1 Gastrointestinal systemManar hajeer, MD University of Jordan Faculty of medicine, pathology department.

2 Diseases of the esophagus

3 OBSTRUCTIVE AND VASCULAR DISEASES1.Mechanical Obstruction Most are discovered shortly after birth, usually because of regurgitation during feeding, and must be corrected promptly. 1.Absence, or agenesis, of the esophagus is extremely rare. 2.Atresia, in which a thin, noncanalized cord replaces a segment of esophagus, is more common. Occurs most commonly at or near the tracheal bifurcation Usually associated with a fistula connecting the upper or lower esophagus to a bronchus or the trachea. Complications: aspiration, suffocation, pneumonia.

4 3.Stenosis: narrowing due to fibrosis of the esophageal submucosa , most often is due to inflammation and scarring, which may be caused by chronic gastroesophageal reflux, irradiation, or caustic injury. Symptoms: dysphagia that is progressive; difficulty eating solids typically occurs long before problems with liquids.

5 2.Functional ObstructionIncreased lower esophageal sphincter (LES) tone can result from impaired smooth muscle relaxation with consequent functional esophageal obstruction. Achalasia is characterized by the triad of 1.Incomplete LES relaxation. 2.Increased LES tone. 3.Esophageal aperistalsis. Primary achalasia is caused by failure of distal esophageal inhibitory neurons and is, by definition, idiopathic. Secondary achalasia may arise in Chagas disease, in which Trypanosoma cruzi infection causes destruction of the myenteric plexus, failure of LES relaxation, and esophageal dilatation.

6 Achalasia is characterized clinically by progressive dysphagiaAchalasia is characterized clinically by progressive dysphagia. Nocturnal regurgitation and aspiration of undigested food may occur. The most serious aspect of this condition is the hazard of developing esophageal squamous cell carcinoma, reported to occur in about 5% of patients and typically at an earlier age than in those without achalasia.

7 3.Esophageal Varices Splanchnic and systemic venous circulations can communicate in the esophagus. Diseases that impede blood flow to the liver via the portal vein cause portal hypertension. Portal hypertension induces development of collateral channels that allow portal blood to shunt into the caval system. These collateral veins enlarge the subepithelial and submucosal venous plexi within the distal esophagus, and are called varices. Varices develop in 90% of cirrhotic patients, most commonly in association with alcoholic liver disease. Worldwide, hepatic schistosomiasis is the second most common cause of varices.

8 Clinical Features Often are asymptomatic.Their rupture can lead to massive hematemesis and death.

9 ESOPHAGITIS 1.lacerations:The most common esophageal lacerations are Mallory- Weiss tears, which are often associated with severe retching or vomiting, as may occur with acute alcohol intoxication. Patients often present with hematemesis. linear lacerations cross the gastroesophageal junction. These tears are superficial and do not generally require surgical intervention. Healing tends to be rapid and complete.

10 2.Chemical Esophagitis Caused by alcohol, corrosive acids or alkalis, excessively hot fluids, cytotoxic chemotherapy and radiation therapy, and heavy smoking. Medicinal pills may lodge and dissolve in the esophagus, rather than passing into the stomach intact, pill-induced esophagitis. Symptoms: self-limited pain, particularly odynophagia (pain with swallowing). Complications: Hemorrhage, stricture, or perforation.

11 3.Infectious esophagitisMost frequent in those who are debilitated or immunosuppressed. Herpes simplex viruses, cytomegalovirus (CMV), or fungal organisms is common. Among fungi, Candida is the most common pathogen, although mucormycosis and aspergillosis may also occur.

12 Morphology: Candidiasis, adherent, graywhite pseudomembranes composed of densely matted fungal hyphae and inflammatory cells covering the esophageal mucosa. Herpesviruses typically cause punched-out ulcers and histopathologic analysis demonstrates nuclear viral inclusions within a rim of degenerating epithelial cells at the ulcer edge. CMV causes shallower ulcerations and characteristic nuclear and cytoplasmic inclusions within capillary endothelium and stromal cells

14 3.Reflux Esophagitis Reflux of gastric contents into the lower esophagus is the most frequent cause of esophagitis. The associated clinical condition is termed gastroesophageal reflux disease (GERD). Conditions that decrease LES tone or increase abdominal pressure contribute to GERD and include alcohol and tobacco use, obesity, central nervous system depressants, pregnancy, hiatal hernia. In many cases, no definitive cause is identified.

15 Clinical Features Most common in adults older than 40 years of age but also occurs in infants and children. Heartburn, dysphagia are the predominent symptoms. Less often, noticeable regurgitation of sour-tasting gastric contents. Rarely, chronic GERD is punctuated by attacks of severe chest pain that may be mistaken for heart disease. Complications : esophageal ulceration, hematemesis, melena, stricture development, and Barrett esophagus

16 Treatment with proton pump inhibitors reduces gastric acidity and typically provides symptomatic relief.

17 Barrett Esophagus A complication of chronic GERD that is characterized by gastric or intestinal metaplasia within the esophageal squamous mucosa. Estimated to occur in as many as 10% of persons with symptomatic GERD. The greatest concern in Barrett esophagus is that it confers an increased risk of esophageal adenocarcinoma.

19 Diseases of the stomach

20 INFLAMMATORY DISEASE OF THE STOMACH1.Acute Gastritis: Transient mucosal inflammatory process. May be asymptomatic or cause variable epigastric pain, nausea, and vomiting. Severe cases : mucosal erosion, ulceration, hemorrhage, hematemesis, melena, or, rarely, massive blood loss. Can occur after disruption of any of the protective mechanisms (mucus, bicarbonate, vascular perfusion and prostaglandins). Causes: Excessive alcohol consumption, NSAIDs, radiation therapy, harsh chemicals and chemotherapy

21 MORPHOLOGY Mild cases : edema and slight vascular congestion. The surface epithelium is intact. More severe cases : active inflammation, erosion, Hemorrhage. If concurrent erosions and hemorrhage acute erosive hemorrhagic gastritis.

22 2.Acute Peptic UlcerationFocal, acute peptic injury. Complication of therapy with NSAIDs OR Physiologic stress which includes: Stress ulcers, most commonly affecting critically ill patients with shock, sepsis, or severe trauma. Curling ulcers, occurring in the proximal duodenum and associated with severe burns. Cushing ulcers, arising in the stomach, duodenum, or esophagus of persons with intracranial disease, have a high incidence of perforation.

23 3.Chronic Gastritis: Symptoms and signs associated with chronic gastritis typically are less severe but more persistent. The most common cause is infection with the bacillus Helicobacter pylori. Autoimmune gastritis represents less than 10% of cases. Less common causes include radiation injury and chronic bile reflux.

24 Helicobacter pylori GastritisAlmost all patients with duodenal ulcers and a majority of gastric ulcers or chronic gastritis. 90% of patients with chronic gastritis affecting the antrum. Increased acid secretion that occurs in H. pylori gastritis may result in peptic ulcer disease of the stomach or duodenum. Hypogastrinemia. Also confers increased risk of gastric cancer. Infection is associated with poverty, household crowding, limited education. Infection often is acquired in childhood and then persists for decades

25 Cont’ H.pylori found within the superficial mucus overlying antral epithelial cells. Over time, chronic antral gastritis may progress to pangastritis, resulting in multifocal atrophic gastritis, reduced acid secretion, intestinal metaplasia, and increased risk of gastric adenocarcinoma and lymphoma in a subset of patients. Generally H.pylori is not seen over intestinal metaplasia, in gastric body, or duodenal epithelium. Thus, an antral biopsy is preferred for evaluation of H. pylori gastritis.

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27 Diagnosis: 1.Serologic test for anti–H. pylori antibodies. 2.Fecal bacterial detection. 3.Urea breath test based on the generation of ammonia by bacterial urease. Treatment: Combinations of antibiotics and proton pump inhibitors.

28 Autoimmune Gastritis Typically spares the antrum and induces hypergastrinemia. Characterized by : 1.Antibodies to parietal cells and intrinsic factor. 2.Antral endocrine cell (G-cell) hyperplasia. 3.Vitamin B12 deficiency and megaloblastic anemia(pernicious anemia) 4.Defective gastric acid secretion (achlorhydria)

29 Diffuse damage of the oxyntic (acid-producing) mucosa (parietal cells).Damage to the antrum and cardia typically is absent or mild. Chief cell loss also can occur. Intestinal metaplasia may develop. Diffuse atrophy with time.

30 Clinical features: Antibodies to parietal cells and intrinsic factor are present early in disease. Pernicious anemia develops in only a minority of patients. The median age at diagnosis is 60 years. Slight female predominance. Often is associated with other autoimmune diseases

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32 4.Peptic Ulcer Disease (PUD)May occur in any portion of the gastrointestinal tract exposed to acidic gastric juices but is most common in the gastric antrum and first portion of the duodenum. Most often is associated with H. pylori infection or NSAID use. The imbalances of mucosal defenses and damaging forces that cause chronic gastritis are also responsible for PUD. Gastric hyperacidity is fundamental to the pathogenesis of PUD.

33 Cofactors in peptic ulcerogenesis include:Chronic NSAID use. Cigarette smoking. High-dose corticosteroids, Alcoholic cirrhosis. Psychologic stress may increase gastric acid production and exacerbate PUD.

34 Zollinger-Ellison syndrome,characterized by multiple peptic ulcerations in the stomach, duodenum, and even jejunum, is caused by uncontrolled release of gastrin by a tumor and the resulting massive acid production.

35 Diseases of the small and large intestines

36 INTESTINAL OBSTRUCTIONHirschsprung Disease Congenital defect in colonic innervation. Males>>females, but more severe in females. Congenital aganglionic megacolon. Distal intestinal segment lacks both the Meissner submucosal plexus and the Auerbach myenteric plexus (“aganglionosis”). Coordinated peristaltic contractions are absent and the subsequent functional obstruction results in dilation proximal to the affected segment.

37 Always rectum involved.Most cases are limited to the rectum and sigmoid colon, but severe disease can involve the entire colon. The aganglionic region may have a grossly normal or contracted appearance, while the normally innervated proximal colon may undergo progressive dilation as a result of the distal obstruction. Diagnosis of Hirschsprung disease requires demonstrating the absence of ganglion cells in the affected segment.

38 Celiac Disease Gluten-sensitive enteropathy.Immune-mediated enteropathy triggered by the ingestion of gluten-containing cereals, such as wheat, rye, or barley. Association with other immune diseases including type 1 diabetes, thyroiditis, and Sjِgren syndrome. Gluten-free diet is the treatment of choice.

39 Morphology: Changes occur in second portion of the duodenum or proximal jejunum. Activation and proliferation of CD8+ intraepithelial T- lymphocytes, which become cytotoxic and kill enterocytes The histopathologic picture is characterized by increased numbers of intraepithelial CD8+ T lymphocytes, with intraepithelial lymphocytosis, crypt hyperplasia, and villous atrophy.

40 Clinical features Adults (30-60) and children.anemia (due to iron deficiency and, less commonly, B12 and folate deficiency), diarrhea, bloating, and fatigue. A characteristic pruritic, blistering skin lesion, dermatitis herpetiformis, also is present in as many as 10% of patients. Serology: The most sensitive tests are the presence of IgA antibodies to tissue transglutaminase or IgA or IgG antibodies to gliadin. Antiendomysial antibodies are highly specific but less sensitive than other antibodies.

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42 Inflammatory Bowel Disease (IBD)chronic condition resulting from inappropriate mucosal immune activation. IBD encompasses two major entities, Crohn disease and ulcerative colitis. Ulcerative colitis is limited to the colon and rectum and extends only into the mucosa and submucosa. Crohn disease, which also has been referred to as regional enteritis (because of frequent ileal involvement), may involve any area of the gastrointestinal tract and frequently is transmural.

43 Crohn Disease may occur in any area of the gastrointestinal tract.The most common sites involved by Crohn disease at presentation are the terminal ileum, ileocecal valve, and cecum. 40% of cases small bowel alone involved. 30% of cases small intestine and colon. 30% colon alone involved. Multiple, separate, sharply delineated areas of disease, resulting in skip lesions. Cobblestone appearance in which diseased tissue is depressed below the level of normal mucosa. Elongated, serpentine ulcers oriented along the axis of the bowel.

44 Histopathology: Fissures frequently develop between mucosal folds and may extend deeply to become sites of perforation or fistula tracts. Transmural edema, inflammation, submucosal fibrosis, all of which contribute to stricture formation. Distortion of mucosal architecture. Noncaseating granulomas , a hallmark of Crohn disease, in about 35% of cases and may arise in areas of active disease or uninvolved regions in any layer of the intestinal wall.

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46 Clinical features In most patients, disease begins with intermittent attacks of relatively mild diarrhea, fever, and abdominal pain. Approximately 20% of patients present acutely with right lower quadrant pain, fever, and bloody diarrhea that may mimic acute appendicitis or bowel perforation. Periods of active disease typically are interrupted by asymptomatic intervals that last for weeks to many months.

47 Iron deficiency anemia may develop in persons with colonic disease.Extensive small bowel disease may result in serum protein loss and hypoalbuminemia, generalized nutrient malabsorption, or malabsorption of vitamin B12 and bile salts. Fistulas, perforations and peritoneal abscesses are common complications. Risk of colonic adenocarcinoma is increased in patients with long-standing colonic Crohn disease.

48 Ulcerative Colitis limited to the colon and rectum.Extends proximally in a continuous fashion to involve part or all of the colon (pancolitis). The small intestine is normal (except for backwash ileitis in severe pancolitis). Broad-based ulcers. Mucosal atrophy. Mural thickening is absent, the serosal surface is normal, and strictures do not occur.

49 Skip lesions are absent and inflammation generally is limited to the mucosa and superficial submucosa. Inflammation lead to colonic dilation and toxic megacolon, which carries a significant risk of perforation. Granulomas are not present.

50 Clinical features Relapsing attacks of bloody diarrhea with expulsion of stringy, mucoid material and lower abdominal pain and cramps, temporarily relieved by defecation. Symptoms may persist for days, weeks, or months before they subside. Infectious enteritis precedes disease onset in some cases. Colectomy cures intestinal disease. Risk of adenocarcinoma is high in longstanding cases.