GI

Question 1

Esophageal Atresia

Answer 1

• portion of conduit replaced by thin, noncanalized cord with blind pouches above and below atretic segment.
• associated with congenital heart defects, GU malformations, and neurologic disorders.
• presentation: regurgitation during feeding.

Question 2

Imperforate Anus

Answer 2

• most common congenital intestinal atresia.
• failure of cloacal membrane to involute.

Question 3

Esophageal Fistula

Answer 3

• connection btw esophagus and trachea or mainstem bronchus.
• swallowed material or gastric fluid can enter the respiratory tract.
• associated with: congenital heart defects, GU malformations, and neurologic disorders.
• presentation: regurgitation during feeding.

Question 4

Esophageal Stenosis

Answer 4

• incomplete form of atresia.
• lumen reduced by fibrous, thickened wall.
• can be congenital or from inflammatory scarring (chronic reflux, irradiation, scleroderma)

Question 5

Congenital Duplication Cysts

Answer 5

• cystic masses with redundant smooth muscle layers throughout GI tract.

Question 6

Diaphragmatic Hernia

Answer 6

• incomplete formation of diaphragm allows cephalad displacement of abd viscera.
• leads to pulmonary hypoplasia incompatable with life.

Question 7

Omphalocele

Answer 7

• abdominal musculature is incomplete and viscera herniate into ventral membranous sac.
• associated with other birth defects in 40%.

Question 8

Gastroschisis

Answer 8

• all layers of abd wall fail to develop (peritoneum to skin).
• viscera herniate into ventral membranous sac.

Question 9

GI Ectopia

Answer 9

• most common gastric mucosa ectopia is proximal esophagus.
  
  • ⇒ dysphagia and esophagitis.
• in small bowel/colon ⇒ occult blood loss or peptic ulceration.

Question 10

Pancreatic Heterotopia

Answer 10

• ectopic in esophagus and stomach.
• in pylorus ⇒ inflammation, scarring, and obstruction.

Question 11

Meckel Diverticulum

Answer 11

• 2% of population, 2:1 male:female
• persistence of vitelline duct ⇒ outpouching within 85cm of ileocecal valve.
• can have pancreatic tissue or heterotopic gastric mucosa (with peptic ulceration).

Question 12

Diverticulum

Answer 12

• blind pouch leading off alimentary tract, lined by mucosa and including all three layers of bowel wall (mucosa, submucosa, and muscularis propria)

Question 13

Pyloric Stenosis

Answer 13

• congenital hypertrophic pyloric stenosis: 1 in 500 births. 4:1 male:female.
  
  • associated with Turner syndrome and trisomy 18.
  • presentation: regurgitation and projectile vomiting within 3 wks of birth, externally visible peristalsis, palpable firm ovoid mass.
  • tx: myotomy (full thickness muscle spitting incision).
• acquired pyloric stenosis: from chronic antral gastritis, peptic ulcers close to pylorus, and malignancy.

Question 14

Hirschsprung Disease

Answer 14

• aka congenital aganglionic megacolon.
• from arrested migration of neural crest cells into the gut ⇒ aganglionic segment lacking peristaltic contractions ⇒ functional obstruction and progressive dilation and hypertrophy of unaffected proximal colon.
• pathogenesis: loss of function mutation in RET tyrosine kinase receptor in 15% sporadic and most familial.
  
  • 4:1 male:female.
• presentation: neonatal failure to pass meconium or abd distention with megacolon.
  
  • risk of peroration, sepsis, or enterocolitis with fluid derangement.
  • acquired megacolon with Chagas disease (lose ganglia), bowel obstruction, IBD, and psychosomatic disorders.

Question 15

Esophageal Spasm

Answer 15

• short or long-lived, focal or diffuse.
• diffuse ⇒ functional obstruction.
• ↑ wall stress can cause diverticula.

Question 16

Zenker Diverticulum

Answer 16

• aka pharyngeoesophageal diverticulum.
• occurs immediately above upper esophageal sphincter.
• contains one or more wall layers, can accumulate food if large and present as a mass with food regurgitation.

Question 17

Traction Diverticulum

Answer 17

• occurs at esophageal mid-point.
• contains one or more wall layers, when large can accumulate food and present as mass with food regurgitation.

Question 18

Epiphrenic Diverticulum

Answer 18

• occurs immediately above lower esophageal sphincter.
• contains one or more wall layers, when large can accumulate food and present as mass with food regurgitation.

Question 19

Mucosal Webs

Answer 19

• ledgelike protrusions of fibrovascular tissue and overlying epithelium.
• mostly in upper esophagus in women >40yrs.

Question 20

Plummer-Vinson Syndrome

Answer 20

• aka Paterson-Brown-Kelly Syndrome.
• constellation of webs, iron deficiency anemia, glossitis, and cheilosis.

Question 21

Esophageal Rings

Answer 21

• aka Schatzki rings.
• similar to webs but circumferential and thicker.
• include mucosa, submucosa, and occasionally hypertrophic muscularis propria.
• A rings = above esophageal junction.
  
  • squamous epithelium.
• B rings = at squamocolumnar junction.
  
  • contain gastric cardia-type mucosa.

Question 22

Achalasia

Answer 22

• triad: incomplete relaxation of LES, ↑ LES tone (cholinergic signaling), and esophageal aperistalsis.
• primary: idiopathic, from failure of distal esophageal neurons to induce LES relaxation during swallowing, or degenerative changes in neural innervation.
• secondary: with Chagas disease, disorders of vagal dorsal motor nuclei (polio, surgical ablation), diabetic autonomic neuropathy, infiltrative disorders (amyloid, sarcoid, cancer).
• tx: myotomy, balloon dilation, botulinum toxin injection to inhibit LES cholinergic neurons.

Question 23

Mallory-Weiss Tears

Answer 23

• longitudinal lacerations at gastroesophageal junction associated with excessive vomiting with alcohol intoxication.
  
  • caused by failure of relaxation of LES preceding vomiting. causes stretching and tearing.
• presentation: hematemesis.

Question 24

Chemical and Infectious Esophagitis

Answer 24

• squamous epithelium damaged by alcohol, corrosive acids or alkalis, excessively hot fluids, heavy smoking, irradiation, chemotherapy, graft-versus-host disease.
• infections common in immunocompromised: HSV, CMV, candida.
• morphology: dense neutrophilic infiltrates.
  
  • granulation tissue if ulceration
  • candidiasis: adherent grey-white pseudomembrane of fungal hyphae and inflammatory cells.
  • HSV: punched-out ulcers.
  • CMV: shallow ulcerations with viral inclusions.
• presentation: pain and dysphagia.
  
  • severe/chronic cases: hemorrhage, stricture, perforation.

Question 25

Reflux Esophagitis

Answer 25

• foremost cause of esophagitis = GERD.
• Pathogenesis: reflux of gastric juices from ↓ LES tone and/or ↑ abd pressure.
  
  • exacerbated by alcohol, tobacco, obesity, CNS depressants, pregnancy, delayed gastric emptying, ↑ gastric volume.
  • can be from hiatal hernia when stomach protrudes into thorax.
• Morphology: hyperemia, edema, basal zone hyperplasia and thinning of superficial epithelial layers, neutrophile and/or eosinophil infiltration.
• Presentation: adults >40yrs with dysphagia, heartburn, regurgitation of gastric contents into mouth.
  
  • complications: ulceration, hematemesis, melena, stricture, Barrett esophagus.
• tx: proton pump inhibitors and/or H₂ histamine receptor antagonists.

Question 26

Eosinophilic Esophagitis

Answer 26

• pts have atopic disorders (dermatitis, asthma, etc.)
• morphology: large numbers of intraepithelial eosinophils.
• presentation: food impaction and dysphagia.
  
  • children: feeding intolerance and GERD-like symptoms.
• tx: dietary restriction and/or steroids.

Question 27

Barrett Esophagus

Answer 27

• complication of 10% chronic GERD.
• intestinal metaplasia within esophageal squamous mucosa.
• ↑ risk of esophageal adenocarcinoma. 0.2-2% pts have pre-invasive dysplasia each yr.
• morphology: patches of red, velvety mucosa up from gastroesophageal junction.
  
  • intsetinal-type columnar epithelium with mucin-secreting goblet cells.
  • dysplasia is low or high grade.
  • intramucosal carcinoma has neoplastic cell invasion in lamina propria.
• presentation: white male btw 40-60yrs. diagnosed both grossly and with biopsy.
• tx: high grade dysplasia or carcinoma needs esophagectomy.

Question 28

Esophageal Varices

Answer 28

• pathogenesis: severe portal HTN ⇒ collateral bypass channels btw portal and caval circulations.
  
  • ⇒ congested subepithelial and submucosal veins in distal esophagus = varices.
  • most common cause in west = alcoholic cirrhosis
  • most common worldwide = hepatic schistosomiasis
• morphology: tortuous dilated veins in distal esophageal and proximal gastric submucosa.
  
  • irregular luminal protrusion of overlying mucosa with superficial ulceration, inflammation, or adherent blood clots.
• presentation: silent until rupture with catastrophic hematemesis.
  
  • rupture from inflammatory erosion, ↑ venous pressure, ↑ hydrostatic pressure from vomiting.
  • 50% die of first bleed from exsanguination or hepatic coma.
  • 50% chance recurrence.
• tx: scleroherapy, balloon tamponade, band ligation.

Question 29

Esophageal Adenocarcinoma

Answer 29

• come from dysplasia in Barret mucosa.
• 7:1 male:female
• pathogenesis: early chromosomal and p53 mutations, amplification of c-ERB-B2, cyclin D, E genes, mutated RB, p16/INK4a cyclin dependent kinase inhibitor.
• morphology: gross = exophytic nodules to excavated and deeply infiltrative masses in distal 1/3 esophagus.
  
  • micro: form glands, produce mucin, intestinal morphology. signet ring tumors not common.
• presentation: white male with dysphagia, weight loss, hematemesis, chest pian, or vomiting.
  
  • 5 yr survival <25%.

Question 30

Squamous Cell Carcinoma (Esophageal)

Answer 30

• adults >45yrs. 4:1 male:female, blacks>whites
• risk factors: alcohol, tobacco, caustic esophageal injury, achalasia, Plummer-Vinson syndrome, scalding hot beverages.
• high incidence in Iran, central China, Hong Kong, Brazil, South Africa.
• morphology: 50% in middle 1/3 of esophagus.
  
  • begin in situ as gray-white plaque-like mucosal thickenings.
  • expand as exophytic, ulcerate, become diffusely infiltrative with wall thickenings and luminal stenosis.
  • submucosal lymphatic network promotes circumferential and longitudinal spread.
  • mod to well defined. less comon verrucous, spindle, and basaloid carcinomas.
• presentation: insidious, late symptoms, dysphagia, obstruction, weight loss, hemorrhage, sepsis from ulceration, respiratory fistulae with aspiration.
  
  • 5 yr survival is 75% if superficial, otherwise 9%.

Question 31

Benign Esophageal Tumors

Answer 31

• mesenchymal origin, in esophageal wall.
• leiomyomas most common.
  
  • also fibromas, lipomas, hemangiomas, neurofibromas, lymphangiomas.
• take form of mucosal polyps

Question 32

Acute Gastritis

Answer 32

• transient mucosal inflammatory process.
• pathogenesis: ↑ acid production with back diffusion, ↓ bicarb or mucin production, or direct mucosal damage.
  
  • chronic use NSAIDs ⇒ ↓ bicarb production and intereres with prostaglandins (which inhibit acid production, promote mucin synthesis and increase vascular perfusion)
  • excessive alcohol and smoking are toxic. ischemia and shock injure mucosa too.
• morphology: moderate edema and hyperemia, some hemorrhage.
  
  • neutrophils invade epithelium, superficial epithelial sloughing (erosion), fibrinous luminal exudate.
• presentation: asymptomatic or with pain, nausea, and vomiting. may have ulceration with hemorrhage = hematemesis or melena.

Question 33

Acute Gastric Ulceration

Answer 33

• focal, acute mucosal defects.
• complication of NSAID use or phsyiologic stress.
  
  • stress ulcer = from shock, sepsis, severe trauma.
  • curling ulcer = proximal duodenum, from burns or trauma.
  • cushing ulcer = gastric, duodenal, and esophageal ulcer arising in pt with intracranial disease. ↑ risk perforation.
• pathogenesis: **NSAIDs **⇒ ↓ bicarb production
  
  • brain injury ⇒ direct vagal stimulation ⇒ gastric acid hypersecretion.
  • systemic acidosis, hypoxia, ↓ splanchnic blood flow.
• morphology: <1cm, multiple, shallow. anywhere in stomach. base is brown.
• presentation: 10-15% bleed, 5% perforate. outcome determined by ability to correct underlying conditions.

Question 34

Chronic Gastritis

Answer 34

• ongoing mucosal inflammation with mucosal atrophy.
• can ⇒ dysplasia and carcinoma.
• causes: H. pylori, alcohol, tobacco, psychological stress, caffeine. 10% are autoimmune
• symptoms less severe but persist.

Question 35

Helicobacter Pylori Gastritis

Answer 35

• most common cause of chronic gastritis.
• spread: fecal-oral, oral-oral, environmental.
• ↑ colonization in lower socioeconomic statuses and crowded areas.
• pathogenesis: in antrum. ↑ acid production and disruption of normal mucosal protection.
  
  • virulence factors: flagella, urease production, bacterial adhesins, toxins.
  • ⇒ multifocal atrophic gastritis and intestinal metaplasia.
  • associated with polymorphisms in IL-1B and TNF genes.
• morphology: erythematous and coarse/nodular mucosa.
  
  • H pylor in superficial mucus over surface and neck epithelium. pit abscesses with neutrophils, lamina propria has plasma cells/macrophages/lymphocytes.
  • long-standing = diffuse mucosal atrophy, prominent lymphoid aggregates with germinal centers.
• presentation: diagnose by Ab serologic test, urea breath test, culture, etc.
  
  • H pylori is risk for: peptic ulcer disease, gastric adenocarcinoma, gastric lymphoma.

Question 36

Autoimmune Gastritis

Answer 36

• spares antrum, associated with hypergastrinemia.
• pathogenesis: CD4 mediated destruction of parietal cells, also Ab to parietal cells and intrinsic factor.
  
  • get achlorhydria (no gastric acid secretion) ⇒ hypergastrinemia and antral G-cell hyperplasia.
  • ↓ production intrinsic factor ⇒ pernicious anemia.
  • bystander damage to chief cells ⇒ ↓ pepsinogen I production.
• morphology: rugal folds lost, diffuse mucosal damage of parietal cells in body and fundus.
  
  • inflammatory infiltrate of lymphocytes, macrophages, and plasma cells. may have lymphoid aggregates.
• presentation: AutoAb found early. takes 20-30yrs for gastric atrophy. present with anemia, B₁₂ deficiency with atrophic glossitis, malabsorption, peripheral neuropathy, spinal cord lesions, cerebral dysfunction.
  
  • associted with other autoimmune diseases.

Question 37

Reactive Gastropathy

Answer 37

• chemical injury from NSAIDs or bile reflux.
• marked by edema, glandular hyperplasia, regenerative changes.

Question 38

Eosinophilic Gastritis

Answer 38

• has heavy eosinophilic infiltration of mucosa and submucosa.
• from infection, allergies to ingested materials, from systemic collagen-vascular disease (scleroerma).

Question 39

Lymphocytic Gastritis

Answer 39

• idiopathic disorder in women.
• associated with celiac disease.
• marked accumulation of intraepithelial CD8 cells.

Question 40

Granulomatous Gastritis

Answer 40

• presence of granulomas.
• sarcoid, Crohn disease, infections.

Question 41

Peptic Ulcer Disease

Answer 41

• in first part of duodenum or in antrum (4:1).
• from H pylori-induced hyperchlorhydric chronic gastritis and NSAID use.
• 10% risk in men, 4% in women.
• pathogenesis: hyperacidity from infection, parietal cell hyperplasia, excessive secretory response, ↑ gastrin production (from hypercalcemia or tumor).
  
  • NSAIDs and steroids reduce PG effects.
  • smoking impairs mucosal blood flow and healing.
• morphology: solitary ulcers, sharply punched out with overhanging mucosal borders and smooth clean ulcer bases.
  
  • thin layers fibrinoid debris, underlying inflammation with granulation tissue and deep scarring. surrounded by chronic gastritis.
• presentation: epigastric gnawing, burning, or aching pain, worse at night and 1-3 hrs post eating, nausea, vomiting, bloating, belching, weight loss.
  
  • complications: anemia, hemorrhage, perforation, obstruction.
• tx: get rid of H pylori, neutralize/reduce gastric acid production.

Question 42

Gastric Dysplasia

Answer 42

• combo of free radical damage and proliferative stimuli to exposed epithelium causes genetic alterations and causes carcinoma.
• are pre-invasic in situe lesions.

Question 43

Ménétrier Disease

Answer 43

• diffuse foveolar cell hyperplasia with protein-losing enteropathy ⇒ systemic hypoproteinemia.
• from overexpression of TGF-alpha
• ↑ risk gastric adenocarcinoma.

Question 44

Zollinger-Ellison Syndrome

Answer 44

• gastrinomas in small bowel or pancreas.
• 5x ↑ gastrin levels in parietal cells, ↑ in mucous neck cells and gastric endocrine cells.
• 75% sporadic, 25% related to MEN type I.
• 60-90% malignant.
• presentation: multiple duodenal ulcers and/or chronic diarrhea.

Question 45

Inflammatory and Hyperplastic Polyps

Answer 45

• 75% of gastric polyps.
• btw 50-60yrs and associated with chronic gastritis.
• morphology: <1cm and usually multiple.
  
  • smooth surface, sometimes superficial erosions.
  • irregular, cystically dilated and elongated glands with variable amounts of acute/chronic inflammation.
• ↑ risk dysplasia with size.
• tx: excision if larger than 1.5cm.

Question 46

Fundic Gland Polyps

Answer 46

• occur sporadically in women >50yrs or with familial adenomatous polyposis.
• ↑ incidence from proton pump inhibitors from ↑ gastrin secretion.
• morphology: single or multiple, smooth, well-circumscribed lesions made of irregular cystically dilated glands, minimal inflammation.

Question 47

Gastric Adenoma

Answer 47

• 10% gastric polyps.
• background of familial adenomatous polyposis and chronic gastritis with atrophy and intestinal metaplasia.
• 3:1 male:female, ↑ risk with age.
• morphology: solitary, <2cm. some dysplasia.
  
  • 30% have carcinoma, especially when >2cm.

Question 48

Gastric Adenocarcinoma

Answer 48

• >90% gastric malignancies. are intestinal or diffuse.
• risk factors: H pylori, diet, partial gastrectomy
• pathogenesis: loss of intracellular adhesion in diffuse gastric cancer.
  
  • mutation of CDH1 for E-cadherin in familial and 50% sporadic.
  • intestinal type associated with familial adenomatous polyposis, mutated proteins that associate with E-cadherin, microsatellite instability, and hypermethylation of TGFBRII, BAX, IGFRII, and p16/INK4a.
• morphology: involves antrum>lesser curvature>greater curvature.
  
  • intestinal = bulky exophytic tumors of glandular structure. develop from precursor lesions (flat dysplasia and adenoma).
  • diffuse infiltrative = made of signet ring cells (mucin vacuoles push nucleus to periphery) that don’t form glands.
    
    • induce fibrous desmoplastic response.
    • rigid thickened gastric wall = leather bottle.
• presentation: insidious. early symptoms = dysphagia, dyspepsia, nausea.
  
  • later symptoms = weight loss, anorexia, altered bowel habits, anemia, hemorrhage.
  • catch early = 90% 5 yr survival.
  • catch late = 20% 5 yr survival.
  • overall 5 yr survival = 30%.

Question 49

Lymphoma (Gastric)

Answer 49

• aka MATLomas, mostly marginal zone B-cell lymphomas
• most common extra-nodal location = GI tract.
• pathogenesis: at sites of chronic inflammation, associated with H pylori infection.
  
  • antibiotics can cause tumor regression.
  • antibiotic resistant ones = t(11,18) mutation, links API2 with MLT
    
    • t(14,18) ⇒ ↑ expression MLT
    • t(1,14) ⇒ ↑ BCL-10 expression
    • all promote B cell growth and survival.
  • can transform to large B-cell lymphomas with inactivated p53 or p16
• morphology: dense atypical lymphocytic infiltrate in lamina propria.
  
  • focal invasion of mucosal epithelium ⇒ lymphoepithelial lesions.
• presenation: dyspepsia, epigastric pain, hematemesis, melena, or weight loss.

Question 50

Carcinoid Tumor

Answer 50

• from diffusely distributed endocrine cells.
• mostly in gut, then lungs. 40% in small intestine.
• morphology: well-differentiated neuroendocrine carcinomas.
  
  • yellow-tan intramural or submucosal masses forming polypoid lesions. firm from desmoplastic response, can cause bowel obstruction.
  • can be islands or sheets of uniform cohesive cells with scant granular cytoplasm and oval, stippled nuclei.
  • positive for neuroendocrine markers (chromogranin A and synaptophysin).
• presentation: peak incidence in 50’s. indolent, slow-growing, symptoms from hormone produced
  
  • gastrin ⇒ Zollinger-Ellison Syndrome
  • ileal tumor ⇒ vasoactive products ⇒ cutaneous flushing, bronchospasm, ↑ bowel motility, right-sided cardiac valve thickening = carcinoid syndrome.
    
    • associated with bulky hepatic metastatic disease.
  • foregut tumors = esophagus, stomach, duodenum. rarely metastasize.
  • midgut carcinoids = jejunum and ileum. agressive and metastatic.
  • hindgut tumors = appendix and colon, found incidentally.
    
    • appendiceal at tip and <2cm, benign.
    • colonic = large and metastasize.
  • rectal = secrete polypeptide hormones, cause pain but don’t metastasize.

Question 51

Gastrointestinal Stromal Tumor (GIST)

Answer 51

• most common gastrointestinal mesenchymal tumor
• 50% in stomach.
• peak age = 60yrs.
• ↑ incidence with neurofibromatosis type 1 and girls with Carney triad (GIST, paragangliomas, pulmonary chondromas).
• pathogenesis: from interstitial cells of Cajal in muscularis propria.
  
  • 75-80% have oncogenic gain of function mutations for tyrosine kinase of c-KIT.
  • 8% have PDGFRA mutation.
  • ⇒ activation of RAS and PI3K/AKT pathways ⇒ tumor cell proliferation and survival.
• morphology: solitary, well-circumscribed fleshy masses, can be >30cm.
  
  • are epithelial or spindle cell type.
  • c-KIT expression can be diagnostic.
• presentation: symptoms from blood loss or mass effects. metastasis rare when <5cm, common when >10cm.
  
  • metastases = peritoneal serosal nodules or liver implants.
• tx: resection or imatinib.

Question 52

Hernias (Intestinal)

Answer 52

• peritoneal wall defects allow peritoneal sac protrusion.
• bowel can be trapped = exernal herniation.
• incarceration = vascular stasis and edema from hernia.
• stranglation = vascular compromise.
• locations = femoral and inguinal canals, umbilicus, surgical scars.

Question 53

Adhesions (Intestinal)

Answer 53

• residua of localized peritoneal inflammation after surgery, infection, endometriosis, or radiation.
• healing ⇒ fibrous bridging btw viscera
• complication = internal herniation, obstruction, strangulation.

Question 54

Volvulus (Intestinal)

Answer 54

• complete twisting of a bowel loop about its mesenteric vascular base ⇒ vascular and luminal obstruction with infarction.
• usually in redundant loops of sigmoid colon

Question 55

Intussusception

Answer 55

• an intestinal segment telescopes into an immediately distal segment, propelled by peristalsis.
• ⇒ obstruction, vessel compression, and infarction.
• spontaneous in infants and kids, or associated with rotaviral infection.
• in older ppl is from a tumor.

Question 56

Ischemic Bowel Disease

Answer 56

• abrupt compromise of major vessel causes infarction of several meters of intestine.
• watershed zone btw SMA and IMA, very vulnerable.
• epithelial cells at tips of villi are more susceptible than crypt epithelial cells.
• causes of ischemia: atherosclerosis, aortic aneurysm, hypercoagulable states, embolization, vasculitis.
  
  • hypoperfusion from cardiac failure, shock, dehydration, vasoconstrictive drugs.
  • also from mesenteric venous obstruction via hypercoagulability, masses, cirrhosis.
• pathogenesis: hypoxic injury with vascular compromise. reperfusion ⇒ most damage via inflammatory cells and mediators.
• morphology: mucosal infarction = patchy mucosal hemorrhage with normal serosa.
  
  • mural infarction = complete mucosal necrosis, variable necrosis of submucosa and muscularis propria.
  • transmural infarction = hemorrhagic bowel segments with serositis. coagulative necrosis of muscularis propria with perforation within 1-4 days.
  • atrophy or sloughing of epithelial surface, crypts may be hyperproliferative.
  • bacterial infection may cause pseudomembrane.
  • chronic vascular insufficiency ⇒ fibrosis of lamina propria and maybe stricture.
• presentation: older ppl with coexisting cardiac or vascular disease. s**evere abd pain, bloody diarrhea or gross melena, abd rigidity, nausea, vomiting. **
  
  • can go to shock. 50% mortality.

Question 57

Angiodysplasia

Answer 57

• tortuous ectatic dilations of mucosal or submucosal veins.
  
  • 1% population
• after 60yrs in cecum or ascending colon.
  
  • from greater wall tension.
• =20% of lower GI bleeding.
• from partial intermittent venous occlusion

Question 58

Malabsorption

Answer 58

• defective absorption of fats, fat-solube and water-soluble vitamins, proteins, carbs, electrolytes, minerals, and water.
• from Celiac disease, pancreatic insufficiency, Crohn disease.
• pathogenesis: intraluminal digestion = emulsification and initial enzymatic breakdown.
  
  • terminal digestion = hydrolysis in brush border
  • transepithelial transport = enterocytes
  • lymphatic transport of absorbed lipids
• presentation: diarrhea, flatus, abd pain, muscle wasting.
  
  • steatorrhea = excessive fecal fat and greasy, malodorous stools.
• consequences = anemia and mucositis (pyridoxine, folate, B12), bleeding (vit K), osteopenia and tetany (Ca, Mg, Vit D), peripheral neuropathy (vit A or B12)

Question 59

Diarrhea

Answer 59

• ↑ stool mass, frequency, or fluidity, over 200g per day.
• if severe, can be fatal without fluid restoration.
• dysentery = painful, bloody, small volume diarrhea.
• secretory = isotonic with plasma, persists during fasting.
• osmotic = unabsorbed luminal solutes ↑ osmotic pull of fluid. can be 50 mOsm or more hyperosmolar to plasma, stops with fasting.
• malabsorptive = fatty, greasy, foul smelling, abates on fasting
• exudative = from inflammatory disease. purulent, bloody stools. persists during fasting.

Question 60

Celiac Disease

Answer 60

• aka gluten sensitive enteropathy, celiac sprue.
• immune mediated diarrhea from ingesting foods with gluten.
• prevalence in whites of European descent = 0.5-1%.
• associated with: dermatitis herpetiformis (10%), lymphocytic gastritis or colitis.
• ↑ risk enteropathy-associated T cell lymphoma and small intestinal adenocarcinoma.
• pathogenesis: delayed type hypersensitivity against a 33 AA alpha-gliadin polypeptide that isn’t digested.
  
  • induces epithelial IL-15 expression, activates and proliferates CD8 cells ⇒ enterocyte apoptosis.
  • ↑ deamidation via transglutaminases ⇒ binds MHC on APC ⇒ CD4 activation and cytokine mediated epithelial damage.
  • defect in terminal digestion and transepithelial transport.
• morphology: diffusely flattened villi and elongated regenerative crypts seen with lamina propria chronic inflammation and intraepithelial CD8 cells.
  
  • worst in proximal intestine.
• presentation: ppl from infancy to middle age, diarrhea, flatulence, weight loss, anemic effects.
  
  • sensitive test = IgA Ab to tissue transglutaminase.
  • IgA or IgG Ab to deamidated gliadin
• tx: gluten withdrawal.

Question 61

Tropical Sprue

Answer 61

• malabsorption syndrome in ppl inhabiting or visiting tropical climates.
• similar to celiac disease but mostly affects distal small bowel.
• of infectious etiology.
• affects terminal digestion and transepithelial transport.
• tx: broad spectrum antibiotics

Question 62

Autoimmune Enteropathy

Answer 62

• X-linked in kids.
• persistent auto-immune driven diarrhea
• affects terminal digestion and transepithelial transport
• severe familial form = IPEX. from mutation of FOXP3 for differentiation of T reg cells
• autoAb to variety of GI epithelial cells.

Question 63

Lactase (Disaccharidase) Deficiency

Answer 63

• lactase is an apical membrane disaccharidse on surface of absorptive cells.
• deficiency causes osmotic diarrhea and malabsorption from unabsorbed and undigested lactase
• affects terminal digestion
• bacteria fermenting lactase ⇒ abd distention and flatus
• congenital autosomal recessive form = mutated lactase gene.
• aquired = down-regulation of lactase gene.
  
  • Native-Americans, African-Americans, and Chinese.

Question 64

Abetalipoproteinemia

Answer 64

• rare autosomal recessive caused by inability of lipids to egress absorptive epithelial cells.
• mutated MTP which no longer allows lipoprotein and fatty acid transport from mucosal cells.
• affects transepithelial transport
• morphology: lipid vacuolation from ↑ enterocyte triglyceride stores.
  
  • burr cells = acanthocytes with altered erythrocyte lipid membranes.
• presentation: infants, failure to thrive, diarrhea, steatorrhea, absence of all lipoproteins with apolipoprotein B.
  
  • don’t absorb fat soluble vitamins ⇒ deficiencies and lipid membrane defects.

Question 65

Cholera (Infectious Enterocolitis)

Answer 65

• from Vibrio cholera = gram (-), transmitted via contaminated water.
  
  • reservoirs = humans, shellfish, plankton.
• pathogenesis: non-invasive, flagella for epithelial attachment.
  
  • diarrhea via cholera toxin = internalized by binding enterocyte surface G_M1 gangliosides
    
    • subunit A is processed to a fragment and enters cytosol, then interacts with ADP ribosylation factors ⇒ activate G_salpha to stimulate adenylate cyclase ⇒ surge of cytosolic cAMP that opens CFTR and releases Cl^- into lumen ⇒ secrete bicarb and Na⁺, taking water with it ⇒ massive diarrhea
• presentation: few get severe diarrhea, up to 1L/hr rice water stool.
  
  • mortality 50% without treatment, from dehydration, hypotension, shock.
  • save via rehydration.

Question 66

Campylobacter Enterocolitis

Answer 66

• via Campylobacter jejuni = gram (-).
• traveler’s diarrhea.
• most common bacterial enteric pathogen in developed countries.
• transmitted from poorly cooked chicken, water or milk.
• pathogenesis: flagellar motility, adherence molecules, cytotoxins, cholera toxin-like enterotoxin.
  
  • extra-intestinal complications = reactive arthritis, erythema nodosum, Guillain-Barré syndrome.
• presentation: diagnose via stool cultures. diarrhea is watery. dysentery in 15%.
  
  • can shed bacteria for 1 month after symptoms resolve.

Question 67

Shigellosis

Answer 67

• from shigella = gram (-), facultative anaerobe.
• most common cause of bloody diarrhea.
• reservoir = humans. transmission = fecal-oral.
• infections and deaths in kids <5yrs.
  
  • in enemic areas causes 10% pediatric diarrhea, 75% diarrhea-related deaths.
• pathogenesis: resistant to gastric acidity. taken up into M cells, escape into lamina propria, ingested by macrophages, undergo apoptosis.
  
  • inflammation and release of shiga toxin causes epithelial damage ⇒ larger bacterial access.
• morphology: mucosa is hemorrhagic and ulcerated, may have pseudomembranes.
• presentation: self-limited diarrhea of 6 days. watery at first then dysenteric in 50%. fever and abd pain, may persist after diarrhea.
  
  • diagnose via stool cultures.
• tx: antibiotics shorten the course and reduce duration of bacterial shedding.

Question 68

Salmonellosis

Answer 68

• gram (-) bacillus, S typhi and S paratyphi ⇒ typhoid fever.
  
  • S. enterides = non-typhoid.
• transmission = contaminated food.
• affects children and elderly.
• pathogenesis: type III secretion system ⇒ bacteria in M cells and enterocytes. bacteria go into phagosomes. may prevent TLR4 activation.
  
  • mucosal T_H17 limits infection to colon.
• presentation: diagnosis via stool culture. self-limited infection lasting about 1 wk.
• tx: NO ANTIBIOTICS, prolong carrier state.

Question 69

Typhoid Fever

Answer 69

• from Salmonella. mostly affects kids and adolescents.
• related to travel to India, Mexico, Phillipines, and less-developed countries.
• reservoir = humans. transmission = contaminated food and water.
• gallbladder colonization ⇒ gallstones and chronic carrier state.
• pathogenesis: resistant to gastric acid, invade M cells, taken up by mononuclear cells in mucosal lymph.
  
  • disseminates via lymphatics and blood vessels ⇒ systemic macrophage and lymph node hyperplasia
• morphology: expansion of Peyer’s patches and draining nodes, acute/chronic inflammatory cell recruitment to lamina propria with necrotic debris and mucosal ulceration.
  
  • liver has focal hepatocyte necrosis with macrophage aggregates = typhoid nodules.
• presentation: dysentery followed by bacteremia, fever, abd pain lasts 2 wks without antibiotics.
  
  • systemic complications = encephalopathy, meningitis, endocarditis, myocarditis, pneumonia, cholecystitis.
  • sickle cell pts prone to osteomyelitis.

Question 70

Yersinia

Answer 70

• by Yersinia enterocolitica and Yersinia pseudotuberculosis.
• ingestion of contaminated pork, milk, or water.
• pathogenesis: invades M cells via adhesions binding beta1 integrins.
  
  • bacterial iron uptake system increases virulence and dissemination.
  • pts with hemolytic anemia or hemochromatosis more likely to become septic and die.
• morphology: invades ileum, appendix, right colon. proliferate in lymph nodes ⇒ region nodal hyperplasia.
  
  • overlying mucosa can be hemorrhagic and ulcerated.
• presentation: abd pain, fever, diarrhea (mimics appendicitis).
  
  • extra-intestinal manifestations = pharyngitis, arthralgia, erythema nodosum.
  • post-infectious complications = sterile arthritis, Reiter syndrome, myocarditis, glomerulonephritis, thyroiditis.

Question 71

Escherichia Coli

Answer 71

• gram (-) bacili.
• enterotoxigenic E. coli (ETEC) = spread through contaminated food or water ⇒ traveler’s diarrhea.
  
  • heat stable toxin ⇒ ↑ intracellular cGMP
  • heat labile cholera-like toxin ⇒ ↑ intracellular cAMP
  • ⇒ Cl^- and water secretion, inhibit epithelial fluid absorption ⇒ non-inflammatory watery diarrhea.
• enterohemorrhagic E. coli (EHEC) = through contaminated meat, milk, and vegetables. Shiga-like toxin.
  
  • O157:H7 type = causes large outbreaks of dysentery and HUS.
  • non O157:H7 type.
• enteroinvasive E. coli (EIEC) = similar to shigella, not toxin producing. invades epithelial cells ⇒ acute self-limited colitis.
• enteroaggregative E. coli (EAEC) = attach epithelium via adherence fimbriae, aided by dispersin (neutralizes neg surface of lipopolysaccharide).
  
  • has shiga-like toxin but NO bloody diarrhea.

Question 72

Pseudomembranous Colitis

Answer 72

• formation of adherent inflammatory pseudomembranes overlying sites of mucosal injury.
• from overgrowth by C. difficile after antibiotics.
  
  • also from Salmonella, C. perfringens, S. aureus.
• morphology: epithelial denudation with plaquelike adhesion of fibrinopurulent necrotic, gray-yellow debris and mucus.
• presentation: C. dif in 30% hospital patients. fever, leukocytosis, crampy abd pain, watery diarrhea. detect toxin in stool.
• tx: metronidazole or vancomycin.

Question 73

Whipple Disease

Answer 73

• caused by Tropheryma whippelii, gram (+) actinomycete.
• morphology: marked villous expansion in small bowel, shaggy appearance to mucosal surface.
  
  • dense accumulation of distended foamy macrophages in small intestine lamina propria, stuffed with PAS-pos bacteria in lysosomes.
    
    • also found in lymphatics, lymph nodes, joints, brain.
  • no active inflammation.
• presentation: diarrhea, weight loss, malabsorption.
  
  • extra-intestinal manifestations = arthritis, fever, lymphadenopathy, neurologic/cardiac/pulmonary disease.

Question 74

Norovirus Gastroenteritis

Answer 74

• aka Norwalk-like virus. ssRNA.
• 50% gastroenteritis outbreaks worldwide.
• from contaminated food or water.
• transmission: person-person.
• presentation: self- limited watery diarrhea, abd pain, nausea, vomiting.

Question 75

Rotavirus Gastroenteritis

Answer 75

• encapsulated, segmented, dsRNA virus.
• most common cause of severe childhood diarrhea.
• transmission: btw ppl, with as few as 10 particles.
• destroys mature small intestine enterocytes, epithelium repopulated with immature secretory cells.
• net secretion of water and electrolytes, malabsorption, osmotic diarrhea.

Question 76

Adenovirus Gastroenteritis

Answer 76

• second most common cause of pediatric diarrhea.
• presentation: self-limited diarrhea, vomiting, abd pain.

Question 77

Ascaris Lumbricoides Enterocolitis

Answer 77

• parasite.
• transmission: fecal-oral.
• intestine-liver-lung-intestine life cycle.
• larvae can cause hepatic abscesses or pneumonitis.
• adult masses ⇒ eosinophil-rich inflammation that can obstruct intestine or biliary tract.
• diagnose by eggs in stool.

Question 78

Strongyloides Enterocolitis

Answer 78

• parasite.
• larvae in soil penetrate unbroken skin ⇒ lungs ⇒ mature into adults in GI tract.
• eggs hatch in intestines, luminal larvae penetrate mucosa = autoinfection.
• strong eosinophilic response.

Question 79

Necator Duodenale Enterocolitis

Answer 79

• hookworms.
• larvae penetrate through skin, mature in lung, migrate up trachea, swallowed, attach in duodenal mucosa, extract blood ⇒ mucosal damage and iron deficiency anemia.

Question 80

Ancylostoma Duodenale Enterocolitis

Answer 80

• hookworms.
• larvae penetrate through skin, mature in lungs, migrate up trachea, swallowed, attach to duodenal mucosa, extract blood ⇒ mucosal damage and iron deficiency anemia.

Question 81

Enterobius Vermicularis Enterocolitis

Answer 81

• pinworms.
• transmission = fecal-oral.
• entire life cycle in intestinal lumen, don’t cause serious illness.
• adult worms migrate at night to anal orifice, deposit eggs ⇒ intense irritation and pruritus.

Question 82

Trichuris Trichiura Enterocolitis

Answer 82

• whipworms.
• infects kids.
• no tissue invasion.
• heavy infestation ⇒ bloody diarrhea and rectal prolapse.

Question 83

Schistosomiasis Enterocolitis

Answer 83

• adult worms in mesenteric veins.
• trapped eggs in submucosa and mucosa cause granulomatous response with bleeding and obstruction.

Question 84

Intestinal Cestodes

Answer 84

• tapeworms.
• from ingesting raw or undercooked fish, pork, or contaminated meats.
• reside in lumen without tissue invasion.
• scolex attaches to mucosa, proglottids contain eggs to shed in feces.

Question 85

Entamoeba Histolytica Enterocolitis

Answer 85

• transmission: fecal-oral.
• ingest acid-resistant cysts, trophozoites colonize colonic epithelium, reproduce anaerobically.
• dysentery when amoebae induce colonic epithelial apoptosis to invade lamina propria and attract neutrophils ⇒ flask-shaped ulcer.
• amoebae can embolize to liver, make abscesses in 40% ppl.
• tx: metronidazole targets pyruvate oxidoreductase.

Question 86

Giardia Lamblia Enterocolitis

Answer 86

• flagellated protozoan, most common pathogenic parasitic infection in humans.
• ingested from fecally contaminated water or food.
• duodenal trophozoites = pear shaped and binucleate.
• does not invade, secretes products to damage microvillus brush border ⇒ malabsorption
• secretory IgA and mucosal IL-6 important for clearance = bad response for immunocompromised.
  
  • persists for prolonged duration through modifying major surface antigen.

Question 87

Cryptosporidium Enterocolitis

Answer 87

• causes self-limited or chronic diarrhea in immunocompromised.
• transmission = contaminated drinking water, as few as 10 cysts to infect
• stomach acid activates proteases to release sporozoites, then internalized by absorptive enzymes.
• Na⁺ malabsorption, Cl^- secretion, ↑ epithelial permeability ⇒ watery diarrhea.

Question 88

Irritable Bowel Syndrome (IBS)

Answer 88

• chronic, relapsing abd pain, bloating, changes in stool frequency or form.
• common btw ages 20-40yrs in women.
• from interplay of psychologic stresors, diet, and abnormal GI motility, from disruption of signaling in brain-gut axis.

Question 89

Inflammatory Bowel Disease

Answer 89

• from inappropriate mucosal immune responses to normal gut flora.
• two disorders: Ulcerative Colities (UC) = severe ulcerating inflammation extending into mucosa and submucosa, limited to colon.
  
  • Crohn Disease (CD aka regional enteritis) = transmural inflammation, anywhere in GI tract.
• more common in women, in adolescence and 20’s. more common in developed countries from hygiene hypothesis.
• pathogenesis: combo of defects in host interactions with GI flora, intestinal epithelial dysfunction, aberrant mucosal immunity.
  
  • mix of innate and adaptive immune responses ⇒ TNF release ⇒ ↑ permeability of tight junctions. self-amplifying cycle of microbial influx and host immune response.
  • NOD2 polymorphisms associated with CD ⇒ less effective at recognizing and combating microbes.
  • CD: helper T cells polarized to make T_H1 cytokines, T_H17 may contribute. IL-23R may be protective.
  • UC: helper T cells polarized to make T_H2 cytokines, mutated IL-10 may be linked to UC.
  • defects in epithelial tight junctions, transporter genes, mutate ECM proteins or metalloproteinases.

Question 90

Crohn Disease

Answer 90

• subset of IBD.
• morphology: involves SI alone in 40%, SI and colon in 30%.
  
  • skip lesions = sharply delinieated disease areas with granular and inflamed serosa and adherent creeping mesenteric fat. bowel wall thick, rubbery, and may be strictured.
  • punched out mucosal alphous ulcers coalescing into axial serpentine ulcers.
  • cobblestone appearance from sparing of interspersed mucosa. also have fissures and fistulas.
  • mucosal inflammation and ulceration, intraepithelial neutrophils and crypt abscesses.
  • chronic mucosal damage with villus blunting, atrophy, pseudopyloric or Paneth cell metaplasia, architectural disarray.
  • transmural inflammation with lymphoid aggregates in submucosa, muscle wall, and subserosal fat.
  • noncaseating granulomas even in uninvolved segments.
• presentation: intermittent attacks of diarrhea, fever, and abd pain. can cause malabsorption, malnutrition, ↓ albumin, iron deficiency anemia, B₁₂ deficiency.
  
  • fibrotic strictures or fistula to adjacent viscera, abd and perineal skin, bladder, vagina.
  • extra-intestinal manifestation: migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, uveitis, cholangitis, amyloidosis.
  • ↑ risk colonic adenocarcinoma in pts with long-standing colon involvement.

Question 91

Ulcerative Colitis

Answer 91

• form of IBD.
• morphology: continuous involvement of rectum traveling retrograde through colon (pancolitis).
  
  • backwash ileitis = inflammation in distal ileum.
  • mucosa reddened, granular, and friable with inflammatory pseudopolyps, easy bleeding. extensive ulceration or atrophic and flattened mucosa.
  • inflammation limited to mucosa. crypt abscesses, ulceration, chronic mucosal damage, glandular architectural distortion, and atrophy.
• presentation: intermittent attacks of bloody mucoid diarrhea, abd pain that persists days to months.
  
  • 30% require colectomy. most relapse within 10 yrs.
  • extra-intestinal manifestation: migratory polyarthritis, sacroiliitis, ankylosing spondylitis, uveitis, cholangitis, primary sklerosing cholangitis, skin lesions.
  • ↑ risk colonic adenocarcinoma.

Question 92

Colitis-Associated Neoplasia

Answer 92

• risk of malignancy in IBD.
• ↑ sharply 8-10 yrs after disease onset
• greater with pancolitis
• ↑ with severity and duration of active inflammation

Question 93

Diversion Colitis

Answer 93

• in blind distal colonic segment after surgery diverts fecal stream to ostomy site.
• from lack of short chain fatty acids and nutrients, and changes in flora.
• mucosal erythema and friability with lymphoplasmocytic inflammation.
• lymphoid follicular hyperplasia

Question 94

Microscopic Colitis

Answer 94

• histology usually normal.
• collagenous colitis = dense submucosal bandlike collagen with mixed inflammation in lamina propria.
• lymphocytic colitis = prominent intraepithelial infiltrate of lymphocytes without band-like collagen
  
  • associated with autoimmune diseases and sprue.
• presentation: middle aged woman with chronic watery diarrhea and abd pain.

Question 95

Sigmoid Diverticulitis

Answer 95

• in 50% of western population above 60yrs.
• pathogenesis: focal bowel wall weakness at site of penetrating blood vessels ⇒ mucosal outpouching when have ↑ intraluminal pressure (constipation).
• morphology: flasklike outpouchings 0.5-1cm in diameter, common in distal colon.
  
  • where vasculature penetrates inner circular layer of muscularis propria in taeniae coli
  • diverticuli lined by mucosa and submucosa without muscularis propria, muscularis btw diverticuli is hypertrophied.
  • diverticulitis = inflammation from obstruction of diverticuli. with tissue damage and ↑ pressure can perforate.
• presentation: usually asymptomatic but can have cramping, abd discomfort, constipation.
  
  • can ⇒ pericolic abscesses, sinus tracts, peritonitis.
  • can cause fibrotic thickening and strictures.

Question 96

Inflammatory Polyps

Answer 96

• masses that protrude into gut lumen. pedunculated or sessile, neoplastic or non-neoplastic.
• from recurrent cycles of injury and healing.
• lamina propria fibromuscular hyperplasia, mixed inflammatory cell infiltrates, mucosal erosion and/or hyperplasia.

Question 97

Juvenile Polyps

Answer 97

• masses that protrude into gut lumen.
• focal hamartomatous malformations of SI and colon mucosa.
  
  • in kids <5yrs in rectum.
  • mutated SMAD4 and BMPR1A in TFGbeta signaling.
  • single large polyp, rounded, pedunculated, cystically dilated glands, and abundant lamina propria.

Question 98

Juvenile Polyposis Syndrome

Answer 98

• autosomal dominant.
• up to 100 hamartomatous polyps.
• may need colectomy to minimize bleeding from polyp ulceration.
• extra-intestinal manifestation: pulmonary arteriovenous malformation.
• ↑ risk colonic adenocarcinoma.

Question 99

Peutz-Jeghers Syndrome

Answer 99

• autosomal dominant. starts around 11yrs old.
• multiple GI hamartomatous polyps, mucocutaneous hyperpigmentation.
• loss of function in LKB1/STK11 encoding a kinase that regulates cell polarization and growth.
• polyps are large, pedunculated, lobulated with arborizing smooth muscle around normal glands; SI>colon>stomach
• can initiate intussusception.
• hyperpigmentation = macules around mouth, eyes, nostrils, buccal mucosa, palms, and genital/perianal regions.
• ↑ cancer risk for: colon, pancreas, breast, lung, gonads, thyroid, and uterus.

Question 100

Cowden Syndrome

Answer 100

• GI hamartomatous polyps, macrocephaly, benign skin tumors.
• mutated PTEN.
• ↑ risk cancer in: breast, thyroid, and endometrium.

Question 101

Bannayan-Buvalcaba-Riley Syndrome

Answer 101

• GI polyps, macrocephaly, skin lesions, mental deficiency, developmental delay.
• mutated PTEN.
• less risk of malignancy than Cowden syndrome: breast and thyroid.

Question 102

Cronkhite-Canada Syndrome

Answer 102

• non-hereditary. age >50yrs.
• hamartomatous polyps throughout GI tract, resembles juvenile polyps.
• presentation: cachexia, diarrhea, abd pain, nail atrophy, hair loss, skin pigmentation changes.
• 50% mortality.

Question 103

Hyperplastic Polyps

Answer 103

• from decreased epithelial turnover with delayed shedding.
• no malignant potential.
• <5mm, made of well-formed, mature, crowded glands

Question 104

Neoplastic Polyps

Answer 104

• colonic adenomas are benign polyp precursors to colorectal carcinomas.
  
  • characterized by epithelial dysplasia
  • 50% incidence by age 50yrs.
  • most don’t become malignant.
  • can cause anemia through occult bleeding, protein and K+ loss cause hypoproteinemic hypokalemia
  • malignancy relates to size and severity of dysplasia.
• morphology: 0.3-10cm, pedunculated or sessile. can have hyperplasia, nuclear hyperchromasia, loss of polarity. are tubular, tubulovillous, and villous.
  
  • sessile serrated adenomas = malignant potential, no dysplastic changes. serrated.
  • intramucosal carcinoma = dysplastic cells invade lamina propria or muscularis mucosa. little metastatic potential, lack lymphatic channels.
  • invasive adenocarcinoma = malignant, metastatic, crossed into submucosa and have lymphatic access.

Question 105

Familial Adenomatous Polyposis

Answer 105

• autosomal dominant from mutations of APC gene.
• adolescents get >100 colonic adenomatous polyps.
• untreated ⇒ colorectal carcinoma in 100% by age 30yrs.
• colectomy eliminates chance of cancer but may develop adenomas in stomach and ampulla vo Vater.
• alternative mutation = MUTYH, a base-excision repair gene..
• attenuated form of FAP = delayed polyp development, colon carcinoma after age 50 yr.

Question 106

Gardner Syndrome

Answer 106

• FAP variant.
• have multiple osteomas, epidermal cysts, fibromatosis, abnormal dentition, ↑ incidence of duodenal and thyroid cancers.

Question 107

Turcot Syndrome

Answer 107

• FAP variant.
• rare. have adenomas and medulloblastomas

Question 108

Hereditary Non-Polyposis Colorectal Cancer (HNPCC)

Answer 108

• aka Lynch syndrome.
• mutations in genes for proteins that detect, excise, and repair DNA replication errors. usually MSH2 and MLH1.
• inherit one defective copy, lose other by mutation, silencing. get microsatellite instability.

Question 109

Colorectal Adenocarcinoma

Answer 109

• most common GI malignancy.
• 15% of cancer deaths in USA.
• risks: ↓ vegetable fiber intake, ↑ refined carbs and fat, antioxidants (vit.s A, C, and E).
• NSAIDs protective.
• pathogenesis: mutated APC/beta-catenin pathway ⇒ beta-catenin accumulates, goes to nucleus, promotes proliferation.
  
  • microsatellite instability = defects in DNA mismatch repair ⇒ ↑ proliferation and diminished apoptosis.
  • K-RAS and p53 mutations promote growth and prevent apoptosis.
  • SMAD mutations ⇒ ↓ TGF-beta signaling, promote cell cycle progression
  • telomerase reactivation prevents cellular senescence.
• morphology: equally distributed along colon. polypoid, exophytic masses in cecum and right colon. annular masses with ‘napkin-ring’ obstruction in distal colon.
  
  • tall columnar cells resemble adenomatous neoplastic epithelium but with invasion into submucosa, muscularis propria, or beyond. a few make extracellular mucin.
  • can be poorly differentiated without glands. rarely see foci of neuroendocrine differentiation, signet-ring features, or squamous differentiation.
  • invasive tumors incite desmoplastic response.
• presentation: insidious. show with fatigue, weakness, iron deficiency anemia, abd discomfort, progressive bowel obstruction, liver enlargement (metastases).
• tx: surgery, varied prognosis based on level of penetration and lymph node involvement.

Question 110

Hemorrhoids

Answer 110

• variceal dilations of anal and perianal submucosal venous plexi.
• 5% of adults
• associated with: constipation, venous stasis during pregnancy, cirrhosis.
• external hemorrhoids = ectasia of inferior hemorrhoidal plexus below anorectal line.
• internal hemorrhoids = ectasia of superior hemorrhoidal plexus above anorectal line.
• can get secondary thrombosis, strangulation, ulceration with fissure formation.

Question 111

Acute Appendicitis

Answer 111

• most common acute abd condition needing surgery (7% ppl get it).
• pathogenesis: 50-80% associaed with obstruction of lumen by fecalith, tumor, or worms (Oxyuriasis vermicularis) ⇒ ↑ intraluminal pressure, then ischemia with edema and exudate and bacterial invasion.
• morphology: early = scant appendiceal neutrophil exudate with subserosal congestion, perivascular neutrophil emigration. serosa is dull, granular, and red.
  
  • late = acute, suppurative. severe neutrophilic infiltration with fibrinopurulent serosal exudate, luminal abscess formation, ulceration, and suppurative necrosis. can ⇒ acute gangrenous appendicitis and perforation.
• presentation: any age, mostly adolescents and young adults. perimbilical pain migrating to RLQ, nausea, vomiting, abd tenderness, mild fever, leukocytosis.
  
  • mimicks = enterocolitis, mesenteric lymphadenitis, systemic viral infection, acute salpingitis, ectopic pregnancy, mittelscherz, Meckel diverticulitis.
  • complications = pyelophlebitis, portal vein thrombosis, liver abscess, bacteremia.

Question 112

Appendiceal Tumors

Answer 112

• carcinoid = most common.
• mucocele = from dilation of lumen by mucinous secretions, innocuous obstruction with inspissated mucus, mucin-screting adenomas, or adenocarcinoma.
• mucinous cystadenocarcinoma = indistinguishable from cystadenomas except has appendiceal wall invasion by neoplastic cells and peritoneal implants. peritoneum is distended with tenacious, semisolid, mucin-producing anaplastic adenocarcinoma cells (pseudomyxoma peritonei). very fatal.

Question 113

Sterile Peritonitis

Answer 113

• from leakage of bile or pancreatic enzymes.

Question 114

Peritonitis

Answer 114

• from bacterial infection, bile/pancreatic enzymes, perforation of biliary system or abd viscera, acute hemorrhagic pancreatitis, foreign material, endometriosis, ruptured dermoid cysts.

Question 115

Bacterial Peritonitis

Answer 115

• when GI bacteria get into abd cavity from bowel perforation, acute salpingitis, abd trauma, or peritoneal dialysis.
• spontaneous = without obvious source, see with ascites (in nephrotic syndrome or cirrhosis).
• morphology: peritoneal membranes become dull and gray, then exudation and frank suppuration, localized abscesses. inflammation remains superficial.

Question 116

Sclerosing Retroperitonitis

Answer 116

• aka Ormond disease.
• dense fibrosis of retroperitoneal tissues, a primary inflammatory process.

Question 117

Peritoneal Tumors

Answer 117

• primary: rare.
  
  • mesothelioma.
  • desmoplastic small round cell tumor = t(11;22) translocation ⇒ EWS-WT1 fusion. resembles Ewing sarcoma.
• secondary: common. derive from any cancer.
  
  • ovarian and pancreatic adenocarcinomas most common.