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The Gastrointestinal Tract GI – Congenital Anomalies Atresias, fistulae, duplications, stenosis Esophageal atresia usually associated with TE fistula Imperforate anus – most common form of congenital intestinal atresia, failure of the cloacal diaphragm to involute GI – Congenital Anomalies Diaphragmatic hernia – incomplete formation of the diaphragm allowing the abdominal viscera to herniate into the chest, associated with pulmonary hypoplasia Omphalocele – abdominal musculature incomplete, abdominal viscera into a ventral membranous sac is herniate Gastroschisis – defect in all the layers of the abdominal wall from peritoneum to the skin GI Ectopia (developmental arrests) – common in the GI tract, e.g. inlet patch (gastric mucosa in upper 1/3 of the esophagus) Meckel diverticulum – blind outpouching of the alimentary tract that is lined by mucosa, communicates with the lumen, includes all three layers of the bowel wall, “rule of 2’s” – 2% of the population, within 2 feet of the ileocecal valve, twice as common in males than females, most often symptomatic by age two GI – Congenital Anomalies Pyloric stenosis Males > females Associated with Turner, Trisomy 18 2nd -3rd week of life New-onset regurgitation Persistent projectile vomiting Hyperperistalis, firm ovoid mass “olive” Hirschsprung Disease Congenital aganglionic megacolon Failure of the normal migration of neural crest cells from cecum to or ganglion cells undergo premature death Functional obstruction Megacolon Failure to pass meconium in immediate post-natal period RET mutation rectum GI - Esophagus Obstruction Nutcracker esophagus Diffuse esophageal spasm Zenker diverticulum Traction diverticulum Epiphrenic Diverticulum Stenosis – most often due to inflammation and scarring Esophageal webs – Plummer-Vinson syndrome (Paterson-Brown-Kelly) Esopahgeal (Schatzki) rings Achalasia – incomplete LES relaxation, increased LES tone, and aperistalsis of the esophagus GI-Esophagus Esophagitis Lacerations – Mallory-Weiss syndrome linear lacerations associated with prolonged vomiting Chemical and Infectious – pillinduced, chemotherapy, radiation therapy, GVH, HSV, fungal, bullous pemphigoid, bullosa, Crohn disease Reflux – GERD –most frequent cause of esophagitis, most common cause of diagnosis in US, hiatal hernia Eosinophilic – atopic individuals CMV, epidermolysis GI GI - Esophagus Barrett esophagus – intestinal metaplasia within the esophageal squamous mucosa, increased risk of esophageal adenocarcinoma, red,velvety mucosa, goblet cells, may progress to dysplasia GI - Esophagus Esophageal varices Portal hypertension, collateral circulation, cirrhosis –most commonly due to alcoholic liver disease, schistosomiasis, massive hematemesis GI- Esophagus Esophageal tumors Adenocarcinoma – GERD, Barrett esophagus, increasing incidence. difficulty swallowing, progressive weight loss, hematemesis, chest pain, vomiting, distal third Squamous cell carcinoma – alcohol, smoking, prior radiation therapy,, HPV, high-risk areas: Iran, China, Hong Kong, Brazil, South Africa, middle third, insidious onset GI - Stomach Acute gastritis Transient mucosal inflammatory process Histologically – continuum from moderate edema and congestion of the lamina propria with an intact epithelium to acute erosive hemorrhagic gastritis GI - Stomach Acute gastric ulceration Stress ulcer Curling ulcer Cushing ulcer Complications Bleeding – most frequent Perforation – accounts for 2/3 ulcer deaths Obstruction - pyloric GI-Stomach Chronic gastritis Symptoms less severe, more persistent Most common cause is infection with H.pylori –spiral shaped or curved bacilli – present in gastric biopsy specimens of all most everyone with duodenal ulcers and the majority with gastric ulcers and chronic gastritis GI – Stomach H.Pylori- flagella, urease, adhesins, toxins Predominantly antral gastritis with high acid production despite hypogastrinemia May progress to involve the entire stomach with multifocal mucosal atrophy, reduced acid secretion, intestinal metaplasia, increased risk of gastric adenocarcinoma Intraepithelial neutrophils, subepithelial plasma cells, pit abscesses, mucosal – associated lymphoid tissue (MALT) GI-Stomach Autoimmune gastritis Hypergastrinemia Antibodies to parietal cells and intrinsic factor Antral endocrine cell hyperplasia Reduced serum pepsinogen I concentration Vitamin B12 deficiency Defective gastric acid secretion (achlorhydria) Damage to the oxyntic (acidproducing cells) Clinical- atrophic glossitis, epithelial megaoblastosis, malabsortive diarrhea, anemia, peripheral neuropathy, spinal cord lesions, cerebral dysfunction GI- Stomach Reactive gastropathy Eosinophilic gastritis Lymphocytic gastritis Granulomatous gastritis GI - Stomach Complications of chronic gastritis Peptic ulcer disease: Imbalances of mucosal defenses and damaging forces that cause chronic gastritis are also responsible for PUD H.pylori -85%-100% duodenal ulcers 65% gastric ulcers NSAID use Sharply punched-out defect, round to oval, four times more common in the duodenum (usually anterior wall near pyloric valve) than in the stomach (along the lesser curvature) Clinical – epigastric burning or aching pain, 1-3 hours after eating, worse at night, relieved by alkali or food GI-Stomach Complications of chronic gastritis Mucosal atrophy and intestinal metaplasia: Increased risk of gastric adenocarcinoma Dysplasia Gastric Cystica: Exuberant reactive epithelial proliferation with entrapment of epithelial-lined cells GI - Stomach Hypertrophic Gastropathies Menetrier disease- excessive production of TGF-alpha, hyperplasia of folveolar mucous cells, hypoproteinemia Zollinger-Ellison syndrome –gastrinsecreting tumor (usually small intestine or pancreas), increase in number of parietal cells, duodenal ulcers, diarrhea,60-90% are slow-growing malignant, 255 associated with MEN-I GI- Stomach Gastric polyps and tumors Inflammatory and hyperplastic polyp- most common, frequently multiple Fundic gland polyp – associated with PPI use Gastric adenoma Gastric adenocarcinoma-loss of E-cadherin function seems to be key step in development, signet-ring cells, linitis plastica, Virchow’s node, Sister Mary joseph node Lymphoma – MALToma, Carcinoid tumor- well-differentiated neuroendocrine tumor, location is most important prognostic factor, flushing, diarrhea, sweating, bronchospasm, colic, right-sided cardiac vavular fibrosis GIST (GI stromal tumor)- tyrosine kinase c-KIT gene mutation, NF type 1 Small Intestine and Colon Obstruction Hernias, adhesions, volvulus, intussusception Ischemic bowel disease Mucosal and mural infarctions Chronic ischemia CMV infection Radiation enterocolitis NEC Angiodysplasia Malformed submucosal and mucosal blood intestinal bleeding, most often cecum or right colon vessels, lower Small Intestine and Colon Malabsorption Defective absorption of fats, vitamins, proteins, carbohydrates, electrolytes, minerals, and water Steatorrhea – excessive fecal fat Most common disorders in US – disease, Crohn disease pancreatic insufficiency, Disturbance in at least one phase of digestion: intraluminal transport terminal digestion tranepithelial transport lymphatic transport Clinical – diarrhea, flatus, abdominal pain, weight loss celiac Small Intestine and Colon Diarrhea Increase in stool mass, frequency, or fluidity ,> 200g per day Dysentery – painful, bloody, smallvolume Categories Secretory Osmotic Malabsortive Exudative Small Intestine and Colon Celiac disease Celiac sprue or gluten-sensitive enteropathy Immune-mediated HLA-DQ2 or HLA-DQ8 Intraepithelial lymphocytosis (CD8+ T cells), crypt hyperplasia, villous atrophy Dermatitis herpetiformis Lymphocytic gastritis or colitis Enteropathy-associated T cell lymphoma Small intestinal adenocarcinoma Small Intestine and Colon Tropical sprue Autoimmune enteropathy Lactase deficiency – congenital or Abetalipoproteinemia acquired Small Intestine and Colon Infectious enterocolitis Cholera – Vibrio cholerae, contaminated drinking water, shellfish, non-invasive, enterotoxin causes secretory diarrhea via increase in cAMP, “rice water” stools Campylobacter – Most common bacterial enteric pathogen in developed countries, traveler’s diarrhea, improperly cooked chicken, dysentery, enteric fever, reactive arthritis, erythema nodosum, Guillain-Barre, invasive Small Intestine and Colon Shigellosis – Bloody diarrhea, Reiter syndrome, Shiga toxin – HUS, in endemic areas is responsible for 75% of diarrheal deaths Salmonellosis – nontyphoid infection, meat (poultry), milk, eggs, antibiotics can prolong carrier state, Typhoid fever – enteric fever, gallbladder colonization, hyperplasia of lymphoid tissues, oval ulcers that may perforate in ileum, typhoid nodules, bacteremia, rose spots, extraintestinal complications, sickle cell disease-osteomyelitis Yersinia – pork, raw milk, contaminated water,lymph node and Peyer’s patch hyperplasia, pharyngitis,arthralgia, erythema nodosum, reactive arthritis, Reiter syndrome, myocarditis, GN,thyroiditis Small Intestine and Colon Escherichia coli – (most E.coli are nonpathogenic) ETEC – principal cause of traveler’s diarrhea, secretory diarrhea EHEC – HUS, 0157:H7, ground beef EIEC – invade epithelial cells EAEC – adherence fimbriae Small Intestine and Colon Pseudomembranous colitis-Clostridium. Difficile, antibiotic-associated, overgrowth of organism, toxins, eruption of damaged crypts leads to pseudomembrane formation Whipple disease – Tropheryma whippelii (gram-positive actinomycete), organism-laden macrophages accumulate causing lymphatic obstruction malabsorption, arthritis, fever, lymphadenopathy, neurologic, cardiac, pulmonary disease Small Intestine and Colon Viral gastroenteritisNorovirus –cruise ships,schools, nursing homes hospitals, Rotovirus – the most common cause of severe childhood diarrhea and diarrhea mortality worldwide, vaccine Adenovirus –second most common cause of pediatric diarrhea Small Intestine and Colon Parasitic enterocolitis – Ascaris lumbricoides-hepatic abscess, pneumonitis, intestinal obstrution Strongyloides - autoinfection Necator duodenale and Ancylostoma duodenale – hook worms, iron deficiency anemia Enterobius vermicularis - pinworms Trichuris trichura – whipworms, rectal prolapse Schistomiasis – granulomatous reaction Intestinal cystodes - tapeworms Entamoeba histolytica – dysentery, hepatic abscesses Giardia lamblia – most common pathogenic parasitic infection in humans Cryptosporidium – chronic diarrhea in AIDS Small Intestine and Colon Irritable Bowel syndrome – diagnosis of exclusion Inflammatory Bowel Disease – idiopathic, combination of defects in host interactions with intestinal microbiota, intestinal epithelial dysfunction, and aberrant mucosal immune responses, hygiene hypothesis Crohn disease Ulcerative colitis Small Intestine and Colon Crohn disease Any area of GI tract Most common terminal ileum, iliocecal valve, cecum Skip lesions, aphthous ulcers, creeping fat, transmural inflammation, noncaseating granulomas, , fistulas and strictures, malabsorption Clinical – intermittent attacks of fever, diarrhea, and abdominal pain Extra-intestinal – uveitis, migratory polyarthritis, sacroillitis,, skin lesions, primary sclerosing cholangitis Small Intestine and Colon Ulcerative colitis Pancolitis to proctitis Backwash ileitis Broad-based ulcers, pseudopolyps, inflammation diffuse and limited the mucosa Toxic megacolon Extra-intestinal – same as Crohn Increased inidence of neoplasia to Small Intestine and Colon Indeterminate colitis Diversion colitis Microscopic colitis Sigmoid diverticulitis Small Intestine and Colon Polyps Sessile vs Pedunculated Inflammatory-solitary rectal ulcer syndrome Hamartomatous – Juvenile, PeutzJeghers ,Cowden, BannayanRuvalcaba , Cronkhite-Canada, Tuberous Sclerosis Hyperplastic Neoplastic – premalignant adenomas Small Intestine and Colon Familial syndromes Familial adenomatous polyposis Hereditary non-polyposis colorectal Lynch syndrome Adenocarcinoma Adenoma-carcinoma sequence Microsatellite instability Mismatch repair deficiency Clinical – right-sided – fatigue and weakness due to iron-deficiency anemia, left-sided – occult bleeding, changes in bowel habits, cramping cancer – Small Intestine and COlon Anal canal tumors – basaloid, squamous cell – HPV Hemorrhoids Acute appendicitis Appendix tumors – carcinoid,mucinous cystadenoma or cystadenocarcinoma – pseudomyxoma peritoneii Peritoneal Cavity Inflammatory - peritonitis Sterile peritonitis- leakage of bile or enzymes Perforation of rupture of biliary system Acute hemorrhagic pancreatitis Foreign material Endometriosis Ruptured dermoid cyst Perforation of abdomen viscera Bacterial Spontaneous bacterial – nephrotic syndrome, ascites pancreatic Peritoneal Cavity Sclerosing retroperitonitis or fibrosis – Ormond disease Cysts and pseudocysts Tumors Primary –mesothelioma, desmoplastic small round cell tumor related to Wilms and Ewing sarcoma) Secondary – most common ovarian, pancreatic, appendiceal