II.

1 Gastrointestinal Tract
Robbins

A. ANATOMIC ANOMALIES DISEASE ETIOLOGY Atresia CHD Other GIT malformations Fistula GERD, Caustric burns, Radiotherapy Congenital, Scleroderma Congenital Long-standing reflux esophagitis Chronic graft-vs.-host disease congenital heart disease, neurologic problems, GU or other GI malformations Aspiration, suffocation from food, pneumonia, fluid & electrolyte imbalance

I.

THE ESOPHAGUS MORPHOLOGY Portion of esophagus is replaced by thin, noncanalized cord, with blind pouches above and below the atretic segment Connection between the esophagus and the trachea or a mainstem bronchus

CLINICAL MANIFESTATIONS

Incompatible with life

Stenosis

Episodic dysphagia

Esophageal wall fibrous thickening

Mucosal webs

Plummer-Vinson Syndrome: Cheilosis, glossitis, iron deficiency anemia Episodic dysphagia

UPPER esophageal muscosal overgrowths

Esophageal rings

Episodic dysphagia

LOWER esophageal muscosal overgrowths A ring: if above the gastroesophageal junction B or Schatzki ring: if at the gastroesophageal juction Muscularis propria hypertrophy

B. LESIONS ASSOCIATED WITH MOTOR DYSFUNCTION DISEASE ETIOLOGY CLINICAL MANIFESTATIONS inhibitory neuron dysfunction degeneration of CNS or peripheral nerves (DM, amyloidosis, cancer) protozoal (Toxoplasma) infection of esophageal myenteric plexus of nerves. Progressive dysphagia Aperistalsis Nocturnal regurgitation and aspiration of undigested food. COMPLICATIONS Inc risk of SCC (~5%). Candida esophagitis. Aspiration pneumonia. Airway obstruction.

MORPHOLOGY

Achalasia

Proximal esophageal dilation Thickened or thinned muscular walls Regurgitation with mucosal dage

Secondary Achalasia

Chagas disease Disorders of the vagal dorsal motor nuclei (polio, surgical ablation) Diabetic autonomic neuropathy Infiltrative disorders (malignancy, amyloidosis, sarcoidosis) Crura (muscles) of diaphragm and the esophagus are not close enough. COMPLICATIONS ulceration with bleeding & perforation. Rolling hernias can have strangulation & obstruction.

Hiatal Hernia

unknown. Rolling hernias can be secondary to surgery.

Sliding (axial): Shortened esophagus Traction of upper stomach into thorax Bell-like dilation of stomach w/in the thoracic cavity Paraesophageal (rolling): Cardia of stomach dissects into the thorax adjacent to the esophagus Outpouchings of the alimentary tract containing one or more wall layers

Diverticula Zenker Diverticulum disordered cricopharyngeal motor function Dysphagia, food regurgitation, mass in the neck Aspiration with pneumonia

UPPER esophagus

From 2015 2B edited by Anj. Anne. How. Jerro. Mark. Joseph. Tin

Page 1 of 8

Traction Diverticulum Epiphrenic Diverticulum Lacerations (Mallory-Weiss Syndrome) Boerhaave Syndrome Esophageal Varices

congenital or result of motor dysfunction discoordination of peristalsis & lower sphincter relaxation Episodes of excessive vomiting Failure of LES relaxation Alcohol Large amounts of alcohol Portal hypertension 90% of patients with alcoholic cirrhosis have esophageal varices. Schistosomiasis

asymptomatic Nocturnal regurgitation of massive amounts of fluid no symptoms until rupture with hematemesis 90% chance of recurrence Massive hematemesis Inflammation Residual ulcer Mediastinitis Peritonitis

Mid-esophageal Just above lower esophageal sphincter longitudinal tears across the esophagogastric junction or in the upper stomach are mucosal or sometimes entirely through the wall with perforation. Pressure rupture of the esophagus just above the diaphragm Tortuous, dilated veins in distal esophageal submucosa/mucosa. Irregular luminal protrusion of overlying mucosa Superficial ulceration, inflammation, adherent blood clots

C. ESOPHAGITIS DISEASE Reflux Esophagitis

ETIOLOGY

CLINICAL MANIFESTATIONS In adults Dysphagia Heartburn Regurgitation of gastric contents in the mouth Hematemesis Melena Stricture or Barrett esophagus

MORPHOLOGY

antireflux mechanisms Sliding hiatal hernias Delayed gastric emptying and gastric volume the esophageal mucosa

Hyperemia and edema Thickened basal zone & thinning of superficial epithelial layers Neutrophil or eosinophil infiltration Superficial necrosis and ulceration with adherent inflammatory exudate

Barrett Esophagus

long-standing gastroesophageal reflux disease (GERD).

In adults may lead to adenocarcinoma

Gross: irregular circumferential band of red, velvety mucosa at the gastroesophageal junction, with linear streaks or patches of similar mucosa in the distal esophagus Microscopic: Normal squamous mucosa of distal esophagus replaced by metaplastic intestinal-like columnar epithelium

Infectious and Chemical Esophagitis

Causes: Prolonged gastric intubation Ingestion of irritants: alcohol corrosive acids or alkalis, excessive hot fluids, smoking Bacteria, viral (Herpesvirus, CMV) or fungal (candidiasis, mucormycosis, aspergillosis) infection Uremia, Chemo- or radiotherapy, Graft-vs-host disease, Autoimmune diseases, Chron disease Systemic desquamative disorders (pemphigoid, epidermolysis bullosa)

A. CONGENITAL ANOMALIES DISEASE ETIOLOGY Pancreatic heterotopia Diaphragmatic Hernia Weakness of the diaphragm

II.

THE STOMACH MORPHOLOGY In the gastric muscle wall

CLINICAL MANIFESTATIONS

Fatal if with respiratory impairment with pulmonary hypoplasia Male to female ratio 4:1

In utero displacement of the stomach cephalad Hypertrophy or hyperplasia of pyloric muscularis propria Visible peristalsis Palpable firm ovoid mass Gross: edema and hyperaemia, acute hemorrhagic erosive gastritis Microscopic: neutrophil invasion, erosion

Pyloric Stenosis B. GASTRITIS NSAIDs, EtOH, tobacco, stress, uremia, chemotherapy, ischemia, radiation, systemic infections.

Acute Gastritis

Chronic Gastritis

H. pylori colonization of mucosa EtOH, tobacco, post-surgical, obstruction, Crohn disease

Gross: reddened, boggy, coarse-textured mucosa Histologically: Lymphocyte and plasma cell infiltrate in lamina propria Intraepithelial neutrophilic infil8s Mucosal gland atrophy Metaplasia of surface columnar epithelium to intestinal-type Dysplasia in long standing C. Gastritis

I.5 The Thyroid Gland (Robbins)

Page 2 of 8

C. PEPTIC ULCER DISEASE Epigastric gnawing, burning, or aching pain, worse at night and 1-3 hrs after meals. Nausea, vomiting, bloating, belching, weight loss COMPLICATIONS: Hemorrhage, perforation, peritonitis, scarring

Peptic Ulcer

exposure to acid and peptic juices

Gross: sharply punched-out defect with overhanging mucosal borders; smooth, clean ulcer bases Microscopic: necrotic debris; granulation tissue; deep scarring

Acute Gastric Ulceration

Severe stress shock, extensive burns, sever trauma (Curling ulcers) ICP (Cushing ulcers) NSAIDs

Acute gastric erosions or ulcers

Ulcers less than 1cm in diameter Ulcer base is brown (blood)

D. MISCELLANEOUS CONDITIONS Gastric outlet obstruction (pyloric stenosis, tumors) Gastric and intestinal atony (ileus) Phytobezoar trichobezoar (hairball) Heavy eosinophilic infiltration of the mucosa or submucosa Idiopathic; Allergy Hypoalbuminemia risk for PUD Protein-losing enteropathy TGF- overexpression (?) Hypochlorydia Hypoproteinemia Hyperchlorydia Excessive gastrin secrxn Gastrinoma (ZollingerEllison) In portal hypertension

Gastric Dilation

Rarely, gastric rupture

Bezoars Eosinophilic gastritis Hypertrophic Gastropathy Menetrier disease Hypertrophichypersecretory gastropathy Gastric Gland hyperplasia Gastric Varices

Luminal concretions

Hyperplasia of mucosal epithelial of gastric rugal folds Hyperplasia of surface mucous (foveolar) cells Fundic gland atrophy Hyperplasia of parietal and chief cells (fundic glands) Parietal cell hyperplasia Occurs near the gastroesophageal junction

Hyperchlorydia

III.
A. CONGENITAL ANOMALIES DISEASE ETIOLOGY Meckel Diverticulum Congenital Aganglionic Megacolon\ (Hirschsprung Disease) Acquired Megacolon Diarrhea

SMALL AND LARGE INTESTINES CLINICAL MANIFESTATIONS MORPHOLOGY Blind pouch leading off the alimentary tract, lined by mucosa and communicating with the gut lumen Absence of ganglion cells and ganglia in muscle wall and submucosa of affected segment (usu. Rectum)

Arrested (proximal to distal) migration of neural crest cells into the gut Assoc with Down syndrome

Male female ratio 4:1 Neonatal failure to pass meconium or abdominal distention Risk: perforation, sepsis, enterocolitis

Occur in Chagas disease, bowel obstruction, inflammatory bowel disease, and psychosomatic disorders

B. ENTEROCOLITIS >250 gm daily stool production with 70%-90% water Dysentery low volume painful diarrhea Secretory Net intestinal fluid secretion >500 mL/day; isotonic with plasma; diarrhea Osmotic >500 mL stool/day; osmotic gap diarrhea Malabsorption Voluminous, bulky stools w/ excess fat and osmolality Exudative Purulent bloody stools diseases Infectious Enterocolitis Rotavirus; Calicivirus (Norwalk/Norwalk-like Acute illness: 1-7 days Viral Entercolitis virus, Sapporo-like Diarrhea, anorexia, fever, virus); headache Enteric adenoviruses; Astroviruses
I.5 The Thyroid Gland (Robbins)

persists during fasting

Shortened villi lamina propria inflammation enterocyte amage (brush border loss & cytoplasmic vascuolization crypt hyperplasia

Page 3 of 8

 Ingestion of preformed Bacterial Enterocolitis Infection w/ enteric

Antibiotic Clostridium difficile toxin Associated Colitis overgrowth after (Pseudomem-branous antibiotic therapy Colitis) Parasitic Nematodes, Cestodes, Enterocolitis Protozoa Immature gut immunity Onset of oral feeding Necrotizing Bacterial colonization Entercolitis Mucosal injury Impaired intestinal blood flow Collagenous Colitis Autoimmune disease, sprue Miscellaneous Intestinal Inflammatory Disorders AIDS-associated HIV diarrheal illness Lymphocytic Colitis Transplantation Drug-induced interstinal injury Radiation enterocolitis Neutropenic colitis (Typhlitis) Diversion colitis Colitis cystic profunda solitary rectal ulcer syndrome C. MALABSORPTION SYNDROME Defects in: Intraluminal digestion Terminal digestion Transepithelial transport NSAID

Explosive diarrhea & abd pain Hrs-days incubation; diarrhea; dehydration; dysentery Yersinial & mycobacterial infections Right colon plaquelike adhesion of fibrinopurulent necrotic, grayyellow debris and mucus to the damaged colonic mucosa

In low-birth-weight or premature neonates Mild diarrhea to fulminant illness with gangrene, perforation, sepsis, shock Chronic watery diarrhea with abdominal pain

Mucosal edema, hemorrhage, necrosis in terminal ileum and proximal colon or entire gut Patches of bandlike collagen under the surface epithelium Intraepithelial infiltrates of lymphocytes In mucosal epithelium Mild lymphocytic infiltrate Crypt epithelial cell apoptosis Focal ulceration Mucosal inflammation

Inflammatory diarrhea Bone marrow transplant Enterostomy Inadequate nutrition Acute inflammatory destruction of the cecal region Chronic lymphoplasmacytic inflammation Lymphoid follicular hyperplasia Acute angulation of anterior rectal shelf Mechanical abrasion Distorted, cystically dilated glands surrounded by proliferating smooth muscle cells

Rectal bleeding Mucosal discharge

MALABSORPTION SYDROME

Celiac Disease

Gluten in wheat, oat, barley, rye

Tropical Travel or habitation (Postinfectious) Sprue exposure

Whipple Disease

Tropheryma whippelii

Lactase Deficiency Abetalipoproteinemia Cannot synthesize apolipoprotein B

Diarrhea, flatus, pain, weight loss, bulky,frothy,greasy stools Anemia, bleeding Ostopenia, tetany Amenorrhea, impotence, infertility, hyperparathyroidism Purpura and petechiae, edema, dermatitis Peripheral neuropathy Diarrhea, flatulence, weight loss, fatgue marked atrophy of villi Antibodies to tissue elongated regenerative crypts transglutaminase and surface epithelial damage with gliadin intraepithelial lymphocytes Dermatitis herpetiformis exuberant lamina propria chronic COMPLICATIONS: iron inflammation and vitamin deficiencies; risk for GI lymphoma Villous blunting Abundant lymphocytes and eosinophils in lamina propria Diarrhea, steatorrhea, malabsorption, abdominal mucosa becomes laden w/ cramps, distention, fever, distended macrophages in the weight loss, migratory lamina propria arthritis, heart disease (+) PAS In whites and males Diarrhea; malabsorption No abnormalities of mucosa Failure to thrive, diarrhea, steatorrea, neurologic and Lipid vacuolation liver disorders, retinitis Burr cells pigmentosa

D. IDIOPATHIC INFLAMMATORY BOWEL DISEASE DISEASE ETIOLOGY CLINICAL MANIFESTATIONS Intermittent attacks of diarrhea, Genetic fever, abdominal pain, anorexia, Infectious weight loss Chron Disease Mucosal integrity Migratory polyarthritis, sacroiliitis, Abnormal host ankylosing spondylitis, erythema immunoreactivity nodosum, uveitis, cholangitis,
I.5 The Thyroid Gland (Robbins)

MORPHOLOGY Non-caseating sarcoid-like granulomas Transmural inflammation Goblet cell population Maintenance of gladular architecture Skip lesions
Page 4 of 8

Ulcerative Colitis

amyloidosis COMPLICATIONS: fistulas, malabsorption, malnutrition, protein-losing enteropathy Risk: bowel cancer Intermittent attacks of bloody mucoid diarrhea;abd pain Toxic megacolon Migratory polyarthritis, , sacroiliitis, ankylosing spondylitis, erythema nodosum, uveitis, cholangitis Risk: carcinoma

cobblestone appearance aphthous ulcers Chrronic mucosal damage; fibrosis; dysplasia Non-granulomatous No skip lesions Mucosa reddened, granular or friable iwth inflammatory pseudopolyps and easy bleeding

E. VASCULAR DISORDERS DISEASE ETIOLOGY

CLINICAL MANIFESTATIONS

Ischemic Bowel Disease

Arterial thrombosis Arterial embolism Venous thrombosis Nonocclusive ischemia

Severe abdominal pain Bloody diarrhea Gross melena Nausea Vomiting Bloating Abdominal wall rigidity

MORPHOLOGY Mucosal infarction: patchy mucosal hemorrhage Mural infarction: complete mucosal necrosis Transmural infarction: sudden and total occlusion of major vasculature; gangrene, peforation Venous thrombosis: acute mesenteric venous occlusion Chronic ischemia: mucosal inflammation, ulceration, fibrosis, stricture Tortuous abnormal dilations of submucosal veins to lamina propria of cecum or ascending colon

Angiodysplasia

Hemorrhoids

Constipation Venous stasis during pregnancy Cirrhosis (portal HPN) Usu asymptomatic Cramping, abd discomfort, constipation COMPLICATION: pericolic abscesses, sinus tracts, peritonitis CLINICAL MANIFESTATIONS

Variceal dilations of anal and perianal submucosal venous plexi

Diverticular Disease

Focal bowel wall weakness

Multi flask-like outpouchings

F. INTESTINAL OBSTRUCTION DISEASE ETIOLOGY Peritoneal wall weakness or defect

MORPHOLOGY Hernia sac Incarceration

Hernias

Adhesions

Peritonitis following surgery, infection, endometriosis, radiation Children rotaviral vaccination or infection Adults tumor

Complications: internal herniation; obstruction; strangulation

Fibrous bridging between viscera Telescoping of one intestinal segment into immediately distal segment

Intussusception Volvolus

Obstruction and infarction

Twisting of a bowel loop about its mesenteric vascular base

IV. APPENDIX
Obstruction of appendicial lumen by fecalith, calculus, intraluminal pressure ischemia bacterial invasion Periumbilical pain migrating to RLQ Nausea or vomiting Abdominal tenderness Mild fever Leukocytosis >15,000 cells/mm3

Acute Appendicitis

Early: scant appendicial wall neutrophil exudates congestion of subserosal vessels perivascular neutrophil emigration Advanced/Acute suppurative: Severe neutrophilic infiltration Fibrinopurulent serosal exudates Luminal abscess formation Ulceration Suppurative necrosis Dilation of appendiceal lumen by mucinous secretions Peritoneum distended Tenaceious semisolid, mucinproducing anaplastic
Page 5 of 8

Mucocele Pseudomyxoma peritonei

Innocuous obstruction with inspissated mucus Mucin secreting adenomas Adenocarcinoma

I.5 The Thyroid Gland (Robbins)

adenocarcinoma cells

V. PERITONEUM
A. INFLAMMATION DISEASE ETIOLOGY Appendicitis, peptic ulcer, cholecystitis, diverticulitis, bowel strangulation, acute salpingitis, abd trauma, peritoneal dialysis, nephritic syndrome, cirrhosis CLINICAL MANIFESTATIONS MORPHOLOGY Peritoneal membranes dull and gray; exudates and frank suppuration Localized abscesses Tuberculous peritonitis exudates studded with minute pale granulomas

1. Peritoneal Infection

Can resolve spontaneously or with therapy

2. Sclerosing Retroperitoni tis

Methydergide use Fibrosing disorders (carcinoid tumors, sclerosing cholangitis, Riedel fibrosing thyroiditis)

Hydronephrosis

Dense infiltrative fibrosing overgrowth of retroperitoneal tissues Lymphocyte, plasma cell, neutrophil infiltrate

3. Mesenteric Cysts

Arise from sequestered lymphatic channels, pinched-off enteric diverticula of developing foregut or hindgut, developmental cysts of urogenital orgin, pancreatic pseudocyts, or walled-off infections

B. TUMORS Primary tumors Mesothelioma Desmoplastic small round cell tumor Secondary tumors

TUMORS OF THE GASTROINTESTINAL TRACT ESOPHAGUS 1. Benign Tumors: a. Intramural or submucosal: Leiomyoma, fibroma, lipoma, hemangioma, neurofibroma, lymphangioma b. Mucosal (larger than 3cm): Squamous papilloma, Fibrovascular polyp, Inflammatory polyp 2. Malignant Tumors DISEASE ETIOLOGY CLINICAL MANIFESTATIONS MORPHOLOGY Adults older than 50 years Gross: lesions may be polypoid (60%), More often in men and blacks Dietary, exhibit necrotizing excavation (25%), or Dysphagia Lifestyle, diffusely infiltrative (15%) Squamous Cell Obstruction Esophageal Microscopic: tumors well differentiated, Carcinoma Weight loss disorders, with or w/o keratinisation (SCC) Hemorrhage Genetic Begin as in situ gray-white, plaquelike Sepsis Predisposition Respiratory tree fistulas with longitudinally/circumferential aspiration Gross: exophytic nodules to excavated and Patients older than 40, more deeply infiltrative masses Barrett Adenocarcinoma often in men Microscopic: mucin-producing glandular esophagus Symptoms of GERD and SCC tumors with intestinal futures; Diffusely infiltrative signet ring cells

STOMACH 1. Benign Tumors a. Non-Neoplastic Polyps DISEASE ETIOLOGY Hyper-plastic or inflammatory polyps Fundic gland polyps Inflammatory fibroid polyps Hamartomatous polyps Occur with Peutz-Jeghers syndrome or; Juvenile polyposis syndrome Assoc with chronic gastritis

CLINICAL MANIFESTATIONS 90% of gastric polyps

MORPHOLOGY Smooth, sessile or pedunculated Epithelial tubules and cysts interspersed Inflamed stroma Fundic gland dilation Fibroblast proliferation in submucosa with eosinophil infiltrate

Occur with FAP

I.5 The Thyroid Gland (Robbins)

Page 6 of 8

b. Neoplastic Polyps Gastric Adenoma 2. Malignant

Chronic gastritis Genetic polyposis syndrome

40% harbour carcinoma

Proliferative dysplastic epithelium Single, can be sessile or pedunculated

Gastric Carcinoma

Environment; Diet; Smoking; chronic gastritis; autoimmune gastritis; partial gastrectomy H. pylori infection c-KIT gene mutation

Usu. Asymptomatic Weight loss, abdominal painm, anorexia, vomiting, altered bowel habits, dysphagia, anemia, hemorrhage

Gastric mucosa dysplasia Tumors are exophytic, flat, or depressed or excavated (See Lauren classification)

Lymphoma (MALT) Gastrointestinal stromal tumor (GIST) Carcinoid Tumors Schwannomas Lipomas

Solid tumor of the gastric mucosa or wall Tumor cells are either epithelioid or spindle cell shaped Enterochromaffin-like cell tumor

TUMORS OF THE SMALL INTESTINE DISEASE ETIOLOGY Adenomas Adenocarcinoma In Px with familial polyposis syndromes

CLINICAL MANIFESTATIONS Clinically silent unless they obstruct the intestinal lumen or CBD Obstruction (cramping pain, nausea, vomiting), weight loss, bleeding

MORPHOLOGY

Metastatic spread to mesentery, regional lymph nodes, liver

TUMORS OF THE COLON AND RECTUM 1. Benign a. Non-neoplastic polyps DISEASE Hyperplastic polyp ETIOLOGY CLINICAL MANIFESTATIONS 6th decade MORPHOLOGY Nipple like hemispheric protrusions Well-formed mature glands with crowding Focal sporadic hamartomatous malformations of SI and colon mucosa Large polyps, rounded, and pedunculated w/ cystically dialted glands and abundant laminar polyp Sporadic hamartomatous mucosal polyps of SI and colon Large polyps, pedunculated, lobulated with arborizing smooth muscle surrounding normal glands

Juvenile polyp

Children <5yrs

Peutz-Jeghers polyp b. Adenoma (Neoplastic polyps) Tubular adenoma Villous adenoma Tubulovillous adenoma Serrated adenoma 2. Malignant Assoc with MSI

risk for carcinomas

Asyptomatic or may cause occult bleeding with anemia SI adenomas cause obstruction and intusseption

Tubular glands, smooth surface Villous frondlike projections of epithelial surface Mixture of first two Features of both hyperplastic polyp and adenoma

Colorectal Carcinoma (FAP)

APC gene mutation; DNA methylation K-RAS, SMADs, p53, telomerase mutation

Asymptomatic at first Fatigue, weakness, iron deficiency anemia, abd discomfort, progressive bowel obstruction, liver enlargement

Gross: polypoid exophytic mass or annular mass with napkin-ring obstruction Histological: tall, columnar cells with invasion

II.1 The Gastrointestinal Tract (Robbins) - Trans

Page 7 of 8

a. Carcinoid Tumors

Asymptomatic but Sx caused by tumor secretory products

Tumors are small, firm, yellow-tan intramural or submucosal masses Fibrosis of muscularis kinking and obstruction Microscopic: islands to sheets of uniform chohesive cells with scant, granular cytoplasm and oval, stippled nuclei (+) for chromogranin and synaptophysin Early lesions: plaquelike mucosal or submucosal expansions Advanced: full mural thickness or polypoid exophytic masses protruding to lumen Microscopic: atypical lymphocytes infiltrate

b. Gastrointestinal Lymphoma c. Mesenchymal Tumors Lipomas GIST Smooth muscle tumors Kaposi Sarcoma (Most common GI mesenchymal tumor)

Amenable to surgical resection; chemoresponsive

Asymptomatic Larger lesions: mucosal ulcerations with bleeding, obstruction, or intusseption

In SI or colon submucosa Spindle shaped ore epitheloid; c-KIT positive Spindle shaped lesions with smooth muscle phenotype Visceral involvement

II.1 The Gastrointestinal Tract (Robbins) - Trans

Page 8 of 8