The Gastrointestinal Tract

The Gastrointestinal Tract

GI – Congenital Anomalies

Atresias, fistulae, duplications, stenosisEsophageal atresia usually associated with TE fistulaImperforate anus – most common

form of congenital intestinal atresia, failure of the cloacal diaphragm to involute

GI – Congenital AnomaliesDiaphragmatic hernia – incomplete formation of the diaphragm allowing the abdominal viscera to herniate into the chest, associated with pulmonary hypoplasia

Omphalocele – abdominal musculature is incomplete, abdominal viscera herniate into a ventral membranous sac

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 AnomaliesPyloric stenosisMales > femalesAssociated with Turner, Trisomy 182nd -3rd week of life New-onset regurgitationPersistent projectile vomitingHyperperistalis, firm ovoid mass “olive”Hirschsprung DiseaseCongenital aganglionic megacolonFailure of the normal migration of neural crest cells from cecum to rectum or ganglion cells undergo premature deathFunctional obstructionMegacolonFailure to pass meconium in immediate post-natal periodRET mutation

GI - EsophagusObstructionNutcracker esophagusDiffuse esophageal spasmZenker diverticulumTraction diverticulumEpiphrenic DiverticulumStenosis – most often due to inflammation and scarringEsophageal webs – Plummer-Vinson syndrome (Paterson-Brown-Kelly)Esopahgeal (Schatzki) ringsAchalasia – incomplete LES relaxation, increased LES tone, and aperistalsis of the esophagus

GI-Esophagus

EsophagitisLacerations – Mallory-Weiss syndromelinear lacerations associated with prolonged vomitingChemical and Infectious – pill- induced, chemotherapy, radiation therapy, GVH, HSV, CMV, fungal, bullous pemphigoid, epidermolysis bullosa, Crohn diseaseReflux – GERD –most frequent cause of esophagitis, most common cause of GI diagnosis in US, hiatal herniaEosinophilic – atopic individuals

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 varicesPortal hypertension, collateral

circulation, cirrhosis –most commonly due to alcoholic liver disease, schistosomiasis, massive hematemesis

GI- Esophagus

Esophageal tumorsAdenocarcinoma – 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 gastritisTransient mucosal inflammatory processHistologically – continuum from moderate edema and

congestion of the lamina propria with an intact epithelium to acute erosive hemorrhagic gastritis

GI - Stomach

Acute gastric ulcerationStress ulcerCurling ulcerCushing ulcerComplicationsBleeding – most frequent Perforation – accounts for 2/3 ulcer deathsObstruction - pyloric

GI-Stomach

Chronic gastritisSymptoms less severe, more persistentMost 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 – StomachH.Pylori- flagella, urease, adhesins, toxinsPredominantly antral gastritis with high acid production despite hypogastrinemiaMay progress to involve the entire stomachwith multifocal mucosal atrophy, reduced acid secretion, intestinal metaplasia, increased risk of gastric adenocarcinomaIntraepithelial neutrophils, subepithelial plasma cells, pit abscesses, mucosal –associated lymphoid tissue (MALT)

GI-StomachAutoimmune gastritisHypergastrinemiaAntibodies to parietal cells and intrinsic factorAntral endocrine cell hyperplasiaReduced serum pepsinogen I concentrationVitamin B12 deficiencyDefective gastric acid secretion (achlorhydria)

Damage to the oxyntic (acid-producing cells)

Clinical- atrophic glossitis, epithelial megaoblastosis, malabsortive diarrhea, anemia, peripheral neuropathy, spinal cord lesions, cerebral dysfunction

GI- Stomach

Reactive gastropathyEosinophilic gastritisLymphocytic gastritisGranulomatous gastritis

GI - StomachComplications of chronic gastritisPeptic ulcer disease:Imbalances of mucosal defenses and damaging forces that cause chronic gastritis are also responsible for PUD

H.pylori -85%-100% duodenal ulcers65% gastric ulcersNSAID useSharply 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 gastritisMucosal atrophy and intestinal metaplasia:Increased risk of gastric adenocarcinomaDysplasiaGastric Cystica: Exuberant reactive epithelial proliferation with entrapment of epithelial-lined cells

GI - Stomach

Hypertrophic GastropathiesMenetrier disease- excessive production of TGF-alpha, hyperplasia of folveolar mucous cells, hypoproteinemiaZollinger-Ellison syndrome –gastrin- secreting 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- StomachGastric polyps and tumorsInflammatory and hyperplastic polyp- most common, frequently multipleFundic gland polyp – associated with PPI useGastric adenomaGastric adenocarcinoma-loss of E-cadherin function seems to be key step in development, signet-ring cells, linitis plastica, Virchow’s node, Sister Mary joseph nodeLymphoma – MALToma,Carcinoid tumor- well-differentiated neuroendocrine tumor, location is most important prognostic factor, flushing, diarrhea, sweating, bronchospasm, colic, right-sided cardiac vavular fibrosisGIST (GI stromal tumor)- tyrosine kinase c-KIT gene mutation, NF type 1

Small Intestine and ColonObstructionHernias, adhesions, volvulus, intussusceptionIschemic bowel diseaseMucosal and mural infarctionsChronic ischemiaCMV infectionRadiation enterocolitisNECAngiodysplasiaMalformed submucosal and mucosal blood vessels, lower intestinal bleeding, most often cecum or right colon

Small Intestine and ColonMalabsorptionDefective absorption of fats, vitamins, proteins, carbohydrates, electrolytes, minerals, and water

Steatorrhea – excessive fecal fat

Most common disorders in US – pancreatic insufficiency, celiac disease, Crohn disease

Disturbance in at least one phase of digestion:intraluminal transportterminal digestiontranepithelial transportlymphatic transportClinical – diarrhea, flatus, abdominal pain, weight loss

Small Intestine and Colon

DiarrheaIncrease in stool mass, frequency, or fluidity ,> 200g per dayDysentery – painful, bloody, small- volumeCategoriesSecretoryOsmoticMalabsortiveExudative

Small Intestine and ColonCeliac diseaseCeliac sprue or gluten-sensitive enteropathyImmune-mediatedHLA-DQ2 or HLA-DQ8Intraepithelial lymphocytosis (CD8+ T cells), crypt hyperplasia, villous atrophyDermatitis herpetiformisLymphocytic gastritis or colitisEnteropathy-associated T cell lymphomaSmall intestinal adenocarcinoma


Tropical sprueAutoimmune enteropathyLactase deficiency – congenital or acquiredAbetalipoproteinemia


Infectious enterocolitisCholera – Vibrio cholerae, contaminated drinking water, shellfish, non-invasive, enterotoxin causes secretory diarrhea via increase in cAMP, “rice water” stoolsCampylobacter – 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 ColonShigellosis – 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


Escherichia coli – (most E.coli are nonpathogenic)

ETEC – principal cause of traveler’s diarrhea, secretory diarrhea

EHEC – HUS, 0157:H7, ground beefEIEC – invade epithelial cellsEAEC – adherence fimbriae


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


Viral gastroenteritis-Norovirus –cruise ships,schools, hospitals, nursing homes

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 ColonParasitic enterocolitis –Ascaris lumbricoides-hepatic abscess, pneumonitis, intestinal obstrutionStrongyloides - autoinfectionNecator duodenale and Ancylostoma duodenale – hook worms, iron deficiency anemiaEnterobius vermicularis - pinwormsTrichuris trichura – whipworms, rectal prolapseSchistomiasis – granulomatous reactionIntestinal cystodes - tapewormsEntamoeba histolytica – dysentery, hepatic abscessesGiardia lamblia – most common pathogenic parasitic infection in humansCryptosporidium – chronic diarrhea in AIDS


Irritable Bowel syndrome – diagnosis of exclusionInflammatory Bowel Disease – idiopathic, combination of defects in host interactions with intestinal microbiota, intestinal epithelial dysfunction, and aberrant mucosal immune responses, hygiene hypothesis

Crohn diseaseUlcerative colitis

Small Intestine and ColonCrohn diseaseAny area of GI tractMost common terminal ileum, iliocecal valve, cecumSkip lesions, aphthous ulcers, creeping fat, transmural inflammation, noncaseating granulomas, , fistulas and strictures, malabsorption

Clinical – intermittent attacks of fever, diarrhea, and abdominal painExtra-intestinal – uveitis, migratory polyarthritis, sacroillitis,, skin lesions, primary sclerosing cholangitis


Ulcerative colitisPancolitis to proctitisBackwash ileitisBroad-based ulcers, pseudopolyps, inflammation diffuse and limited to the mucosaToxic megacolonExtra-intestinal – same as CrohnIncreased inidence of neoplasia


Indeterminate colitisDiversion colitisMicroscopic colitisSigmoid diverticulitis


PolypsSessile vs PedunculatedInflammatory-solitary rectal ulcer syndromeHamartomatous – Juvenile, Peutz-Jeghers ,Cowden, Bannayan- Ruvalcaba , Cronkhite-Canada, Tuberous SclerosisHyperplasticNeoplastic – premalignant adenomas

Small Intestine and ColonFamilial syndromesFamilial adenomatous polyposisHereditary non-polyposis colorectal cancer – Lynch syndromeAdenocarcinomaAdenoma-carcinoma sequenceMicrosatellite instabilityMismatch repair deficiencyClinical – right-sided – fatigue and weakness due to iron-deficiency anemia, left-sided – occult bleeding, changes in bowel habits, cramping

Small Intestine and COlon

Anal canal tumors – basaloid, squamous cell – HPVHemorrhoidsAcute appendicitis Appendix tumors – carcinoid,mucinous cystadenoma or cystadenocarcinoma – pseudomyxoma peritoneii

Peritoneal CavityInflammatory - peritonitisSterile peritonitis- leakage of bile or pancreatic enzymesPerforation of rupture of biliary systemAcute hemorrhagic pancreatitisForeign materialEndometriosisRuptured dermoid cystPerforation of abdomen visceraBacterialSpontaneous bacterial – nephrotic syndrome, ascites

Peritoneal Cavity

Sclerosing retroperitonitis or fibrosis – Ormond diseaseCysts and pseudocystsTumorsPrimary –mesothelioma, desmoplastic small round cell tumor related to Wilms and Ewing sarcoma)Secondary – most common ovarian, pancreatic, appendiceal

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The Gastrointestinal Tract