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presence of eosinophils in GERD third esophagus lower Inflammatory Lesions of the Esophagus Eosinophilic Esophagitis: Eosinophilic esophagitis occurs in all age groups but is seen more frequently in young children with atopic symptoms such as eczema, asthma, and food allergies. Symptoms manife...

presence of eosinophils in GERD third esophagus lower Inflammatory Lesions of the Esophagus Eosinophilic Esophagitis: Eosinophilic esophagitis occurs in all age groups but is seen more frequently in young children with atopic symptoms such as eczema, asthma, and food allergies. Symptoms manifest differently in different age groups: whereas infants and children often present with feeding difficulties, regurgitation, dyspepsia, abdominal pain, and vomiting, adults usually describe dysphagia and food impaction with or without chest or abdominal pain. If not recognized early, EoE can progress to odynophagia and stenosis. Pathological features Gross Findings: Endoscopic examination reveals mucosal rings, furrows (“trachealization” of esophagus), erythema, and granularity. Microscopic Findings ■ Marked increase in intraepithelial eosinophils (≥15/hpf). Of eosinophils D 650098 61T upper Reflux Esophagitis (Gastroesophageal Reflux Disease; GERD) thick duodenum Reflux of acidic gastric juice into the lower esophagus occurs several times a day even in normal individuals—without producing symptoms or inflammation. Symptomatic esophagitis is believed to occur when there is prolonged exposure of the mucosa to refluxed gastric contents due to (1) excessive reflux, both in number of episodes and volume,resulting from incompetence of the lower esophageal sphincter; and (2) when the normal mechanisms for clearing the lower esophagus are impaired. LEE Bad ages Pathology: Before Reflux esophagitis can be recognized endoscopically as reddening and superficial erosion of the lower esophagus. Histologically, reflux esophagitis is characterized by (1) hyperplasia of the basal cells of the squamous epithelium to more than 15% of mucosal thickness; (2) elongation of lamina propria papillae to more than 70% of mucosal thickness; and (3) the presence of intraepithelial neutrophils and eosinophils.. Clinical Features Reflux of acidic gastric juice into an inflamed esophagus causes a low retrosternal sensation of burning pain (heartburn), typically when the patient lies flat. In chronic cases, pain may be constant and dysphagia may occur as a result of fibrous stricture formation. Complications: include reflux esophagitis, peptic ulceration, fibrosis and stricture formation, and Barrett's esophagus. auto Barrett's Esophagus neopy Prolonged reflux esophagitis commonly leads to metaplasia of the esophageal epithelium from squamous to glandular. Barrett's esophagus is defined as the presence of a glandular mucosa showing intestinal metaplasia. The metaplasia is characterized by the presence of globlet cells. The picture shows tongue-like extension of red metaplastic mucosa into native white squamous mucosa above line of gastro-esophageal junction. fine ion The picture shows metaplastic intestinal type epithelium of Barrett’s esophagus. Most primary adenocarcinomas of the lower esophagus arise in Barrett's esophagus, which therefore is considered a precancerous lesion. An estimated 5–10% of patients with Barrett's esophagus develop adenocarcinoma. The glandular epithelium passes through progressively increasing dysplastic changes that permit histologic recognition of imminent cancer. Patients with Barrett's esophagus are kept under regular surveillance with endoscopy and biopsy to detect epithelial dysplasia. The finding of high-grade dysplasia is an indication for prophylactic esophageal resection. Hiatus Hernia A hiatal hernia is defined as protrusion of part of the stomach through the diaphragmatic hiatus . It is divided into two types: A: Rolling type (10%), characterized by herniation of the gastric cardia into the thorax through the diaphragmatic hiatus alongside the normal esophagus. Note that the normal cardioesophageal angle is maintained; reflux is rare. serif is B: Sliding type (90%), characterized by shortening of the esophagus and entry of the gastroesophageal junction and proximal stomach into the thorax. The normal cardioesophageal angle is lost, and reflux of gastric juice is common. In lammatory Lesions of the Stomach Acute Erosive Gastropathy: Acute erosive gastropathy is common. It is characterized endoscopically by diffuse hyperemia of the mucosa with multiple small, superficial erosions and ulcers. (Note: an erosion is a denudation of the surface epithelium with the deep part of the mucosa remaining intact-muscularis mucosa-; an ulcer involves the full thickness of the mucosa). Typical appearance of a flat surface erosion with homogeneous eosinophilic necrosis due to an acute toxic insult, such as NSAIDs, alcohol, bile reflux, or ischemia. Microscopically, there is surface epithelial injury and denudation and variable necrosis of superficial glands. Inflammatory cells are not present in large numbers. Etiology & Pathogenesis 1-Drugs: These include: Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, ibuprofen, and corticosteroids. These probably act by inhibiting prostaglandin synthesis in the mucosa, thus making it more susceptible to acid. 2-Cigarette smoking also inhibits prostaglandin synthesis and tends to aggravate all forms of ulceration. 3-Luminally Acting Toxic Chemicals: Ethyl alcohol causes acute gastropathy, most commonly after a bout of heavy drinking. 3-Stress: Severe burns (Curling's ulcers), myocardial infarction, intracranial lesions (Cushing's ulcers), and the postoperative period are some of the stressful states associated with gastric erosion. Endogenous corticosteroids may be responsible. 4-Chemotherapy: Chemotherapy, in particular hepatic arterial infusion of cytotoxic drugs, may cause direct mucosal toxicity. 5-Ischemia: severe vasoconstriction of the splanchnic circulation causes erosive gastropathy. I osin MajorCause Lbacteria 000 6 I sure mE renren ms Chronic Gastritis Chronic gastritis is defined histologically as an increase in the number of lymphocytes and plasma cells in the gastric mucosa. Most cases of chronic gastritis are of one of two types—type A, which is an autoimmune gastritis that primarily involves the body and is associated with pernicious anemia; and type B, which primarily involves the antrum and is associated with Helicobacter pylori infection . Type -A Chronic Gastritis (Autoimmune Type Associated with Pernicious Anemia): Pernicious anemia results from failure of vitamin B12 absorption caused by lack of intrinsic factor due to autoimmune chronic gastritis. The autoimmunity is directed against the parietal cells in the body and fundus of the stomach that secrete both intrinsic factor and acid. Several autoimmune mechanisms exist: (1) a T cell-mediated response against parietal cells, (2) a humoral response associated with the presence of three different serum autoantibodies that are of diagnostic value: (a) in 90%, anti-parietal cell antibody (also called parietal canalicular antibody); (b) in 75%, intrinsic factor blocking antibody (interferes with intrinsic factor complexing to dietary vitamin B12); and (c) in 50%, intrinsic factor binding antibody (binds with the intrinsic factor–vitamin B12 complex, preventing absorption of vitamin B12). The autoimmune reaction manifests as a lymphoplasmacytic infiltrate in the mucosa around parietal cells, which progressively decrease in number. Neutrophils are rarely seen, and H pylori is absent. The fundic and body mucosa decreases in thickness, and the glands become lined predominantly by mucous cells (called pyloric metaplasia or antralization as in the picture –A-). Activesmoking The mucosa frequently shows intestinal metaplasia (as in figure –B-), characterized by the appearance of goblet cells and Paneth cells. For this reason it is sometimes called (autoimmune metaplastic atrophic gastritis). The functional results are as follows: (1) Failure of secretion of acid (achlorhydria) associated with parietal cell loss. This causes an increase in serum gastrin level and frequently leads to hyperplasia of the neuroendocrine cells in the gastric mucosa. In some patients, multiple small carcinoid tumors may occur. (2) Failure of absorption of vitamin B12, due either to defective secretion of intrinsic factor, blocking of intrinsic factor complexing with dietary vitamin B12 (blocking antibody), or to prevention of absorption of the intrinsic factor–vitamin B12 complex (binding antibody). Failure of vitamin B12 absorption causes the hematologic (megaloblastic anemia) and neurologic (subacute combined degeneration of the cord) manifestations of pernicious anemia. Patients with pernicious anemia have an increased incidence of gastric carcinoma—ie, type A autoimmune chronic gastritis is a premalignant lesion. The epithelial cells show increasing degrees of dysplasia before cancer develops. Regular endoscopic surveillance with biopsy is indicated in all patients with pernicious anemia; recognition of high-grade dysplasia in a biopsy specimen is an indication for prophylactic gastric resection. Type B Chronic Gastritis (Chronic Antral Gastritis; Helicobacter Pylori Gastritis) Type B chronic gastritis has a strong association with H pylori. In 60–70% of patients, H pylori is demonstrable in biopsies by histologic examination or culture. In many patients in whom the organism is not demonstrable, serologic studies show antibodies against H pylori, indicating previous infection. Type B chronic gastritis maximally involves the antrum, which is the favored site of infection with H pylori. Early cases show lymphoplasmactyic infiltration of the superficial gastric mucosa. Active infection with H pylori is almost always associated with the presence of neutrophils, both in the lamina propria and the antral mucous glands. As the lesion progresses, there is extension of the inflammation to involve the deep mucosa as well as the body of the stomach. Deep mucosal involvement is associated with destruction of the antral mucous glands and the appearance of intestinal metaplasia .H pylori disappears in glands showing intestinal metaplasia because it cannot survive in the milieu of intestinal epithelium. Reactive lymphoid hyperplasia, characterized by reactive follicles in the mucosa, is common. Helicobacter gastritis is associated with numerous diseases of this region, and the relationships have not been completely clarified. These include: (1) chronic duodenal ulcer, which has a nearly 100% association, (2) chronic gastric ulcer (75%), (3) gastric adenocarcinoma (> 80%), (4) malignant lymphoma arising in the mucosa-associated lymphoid tissue. Patients with type B chronic gastritis have an increased incidence of gastric cancer. The risk is very low and does not justify regular surveillance in all patients with type B chronic gastritis. 58 REACTIVE (CHEMICAL) GASTROPATHY Reactive gastropathy is one of the most common diagnosis rendered in gastric biopsies. It is commonly asymptomatic; however, some patients report vague upper abdominal pain, nausea, and vomiting. The mean age at presentation is 66 years (range, 22–88 years), without any gender predilection. Common causes include chronic aspirin or other NSAID use and various medications (e.g., ferrous sulfate), bile reflux after gastro enterostomies, vagotomy, and pyloroplasty. In nonsurgical patients, bile reflux may be caused by an incompetent pyloric sphincter or gastric dysmotility. Other putative causes include alcohol intake and smoking. Reactive gastropathy involving antral mucosa and showing foveolar hyperplasia and corkscrew appearance of gastric pits (A). Note the mucin-depleted surface and lamina propria with smooth muscle proliferation and paucity of inflammatory cells (B). Peptic Ulcer Disease Peptic ulcers are ulcers occurring in any part of the gastrointestinal tract exposed to the action of acidic gastric juice. They occur principally in the duodenum (duodenal ulcer) and stomach (gastric ulcer) .Duodenal ulcer is two to three times more frequent in males, particularly those under the age of 50 years. peptica items comp Pathogenesis: 1-Hypersecretion of Acid Acid is necessary for peptic ulcers to form, and ulcers do not occur in achlorhydric states. However, the exact causal role played by the acid is uncertain. Patients with duodenal ulcers have increased acid secretion with heightened responses to normal stimuli, but patients with gastric ulcers frequently have normal or low acid production. A marked increase in acid secretion occurs in patients with Zollinger-Ellison syndrome, caused by a gastrin-producing neoplasm of the pancreas. The high gastrin levels stimulate continuous maximal acid secretion by parietal cells. These patients have severe intractable peptic ulcers affecting the stomach, duodenum, and jejunum. In Zollinger-Ellison syndrome, high acid output is clearly the primary cause of peptic ulceration. 2-Decreased Mucosal Resistance to Acid Decreased resistance of the mucosa to acid is believed to be the primary cause of most gastric ulcers. Prostaglandin E2 levels in gastric juice have been shown to be consistently decreased in patients with peptic ulcer. Prostaglandin e2 (PGE2) levels rise during the healing phase and remain low in patients whose ulcers do not heal. Inhibitors of prostaglandin synthesis such as aspirin and ibuprofen—and cigarette smoking—are known to have an adverse effect on the healing of peptic ulcers. 3-Helicobacter Pylori Infection H pylori infection of the pyloric antrum is present in nearly all patients with chronic duodenal ulcer and approximately 75% of patients with chronic gastric ulcer.. Chronic peptic ulcer differs from acute erosive gastropathy in its etiologic factors and in the size, number, and distribution of lesions . Ulcers in acute erosive gastropathy tend to be small (< 1 cm), multiple, and distributed throughout the stomach, whereas chronic ulcers are large, solitary, and usually found on the lesser curvature or pyloric antrum Microscopically, the base of a chronic peptic ulcer is composed of a surface layer of necrotic, acutely inflamed debris below which is a zone of granulation tissue. Complications of peptic ulcer disease: 1-Bleeding Bleeding is the result of erosion of a blood vessel by the ulcer and occurs in about 30% of patients with peptic ulcer. 2-Perforation Perforation occurs in about 5% of peptic ulcer patients and is most common with anterior duodenal ulcers. 3-Pyloric Obstruction The fibrosis associated with an ulcer in the pyloric canal or first part of the duodenum may result in gastric outlet obstruction. 4-Penetration The ulcerative process may extend through the full thickness of the gut wall into adjacent organ. DISEASE OF THE SMALL AND LARGE INTESTINE Celiac disease: into giving Celiac disease is caused by hypersensitivity to a component of gluten. Celiac disease causes atrophy of small intestinal villi due to an abnormal sensitivity to gluten, a protein in flour of wheat, barley and rye (gluten-sensitive enteropathy). The disease can present at any age, and in infants and children it is an important cause of failure to thrive. Diagnosis is suggested when histological changes are seen in biopsy of small bowel mucosa but final confirmation of diagnosis requires clinical correlation and serological tests for markers of Celiac disease. in Serological test is the first-line test for celiac disease, which include evaluation of titer of IgA anti-tissue transglutaminase (anti-TTG). This may be performed in conjunction with serum IgA levels because rarely the patients may have selective IgA deficiency and this will give a false negative TTG result. The presence of IgAendomysial antibodies (EMA) supports the diagnosis in patients with equivocal TTG titers. Assays for IgG-TTG, IgG-DGP, and IgG-EMA are available for IgA deficient patients. Histologically there are three criteria used for initial diagnosis of Celiac disease (Modified MARSH criteria): 1) Increase in intraepithelial lymphocytes more than 30 intra-epithelial lymphocytes /100 enterocytes. 2) Loss of villous architecture, ranging from blunting (partial villous atrophy) to complete flattening (total villous atrophy). 3) Increase in depth of crypts, which produce more epithelial cells to compensate for those lost through damage (known as crypt hyperplasia). Complete withdrawal of gliadin from the diet (gluten-free diet) leads to gradual recovery of villous structure, which may be partial or complete. Long-term complications of coeliac disease include the development of primary Tcell lymphoma of the small intestine and, rarely, development of adenocarcinoma. TIFropathyAssociated f cedmphoma be f and Pt Normal histology of duodenal mucosa. t Celiac disease. A and B, Celiac disease with mild villous blun ng and increased intraepithelial lymphocytes par cularly in the villous .C and D, Celiac disease with almost completely blunted villi, marked intraepithelial lymphocytosis, hyperplas c crypts, and expanded lamina propria by chronic inflamma on. Intestinal tuberculosis: This usually affects the terminal ileum. The primary infection is usually caused by drinking milk infected by bovine tuberculosis. The condition results in a trivial lesion in the ileal mucosa associated with enlarged, caseating mesenteric nodes. Secondary tuberculosis is the result of swallowing infected sputum in the presence of severe pulmonary tuberculosis. This results in deep transverse ileal ulcers which heal by scarring, and cause strictures. Sometimes the disease can involve the ileocecal valve and cause a picture which is macroscopically indistinguishable from that of Crohn's disease. Antibiotic therapy is the treatment of choice for intra-abdominal tuberculosis, but surgery is often required for complications, or to obtain I m cells tissue for diagnosis. Complications include obstruction by adhesions, perforation of ulcers (rare) and malabsorption due to extensive mucosal damage or lymphatic obstruction. muttinght ig macrophages cells infected Dead CHRONIC INFLAMMATORY BOWEL DISEASE Idiopathic chronic inflammatory bowel diseases show primary inflammation of the intestinal wall. The idiopathic inflammatory bowel diseases, of which there are two main members, have no known cause. In Crohn's disease there is a granulomatous inflammatory pattern of disease that affects the full thickness of the bowel wall. It is most common in the terminal ileum, but may affect any part of the gastrointestinal tract in a discontinuous pattern. With ulcerative colitis, a chronic inflammatory disease of the rectal mucosa, inflammation may extend to involve the whole of the colon in continuity. Importantly, both types of inflammatory bowel disease are associated with systemic manifestations outside of the intestine. Crohn’s disease listurs Crohn's disease can anywhere between the mouth and the anal canal. The disease in con nuous and The disease involved GIT in discontinuous pattern (there are start from rectum to spread to normal parts between affected en re colon. areas that are skipped-skip lesions). f g mon Ulcera ve coli s occur limited to the colon and rectum. aggressivethanone feminist is action The inflammation involved all layers of intestinal wall (transmural). The inflamma on is limited to layer of mucosa. Non-caseating epithelioid granulomas in 60% of biopsies. Granulomas are very rare (may be seen in rela on to destroyed crypts). The inflamma on is patchy and mul focal. The inflamma on is diffuse and uniform in the affected part. Fistulas are common. Fistulas are rare. In diagnosing idiopathic inflammatory bowel disease, infective causes of inflammation have first to be excluded. Investigation is by imaging and biopsy. Crohn's disease: is more common in women than in men, patients usually being 20-60 years old. It particularly affects the terminal ileum (synonym: regional ileitis), but can occur anywhere in the gut, especially in the mouth, colon, and anus. Giant cells 29.3TB d Caseastion In established chronic disease the bowel mucosa shows a cobblestone pattern due to a combination of submucosal oedema and interconnecting deep fissured ulcers. The bowel wall is thickened by oedema and fibrosis and, commonly, there is stricture formation. Regional lymph nodes usually become enlarged. Disease is not continuous and areas of normal bowel may be present between the diseased segments (skip lesions).The normal bowel proximal to a segment of Crohn's disease is often dilated due to partial obstruction. Crohn's disease is histologically characterized by inflammation of all layers, submucosal oedema, ulcers that extend deep into the bowel wall and form fissures, and fibrous scarring. Non-caseating granulomas may be present (70% of cases). Inflammation in Crohn's disease is transmural, and serosal involvement leads to inflammatory adhesion to other loops of bowel, to the parietal peritoneum of the anterior abdominal wall, or to the bladder. Deep penetration of fissured ulcers, which may extend through the full thickness of the bowel wall into the adherent viscus, causes { fistulae} (tracks between two cavities) and {sinuses} (a track from a viscus to an outside surface). This is particularly seen in the perianal region. Ulcerative colitis :affects the rectum and variable amounts of colon Ulcerative colitis starts at the rectum (proctitis) and may extend for a variable distance around the colon. There are three clinical patterns of disease: 1 In { active acute disease} the mucosa in the rectum and affected colon shows areas of shallow ulceration; inflammation is limited to the mucosa and lamina propria. 2 In { chronic quiescen or treated disease} ulceration is not prominent and the mucosa appears red, granular and thinned. 3 In { fulminant active disease} the colon shows extensive confluent mucosal ulceration.The colon progressively dilates (toxic dilatation - 'acute toxic megacolon'). The direct local complications of ulcerative colitis include blood and fluid loss from extensive ulceration. Acute disease may progress rapidly to toxic dilatation and perforation and, in long-standing disease, dysplasia and neoplastic change may occur . The natural history of ulcerative colitis can be divided into three main patterns: • 10% of patients develop severe disease requiring early surgery. • 10% of patients have persistent active disease despite treatment. • 80% of patients have chronic quiescent colitis with infrequent episodes of relapse. In active disease (a) the ulcerated areas are haemorrhagic, leading to bloody diarrhoea. Intact mucosa remains as islands sitting above areas of ulceration (pseudopolyps). Histology of the intact mucosa (b) shows oedema and an increase in numbers of lymphoid cells and plasma cells in lamina propria. Neutrophils are seen in lamina propria as well as in gland epithelium –cryptitis-. Neutrophils migrate through the walls of glands to form collections, termed crypt abscesses, in the gland lumen. There is depletion of goblet cells and mucin from gland epithelium. Indeterminate Colitis: Approximately 10% of cases of inflammatory bowel diseases exhibit the features of both Crohn's disease and ulcerative colitis. These are typically known as indeterminate colitis. Antibiotic-associated Colitis This is due to overgrowth of Clostridium diffidle in the colon following suppression of the normal bowel flora by broad- spectrum antibiotics. The disease can be mild or severe. Histologically, there is superficial loss of epithelial cells which become embedded in an exudate containing mucin, polymorphs, and abundant fibrin, forming a pseudomem brane on the surface-hence the term 'pseudomembranous colitis' with occasional (volcano-like) appearance. sure rotates t so take biopsy Microscopic colitis: When patients complain of non-bloody diarrhea and total colonoscopy is performed for finding a cause, one may find no endoscopic abnormity but a biopsy may show evidence of inflammation. This is called microscopic colitis. There are two sub-types: 1) Collagenous colitis: The sub-epithelial collagen band thickness is more than diagnostic cut-off point of 10 microns. Usually it is seen in elderly women (slides A&B in the picture below). 2) Lymphocytic colitis: The intra-epithelial lymphocyte count is more than 20 per 100 colonocytes with lymphocytic cryptitis. The subepithelial collagen band has normal thickness. (Slices C&D in the picture below) Drug induced colitis: Certain drugs can cause a pattern of colitis that can mimic Crohn’s disease. One such drug is Mycophenolate Mofetil (CellCept). Another example is Olmesartan that can caused Celiac-like enteropathy that is not responding to gluten withdrawal from diet but disappears after cessation of the drug. A well-known group are NSAID which can various patterns of colitis. NSAID related non-specific ulceration of large bowel. Hirschsprong's Disease This condition is characterized by a lack of normal ganglion cells in the myenteric plexus of part of the bowel. It is due to the failure of migration of primitive neurobla ts into the developing gut. The distal large bowel is usually affected, but the abnormality may extend to involve the entire colon and even part of the small intestine. Diagnosis can be made on biopsies by demonstrating a lack of ganglia and the associated unchecked proliferation of parasympathetic acetylcholinesteraseproducing nerves in the mucosa. Solitary rectal ulcer syndrome (Rectal mucosal prolapse syndrome): Protrusion of part of the wall of the rectum into the anal canal is most commonly seen in women. If the mucosa alone is involved, the presentation may be as a solitary rectal ulcer which can be identified on biopsy by a characteristic pattern of crypt hyperplasia and congestion, fibrosis and muscularization of the lamina propria. These lesions may closely mimic malignant ulcers on clinical assessment. Hematoxylin & eosin shows polypoid ulcerated rectal mucosa with underlying fibromuscular proliferation in the lamina propria and serrated, branching, haphazardly arranged crypts .