Subject: Pathology Topic: Esophagus and Stomach Lecturer: Dr.

Cruz Transcriptionist: Miu Editor: Chorale Tenor Pages: 11

ESOPHAGUS

Anatomy Hollow distensible muscular tube Length: C6 to T11/T12 (25cm in adults) Has upper esophageal sphincter and lower esophageal sphincter mostly devoid of serosal coat 3 constrictions when it crosses o left mainstem bronchus and left atrium o diaphragm o cricoid cartilage Pathology varices. hernias, webs, achalasia (will be discussed later) The above mentioned disorders produce similar symptoms: dysphagia pain heartburn hematemesis Congenital anomalies 1. atresia/agenesis and fistula discovered after birth due to regurgitation during feeding agenesis or absence of esophagus is extremely rare atresia, in which development of the esophagus is incomplete in esophageal atresia a thin, noncanalized cord replaces a segment of esophagus causing a mechanical obstruction. Atresia occurs most commonly at or near the tracheal bifurcation and is usually associated with fistula connecting the upper of lower esophageal pouches to a bronchus or the trachea (Figure 1-A). Fistula can lead to aspiration, suffocation, pneumonia and severe electrolyte imbalances. Esophageal atresia is associated with congenital defects, GUT malformation and neuorologic disease.

Figure 1. Atresia with fistula. Most common is (A) blind upper segment with fistural between lower segment. It follows a h formation. 2. Stenosis o Most often due to inflammation and scarring that may be cause by chronic gastroesophageal reflux, irradiation or caustic injury.

3. Schatzkis rings (lower esophagus) o Similar to webs but are circumferential and thicker. Rings include mucosa, submucosa and hypertrophic muscularis propria. o If above the gastroesophageal junction, it is termed as A rings and covered by squamous mucosa o If below, it is called as B ring and may have gastric type mucosa on their undersurface. 4. Esophageal webs (rings in the upper esophagus) o are uncommon ledge-like protrusion of mucosa that may cause obstruction o Semi-circumferential eccentric lesions. o often associated with GERD, chronic graft vs host disease or blistering skin disease. o Patterson-Kelly or PlumberVinson syndrome: IDA + glossitis + Esophageal web + cheilosis

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Lesions associated with motor dysfunction ACHALASIA failure of relaxation with consequent dilatation (progressive dysphagia) characterized by the triad of incomplete LES relaxation, increase LES tone and aperistalsis of esophagus primary achalasia is caused by failure of distal esophageal inhibitor neurons, often idiopathic secondary achalasia may arise in chagas dse HIATAL HERNIA separation of the diaphragmatic crura and widening of the space between the muscular crura and esophageal wall i. sliding (95% of cases, axial type) ii. paraesophageal(rolling type)

Varices collateral bypass channels formed because of diversion of portal flow into the coronary veins of the stomach Secondary to portal hypertension with cirrhosis and schistosomiasis. rupture leads to massive hemorrhage submucosal channels with superficial erosive changes of the epithelium

Figure 3. Esophageal varice ESOPHAGITIS Secondary to: Reflux esophagitis gastric intubation ingestion of irritants cytotoxic anticancer therapy/radiation infection uremia systemic conditions BARRETS ESOPHAGUS Long standing gastroesophageal reflux columnar metaplasia of distal squamous mucosa as a response to prolonged injury stratified squamous columnar secretory (+) Goblet cells which define intestinal metaplasia and necessary for dx of Barrets Esophagus Lacerations Mallory Weiss Syndrome consequence of severe retching with production of longitudinal tears Diverticula motor dysfunction outpouching Microscopically: Shows dysplastic change, stratification of cells, hyperchromaticity, enlargement of nuclei low grade: basal orientation of nuclei high grade : apical orientation of nuclei

Figure 2.

Zenkers : weak junctional area of the pharyngeal constrictor muscles; pulsion type Traction type : develops from a fibrosing mediastinal reaction

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Tumors Benign tumors are usually mesenchymal in origin LEIOMYOMA MUCOSAL POLYPS Malignant tumors SQUAMOUS CELL CARCINOMA ADENOCARCINOMA Squamous cell Carcinoma adults over 50 yrs; M > F synergistic action of environmental and dietary factors most common in the middle third of esophagus causing constriction and may appear either as: o protruded o diffuse infiltrative o excavated o superficial esophageal carcinoma (in-situ) The sites of lymph node metastasis vary with tumor location: cancers in the upper third cervical lymph node ca in the middle third mediastinal, paratracheal and tracheobronchial nodes ca in the lower third gastric and celiac nodes Clinical feature: dysphagia, odynophagia and obstruction

25% of all esophageaL cancers, M > F poor prognosis; 15% 5 yr survival rate risk factors: tobacco use, obsesity and prior radiation therapy occurs in the distal third of the esophagus

Morphology occurs in the distal esophagus invading the cardia initially flat or raised patches which may enlarge to 5 cm nodular mass or infiltrative mucin producing glandular tumors Clinical Feature: Dysphagia, odynophagia, weight hematemesis, chest pain and vomiting. ANATOMY GLANDULAR DIGESTIVE ENDOCRINE ORGAN Anatomic Region Cardia Fundus lined by foveolar (mucous) cell parietal chief cells chief cells loss,

STOMACH

AND

GI peptides mucin/mucous acid pepsin pepsin

Body - incisura - angularis Antrum foveolar cell Mucin G cells Gastrin Mnemonic: Car: mu Fundus: pH P for parietal; pH for acid

Figure 4. Esophageal squamous carcinoma in situ. Adenocarcinoma Barrets esophagus dysplasia origin with

Figure 5. Parts of the stomach ACID SECRETION Physiology: stimulation of parietal cells

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o o o o

neural - vagal stimulation which then causes secretion of gastric acid. endocrine - gastrin secretion local - histamine released by mast cells CHIEF CELLS concentrated at the base of gastric glands release of pepsinogen I/II by exocytosis by calcium and cAMP-mediated mechanisms

CONGENITAL ANOMALIES A. HETEROTOPIC RESTS Small patches of ectopic gastric mucosa in the small bowel or colon, may prswent with occult blood loss due to peptic ulceration of adjacent mucosa Usually occurs in the upper third of esophagus where it is referred to as an inlet patch. B. DIAPHRAGMATIC HERNIAS weakness or partial-to-total absence of a region of the diaphragm without involving the hiatus C. PYLORIC STENOSIS Can be Congenital hypertrophic stenosis or acquired M>F Generally presents in the 2nd or 3rd wk of life as new-onset of regurgitation and presisten, projectile nonbilious vomiting.

Gastric Mucosal Protection Gastric lumen is strongly acidic with pH close to 1. This harsh environment pose a potential damage to gastric mucosa and thus multiple defense mechanism act and as follows: 1. mucous secretion o secreted by foveolar cells which forms a thin layer of mucus that prevents large food particles from directly touching the epithelium. o The mucus layer promotes formation of an unstirred layer of fluid over the epithelium that protects the mucosa. 2. bicarbonate secretion o neutralizes pH 3. epithelial barrier 4. mucosal blood flow o delivers oxygen, bicarbonate and nutrients o Washes away acid that has back diffused into the lamina propria. 5. prostaglandin protection o provides cytoprotection o enhances bicarbonate secretion, inhibit acid secretion, promoste mucin synthesis and increase vascular perfusion 6. neural and muscular components o stimulation of vagal nuclei gastric secretion

Figure 6. Mechanism of gastric injury and protection.

GASTRITIS inflammation of the gastric mucosa Regenerative change o increased mitosis in the neck region of gastric glandsmetaplasia columnar cells of the intestinal type atrophy loss of glandular structures

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TYPES OF GASTRITIS 1. ACUTE acute mucosal inflammatory process usually of a transient nature asymptomatic to overtly massive hematemesis , melena MORPHOLOGY presence of neutrophils above the basement membrane loss of superficial epithelium (EROSION) can also lead to ACUTE EROSIVE HEMORRHAGIC GASTRITIS

Figure 7. Acute Gastritis 2. Chronic gastritis presence of chronic mucosal inflammatory changes leading eventually to mucosal atrophy and epithelial metaplasia usually in the absence of erosions inflammatory infiltrates of lymphocytes and plasma cells PATHOGENESIS Immunologic Helicobacter pylori infection TOXIC: alcohol/cigarette motor and mechanical granulomatous conditions

3. Automimmune Gastritis Characterized by: o Ab to parietal cells and intrinsic factors that can be detected in serum and gastric secretion o Reduced serum Pepsinogen I o Antral endocrine hyperplasia o Vit B12 Deficiency o Defective gastric acid secretion (achlorhydia) o In contrast to anemia, neurologic changes cannot be treated with Vit B12 therapy. Pathogenesis Loss of parietal cells, responsible for section of gastic acid and instrisc factor, stimulates gastrin relase. This then results in hypergastrinemia and hyperplasia of antral gastrin producing G cells. Lack of intrinsic factor disables ieal vit B12 absorption pernicious anemia Reduced serum pepsinogen I chief cell destruction CD4+ cells directed against parietal cell components, including the H+, K+. ATPase, are the principal agents of injury. MORPHOLOGY diffuse mucosal damage of body-fundic area with less intense or absent antral damage intestinal metaplasia with goblet cells 4. Environmental tends to affect antral mucosa area more or both 5. H. Pylori Gastritis Antral gastritis with increase in acid production despite hypogastrinemia Most common cause of chronic gastritis Location Inflammato ry infiltrate Acid production Gastrin Other lsion Serology Sequalae H. pylrori assoc Antrum Neutrophil, subepithelial plasma cells Inc to slightly dec Normal to dec Hyperplastic Antibodies to H. pylori PUD, adenocarcinoma Autoimmune Body & fundus Lymphocytes, macrophages Decrease Increase Neuroendocrin e hyperplasia Antibodies to parietal cell Atrophy, pernicious anemia, adenoca, carcinoid

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Association

Low SES, poverty, residence in rural areas

tumor Autoimmune dse, Hashimoto Thyroiditis, DM type 1, Graves dse

Gastric ulceration breach in the mucosa of GIT tract extending through the muscularis mucosa into the submucosa or deeper 1. PEPTIC ULCER Chronic, most often solitary lesions that occur in any portion of the GIT exposed to the aggressive action of acid-peptic juices DISTINCTIVE FEATURES OF PUD o usually a SOLITARY LESION o LESS THAN 4 CM IN DIAMETER o RECURRENT WITH INTERMITTENT HEALING o Occurs in (in descending order) DUODENAL(1st part) stomach (antral) Barrets esophagus stomal ulcers Meckels diverticulum with gastric mucosa Morphology 1st portion of the duodenum more in the anterior wall than posterior wall gastric ulcers more in the lesser curvature in the border zone of antrum and corpus usually larger than 0.6cm in diameter round to oval with sharp demarcations margins at level with surrounding mucosa more of sharply puched out defect while malignant cancers is characterize as heaping-up smooth base HISTOLOGIC APPEARANCE base and margins have a superficial thin layer of necrotic fibrinoid debris beneath is a zone nonspecific inflammatory infiltrates, polys in the base of the ulcer, active granulation tissue with monos solid fibrous or collageneized scar

Pathogenesis produced by imbalance between gastroduodenal mucosal defense mechanisms and damaging forces Most commonly due to H. pylori and NSAID. Other causes: alcoholism, cigarette smoking (impairs blood flow and healing), high dose corticosteroid (suppress Prostaglandin), Complication BLEEDING PERFORATION OBSTRUCTION INTRACTABLE PAIN Iron deficiency Anemia Frank hemorrhage Clinical feature: Pain 1-3 hours after meal; worsens at night, relieved by alkaline food

AGGRESSIVE FORCES PUD H. pylori infection NSAIDs, ASPIRIN CIGARETTE/ ALCOHOL IMPAIRED ACID-PEPSIN SECRETION REGULATION ISCHEMIA DUDODENAL-GASTRIC REFLUX DELAYED GASTRIC EMPTYING

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2.a Stress ulcers generally multiple, less than 1.0cm encountered in patients with shock, extensive burns, severe trauma and increased ICP 2.b Curlings ulcers proximal duodenum associated with severe trauma and burns 2.c Cushing ulcers gastric, duodenal and esophageal ulcers in persons with intracranial diasease. Carry a high incidence of perforation.

2. ACUTE GASTRIC ULCERATION Well-known complication of therapy with NSAID inhibit COX inhibit Prostaglandin synthesis reduced bicarbonate secretion, increase gastrin secretion, inhibit mucin synthesis, decrease vascular perfusion. Gastric mucosal defects are a wellknown complication of therapy with NSAIDs. Some of these are given specific names, basedon on location and clinical associations, for example:

MISCELLANEOUS CONDITIONS A. Hypertrophic Gastropathy Characterized by giant cerebiform enlargement of rugal folds due to epithelial hyperplasia without inflammation. A.1 Menetriers disease o hyperplasia of surface mucous cells with accompanying glandular atrophy o secondary to excessive secretion of TGF-alpha A.2 Hypertrophic-hypersecetory gastropathy o hyperplasia of of the parietal and chief cells within gastric glands A.3 Gastric gland hyperplasia o aka Zollinger-Ellisojn Snydrome o secondary to excessivve gastrin secretion

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commonly found in the small intestine or pancreas

true neoplasm; contains proliferative dysplastic epithelium with malignant potential commonly located in the distal portion adenomatous change may carpet a large region of flat gastric mucosa without forming a mass lesion 50-60 Y.O; M > F Occurs on a background of chronic gastritis with atrophy and intestinal metaplasia GASTRIC MALIGNANCIES

Epidemiology BENIGN TUMORS 1. GASTRIC POLYPS any nodule that projects above the level of the surrounding mucosa majority are non-neoplastic, usually inflammatory or hyperplastic HYPERPLASTIC , small and sessile , seen in a setting of chronic gastritis, usually multiple no malignant potential CARCINOMA ..90-95% -most important and most common LYMPHOMA 4% CARCINOIDS .3% Malignant spindle cell tumors .2% ------------------------------------------------------------1. GASTRIC CARCINOMA

Types of Gastric Polyp a. Inflammatory and Hyperplastic polyps i. Mean age: 50-60 ii. Assoc with chronic gastritis b. Funding Gland Polyp i. Aka Familial Adenomatous Polyposis (FAP) ii. Result of proton pump inhibitor therapy inc gastrin secretion glandular hyperplasia 2. ADENOMA OF THE STOMACH

Epidemiology worldwide in occurrence decreasing annual mortality rate in U.S. dismal 5-yr survival reate : < 10% Types of Gastric Carcinoma A. intestinal type, chronic gastritis setting, older tend to form bulky tumor composed glandular structures B. diffuse gastric type no change in 60 years, younger population, poorly differentiated. composed of signet ring cells dont form glands but have large mucin vacuoles that expands and push nucleus to peripheral signet cell looks like leather bottle aka linitis plastic Pathogenesis of Gastric Carcinoma 1. Environmental factors most important nitroso-compunds ; benzopyrenes 2. acquired host factors chronic antral gastritis with atrophy (18x) chronic atrophic gastritis with pernicious anemia (3%) partial gastrectomy increased risk 3. infection with H. pylori 4. genetic and racial factors

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FEATURES OF LAURENS CLASSIFICATION GASTRIC CARCINOMA Feature Gross Microscopic Differentation Mucin prodn Growth pattern Intestinal metaplasia Clinical Mean age Sex Ratio (M:F) Incidence Intestinal Polypoid, fundating Well-diff, gland-forming Limited to gland lumen Expansile; (+) inflammation Universal Diffuse Ulcerative, infiltrative Poorly diff, signet cells Extensive Noncohesive, infiltrative Frequent

55 2:1 Decreasing

48 equal No change

FIGURE 8. Gastric Adenocarcinoma. Signet cells can be recognized by their large cytoplasmic mucin vacuoles and peripherally displaced, crescent shaped nuclei. 2. GASTRIC LYMPHOMA 40% of extranodal lymphoma occurs in the GIT sporadic is most common form B-cell type from Mucosa-associated Lymphoid tissue (MALT) is the most common of which are indolent and arise at sites of chronic inflammation Occurs in (descending order) o stomach(55%) o duodenum o small intestine (25%) o colon (20%) Primary : no evidence of liver,spleen or bone marrow involvement Morphology: Infiltrate the gastric gland focally to create diagnostic lymphoepithelial lesion. Tumor cells accumulate large amounts of pale cytoplasm, a featured referred to as monocytoid change (refer figure 9).

Figure 7. The major types of gastric cancer

Figure 9. Monocytoid change

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Clinical Feature Dyspepsia Epigastric pain Hematemesis Melena Weight loss 3. Carcinoid Tumor 40% occurs small intestine Considered to be well-dfferentiated neuroendocrine carcinomas Are intramural or submucosal masses that create small polypoid lesions Assoc with endocrine hyperplasia, Chronic atrophic gastritis, Zollinger Ellison Syndrome

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The most important prognostic factor for GI carcinoid tumors is location a. Foregut carcinoid tumors stomach, dueoenum proximal to the ligament of Treitz and esophagus b. Midgut carcinoid tumors arise in the jejunum and ileum and often multiple and aggressive c. Hindgut carcinoid arrises from appendix and colorectum 4. Gastrointestinal Stromal Tumor most common mesenchymal tumor of the abdomen related to Carney Triad: GIST, paranganglioma, pulmonary chondroma, young female due to mutation of the gene tyrosine kinase c-KIT, thus making it as a tumor marker.

Classification of GIST I. Spindle cell type thin elongated cell II. Epitheloiod type dominated by epithelial appearing cells Clinical feature: Gastric GIST are less aggressive tha those arising in the small intestine. Metastasis is rare Blood loss, anemia -------------------End of Transcription--------------Hello Section B 2014!! Hello ke ate des, ate joyce, shar, jc, Sheila, ace tin, kate, pinay, jobell, christel, soler bros. GO 2014 JFT chorale!!!! GO 2014 JFT Band!!!!

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