Fundamentals of Pathology PDF

FUNDAMENTALSOF PATHOLOGY VI. ACHALASIA A. Disordered esophageal motility with inability to relax the lower esophageal sphincter (LES) B. Due to damaged ganglion cells in the myenteric plexus 1. Ganglion cells of myenteric plexus are located between...

FUNDAMENTALSOF PATHOLOGY VI. ACHALASIA A. Disordered esophageal motility with inability to relax the lower esophageal sphincter (LES) B. Due to damaged ganglion cells in the myenteric plexus 1. Ganglion cells of myenteric plexus are located between the inner circular and outer longitudinal layers of the muscularis propria and are important for regulating bowel motility and relaxing the LES. 2. Damage to ganglion cells can be idiopathic or secondary to a known insult (e.g., Trypanosoma cruzi infection in Chagas disease). C. Clinical features 1. Dysphagia for solids and liquids 2. Putrid breath 3. High LES pressure on esophageal manometry 4. 'Bird-beak' sign on barium swallow study (Fig. 10.7) 5. Increased risk for esophageal squamous cell carcinoma VII. GASTROESOPHAGEAL REFLUX DISEASE (GERD) A. Reflux of acid from the stomach due to reduced LES tone B. Risk factors include alcohol, tobacco, obesity, fat-rich diet, caffeine, and hiatal hernia. C. Clinical features 1. Heartburn (mimics cardiac chest pain) 2. Asthma (adult-onset) and cough 3. Damage to enamel of teeth 4. Ulceration with stricture and Barrett esophagus are late complications. VIII.BARRETT ESOPHAGUS A. Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to nonciliated columnar epithelium with goblet cells (Fig. 10.8); seen in 10% of patients with GERD 1. Response oflower esophageal stem cells to acidic stress B. May progress to dysplasia and adenocarcinoma IX. ESOPHAGEAL CARCINOMA A. Subclassified as adenocarcinoma or squamous cell carcinoma B. Adenocarcinoma is a malignant proliferation of glands; most common type of esophageal carcinoma in the West 1. Arises from preexisting Barrett esophagus; usually involves the lower one-third of the esophagus Fig. 10.7 'Bird-beak' sign, achalasia.(Courtesyof Fig. 10.8 Barrett esophagus. F.Farrokhl,MD and M. Vaezi,MD)  Gastrointestinal Pathology C. Squamous cell carcinoma is a malignant proliferation of squamous cells; most common esophageal cancer worldwide 1. Usually arises in upper or middle third of the esophagus; major risk factors include i. Alcohol and tobacco (most common causes) ii. Very hot tea iii. Achalasia iv. Esophageal web (e.g., Plummer-Vinson syndrome) v. Esophageal injury (e.g., lye ingestion) D. Esophageal carcinoma presents late (poor prognosis). 1. Symptoms include progressive dysphagia (solids to liquids), weight loss, pain, and hematemesis. 2. Squamous cell carcinoma may additionally present with hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement). E. Location of lymph node spread depends on the level of the esophagus that is involved. 1. Upper 1/3-cervical nodes 2. Middle 1/3-mediastinal or tracheobronchial nodes 3. Lower 1/3-celiac and gastric nodes STOMACH I. GASTROSCHISIS A. Congenital malformation of the anterior abdominal wall leading to exposure of abdominal contents (Fig. 10.9) II. OMPHALOCELE A. Persistent herniation of bowel into umbilical cord B. Due to failure of herniated intestines to return to the body cavity during development 1. Contents are covered by peritoneum and amnion of the umbilical cord (Fig. 10.10). III. PYLORIC STENOSIS A. Congenital hypertrophy of pyloric smooth muscle; more common in males B. Classically presents two weeks after birth as 1. Projectile nonbilious vomiting 2. Visible peristalsis 3. Olive-like mass in the abdomen C. Treatment is myotomy. Fig. 10.9 Gastroschisis. (Courtesy of humpath. Fig, 10.10 Omphalocele. (Courtesy of J.T.Stocker, Fig. 10.11 Intestinal metaplasia, chronic gastritis. corn) MD)  FUNDAMENTALS OF PATHOLOGY IV. ACUTE GASTRITIS A. Acidic damage to the stomach mucosa B. Due to imbalance between mucosa! defenses and acidic environment 1. Defenses include mucin layer produced by foveolar cells, bicarbonate secretion by surface epithelium, and normal blood supply (provides nutrients and picks up leaked acid). C. Risk factors 1. Severe burn (Curling ulcer)-Hypovolemia leads to decreased blood supply. 2. NSAIDs (decreased PGE) 3. Heavy alcohol consumption 4. Chemotherapy 5. Increased intracranial pressure (Cushing ulcer)-Increased stimulation of vagus nerve leads to increased acid production. 6. Shock-Multiple (stress) ulcers may be seen in ICU patients. D. Acid damage results in superficial inflammation, erosion (loss of superficial epithelium), or ulcer (loss of mucosa! layer). V. CHRONIC GASTRITIS A. Chronic inflammation of stomach mucosa B. Divided into two types based on underlying etiology: chronic autoimmune gastritis and chronic H pylori gastritis C. Chronic autoimmune gastritis is due to autoimmune destruction of gastric parietal cells, which are located in the stomach body and fundus. 1. Associated with antibodies against parietal cells and/or intrinsic factor; useful for diagnosis, but pathogenesis is mediated by T cells (type IV hypersensitivity) 2. Clinical features i. Atrophy of mucosa with intestinal metaplasia (Fig. 10.11) ii. Achlorhydria with increased gastrin levels and antral G-cell hyperplasia iii. Megaloblastic (pernicious) anemia due to lack of intrinsic factor iv. Increased risk for gastric adenocarcinoma (intestinal type) D. Chronic H pylori gastritis is due to H pylori-induced acute and chronic inflammation; most common form of gastritis (90%) l. H pylori ureases and proteases along with inflammation weaken mucosa! defenses; antrum is the most common site (Fig. 10.12). 2. Presents with epigastric abdominal pain; increased risk for ulceration (peptic ulcer disease), gastric adenocarcinoma (intestinal type), and MALT lymphoma 3. Treatment involves triple therapy. i. Resolves gastritis/ulcer and reverses intestinal metaplasia ii. Negative urea breath test and lack of stool antigen confirm eradication of Hpylori. Fig.10.12Hpylori.(Courtesyof EdUthman,MD) Fig. 10,13Gastriculcer.A, Pepticulcer disease.B,Carcinoma.(Courtesyof Aliya Husain,MD)  Gastrointestinal Pathology VI. PEPTIC ULCER DISEASE A. Solitary mucosa! ulcer involving proximal duodenum (90%) or distal stomach (10%) B. Duodenal ulcer is almost always due to H pylori (> 95%); rarely, may be due to ZE syndrome 1. Presents with epigastric pain that improves with meals 2. Diagnostic endoscopic biopsy shows ulcer with hypertrophy of Brunner glands. 3. Usually arises in anterior duodenum; when present in posterior duodenum, rupture may lead to bleeding from the gastroduodenal artery or acute pancreatitis C. Gastric ulcer is usually due to H pylori (75%); other causes include NSAIDs and bile reflux. 1. Presents with epigastric pain that worsens with meals 2. Ulcer is usually located on the lesser curvature of the antrum. 3. Rupture carries risk of bleeding from left gastric artery. D. Differential diagnosis of ulcers includes carcinoma. 1. Duodenal ulcers are almost never malignant (duodenal carcinoma is extremely rare). 2. Gastric ulcers can be caused by gastric carcinoma (intestinal subtype). i. Benign peptic ulcers are usually small (< 3 cm), sharply demarcated ("punched-out"), and surrounded by radiating folds of mucosa (Fig. 10.13A). ii. Malignant ulcers are large and irregular with heaped up margins (Fig. 10.13B) iii. Biopsy is required for definitive diagnosis. VII. GASTRIC CARCINOMA A. Malignant proliferation of surface epithelial cells (adenocarcinoma) B. Subclassified into intestinal and diffuse types C. Intestinal type (more common) presents as a large, irregular ulcer with heaped up margins; most commonly involves the lesser curvature of the antrum (similar to gastric ulcer) 1. Risk factors include intestinal metaplasia (e.g., due to H pylori and autoimmune gastritis), nitrosamines in smoked foods (Japan), and blood type A. D. Diffuse type is characterized by signet ring cells that diffusely infiltrate the gastric wall (Fig. 10.14B);desmoplasia results in thickening of stomach wall (linitis plastica, Fig. 10.14A). 1. Not associated with H pylori, intestinal metaplasia, or nitrosamines E. Gastric carcinoma presents late with weight loss, abdominal pain, anemia, and early satiety; rarely presents as acanthosis nigricans or Leser-Trelat sign F. Spread to lymph nodes can involve the left supraclavicular node (Virchow node). G. Distant metastasis most commonly involves liver; other sites include 1. Periumbilical region (Sister Mary Joseph nodule); seen with intestinal type Fig, 10.14 Gastriccarcinoma,diffuse type. A, Llnltls plastlca.B, Signet-ringcells.(A, Courtesyof Ed Uthman,MD)