Gastrointestinal Pathology

1. Gastrointestinal Pathology Things sweet to taste prove in digestion sour William Shakespeare

2. Esophagus • The esophagus is a relatively straight muscular tube that passes food from the pharynx to the stomach • It lies behind the trachea and it passes through the muscular diaphragm before it reaches the stomach • Common clinical features: dysphagia –difficulty swallowing heartburn- presents as a burning or painful sensation and retrosternal pain odynophagia- painful swallowing hematemesis- vomiting of blood

3. Esophagus Both ends of the esophagus are closed off by sphincters at the lower and upper end, known as the lower esophageal sphincter and upper esophageal sphincter respectively

4. Anatomic Disorders of Esophagus • Stenosis- (of the esophagus) it presents as lower esophageal narrowing due to chronic inflammation i.e. gastroesophageal reflux disease. There is progressive dysphagia to solids and liquids • Esophageal atresia- it is a congenital defect, in which there is obliteration of the esophageal tube . It may be associated with tracheoesophageal fistula. It typically presents in a neonate with regurgitation and chemical pneumonia

5. Tracheoesophageal fistula A. This is the most common type of tracheoesophageal fistula. B and C are less common types

6. Anatomic Disorders of the Esophagus • Esophageal webs- web-like protrusions of esophageal mucosa into lumen. - It is associated with Plummer Vinson sydrome , which includes: iron deficiency anemia, esophageal webs - This causes dysphagia to solids • Esophageal rings are plates of tissue that extend into and occlude part of the lumen, either at or above the gastroesophageal junction. This causes dysphagia to solids • Esophageal diverticula- these are outpouchings of the GI wall. This causes food to regurgitate occasionally and it leads to bad breath, neck mass, and dysphagia

7. Achalasia • Neuromuscular disorder • Failure of the LES to relax with swallowing, due to the absence of the myenteric plexus. • This results in increased pressure, along with dilation of the proximal esophagus May be primary or secondary. • It may be caused by loss of innervation of the LES or by Chagas disease (trypanosomacruzi), which destroys the myenteric plexus of the esophagus, etc • Note: DM or polio may be other causes of acquired achalasia

8. Achalasia con't • Stasis of food may lead to the presence of infections and ulcers. • Long term exposure increases risk of squamous carcinoma • Clinical findings include: progressive dysphagia and regurgitation of food • Diagnosis: barium swallow manometry

9. Barium swallow The esophagus appears dilated, and contrast material passes slowly into the stomach as the LES opens intermittently. The distal esophagus is narrowed and has been described as resembling a bird's beak

10. Hiatal hernia • This is like a sac like protrusion of the stomach above the diaphragm, due to the widening of the diaphragmatic crura • There are two types: sliding hernia and paraesophageal hernia 1. sliding hernia- bell shaped dilation; shortened esophagus C/F include: heartburn and acid reflux; ulceration, hematemesis, and perforation are complications 2. paraesophageal hernia- cardia or part of the greater cuvature extend into the thorax Complications include: strangulation and infarction; acid reflux is uncommon

11. Types of Hernias

12. Mallory Weiss Syndrome • These are lacerations of the esophagus at the gastroesophageal junction, which occur after a bout of severe vomiting • The incomplete relaxation of the LES, during the episode of vomiting, exerts a great force at the gastroesophageal junction – leads to tears • The most common cause: alcoholism • C/F include: hematemesis- usually remits, with minimal complication • Complication includes: Boerhaave syndrome – esophageal ruptures

13. Mallory Weiss Syndrome

14. Esophageal Varices • The portal vein carries blood from the small and large bowel, the spleen, and the stomach to the liver. • Obstruction of portal venous flow usually results in a rise in portal venous pressure (portal hypertension), which leads to the development of collaterals. Thus, the obstructed blood diverts to systemic veins • Blood flows through stomach veins  esophageal submucosal veins  azygos veins  SVC • Varices are dilated, tortuous veins, due to increased pressure in the esophageal veins

15. Esophageal Varices • Common in cirrhotic patients, which is usually due to chronic alcohol abuse • Rupture of these tortuous veins leads to hematemesis or massive upper gastrointestinal bleeding. There is a high chance of rebleed and increased risk of mortality with each episode. • Other causes of massive bleed include: gastritis, peptic ulcer disease, etc • Diagnosis: endoscopy • Treatment: sclerotherapy/ endoscopic ligation

16. Esophageal varices-endoscopy This is an endoscopic view of esophageal varices, which appear as tortuous, dilated, blue veins running along the long axis of the esophagus

17. Esophagitis • The most common cause of esophagitis is gastroesophageal reflex disease (GERD). • Other important, but less common, causes are : • infections, medications, radiation therapy, systemic disease, and trauma,chemicals. • Infectious esophagitis - usually seen in HIV patients - causative agents include: HSV, Candida, and CMV - the patient presents with odynophagia

18. Esophagitis • Chemical esophagitis - Prolonged gastric intubation -Ingestion of irritants i.e. lye and HCl -Uremia -Chemo- or radio-therapy Complications of chemical esophagitis -Stricture formation -Perforation -Squamous cell carcinoma

19. Esophagitis GERD- Caused by enhanced relaxation of LES with regurgitation of gastric secretions →inflammation of distal esophagus. Predisposing factors for GERD include: - Sliding hiatal hernias - Pregnancy - Peptic ulcer disease - Factors lowering LES tone- ß-adrenergics, alcohol, smoking, caffeine, fatty foods

20. GERD Clinical findings: - heartburn and “sour brash” +/- - chest pain mimics MI - nocturnal asthma Complications include: -stricture formation -Barrett’s esophagus -hematemesis

21. Barrett esophagus • It is the change in the esophageal mucosa from metaplasia of the normal squamous epithelium to the columnar type. This is a protective mechanism, due to chronic exposure to gastric acid • Barrett esophagus is well recognized as a complication of gastroesophageal reflux disease (GERD) • Pathogenesis: chronic exposure to gastric secretions leads to inflammation and ulceration of the normal squamous epithelium  differentiation into metastatic columnar epithelium (with goblet cells)

22. Barrett Esophagus • Clinical findings: dysphagia, history of acid reflux • Complications include: stricture and ulcer formation dysplasia and risk of esophageal adenocarcinoma • Diagnosis: endoscopy + biopsy of tissue. Note: there is a high risk of high grade dysplasia

23. Barrett Esophagus – M/E The normal squamous epithelium has been replaced by glandular or columnar epithelium

24. Barrett Esophagus- Endoscopic view Note the reddish columnar mucosa lining the distal esophagus. Erythema and erosions caused by GERD can be seen in the adjacent squamous epithelium.

25. Barrett Esophagus- gross This gross specimen appears reddish and velvety closer to the stomach. Note: this is high grade dysplasia of Barrett esophagus

26. Esophageal Carcinoma • Over the past several decades, there has been an increasing trend of adenocarcinoma of the esophagus in the U.S. compared to the incidence of Squamous cell carcinoma. • Squamous cell carcinoma is the common type of esophageal cancer worldwide • Adenocarcinoma is due to the high association of Barrett esophagus.

27. Esophageal Carcinoma • Clinical findings: progressive dysphagia weight loss bleeding • Diagnosis: endoscopy + biopsy • Treatment: surgery is curative, if it is confined to the mucosa or submucosa

28. Squamous Cell Carcinoma of Esophagus • It predominantly affects males more than females • It affects African Americans more than Caucasians Chronic esophageal irritation is the cause. Commoner in the middle third of the esophagus. • Risk factors include: Chronic Esophagitis Plummer-Vinson syndrome heavy alcohol use and smoking nitrosamines /nitrites achalasia • There may be association with p53,INK4, and p16 mutations

29. Squamous Cell Carcinoma of Esophagus • Grossly, there may be gray white plaques, initially; it may progress to a polypoid mass, ulcerative lesion, or infiltrating neoplasm • Prognosis is poor

30. Squamous Cell Carcinoma of Esophagus SCC- M/E Normal squamous epithelium SCC- Keratin pearls

31. SCC esophagus-gross squamous cell carcinoma of the esophagus in The oval structure adjacent to the esophagus is a metastatic lymph node.

32. Adenocarcinoma of the Esophagus • Associated with Barrett esophagus. • Distal 1/3rd of the esophagus • The succession of events from Barrett esophagus to adenocarcinoma of esophagus are: gastroesophagealrefluxmetaplasia low grade dysplasia high grade dysplasia  adenocarcinoma • These are mucin producing tumors. • Grossly, they may appear as ulcerative or infiltrative lesions • Note: mutations in p53, HER-2/NEU, and beta catenin may be present.

33. Anatomy of Stomach

34. Stomach • Congenital Gastric Anomalies Pyloric stenosis Diaphragmatic hernia Gastric heteropia- uncommon Pyloric stenosis - it is hypertrophy of the muscles in the pyloric sphincter; it is the most common cause of intestinal obstruction in infancy. - clinical findings: persistent, projectile, and non-bilous vomiting 2 weeks after birth, peristaltic waves seen on abdomen , and visible oval shaped mass- “olive” shaped

35. Stomach • Diaphragmatic hernia - It is normally a congenital defect of the newborn. - It is the diaphragm’s inability to close, which leads to the herniation of stomach and abdominal contents to enter the thorax, Note: the stomach is the most common organ involved - This leads to acute respiratory distress of the newborn and pulmonary hypoplasia

36. Acute Gastritis Inflammation of the gastric mucosa, in which sloughing of the mucosal epithelium leads to GI bleeding • Erosions do not extend beyond muscularis mucosa • Risk factors include: NSAIDS – aspirin Smoking and alcohol consumption Chemotherapy Uremia Trauma Surgery Ischemia

37. Acute Gastritis • Pathogenesis: - The common mechanism of injury is an imbalance between the aggressive and the defensive factors that maintain the integrity of the gastric lining (mucosa). • Factors involved in the pathogenesis include: increased H⁺/ decreased HCO3⁻/ decreased blood flow/ epithelial damage/ mucosal barrier breakdown etc. • Grossly , it may appear as erosions and hemorrhage; microscopically, there is an infiltrate composed of neutrophils and mucosal edema

38. Acute Gastritis • Clinical findings include: epigastric pain nausea and vomiting melena hematemesis- particularly in alcoholics/ long term usage of NSAIDS

39. Chronic Gastritis • It is the chronic inflammation of the gastric mucosa • Two main types of chronic gastritis: 1) Helicobacter pylori gastritis (antraltype and may progress to pangastritis) 2) Autoimmune gastritis (fundus) Clinical findings include: abdominal discomfort nausea and vomiting

40. Chronic Gastritis Helicobacter pylori gastritis -The corkscrew-shaped bacterium called H pylori is the most common cause of gastritis - These are urease producing gram-negative rods that have the ability to colonize and infect the stomach. -The bacteria survive within the mucous layer that covers the gastric surface epithelium and antrum -They may be predispose the individual to the development of duodenal ulcer (antral type)/ gastric peptic ulcers and adenocarcinoma (multifocal mucosal atrophy)

41. Chronic Gastritis Helicobacter pylori - On M/E: H. pylori is seen in the mucosal layer of the surface epithelium; acute inflammatory cells (neutrophils) and chronic inflammation (lymphocytic and plasma cell infiltrate) - Gastric lymphoma may occur due to chronic growth of lymphoid tissue - There is an increased risk of intestinal metaplasia and gastric carcinoma -Most patients remain asymptomatic

42. Chronic Gastritis Helicobacter pylori -Diagnosis: urea breath test serology (Ag or Ab detection) endoscopic biopsy + tissue sampling -Treatment with antibiotics and proton pump inhibitors are given to symptomatic patients -Recurrence is common even after treatment

43. Chronic Gastritis Autoimmune gastritis 10% of chronic gastritis -This type of gastritis is associated with serum antiparietal and anti-intrinsic factor (IF) antibodies. -The injury leads to mucosal atrophy and gland destruction; loss of parietal cells; decreased acid production ( affects acid producing enzymeH⁺ K⁺ ATPase) -Lack of intrinsic factor leads to pernicious anemia and megaloblastic anemia ( due to vitamin B12 malabsorption)

44. Chronic Gastritis Autoimmune gastritis - M/E reveals mucosal atrophy and loss of parietal cells ; lymphocytic infiltration -There is an increased risk of intestinal metaplasia and gastric carcinoma -Hypochlorhydria and/or achlorhydria may be present; increased gastrin levels

45. Chronic gastritis- M/E Chronic gastritis with chronic inflammatory cell infiltration and lymphoidfollicle formation (arrowhead) in the gastric mucosa. Atrophy of the gastric glands is seen(arrow)

46. Chronic gastritis- intestinal metaplasia-M/E Intestinal metaplasia in chronic gastritis (arrow). Note goblet cells and lymphcyteand plasma cell infiltration (arrowhead)

47. H.Pylori Gastritis

48. Menetrier's disease • Hypertrophic gastropathy characterized by markedly enlarged convoluted rugae and hypo or achlorhydria, which may be due to the atrophy of parietal cells • Microscopically, there is striking foveolar hyperplasia • Grossly, there is marked hypertrophic rugae • There is an increased risk of gastric carcinoma

49. Menetrier’s disease- M/E There is marked hyperplasia of the crypts accompanied by mild atrophy of the underlying secretory mucosa.

50. Zollinger-Ellison Syndrome (ZES) • Caused by a gastrin-secreting tumor of the pancreas that stimulates the acid-secreting cells of the stomach, with consequent gastrointestinal mucosal ulceration. • The majority of the ulcers are caused by non beta islet cells of the pancreas • The symptoms of ZES are secondary to hypergastrinemia, which causes hypertrophy of the gastric mucosa, leading to increased numbers of parietal cells • Clinical findings include: epigastric pain, diarrhea, heartburn