GI Flashcards

Question

**Reflux Esophagitis**

Answer 1

* 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 t**hinning 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.

Answer 2

* 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.

Answer 3

* 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.

Answer 4

* _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.

Answer 5

* 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%.

Answer 6

* **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%.

Answer 7

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

Answer 8

* 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.

Answer 9

* **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.

Answer 10

* **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.

Answer 11

* **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**.

Answer 12

* **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.

Answer 13

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

Answer 14

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

Answer 15

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

Answer 16

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

Answer 17

* 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.

Answer 18

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

Answer 19

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

Answer 20

* **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.**

Answer 21

* 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.

Answer 22

* 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**.

Answer 23

* 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.

Answer 24

* \>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%.

Answer 25

* 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**.

Answer 26

* 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.

Answer 27

* **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.

Answer 28

* **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.

Answer 29

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

Answer 30

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

Answer 31

* 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**.

Answer 32

* **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.

Answer 33

* **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**

Answer 34

* **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)

Answer 35

* **↑ 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**.

Answer 36

* 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.

Answer 37

* **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

Answer 38

* **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**.

Answer 39

* 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.

Answer 40

* **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.

Answer 41

* 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.

Answer 42

* via Campylobacter jejuni = gram (-). * **traveler's diarrhea**. * **most common bacterial enteric pathogen in developed countries**. * transmitted from **poorly cooked chicken, water or milk.** * _pathogenesis_: **flagella**r 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.

Answer 43

* 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.

Answer 44

* 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.

Answer 45

* 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**.

Answer 46

* 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.**

Answer 47

* 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**.

Answer 48

* **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.

Answer 49

* 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.**

Answer 50

* 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**.

Answer 51

* **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**.

Answer 52

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

Answer 53

* 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.

Answer 54

* 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**.

Answer 55

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

Answer 56

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

Answer 57

* **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**.

Answer 58

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

Answer 59

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

Answer 60

* 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**.

Answer 61

* _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**.

Answer 62

* 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**.

Answer 63

* 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**.

Answer 64

* **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.**

Answer 65

* 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**.

Answer 66

* 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.

Answer 67

* 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**.

Answer 68

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

Answer 69

* 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**

Answer 70

* 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**.

Answer 71

* 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**.

Answer 72

* **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**.

Answer 73

* 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**.

Answer 74

* **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**.

Answer 75

* **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**.

Answer 76

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

Answer 77

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

Answer 78

* 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.

Answer 79

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

Answer 80

* **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.

Answer 81

* **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.

Answer 82

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

Answer 83

* FAP variant. * rare. have **adenomas** and **medulloblastomas**

Answer 84

* 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**.

Answer 85

* 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 f**atigue, 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.

Answer 86

* **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.

Answer 87

* 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**.

Answer 88

* **_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**.

Answer 89

* from leakage of **bile or pancreatic enzymes**.

Answer 90

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

Answer 91

* 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.**

Answer 92

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

Answer 93

* **_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.