GIT , and first we'll start with the esophagus . Esophageal diseases are categorized into obstructive disease , including mechanical and functional obstruction , esophagitis which is a very common disorder , specially gastroesophageal reflux disease , and tumors of the esophagus , First we'll talk about obstructive and vascular diseases of the esophagus. Mechanical obstruction could be congenital or acquired disease. The congenital one is usually discovered shortly after birth because any obstruction of the esophagus will cause regurgitation of the food and fluid or milk and aspiration to the lung instead of going to the stomach. Causes of mechanical obstruction: -Absence or agenesis , a rare condition in which the esophagus is not present . -Atresia which is more common. you know that the esophagus is a hollow organ there is a lumen in the center . in atresia this lumen is lost and replaced by a fibrous segment leading to obstruction , so it's a thin noncanalized cord replaces a segment of the esophagus . most of the time it's associated with a fistula connecting the esophagus to the bronchus or the trachea. Complications of atresia : regurgitation of the food or drink to the air ways which could lead to pneumonia ( infection of the lung ) , suffocation , aspiration . Aspiration is when the material like food particles enter the lungs ( foreign body aspiration ) and initiates inflammatory reaction. Third cause of mechanical obstruction is stenosis , it's narrowing of the esophagus due to fibrosis of the submucosa. ( layers of the wall of the esophagus : mucosa , submucosa , muscularis , serosa ) When fibrosis happens in the wall of the esophagus , there will be narrowing which impedes the flow of food and fluid through it . this fibrosis is often due to inflammation and scarring , which may be caused by chronic GERD ( gastroesophageal reflux disease ) , which is when the gastric contents goes back to the lower esophagus , irradiation is another cause of inflammation , and caustic injury . caustics are chemical substances that causes burning like acids. Symptoms of stenosis : dysphagia ( difficulty in swallowing ) is the main symptom. it's progressive , it starts with difficulty swallowing solid food , with time it progresses to include liquids . Tumors can also cause mechanical obstruction . Functional obstruction: there is abnormality in the muscles or the innervation , there is no lesion . Normally when we swallow food peristaltic movement and gravity aid moving food to the stomach , gravity alone doesn't work , there should be peristaltic movement . When food gets to lower esophageal sphincter ( LES ) it should dilate to let the food get to the stomach then it should close. Any problem with the LES whether it dilates too much or it's contracted too much , will lead to abnormality. In functional obstruction there is increased tone of the LES which can result from impaired smooth muscle relaxation with consequent obstruction. The disorder of functional obstruction is achalasia , it's abnormality of the LES which is characterized by the triad of : incomplete LES relaxation , increased LES tone ( LES is contracted all the time ) , and esophageal aperistalsis ( with time due to the contracted sphincter , food will accumulate in the esophagus and it will dilate , so peristalsis movement will be lost ). The end result of this disorder is distention of the esophagus. Constant contact between food and the mucosa could be carcinogenic with time. Achalasia could be primary or secondary . Primary means idiopathic , no underlying cause , it's failure of the distal esophageal inhibitory neurons which normally inhibit the contraction. Secondary achalasia is due to infection or chagas disease , it's infection by trypanosome cruzi that causes destruction of the myenteric plexus between the muscle fibers in the wall of the esophagus , and failure of the LES relaxation , and esophageal dilatation. Achalasia is characterized by progressive dysphagia , nocturnal regurgitation ( at night ) , and aspiration of undigested food to the airways. The most serious problem is development of squamous cell carcinoma in about 5% of patients at an earlier age than in those without achalasia. Third disorder of the esophagus is ectopia. Ectopia means normal tissue in abnormal place. Normal lining of the esophagus is squamous . when there's gastric mucosa in the esophagus this is ectopic gastric mucosa . most frequently seen in the upper third of the esophagus. This gastric mucosa secretes acids , leading to irritation and inflammation and esophagitis , with time esophagitis could lead to barrett esophagus and adenocarcinoma. The main symptom in ectopia if it caused inflammation is dysphagia. Fourth disease is esophageal varices. Normally blood that goes out of the GIT goes to the liver through the portal vein to be filtered . circulation in the liver is called splanchnic circulation where veins of the GIT collect together then to the portal vein and the liver. Any impedance of the blood flow to the liver through the portal vein results in portal hypertension. Then blood won't be able to go to the liver, so it will go to the places where there's anastomosis(communication) between this splanchnic circulation and systemic venous circulation. The lower esophagus is one of the places where these circulations communicate. Diseases that impede blood flow to the liver , make portal hypertension and this induces development of collateral channels in the lower esophagus. When blood flows through collateral veins they will dilate ( just like varices of the lower limb) , in the mucosa and submucosa of the esophagus with a risk of rupture and bleeding. Varices develop in 90% of cirrhotic patients. Cirrhosis could be alcoholic or viral( hepatitis ) The second most common cause of varices is hepatic schistosomiasis , which is bilharzias when it involves the liver , it impedes blood flow to the liver and causes portal hypertension. Often these varices are asymptomatic except when they're distended very much , and discovered usually by endoscopy or angiography. Their rupture can lead to massive bleeding, hypovolemic shock and even death. Varices rupture is a medical emergency and despite intervention , as many as half of the patients die from the first bleeding episode. So as a result , greater then half the deaths associated with liver cirrhosis is because of varices rupture. - Esophagitis ( inflammation of the esophagus ) The first cause of esophagitis is lacerations, the most common laceration is called Mallory weiss tears. These tears are often associated with sever vomiting and may occur with acute alcohol intoxication. This tear happens because of the sudden opening of the sphincter during vomiting and the passage of food which lacerates the esophagus. These lacerations are usually at the gastroesophageal junction , at the place of the sphincter. They're superficial and usually don't go deep to the muscles and don't penetrate the esophagus. They heal spontaneously without intervention. The most common symptom is hematemesis , which is vomiting of blood. The second one is chemical esophagitis , caused by alcohol , corrosive acids or alkalis , hot fluids and heavy smoking. Medical pills may lodge and dissolve in the esophagus , if it was swallowed without water , rather than passing into the stomach , this is called pill induced esophagitis. Symptoms: self limited pain , particularly odynophagia ( pain when swallowing). Complications : hemorrhage , with time healing with fibrosis could lead to stenosis or stricture . if there's very severe inflammation it could lead to perforation. Sometimes chemical esophagitis could be iatrogenic because of chemotherapy or radiation therapy (complication of treatment ). Infectious esophagitis is not very common , it could be viral or fungal. Among viruses, herpes simplex virus and cytomegalovirus (CMV) are the common. Among fungi, Candida is the most common pathogen, although mucormycosis and aspergillosis may also cause it. Infectious esophagitis occurs usually in those who are immunosuppressed or debilitated. Morphology in candidiasis: there's a whitish membrane that is adherent to the esophagus composed of inflammatory cells and debris and densely matted fungal hyphae. Herpes virus usually infects epithelial cells , it makes multi nucleation , abnormality in the chromatin, and nuclear inclusions and ulcers . CMV makes cells larger , causes shallower ulcerations and characteristic nuclear and cytoplasmic inclusions within capillary endothelium and stromal cells. - The fourth type of esophagitis is reflux esophagitis , it's very common , it's caused by the reflux of the gastric contents which are acidic into the lower esophagus through the partially relaxed sphincter. The clinical condition is called gastroesophageal reflux disease ( GERD) Conditions that decrease LES tone or increase abdominal pressure contribute to GERD. These conditions include alcohol and tobacco use ( decrease LES tone ), obesity and pregnancy ( increase abdominal pressure ), CNS depressants which make muscle relaxation, hiatal hernia is another cause. In many cases , no definitive cause is identified. This disease is more common in adults , but it can occur in infants and children. Main symptoms are heartburn and dysphagia. Less often, noticeable regurgitation of sour-tasting gastric contents. Rarely in chronic GERD could be attacks of severe chest pain that may be mistaken for heart disease. Complications include ulceration , hematemesis, melena ( blackish stool due to upper GIT bleeding ) , stricture , barrett esophagus. Treatment is by proton pump inhibitors that reduce gastric acidity and provide symptomatic relief. Hiatal hernia is one of the causes of GERD. It's separation of the diaphragmatic crura and protrusion of the stomach into the thorax through the resulting gap. The pressure in the thorax is less than in the abdomen, so there will be symptoms of GERD, but it's asymptomatic in 90 % of adult cases. ( the crura of the diaphragm are tendinous structures extend inferiorly from the diaphragm to attach to the vertebral column ). Barrett esophagus is a complication of GERD, it's gastric or intestinal metaplasia(columnar epithelium , more resistant to acids ), within the esophageal squamous mucosa. It occurs in 10 % of people with symptomatic GERD, it increases the risk of esophageal adenocarcinoma. Metaplasia could lead to dysplasia which could be low grade or high grade on the basis of its morphology. It's a preinvasive condition, develops in 0.2 % to 1% of persons with barrett esophagus each year. ( the squamous mucosa of the esophagus is normally pinkish, the mucosa of the stomach is reddish ) -Esophageal tumors are mainly two. Squamous cell carcinoma is more common, but in the US and western countries adenocarcinoma is on the rise. -Adenocarcinoma typically arises in a background of barrett esophagus and long standing GERD. It usually occurs in the distal third of the esophagus and may invade the gastric cardia(below the sphincter ). Other causes of adenocarcinoma: tobacco use, obesity, radiation therapy. Male to female ratio7:1 The main mutation that happens here is TP53 mutation (TP53 is a tumor suppressor gene). Clinical features: pain or difficulty swallowing, weight loss, chest pain, vomiting. By the time symptoms appear, the tumor usually has spread to the submucosal lymphatic vessels. In cases that are just limited to mucosa and submucosa there's 80% chance of 5 years of survival , which is not always the case. -Squamous cell carcinoma affects adults older than 45 years of age , and affects males 4 times higher than females. Risk factors include: alcohol, tobacco use, poverty, caustic injury, achalasia, consumption of hot beverages, radiation, nitrosamines that are usually in the soil, mutagenic compounds such as those found in fungus contaminated food , polycyclic hydrocarbons. Half of it occur in the middle third of the esophagus. It begins as dysplasia( carcinoma in situ) then squamous cell carcinoma. The rich submucosal lymphatic network promotes circumferential( could cause mechanical obstruction) and longitudinal spread. Intramural tumor nodules may be present several cms away from the principal mass. Clinical features: dysphagia, odynophagia , obstruction , weight loss, hemorrhage, sepsis, lymph node metastases. The 5 year survival chance is 75% if it's still in situ or is just in the mucosa. The stage of the disease is the most important determinant of prognosis.