Weeks 5 and 6 (GI) Flashcards

Question

Gastric tumors

Answer 1

**Polyps** (**benign**): gastric hyperplastic polyp, fundic gland polyp, adenoma **Carcinoma**: most common malignant tumor of stomach

Answer 2

Macroscopic growth patterns: exophytic, flat or depressed, excavated, **linitis plastica** (leather bottom) **Metastasis**: Virchow's nodes, Krukenberg tumor

Answer 3

**Intestinal**: cohesive tumor cells that form **recognizable glands** regardless of their degree of cytologic differentiation or cell of origin, usually **bulky tumors** (Borrmann types I-III) **Diffuse**: **discohesive** cells that penetrate **diffusely** through the stomach embedded in a desmoplastic stroma, usually develops as **linitis plastica** (Borrmann type IV)

Answer 4

**Lymphoma** **Neuroendocrine** (aka carcinoid) Stromal tumors (**GIST**)

Answer 5

AKA antibiotic-associated colitis Usually but not always caused by **C. difficile** Term is applied to diarrhea developing during or after course of **antibiotic thearpy** Thought to be caused by disruption of normal flora by antibiotic (3rd gen cephalosporins, and immunosuppression is predisposing factor)

Answer 6

**Atresia** **Omphalocele** and **gastroschisis** **Meckel diverticulum** **Hirschsprung's disease**

Answer 7

Bowel ends in **blind pouch** Often along with other anomalies Accompanied by **polyhydramnios** since fetus has impaired swallowing and absorption of amniotic fluid Half duodenal atresias occur with Down syndrome (but few cases of Down syndrome overall have atresia)

Answer 8

**Incomplete closure** of abdominal musculature Abdominal viscera herniate into ventral **membranous sac**

Answer 9

**Lack of formation** of a portion of abdominal wall, involving all layers from peritoneum to skin Viscera herniate out, and are **not covered by a membrane**

Answer 10

Most common and innocuous anomaly Occurs in **terminal ilium** Diverticulum is blind out pouching of GI tract: lined by mucosa, opens/communicates to main lumen **True** diverticulum such as Meckel includes all **three** layers of bowel wall (**mucosa, submucosa, muscularis propria**) Results from **failed involution** of omphalomesenteric duct, which connects lumen of developing gut to yolk sac Small pouch extending from anti-mesenteric side of bowel Rule of 2s: **2% of population**, present within **2 feet of ileocecal valve**, **2 inches long**, **2x as common in males** as in females, **symptomatic by age 2** (if it is gastric tissue, can get peptic ulceration of adjacent small intestine (mysterious occult bleeding or abdominal pain like appendicitis), could get **bacterial overgrowth** that depletes vitamin B12)

Answer 11

**Absence** of normal postganglionic autonomic cell bodies (ie ganglion cells) in both submucosal and myenteric plexuses **Aganglionic** segment becomes **narrowed** (functional obstruction) with **proximal dilation** (congenital **megacolon**) Results from mutation of susceptible genes interacting with other factors Half of **familial** cases and 15% of **sporadic** cases associated with **mutations in RET genes** and ligands (RET signaling required for **development** of myoenteric nerve plexus and provides direction to migrating neural crest cells) Infants present with delay in passage of **meconium**, followed by **vomiting** Diagnosis established by documenting **absence of ganglion cells** in nondistended bowel segment

Answer 12

**Acquired** diverticula Secondary to focal **weakness** in muscle wall and **increased luminal pressure** More common in **left** colon/sigmoid colon, in older patients, in developed nations with **low fiber diet** resulting in reduced stool bulk **Flasklike** outpouchings Exaggerated peristalsis induces muscular **hypertrophy** in affected segments Can become **inflamed** leading to **diverticulitis** and possibly **perforation** (perforation may lead to localized **peritonitis** or **abscess** formation)

Answer 13

Chronic inflammatory diseases of intestine with some extra-intestinal manifestations **Idiopathic**: resulting from abnormal local immune responses against unknown microbes and/or self antigens in intestine Two main types: **ulcerative colitis** and **Crohn's disease**

Answer 14

One type of **IBD** Severe **ulcerating** inflammatory disease that is generally limited to **colon** (**left** side) and **rectum** Inflammation extends only into **mucosa** and maybe submucosa with superficial ulcers **Pseudopolyps** seen grossly: bulging mass of inflamed residual mucosa surrounded by extensive area of ulceration **Diffusely inflamed** mucosal surface from rectum to cecum (but right colon less involved)

Answer 15

Another type of **IBD** May involve **ANY area of GI tract**, but **ileum** frequently affected **Skip lesions** are present (diseased areas **sharply** **demarcated** from adjacent uninvolved bowel) Inflammation typically **transmural** with non-necrotizing granulomas, ulcerations and fissures **Thick wall** due to edema, inflammation, fibrosis and hypertrophy of muscularis propria **Serosa thickened** and fibrotic, leading to strictures Often mesenteric fat wraps around bowel surface (**creeping fat**)

Answer 16

**Crohn's disease**: **transmural** and **granulomatous** inflammation; **ileum** and maybe colon, **skip** **lesions**, strictures, **thick** wall, transmural inflammation, marked **fibrosis** and serositis, **deep ulcers**, fissures and fistulas **Ulcerative colitis**: **mucosal** inflammation with ulceration; **colon** only, **diffuse** distribution, rare strictures, **thin** wall, inflammation just in mucosa, mild/no fibrosis and serositis, **superficial ulcers**, no granulomas, no fissures and fistulas

Answer 17

**Toxic megacolon**: rare complication of ulcerative colitis; ulcers lead to **perforation** and **pericolonic abscess** formation and exposure of muscularis propria to fecal material may lead to complete shutdown of neuromuscular function --\> colon progressively **swells** and becomes **gangrenous** **Dysplasia** and **carcinoma**: regular surveillance is needed with colonoscopies and biopsies

Answer 18

**Neoplastic** **epithelial** tumors: **adenomas**, **adenocarcinomas** (connection to polyps/adenomas), **squamous cell carcinomas** **Neoplastic** **non-epithelial**: GI **stromal** tumors, **neuroendocrine** tumors, **lymphomas**

Answer 19

**Tumor** originally applied to swellings caused by **inflammation** **Polyp** is a mass that **protrudes** into lumen of gut

Answer 20

**Non-neoplastic**: due to abnormal mucosal maturation, **inflammation** or architecture; no malignant potential; can be **hyperplastic**, inflammatory, hamartomatous (juvenile or Peutz-Jeghers) **Neoplastic epithelial**: adenomatous polyps/adenomas; due to epithelial proliferation and **dysplasia**; **precursors of carcinomas**; can be **benign** (tubular, tubulovillous, villous, sessile serrated) or **malignant** (adenocarcinoma)

Answer 21

Neoplastic epithelial polyps All adenomas arise as result of **epithelial proliferation and dysplasia** Dysplasia may range from mild to severe (carcinoma) **Low** or **high** **grade** depending on architectural and nuclear atypia Gross/macroscopic features: **pedunculated** (stalk) vs. **sessile** (no stalk) Microscopic features: **tubular, tubulovillous**

Answer 22

Architecture: **crowding** of glands and **irregular**, **branching** glands Cytology: **pseudostratification** of cells and nuclei; slightly **larger** and **elongated** **nuclei**

Answer 23

Architecture: marked **crowding** of glands including **complex cribriforming structures** Cytology: loss of cell polarity; **nuclear enlargement** and rounding

Answer 24

**Multistep process** of progression from normal mucosa to carcinoma (involves series of mutations in multiple genes, like all cancers) **Specific gene mutations** correlate with **distinct histopathologic changes**: normal mucosa --\> adenomatous polyp --\> carcinoma Mutations can be **inherited** (familial) or **acquired** (somatic) Most sporadic invasive colorectal adenocarcinomas (CRC) arise in pre-existing adenomas, although a few adenomas become invasive cancers Patients with **adenomas** have **increased risk of cancer** (have lag time to develop cancer though)

Answer 25

1) **APC** at 5q21 is **"first hit"** (inherited or acquired mutation of cancer suppressor gene) 2) **APC/beta-catenin** is **"second hit"** (methylation abnormalities and inactivation of normal alleles) 3) **K-Ras** at 12p12 is protooncogene mutation 4) **p53**, **LOH** mutations cause homozygous loss of additional cancer suppressor genes (or overexpression of COX-2) 5) **Telomerase** or other gene mutations or gross chromosomal alterations

Answer 26

As with staging of other cancers, it indicates **extent** of cancer and is best predictor of **survival/prognosis** Unlike with other tumors, the T refers to the **depth** of penetration into the bowel wall (rather than the size of the tumor)

Answer 27

Associated with **HPV** infection HPV --\> squamous intraepithelial dysplasia --\> squamous cell carcinoma Like with other SCC, get pink keratin pearls! Remember, anus has squamous epithelium unlike intestine which has columnar epithelium

Answer 28

**Mesenchymal** neoplasm Varies from low risk to overtly malignant Most have somatic mutation in **c-KIT (CD117)** gene which encodes a tyrosine kinase receptor See **spindle** **cells** with elongated nuclei, fine chromatin and **eosinophilic** cytoplasm

Answer 29

NE cells normally dispersed along GI tract mucosa and have role in gut function Almost all are **potentially** **malignant** (except those found with pernicious anemia?!) Small, polypoid solid, yellow/tan lesions Can cause kinking of bowel when **invade** mesentary and produce obstructive symptoms **Monotonous** cells arranged in sheets, islands, trabeculae, round to oval nucleus with salt and pepper chromatin, scant eosinophilic cytoplasm, EM shows neurosecretory granules

Answer 30

Any segment of the GI tract may be involved in dissemination of lymphoma 40% of lymphomas arise in sites other than lymph nodes and GI tract is most common extra-nodal location 1-4% of all GI malignancies are lymphomas Most common GI lymphoma is **MALT** lymphoma that originates in B cells of mucosa-associated lymphoid tissue May arise anywhere in gut but most common in stromach in setting of **H. pylori chronic gastritis** Malignant cells are **discohesive** with prominent **nucleoli** and occasional **mitotic** figures

Answer 31

**Outpocketings** of the colonic mucosa and submucosa through weakness of muscle layers in the colon wall Is actually **pseudo**-diverticula because doesn't include all 3 layers of the colon wall! Includes mucosa and submucosa but NOT muscularis propria Alone, they are not an issue but can lead to **diverticular bleeding** or **diverticulitis** Caused by increased intra-colonic presure (low fiber diet)

Answer 32

Recommended to get 30 grams per day Beans Squash Cereal bran flake Brown rice Apple

Answer 33

**No symptoms** so no medical attention sought **Diverticular bleeding**: **BRBPR**, usually minor or self-limited but severe in 5% **Diverticulitis**: inflammation of a diverticulum; **LLQ pain**, fever, leukocytosis

Answer 34

**Angiodysplasia** (AVM), **right** more than left Anorectal: **hemorrhoids**, fissure Malignancy: colorectal **cancer** **Inflammatory bowel disease** Other colitides (ischemic) Upper GI bleeding

Answer 35

Chronic injury to **vasa recta** adjacent to lumen of diverticulum

Answer 36

**Nuclear scan** (tagged RBC scan) **Angiography** **Colonoscopy**

Answer 37

**Supportive** care (most resolves spontaneously): **volume resuscitation** but if persists then investigate coagulation abnormalities For ongoing bleeding, do **angiography** and **embolization**, colonoscopic intervention, emergency surgery with **resection**

Answer 38

Hardened **feces** trapped in **diverticulum** and gets **infected** Matter inspisates within diverticulum and erodes through wall Symptoms: **LLQ** **pain**, **fever**, **leukocytosis**, peritonitis (acute abdomen: rigidity, rebound tenderness, involuntary guarding, consistent with perforation), Less commonly **UTI**, **pneumaturia**

Answer 39

Gastroenteritis Crohns Ulcerative colitis Cancer Ischemic colitis Kidney stones Ruptured aneurysm PID (other gyn problem) Others

Answer 40

If **mild** (able to eat, just LLQ pain): oral **antibiotics** If **moderate** (unable to eat/drink): **antibiotics**, bowel rest, **supportive** care, most improve in 48-72 hours, treat until pain/diet improved, discharge on oral antibiotics, study colon in 4-6 weeks If **severe** (perforation): surgical **resection**

Answer 41

**20-22cm** long muscular tube Inner circular and outer longitudinal muscle layer (**ICOL**) Upper 5% **striated** muscle Middle 35-40% **mixed** Lower 50-65% **smooth** muscles **Upper esophageal sphincter** **Lower esophageal sphincter** (near diaphragm)

Answer 42

Control by **CNS** **Nucleus ambiguus** **Sequential** motor neuron activation by neurons coming from the nucleus ambiguus

Answer 43

Sensory is nucleus tractus solitarious (NTS) Motor is **dorsal vagal motor nucleus** (vagus nerve) to the **myenteric plexus** Myenteric plexus neurons use **NO** as a neurotransmitter to **hyperpolarize** smooth muscle, then when NO broken down after the stimulus, smooth muscle **contracts** and causes peristalsis (**"off response"**)

Answer 44

Neuromuscular diseases: CNS (**stroke**, MS, ALS, Parkinson's, tumor), PNS (polio, **myasthenia**, **neuropathy**), myopathy (muscular dystrophy, **polymyositis**) Oropharyngeal dysphagia: food **sticks** in anterior throat above suprasternal notch; difficulty **initiating** swallows, cough, choking, nasal regurg, nasal speech; takes a long time to eat

Answer 45

Cannot get food **started** down esophagus

Answer 46

**Collagen vascular diseases** (CREST, scleroderma, SLE) Muscular dystrophies Familial visceral myopathies Pathology: muscle degeneration and replacement by **fibrous connective tissue**

Answer 47

Food sticks at **suprasternal notch** or substernal Note: location does not predict level of lesion (obstruction is usually distal to sensation)

Answer 48

UES functions well and striated muscle contracts, but **no function of smooth muscle** and **LES is weak**

Answer 49

Myenteric neuropathy **Failure of peristalsis**, LES does not relax (elevated LES pressure), **loss** **of nitric oxide synthase-containing neurons from myenteric plexus** Get **powerful random contractions** of smooth muscle of esophagus **or simultaneous pressure waves** that do not cause peristalsis Clinical presentation: **dysphagia** (solid more than liquid), **regurgitation**, chest **pain**, heartburn, aspiration, weight loss, halitosis **Bird's beak** at LES, dilated esophagus, sigmoid esophagus, failed primary primary peristalsis

Answer 50

Less than 1% of dysphagia (not common) Mean age of 40 **Chest pain** (mimic cardiac pain), **dysphagia**, **heartburn** See increased pressure within smooth muscle of esophagus due to spasm?

Answer 51

**Pacemakers/conductors** that control **gastric peristalsis** Between muscles and nerves Impulse transmitted from nerve through ICC to muscle to allow for contraction (if no ICC then no muscle contraction!), **network** that initiates/propagates electrical signal in stomach

Answer 52

Idiopathic **Diabetes** (if glucose over 170, stomach doesn't work because no ICCs) Post-gastric Par. dis.

Answer 53

Nausea, vomiting, **bloating**, **early satiety**, abdominal **pain**, weight loss Pathophysiological changes are **impaired accommodation**, antral **hypomotility** and **distension**, **dysrhythmia** Abnormal emptying is a marker or neuromuscular dysfunction, rather than a cause of symptoms

Answer 54

More in **men** than in women (except northern Iran where SCC associated with Plummer Vinson Syndrome which is iron deficiency anemia and dysphagia due to growths of tissue that cause blockage) More in **AA than** caucasians Causes/risk factors: **tobacco**, **alcohol**, **achalasia** (33x risk!), head and neck SCC, Tylosis, eating lye, ionizing radiation, celiac, HPV 16 and 18, Hot Mate drinking

Answer 55

Causes/risk factors: **Barrett's esophagus** as result of **reflux** esophagitis Symptoms: **none** early on, **dysphagia**, **odynophagia**, anorexia/weight loss, retrosternal pain, cough, hoarseness, bone pain if skeletal metastases

Answer 56

**Benign strictures** (peptic acid esophagitis, caustic ingestion) **Malignant stricture** **Motility disorder** (achalasia, scleroderma)

Answer 57

Cachexia Lymphadenopathy Hepatomegaly Fecal occult blood

Answer 58

Endoscopy allows for biopsy Barium swallow

Answer 59

Determinants of survival: **depth** of invasion, **lymph node** metastases (distant vs. local), patient factors

Answer 60

**Endoscopic** **Surgery**: potential for cure; **esophagectomy** (transthoracic or transhiatal), **replacement** of esophagus (with stomach, colon, jejunum); mortality is 1-15% **Chemotherapy** **Radiation** therapy **Palliative**: laser, photodynamic, esophageal **stent**

Answer 61

**Males** more than females Mean age 68 More in Costa Rica, Japan and less in North America, Africa, India and SE Asia Etiology: carb-rich diet, high salt, nitrates, alcohol and tobacco maybe, **H. pylori**, genetics (familial adenomatous polyposis, hereditary non-polyposis coli, **E-cadherin** mutation)

Answer 62

**None** early on **Anorexia**, weight loss, **epigastric** **pain**, **early satiety**, **meal-induced dyspepsia**, abdominal **bloating**, **dysphagia**, gastric outlet obstruction, GI **bleeding** Occult blood in stool, palpable gastric mass, **hepatomegaly**, **ascites**

Answer 63

Early: **endoscopic** Local: **surgery** Late: **chemotherapy**, **radiation** therapy, **palliative**

Answer 64

**Adenocarcinoma** **Intraductal** **papillary** **mucinous** neoplasm (IPMB) **Neuroendocrine** (Islet cell tumor) **Cystic** neoplasms (serous, mucinous) **Acinar carcinoma**

Answer 65

Almost all die within a **year** of diagnosis Risk factors: **family** **history** (familial atypical multiple mole melanoma syndrome, BRCA2, Peutz-Jeghers syndrome, hereditary pancreatitis), **environmental** factors (asbestos, pesticides, dyes), **diet** (meat and fat), **diabetes**, older age, **male** Typical presentation: weight loss, **pain**, **jaundice**, new diagnosis **diabetes**, **pancreatitis**, metastatic disease Note: painless (obstructive) jaundice with palpable gallbladder (**Courvoisier's sign**) is cancer in **head of pancreas** until proven otherwise

Answer 66

Chronic activation of **trypsin** **Autosomal dominant** Younger patient with pancreatitis for no apparent reason (early progressive fibrosis) **40x risk of pancreatic cancer**

Answer 67

**15-20% resectable** (not metastatic, does not involve blood vessels; surgical resection is only treatment associated with cure) **40% metastatic** 30-40% locally advanced 5-year survival is 25-35% with pancreatic resection but only 5% with no treatment Note: most patients present when already have **metastatic** disease and treatment is difficult; however many patients are not even referred to a surgeon because primary care doctors think pancreatic cancer is not treatable

Answer 68

**Resectable**: 10-20 months Locally advanced: 8-12 months Metastatic: 3-6 months

Answer 69

Chemo is **not very effective** for pancreatic cancer, but is **used** (along with resection) 1 year survival for combination chemotherapy is 26-45% **Gemcitabine** modestly increases survival compared to **5FU** (only prolongs survival **3 weeks** though)

Answer 70

**Ductal epithelium** becomes dysplastic and those (called PanINs) cause pancreatic cancer PanINs look more **"angry"** as **grade** gets higher

Answer 71

**Helical (spiral) CT** (best study, gives info on resectability) Endoscopic ultrasound PET, MR, MRCP (MR cholangiopancreatography) ERCP FNA (percutaneous/EUS) Laparoscopy Tumor markers (**CA19-9** tells you how far cancer spread)

Answer 72

**Local** disease **No distant metastasis** Regional node involvement OK! Vascular involvement Comorbidity

Answer 73

**Remove** entire **duodenum** End-to-side pancreatojejunostomy Pylorus-preserving and non-pylorous-preserving

Answer 74

Adjuvant therapy is treatment given **after "curative" resection (Whipple)** with intent to eradicate any remaining tumor with the goal to cure patient or further prolong survival

Answer 75

**Systemic recurrent disease** is what kills people However, most people also have local recurrent disease as well

Answer 76

**Chronic** condition Significant morbidity 35% lifetime prevalence 40-50% have **monthly** symptoms 10-20% have **weekly** symptoms 5-10% have **daily** symptoms

Answer 77

Injurious factors: acid, potency of refluxate **Defensive** factors: acid clearance, mucosal resistance (most important)

Answer 78

Transient lower esophageal sphincter relaxations (**tLESRs**): different from swallow-induced relaxation, increased by **gastric** **distension**, integrated motor response (crural diaphragm inhibition, esophageal shortening, costal diaphragm contraction), vagally mediated reflex; **most mild symptomatic GERD** related to tLESRs **Hypotensive lower esophageal sphincter**: tonically contracted smooth muscle, reduce LES pressure (gastric distension, foods, smoking), strain induced reflux, free reflux; usually associated with more **severe GERD** **Hiatal hernia**: diaphragm, reduced threshold for **tLESRs**, "malfunction" of GE barrier (during periods of low LES pressure, during normal swallow LES relaxation, during deep inspiration or straining); severity of esophagitis correlates with **size** of hernia; usually associated with more **severe GERD** Motility disorders and delayed gastric emptying don't have clear role but some people think they might

Answer 79

**Peristalsis** Acid neutralization by **saliva** (salivary bicarbonate) Prolonged clearance in 50% with esophagitis Prolonged clearance w/hiatal hernia Gravity assists (so sleeping impairs ability to clear acid)

Answer 80

Just having H+ on top of mucosa is NOT enough to cause acid reflux symptoms! H+ diffusion **into** **mucosa** (usually this involves an injuy) Cellular acidification and necrosis **Pepsin** (zymogen released by chief cells, degrades food proteins) increases mucosal permeability and now H+ can enter Note: increased gastric acid secretion does not equal esophagitis

Answer 81

Pre-epithelial factors: surface mucous and bicarb for pH gradient (poorly developed in the esophagus); not very relevant role **Epithelial** factors: tight junctions, lipid rich matrix, Na/H exchanger and Cl/HCO3 exchanger Post-epithelial factors: blood flow

Answer 82

**Symptoms** or **mucosal** **damage** from abnormal **reflux into esophagus** Esophageal inflammation **not** required Pathophysiology is multifactorial **Classic** symptoms: **heartburn** (in retrosternal area), **regurgitation** (into mouth or hypopharynx), **dysphagia** (if inflammation or complications) **Atypical** symptoms: atypical **chest pain**, hoarseness, nausea, **cough**, odynophagia, **asthma**, globus sensation, recurrent laryngitis, recurrent sore throat, subglottic stenosis, dental enamel loss

Answer 83

History: heartburn (pyrosis), regurgitation Response to **empiric trial of therapy** (note: don't need to go beyond this 95% of the time) Endoscopy (but **50% EGDs are normal**) Radiologic findings **Ambulatory esophageal pH monitoring** (this will catch everyone, but is annoying and unncessary so don't need it if empiric therapy works!)

Answer 84

Advantages: detection, stratification, management **50%** with **normal** EGD Interoperator variability (esophagitis grading scheme; LA classification) For any patient who requires **continuous maintenance medical therapy** (5 years or more--are looking for Barrett's esophagus) EGD is most useful modality to evaluate **complicated** **GERD** Bleeding, dysphagia, unexplained weight loss or significant **change in symptoms** while on effective therapy Later age of onset

Answer 85

**Granular** appearance of mucosa **Thickening** of longitudinally oriented esophageal **folds** Shallow **ulcers** and **erosions** (tiny pooling of barium collections in distal esophagus) Smooth tapered **narrowing** (peptic **stricture**)

Answer 86

Patients with **persistent symptoms and normal EGD** Transnasal catheter for 24 hours Wireless capsule shaped device for 48 hours 5cm above LES pH 4 is threshold

Answer 87

**Esophagitis** **Peptic strictures**: solid food dysphagia, result of healing of ulcerative esophagitis, collagen deposition, usually short in length **Barrett's esophagus**: chronic esophagitis heals in metaplastic process (abnormal columnar replace squamous cells) **Adenocarcinoma** Possibly asthma or ENT issues

Answer 88

Risk factors: men, **tobacco**, **obesity,** elderly DNA alterations Dysplasia (grade is dependent on observer) **Malignant transformation**: activation of protooncogenes (**cyclin D1**), disable tumor suppressor genes (**p53, p16**)

Answer 89

34-89% of asthmatics have GERD Esophagitis in up to 40% of asthmatics Possible mechanisms: microaspiration with consequent bronchospasm; vasovagal reflex causing bronchoconstriction Usually requires **higher doses of PPI** to treat

Answer 90

"Laryngopharyngeal reflux" Laryngitis Laryngeal and tracheal stenosis Laryngeal cancer

Answer 91

**Lifestyle modifications**: head of **bed** **elevated** 6in, **smoking** cessation, **weight** **loss,** avoid recumbency post-prandially, avoid large meals and trigger **foods**, avoid exacerbacting **meds** **H2 blockers** (ranitidine, famotidine, nizatidine, cimetidine): since histamine stimulates parietal cells to make acid; **rapid** onset of action; higher doses more effective; **tachyphylaxis** (just stop for a few days then begin again and will be fine!) **PPIs** (omeprazole, lansoprazole, esomeprazole, pantoprazole, rabeprazole): continuous or non-continuous, best **maintenance** therapy, best symptom control, shortest healing time, no diff among PPIs, take 30 min prior to meals, take a while to start working? Can cause **osteoporosis** Note: **lifestyle modifications** and **PPIs** most effective

Answer 92

Consider in **young** patients on high doses of PPIs who may require lifelong therapy Controversial use in patients refractory to high dose PPIs Up to 2/3 of patients in one study **continued to use PPIs** after antireflux surgery after 10 years follow up Surgical options: restoring physiologic equivalent of LES, **Nissen fundoplication** (wrap fundus of stomach around esophagus; pre-operative esophageal manometry, tightness of wrap cricual and dysphagia if too tight), good initial symptomatic improvement in 85-90% but long term results variable, less effective with atypical symptoms

Answer 93

**Genetic** predisposition Mucosal **immune** system (innate/adaptive dysfunction) **Environmental** triggers (lumenal bacteria, infection)

Answer 94

**Ulcerative colitis** symptoms: **bloody** diarrhea, rectal **urgency**; **colon** **only**; **continuous**; **mucosal**; megacolon, adverse effect of smoking cessation; family history **Crohn's disease** symptoms: **pain**, **diarrhea**, weight loss, **perianal** disease; anywhere in GI (**skip lesions**, patchy?); **transmural**, histology **granuloma** (\<20%), adverse effect of smoking, family history; complications include **fistula/stricture/abscess**

Answer 95

Serum and stool inflammatory markers (**ESR, CRP**; calprotectin, lactoferrin) Serologic markers: **pANCA** for **UC** (or CD in COLON); ASCA, OmpC I2, CBir1 for small bowel CD Imaging: **barium small bowel series**, **CT** and **MR** enterography **Endoscopy**: colonoscopy, upper endoscopy, enteroscopy, capsule endoscopy

Answer 96

Central and peripheral **arthritis**, sacroileitis Eye manifestations: **uveitis**, episcleritis Skin manifestations: **erythema nodosum**, **pyoderma gangrenosum** **Primary sclerosing cholangitis**: increased alkaline phosphatase and/or liver enzymes, diagnosed with MRCP/ERCP, can be progressive (cholangitis, liver failure, liver transplant), **increased cancer risk** (cholangiocarcinoma, colon cancer), no good treatment; looks like **string of beads**

Answer 97

Risks: side effects, reactions, cancer risk?, unknown Benefits: improve **quality of life**, avoid surgery, reduce growth/development, reduce cancer risk?, avoid steroids, **avoid disease progression**

Answer 98

First **inflammatory**, then **stricturing** and **penetrating** (formation of fistulas)

Answer 99

"Step up" approach 1) 5-aminosalicylates (**5-ASA**): mesalamine, balsalazide, sulfasalazine, Pentasa; for **induction** and **maintenance** of ulcerative colitis, excellent **safety** (rare interstitial nephritis, worsening IBD), chemoprevention of colon cancer?, many pills per day or rectal enema/suppository for distal disease 2) **Corticosteroids**: first line for **moderate-severely active** disease (CD or UC), topical or oral or IV, cheap but not long term, start **high dose and taper off**, side effects (bone loss, infection, cataracts, diabetes, more); **Budesonide** (pH-dependent ileal-releasing steroid) is low systemic bioavailability, first line for active ileal CD and right colitis (not UC) and have fewer side effects than prednisone 3) **Immunomodulators**: **6-mercaptopurine/azathioprine**; maintenance only because **onset of action delay 3-6 months**, routine monitoring of liver and blood count, can measure metabolites, side effects (pancreatitis, hepatotoxicity, bone marrow suppression, lymphoma?) 4) **Biologics**: infliximab, adalimumab, certolizumab (CD), Natalizumab (CD); also cyclosporin (for UC, not a biologic) 5) **Surgery**: for **CD**: small bowel/**partial colon resection**, **stricturoplasty**, perianal disease (**fistulotomy**, **flaps**), ileostomy/colostomy; for **UC**: **colectomy** with **ileostomy or J-pouch**

Answer 100

**IV**, chimeric (25% murine) **Induction** and **maintenance** of remission for moderate to severe **CD and UC** Rule of 1/3 First line for **fistulizing** disease Rare but serious side effects (**infection** (TB, fungal), **lymphoma** (NHL, HSTCL)

Answer 101

Subcutaneous **anti-TNF alpha mAb** Equal efficacy to infliximab, similar safety profile to infliximab Less immunogenicity/attenuation than infliximab

Answer 102

**Anti-alpha4 mAb** (blocks **leukocyte** migration to **gut**) Excellent efficacy and safety profile **JC virus/PML risk** if already had virus (check JCV Ab before starting) **Second line**, only after failing anti-TNF therapy

Answer 103

Colorectal **cancer screening** Metabolic bone disease (steroids, Crohn's, malnutrition) **Vaccinations** (unpredictable need for immunosuppression, disease risk from preventable infections) **Smoking** (increases CD prevalence and recurrence, and poor response to infection)

Answer 104

**Second** most common cancer in US Second leading cause of cancer death 90% of CRC cases in patients **older than 50** Incidence in younger people is rising even though total incidence is falling Risk factors: age, **ulcerative colitis**, **polyps** (1.5-2x risk), **CRC** (1.5-2x risk), obesity, high-fat or low-fiber diet, family history of CRC, adenomas, IBD, **FAP**, **HNPCC**; other cancers doesn't increase risk significantly

Answer 105

**Colonoscopy** (gold standard) Sigmoidoscopy: only examines lowest 1/3 of colon, primary care MDs and nurses can do this, takes less than 5 min; used with FOBT Virtual colonoscopy: requires biopsy Fecal occult blood test: old, in rural places, not sensitive or specific Only 40% of eligible adults screened!

Answer 106

Examines **entire colon** Requires intensive prep (compared to sigmoidoscopy), sedation **\>95% accurate** **CT colography** (virtual): high resolution, air contrast, less invasive/expensive; as good as colonoscopy for lesions greater than 1cm

Answer 107

Begin at age **50** (age **45 if AA**) FOBT anually OR flexible sigmoidoscopy OR both OR **colonoscopy** (repeat **every 10 years** if normal) OR double-contrast barium enema (repeat every 5 years if normal) If **high risk** (cancer/adenoma in first degree relative under 60 or 2+ relatives): start by **age 40** and repeat every **5-10 years**

Answer 108

Normal --\> loss of both **APC** --\> **adenoma**, and then: 1) **CIN** to LOH, aneupoloidy --\> **p53, LOG, K-ras, SMAD** --\> cancer 2) **MIN** to hypermutable phenotype --\> **TGF-betaII receptor, BAX, MMR, MBD4, TCF-4, IGF2R** --\> cancer

Answer 109

On 5q21 Deleted in **85%** of **sporadic polyps** **Adhesion molecule** **Tumor suppressor gene** Interacts with beta catenin and when APC is mutated, the complex **accumulates** in cell leading to transcriptional **activation** of other **tumor promoting genes** **Germline** **mutation** in APC in **Familial Adenomatous Polyposis (FAP)**

Answer 110

FAP **Autosomal dominant** 100% chance of cancer if no surgery Innumerable **polyps** Other cancers Mutation in **tumor suppressor gene APC**

Answer 111

K-ras **activation** occurs early in adenoma-carcinoma pathway (signal transduction increased) **GTPase** mutated in 50% large polyps and cancers Farnesylation required for translocation Involved in signal transduction through **MAP kinase, Raf kinase**, other pathways First **biomarker** in CRC **Predicts response** to **anti-EGFR drugs** Example of how we can personalize cancer therapy

Answer 112

**Deleted** in 50% of adenomas and 70% of colorectal cancers Thought to be **DCC, SMAD2, SMAD4** also on 18q SMAD proteins part of **TGF-beta** signaling pathway regulates **growth/apoptosis** Germline mutation in **SMAD4** leads to **juvenile polyposis** (hereditary cancer syndrome)

Answer 113

"**Guardian of the genome**" Critical component in cell cycle, senescence, apoptosis, viral defense Most commonly altered gene in human cancers Mutated in up to 75% of CRC

Answer 114

Involves inactivation of MMR (**mismatch repair**) genes (MSH2, MLH1, MSH6, PMS1, PMS2, EXO1, others) Function of MMR genes is to correct errors such as base mismatches and IDL that occur in DNA replication Base-base mismatches lead to single substitutions IDLs lead to insertion or deletion resulting in **microsatellite instability**

Answer 115

**Base-base mismatches** MSI is defined as "a **change of length** due to either insertions or deletions of repeat units in a microsatellite within a **tumor** compared to normal tissue" Can be divided into MSI-H and MSI-L 15% of sporadic cancers Right and female \> left and male Better prognosis Germline: **HNPCC** (Lynch syndrome)

Answer 116

AKA Lynch Syndrome Germline 2-3% of CRC **Early** onset, **right** sided, synchronous **Autosomal dominant** Lynch I is CRC and Lynch II is CRC+ Diagnosis based on Amsterdam and Bethesda Criteria 90-100% lifetime risk of CRC **DNA mismatch repair genes** May need total proctocolectomy (patient will need permanent ileostomy)

Answer 117

Mutations in **tumor**: **CIN**: K-ras, APC, DCC, p53 (85%); **MIN**: DNA mismatch repair (15%) Mutations in **patient**: FAP, HNPCC, methylating genes; approximately **5%** of CRC from inherited genetic mutations

Answer 118

**Adenomas** are clonal benign neoplasms Almost all CRCs begin as adenomas, though few adenomas become CRCs Patients with adenomas have **increased risk** of cancer **Size of** adenoma correlates with **risk** of cancer Lag time to develop cancer

Answer 119

**Asymptomatic** (found on screening) **Microcytic anemia** (iron deficiency) so every patient with microcytic anemia older than 45 needs colonoscopy Bleeding: **melena** for right sided and **hematochezia** (BRBPR) left sided **Obstruction** (rectal) Changes in **bowel movements**

Answer 120

Staging: degree of tumor penetration through bowel wall, nodal involvement, distant metastases Indicators of **poor** **prognosis**: bowel **obstruction** or **perforation**, elevated pretreatment **CEA** (carcinoembryonic antigen) **Microsatellite instability** associated with **improved survival** Loss of chromosome 18q and thymidylate synthase expression unknown status as prognostic markers (need validation)

Answer 121

Malignant polyp: **polypectomy** Stages I, II, III: **surgery** Rectal cancer: **radiation** (ONLY for rectal) Stage III, IV: **chemotherapy** (for stage IV biologic therapy too but surgery ONLY if symptomatic) Note: laparascopic surgery now standard of care

Answer 122

**Colon** cancer (Dukes C): **5FU/LV** reduces recurrence by 1/3; **FOLFOX** combination therapy further reduces recurrence **Rectal** cancer (Dukes B2 and C): **5FU/LV + radiation preop** better than postop

Answer 123

**5FU**: antimetabolite incorporates into DNA Oral fluoropyrimidines: prodrug of 5FU Irinotecan: topoisomerase inhibitor **Oxaliplatin**: DNA binding **Cetuximab**: mAb to EGFR **Bevacizumab** (Avastin): mAb to VEGF; binds/neutralizes all forms of VEGF-A; used with chemo in metastatic CRC; improves survival up to 1/3 **Panitumumab**: mAb to EGFR Regorefanim (just approved): kinase inhibitor of VEGFR

Answer 124

**Angiogenesis inhibitors** **Growth factor receptor antagonists:** EGFR is best studied

Answer 125

**Self-sufficiency** in growth signals **Insensitivity** to anti-growth signals Tissue **invasion** and metastasis **Evading apoptosis** Sustained **angiogenesis** (angiogenic switch when small tumors acquire ability to stimulate angiogenesis by upreg VEGF and downreg thrombospondin 1) Limitless **replicative** potential

Answer 126

Transition from **columnal rectum** to **squamous anus** **Dentate line**: anal crypts and anal glands

Answer 127

**Internal** sphincter: thickening of inner circular **smooth** muscle of gut wall; controlled by **ANS** (not under voluntary control); relaxes **reflexively** once stool enters rectum (recto-anal inhibitory reflex); 2.5-4cm long and 2-4mm thick; maintains continence at rest **External** sphincter: 3 parts (subcutaneous, superficial, deep); continuation of levator muscles; **skeletal** muscle (under **voluntary** control); active control of continence

Answer 128

**Above dentate line**: pelvis (**internal iliac nodes**, along inferior mesenteric chain) **Below dentate line**: groin (**inguinal nodes**), **perirectal nodes**

Answer 129

Congenital vascular "cushions" **Arteries, veins, connective tissue** Classic distribution [3 quadrants]: right anterior and posterior, left lateral **Internal** or **external** hemorrhoids

Answer 130

Above dentate line, **columnar** epithelium (mucosa), no nerve endings (**painless**) Protrusion, bleeding, ache, wetness, straining 4 grades (I to IV)

Answer 131

**Below dentate line**, **squamous** epithelium (skin), nerve endings (**painful**) Difficulty with hygiene, itching, burning, severe pain when **thrombosed**

Answer 132

Hereditary Poor **dietary** habit Constipation, diarrhea **Pregnancy** Post-surgical

Answer 133

**Conservative management**: **sitz** bath, **fiber** supplementation, 6-8 glasses of fluid per day, **stool softeners**, suppositories and creams (soothing but nor effective in eliminating) Office based for internal hemorrhoids: **sclerotherapy** (use needle to inject and shrink hemorrhoid), infrared **coagulation**, **rubber band ligation** (more effective than sclerotherapy), application sites above level of sharp pain fibers (no anesthetic needed) **Hemorrhoidectomy**: incarcerated/gangrenous hemorrhoids, anemia, failure of conservative treatment, patient preference (for external)

Answer 134

**Painful** lump Induced by constipation, exercise, or diarrhea Worse pain for 24-72 hours, then **subsides** Body will **resorb** this and will cause bleeding (tell pt this is normal) **Surgical excision** for relief

Answer 135

1) **Constipation**, diarrhea, operation, instrumentation 2) **Trauma** (cut) 3) **Increased** internal anal sphincter tone 4) **Decreased** blood flow 5) **Ischemic** ulcer/fissure Vicious cycle!

Answer 136

**Hemorrhoids** **Fissure** **Fistula** and **abscess** Condyloma (**warts**) and **neoplasms**

Answer 137

Symptoms: **pain**, **bleeding**, protrusion, seepage and soilage, itching, change in bowel movement Signs: **tenderness**, **fluctuance**, erythema, mass, ulcer, lesion

Answer 138

Both arteries and veins are **dual supply** to rectum **Ischemia uncommon** because good (dual) blood supply Venous drainage to portal system so can develop **rectal varices** Arteries: **IMA** to **superior rectal**; **internal iliac** to **middle rectal, inferior rectal** Veins: internal and external **rectal plexuses**, perimuscular rectal plexus, **inferior/middle rectal vein**; **superior rectal vein** to **sigmoid** vein to **IMV**, **internal pudendal** veins

Answer 139

Like an **ulcer** or **tear** in anal lining May be able to **see internal anal sphincter** through tear Symptoms: **pain**, **spasm**, **bleeding**, itching Location: 80-85% on **posterior** anus; anterior more common in women May be associated with Crohn's, ulcerative colitis, syphilis, TB, leukemia, HIV, CMV, trauma Atypical fissure: other location, **multiple** fissures (may be associated with other disease) **Sentinel pile** is sign of **chronic** anal fissure

Answer 140

**Conservative** **management** (try this first): chemical relaxation with diltiazem, nitroglycerin, nifedipine ointment; stool softeners, fiber, laxatives **Surgical** options: anal dilation (not done much anymore), **botox** injection with fissurectomy, **lateral internal sphincterotomy** (cut portion of muscle to relieve spasm but small risk of incontinence)

Answer 141

"**Cavity with pus**" Most commonly develops secondary to **infection** in anal gland

Answer 142

"**Tunnel** with entrance and exit"

Answer 143

**Fistulas** arise from rupture or surgical drainage of an **abscess** Risk factors: male in 20-40s Symptoms: pain, swelling, drainage, bleeding, urinary difficulties, fever and chills Etiology: cryptoglandular disease, infection of anal gland, Crohn's, cancer, radiation, foreign body, trauma, surgery, STDs, TB Types of abscesses: intersphincteric, perianal, ischiorectal, supralevator Types of fistula: intersphincteric, transsphincteric, suprasphincteric, extrasphincteric Treatment: **fistulotomy**, **endorectal advancement flap**

Answer 144

From **HPV** (human papilloma virus) Risk factors: anoreceptive intercourse, immunosuppression, HIV Treatment: caustic agents (**podophyllin**) for small warts; surgical therapy if fail medical therapy (**excision**, fulguration, laser, **cryotherapy**); immunotherapy (autologous vaccines, **Imiquamod** (Aldara), interferon) or chemotherapy (**5FU**, bleomycin) if recur after surgery

Answer 145

**Squamous cell carcinoma** HPV implicated Often cure by **chemoradiation** If treatment failure or recurrence, have **abdominoperineal resection** (excision of anorectum with permanent colostomy)

Answer 146

**Peptic ulcers**: **deep**; complete loss of mucosal surface; **penetrates muscularis mucosa** and beyond; diameter **\>5mm**; can even perforate into peritoneal cavity or into blood vessel to cause hemorrhage **Erosions**: **shallow**; **superficial** mucosal lesion only; diameter **\<5mm**; mucosa turns over every 4-5 days so this healing is very protective

Answer 147

**Epigastric dyspeptic pain**: gnawing, aching like a hunger pang; relieved by food, milk, antacids; recurs 2-4 hours after eating (because gastric emptying causes relative increase in acid again); often awakens patient during night Both upper endoscopy (**EGD**) and contrast radiography (**UGI series** (using barium)) diagnostic in 90%

Answer 148

In order of relevance: **H. pylori** infection **NSAIDs** and ASA **Tobacco** (prevents healing) and **cocaine** Inherited host factors Zollinger-Ellison Syndrome Viral infections Host factors: variations in HCO3 secretion, PG synthesis, variations in gastric emptying, different levels of vagal release

Answer 149

Transmission: **person to person**, childhood, oral-oral, fecal-oral High prevalence: developing countries, crowded living conditions, **poor sanitation**, contaminated water? Healthcare personnel at increased risk

Answer 150

**Acute** and **chronic** **gastritis** **Peptic ulcer disease** (PUD) **Gastric adenocarcinoma** **Gastric MALT lymphoma** Note: inhabits **mucosa layer** and attaches to but **does not invade gastric epithelial cells**

Answer 151

Follows brief acute gastritis infection episode Muted chronic immune response (because doesn't even get into tissues, is not invasive!) Usually **asymptomatic** Often progresses to atrophic gastritis over time Only minority of people ever develop clinical disease (symptoms) Dimorphic anatomic distribution: **antral**-predominant gastritis (**duodenal** ulcers) or corpus-predominant/**pangastritis** (**gastric** ulcers and **cancer**) Note: any gastric ulcer is considered cancer until proven otherwise!

Answer 152

**H pylori** involved in **80-90% of duodenal ulcers** and **60-80% of gastric ulcers** \<20% of H pylori infections cause peptic ulcer disease though H pylori **eradication** is **curative** in 90% of cases! Antisecretory treatment alone is only curative in \<30% So treat the H pylori infection to get rid of ulcers!

Answer 153

1) **Antral**-predominant **H pylori gastritis** 2) **Depressed** **somatostatin** release (H pylori destroys D cells) 3) Chronic **hypergastrinemia** 4) **Gastric acid hypersecretion** 5) Duodenal **metaplasia** 6) H pylori **duodenitis** 7) Duodenal **ulcer** Note: reversed by H pylori eradication

Answer 154

Older population H pylori **pangastritis** and atrophy Most **normo-** or **hypo-acidic** **Abnormal duodenogastric reflux** (more reflux of duodenal juice w/bile salts into antrum of stomach) **NSAID** use highly prevalent Ulcer develops in vulnerable mucosa

Answer 155

Invasive: histology, culture, rapid **urease** (swab stomach and put on colormetric plate to indicate activity of urease) Non-invasive: **serology** (IgG detected but but doesn't tell you past or present infection), **urea breath test** (ingest C14 urea then measure C14 CO2), stool antigen

Answer 156

**"Test and treat" strategy**: noninvasive diagnosis (no anatomic confirmation of ulcer), empiric course of treatment then endoscopy for treatment failure Regimen: antisecretory agent and antibiotics Multiple FDA-approved regimens No effective single agent First-line: **triple therapy** (**PPI** standard does bid + **clarithromycin** 500mg big + **amoxicillin** 1g bid for 7-10 days) Second-line: quadruple therapy (triple therapy plus **bismuth** (pepto bismol))

Answer 157

Avoid "test and treat" and instead endoscope early if the below **cancer alarm symptoms** present: **Bleeding** or **anemia** Repetitive **vomiting** **Weight loss** or anorexia **Dysphagia** Severe or atypical **pain**

Answer 158

1) Intractable **pain** 2) **Hemorrhage** 3) **Obstruction** 4) **Perforation** (note: only **duodenal** ulcers perforate, not gastric ulcers)

Answer 159

Usually only used for acute ulcer complications "damage control": **bleeding, perforation, obstruction** Additional indications: **failure to heal**, suspicion of **malignancy** Must **excise** or **biopsy** gastric ulcer to **rule out cancer** For **duodenal** ulcers, increased **acid** so traditionally would do **vagotomy** or proximal gastric vagotomy (to decrease acid secretion) For **gastric** ulcers, decreased resistance/defense so traditionally would do **gastrectomy** (take out ulcer to make sure not malignant) Procedures to ensure good drainage of the stomach after **truncal vagotomy** made it so no more stomach motility: **gastrojejunostomy**, **pyloroplasty** **Antrectomy** to remove antrum (Billroth I or II)

Answer 160

Reflux esophagitis Small pouch syndrome Reflux gastritis Marginal ulcer Efferent loop obstruction Early dumping syndrome Afferent loop syndrome Pancreatitis Leaking stump Post-vagotomy diarrhea

Answer 161

**Vagotomy** **Gastric resection** Note: these not done as much any more!

Answer 162

Hopefully within 10 years Vaccine target antigens: **urease**, virulence factors (CagA, VacA) Multi-component formulations appear more effective

Answer 163

Stool weight \>200g per day Increased frequency of stool (\>3 times per day) **Looser stool consistency**

Answer 164

10L of fluid **Oral** intake, **saliva**, **gastric** juice, **bile**, **pancreatic** juice, **intestinal secretion**

Answer 165

**85%** of fluid load absorbed by **small bowel** Folds, villi, microvilli increase surface area

Answer 166

**Malabsorption** of solutes in intestine (**osmotic** diarrhea) Solute and water **transported** **into** lumen of intestine (**secretory**) **Not enough time** to absorb water, or decreased transit time

Answer 167

Determined by **transit time:** Longer: hard stools Shorter: watery stools

Answer 168

**Acute** vs. **chronic** **Osmotic** vs. **secretory** **Inflammatory** vs. **non-inflammatory** **Infectious** vs. **non-infectious**

Answer 169

**Acute** diarrhea: **\<4 weeks** duration, often due to **infection**, evaluate if fevers, abdominal pain, elderly/immunocompromised, bloody, hypovolemic **Chronic** diarrhea: **\>4 weeks**, evaluate because possible serious disease and has effect on quality of life

Answer 170

Non-absorbed particles **draw in water** **Improves** with **fasting** **Stool osmotic gap**: is 290 - 2(Na + K); in osmotic diarrhea gap is **\>125** mosm/kg; **non-electrolytes** make up most of stool osmolality (poorly absorbed carbohydrates (lactose intolerance), any malabsorption (celiac, Crohn's pancreatic insufficiency)) Note: 290 is serum osmolality (not stool, because hard to measure)

Answer 171

**Ion transport** into lumen by epithelial cells Osmotic activity mainly due to **electrolytes** Stool osmotic gap **\<50** mosm/kg Large volume (3-20L per day) **Does NOT improve** with **fasting** Examples: infectious (**cholera**, bacterial toxins), **drugs** (colchicine, quinidine, castor oil), endogenous (**neuroendocrine tumors, bile salts**)

Answer 172

Most diarrhea has **both** osmotic and secretory components **Mucosal** **damage** (ie Crohn's disease): osmotic (**destruction** of villi/**absorptive** cells, loss of brush border enzymes) and secretory (relative **excess** of crypt **secretory** cells, cytokine release causes mucosal cell secretion) Stool osmotic gap is **50-125**

Answer 173

**Damaged** mucosal cells: cytokine release, fecal **leukocytes** present, can be **bloody**, ESR and CRP may be elevated Due to **inflammatory bowel disease** (CD, UC, microscopic colitis), **infections** (C. difficile, E. coli)

Answer 174

Acute: usually **bacterial** or **viral**, exact cause often unknown, most are **self-limited** and not investigated unless signs/symptoms of severe infections Can be inflammatory or non-inflammatory (**inflammatory** would invade intestinal mucosa and/or produce toxins, can be bloody; **non-inflammatory** colonize in lumen and/or produce toxins and are watery/non-bloody) Causes: E coli, salmonella, shigella, vibrio, campylobacer, yersinia, gonococcus, syphillis, mycobacterium, C difficile, rotavirus, norwalk, astroviruses, HSV, strongyloides, giardia, cryptosporidiun, E histolytica

Answer 175

Drugs: **antibiotics** (malabsorbed carbs due to normal bowel flora different, C diff), **chemotherapy** (distupt balance of proliferation/apoptosis), **anti-acids**, diet foods/drinks/gum Blood is marker of **inflammation** or **ischemia**, suggestive of **colonic** disease **Tenesmus** (feeling of incomplete defecation) suggests **rectosigmoid** disease Stool volume: **frequent** **small** vol suggests colonic disease and **large** vol suggests **small intestine** disease Fasting improves diarrhea suggests osmotic and does not improve suggests secretory Recent travel/sick contacts suggests infectious Fat droplets suggests malabsorption of fat Floating stool due to gas (not fat!) **Weight loss** suggests **malabsorption**, **malignancy**, **inflammatory bowel disease**, **hyperthyroidism** **Prior intestinal surgery** suggests **short gut**, **bile salt** diarrhea (50-100cm TI resected), f**at malabsorption** (\>100cm TI resected)

Answer 176

Fecal **leukocytes** (inflammatory diarrhea) Sodium (**Na**) and potassium (**K**): osmotic gap is 290 - 2(Na + K); \<50 suggests secretory and \>125 suggests osmotic diarrhea; the 290 is serum osmolality, not stool (too hard to measure) **pH \<6** suggests **carbohydrate** **malabsorption** (due to bacterial fermentation in colon) **Sudan stain**: fat malabsorption

Answer 177

**Stool studies** to evaluate for infection **Colonoscopy** to evaluate for colitis, malignancy, ischemia

Answer 178

Maldigestion of **fat** (pancreatic insufficiency, lack of bile): thearpeutic trials of pancreatic and bile salt replacement **Celiac** disease: serologies, enteroscopy with biopsies

Answer 179

**Anti-acids** (magnesium): stop med, trial of other anti-acid Poorly absorbed **carbs** (ie sorbitol): avoid in diet **Carb malabsorption** (ie lactose intolerance): trial of dairy-free diet, H+ breath test

Answer 180

Broad differential diagnosis: **Infection**: cholera (stool eval, rehydrate early) **Bacterial** overgrowth (breath test, empiric treatment) **Structural** disease: bile salt diarrhea, IBD, tumors (labs, imaging, endoscopy) **Endocrine** disorders: DM, hyperthyroidism, Addison's disease **Small bowel diseases** (serologies, endoscopy + biopsy)

Answer 181

**Nonspecific** anti-diarrheal medications decrease stool frequency **Opiates** (mu opiate receptor selective) slow gut transit (ie diphenoxylate, loperamide, tincture of opium) **Bile acid binding resin** used in bile acid deficiency but als non-specific diarrhea (ie cholestyramine) **Fiber supplements** solidify stool consistency, useful in coexisting fecal incontinence (ie psyllium) **5HT₃ antagonist** used in IBS diarrhea but boxed warning against acute ischemic colitis (ie alosetron) **Somatostatin analog** used in carcinoid syndrome, other endocrine disorders, AIDS (ie octreotide)

Answer 182

\>25% of bowel movements with: **straining**, **lumpy**/hard stools, sensation of **blockage**, sensation of i**ncomplete evacuation**, need to manually facilitate evacuation **\<3** bowel movements per **week**

Answer 183

**Metabolic** disease: DM, hypothyroidism, hypercalcemia, heavy metal intoxication **Obstruction**: stricture, colon cancer, extrinsic compression, rectocele, anal stenosis **CNS damage** **Peripheral nerve damage** **Hirschsprung's disease** **Medications**

Answer 184

**CNS damage**: can **slow transit** but anal reflexes intact; trigger defecation by digital stimulation of anal canal **Peripheral nerve damage**: sacral/pudendal nerve lesions (parasympathetic innervation to distal colon/rectum, cauda equina syndrome, hypomotility, decreased rectal tone/sensation)

Answer 185

**Congenital** disorder **Arrest** of **caudal migration of neural crest cells** during embryonic development --\> **aganglionosis** of **submucosal** and **myenteric plexus** Obstipation from birth (do not pass myconium) Lifelong constipation ("adult" form) Colonic dilatation proximal to diseased segment Treat by **surgical resection of aganglionic segment**

Answer 186

**Anticholinergic** agents: anti-spasmodics (hyoscyamine), anti-depressants (TCAs, SSRIs, SNRIs), anti-psychotics **Cation** **containing** agents: Ca2+ supplements, iron supplements, aluminum (antacids, sucralfate) **Neurally active** agents: opiates, ganglionic blockers, Ca2+ channel blockers

Answer 187

Prevalence up to **30%** **Slow transit:** reduced motor activicy after meals/waking; daytime motor activity preserved, **loss** of **myenteric plexus** ganglion cells, **paucity** of **interstitial cells of Cajal** **Normal transit:** patients mis-perceive bowel frequency, unresponsive to laxatives and fiber supplements, exhibit increased psychosocial stress **Dyssynergic defecation:** paradoxical **external anal sphincter contraction** when bearing down **Constipation predominant IBS**: pain gets better after defecation

Answer 188

**Bearing down** normally **relaxes puborectalis** muscle (sling) --\> straightens anorectal angle --\> descent of pelvic floor --\> **relaxes EAS**

Answer 189

History: duration, stool consistency, frequency, maneuvers used for BM (meds, digital manipulation) PE and DRE: fissures, sphincter tone (rest/squeeze/relax), stool presence, form **Alarm** symptoms: **blood** in stool, **weight loss** \>10lbs, FH of **CRC** or **IBD**, **anemia**, positive **fecal occult blood tests**, acute onset in the **elderly** Evaluate for structural abnormalities (colonoscopy or CT) if alarm symptoms **Anorectal manometry**: anal sphincter pressures (**dyssynergic defecation**), recto-anal inhibitory reflex (rectal distension by balloon causes IAS relaxation and if absence then could be **Hirschsprung's disease**), rectal sensation (hyposensitivity may suggest **neurologic disorder**) **Balloon expulsion tes**t: 2 minutes to expel 50-60cc balloon from rectum (inability means **dyssynergic defecation**)

Answer 190

Patient education: increase **fluid**, increase dietary **fiber**, **exercise** **Stool softeners**: docusate (lowers surface tension so water enters easily, safe but low efficacy) **Bulking agents**: **cellulose** derivatives (resist digestion, absorb water, increase fecal mass, soften stool), **psyllium**, methylcellulose, wheat bran; adverse effects are abdominal **bloating** and **flatulence**, so start low dose and increase slowly **Laxatives** Prescription (**lubiprostone**, **tegaserod**) If no alarm symptoms, empiric treatment If empiric treatment unsuccessful, evaluate further

Answer 191

Measure colonic transit Sitzmark capsule: **24 radioopaque markers** Ingest capsule on day 0 --\> abdominal X-ray on day 5 --\> **retention of \>5 markers** (20%) indicates **prolonged colonic transit** **Distribution** suggests underlying problem: **scattered** throughout means **hypomotility** and **clustered in recturm** suggests **dyssynergic defecation** Perform on high fiber diet, avoid meds that alter bowel function (laxatives/enemas, narcotic pain meds)

Answer 192

**Stimulant** laxatives (bisacodyl, senna): alter electrolyte transport by intestinal mucosa, increase intestinal motor activity, chronic use can cause hypokalemia, salt overload **Saline** laxatives (milk of magnesia): poorly absorbed, hyperosmolar solutions, **draw fluid into colon**, caution because hypermagnesemia in renal failure **Osmotic** laxatives: **draw water into lumen**, synthetic **sugars** (lactulose, sorbitol), **polyethylene glycol** electrolyte solution

Answer 193

Prescription drug Locally acting **chloride channel activator** Enhances Cl rich intestinal fluid secretion **Nausea** most common adverse effect

Answer 194

Prescription drug Partial **5HT4 agonist** **Removed** from market in 2007 due to risk of severe **cardiovascular events** (stroke, MI) Only available for "compassionate" use

Answer 195

Don't give laxatives in these situations! **Dyssynergic** **defecation**: anorectal **biofeedback** **Hirschsprung's disease**: surgical **resection** of aganglionic segment **Laxative-refractory slow-transit constipation**: subtotal **colectomy** with ileo-rectal anastomosis

Answer 196

**Cut vagus nerves** above where they innervate the stomach Now **no acid secretion** of stomach (used to cure duodenal ulcers which are caused by too much acid) Also no innervation of stomach at all so **no stomach motility, no emptying** (have to do gastrojejunostomy or pyloroplasty to ensure that stomach will still empty)

Answer 197

**Gastrojejunostomy**: connect jejunum to body of stomach, bypassing the immotile antrum? **Pyloroplasty**: cut through wall/pylorus then re-sew in the opposite direction so have closure but no more pyloric sphincter

Answer 198

Remove antrum because gastric ulcers there, then reconstruct using: **Billroth I**: connect end of **duodenum** to stomach **Billroth II**: connect **jejunum** to stomach and leave blind pouch of duodenum

Answer 199

More **selective** than truncal vagotomy Cut vagus **near fundus/corpus** of stomach (where parietal cells make acid) and leave antrum and pylorus innervated so **stomach can empty** Only used for intractable pain, if perforated, or if failed medical therapy

Answer 200

**Secretory** diarrhea Bile acids induce net **secretion** in colon crypt epith cells **Resolves** with **fasting** because bile acids are only released when you eat

Answer 201

**Epithelium**: absorption, secretion, metabolism, protection/surveillance (alpha defensins, mucins, secretory IgA, submucosal cells) **Commensal bacteria**: absorptive homeostasis, metabolism, protection **Enteroendocrine** cells: absorption

Answer 202

Proximal gut (duodenum, jejunum): carbohydrates, fat, protein, iron, folate, xylose **Terminal ileum**: bile salts, vitamin B12 Colon: water Note: stomach absorbs alcohol but not nutrients

Answer 203

Impaired **transport** across **mucosa** **Maldigestion** (impaired **hydrolysis** of luminal contents) leads to malabsorption too though **Diarrhea** is **NOT** malabsorption because diarrhea is a **sign or symptom**

Answer 204

Fat: **steatorrhea**, weight loss Carbs: gas, **diarrhea** Protein: **muscle wasting, edema** Iron, folic acid or B12: **anemia** Bile salts: **diarrhea** Vitamin A: **night blindness** Vitamin D: **osteopenia**, osteomalacia Vitamin E: **wound healing** impairment Vitamin K: **bleeding**, bruising, increased INR B vitamins: cheilosis, **glossitis**, dermatitis, neuropathy Ca2+ and Mg2+: **paresthesias**, tetany

Answer 205

Small bowel diarrhea (**Crohn's**): reservoir capacity intact, **large** stool volume, modest increase in number, no urgency, tenesmus, mucus, blood "Left-sided" diarrhea (**UC**): reservoir capacity decreased, **small** stool volumes, **frequent** stools, **urgency, tenesmus, mucus, blood**

Answer 206

These are tests you COULD do, but **don't really** do them commonly Serum: iron, B12 (Schilling), folate, vitamin D, carotene (total, not beta) Fat: qualitative, quantitative Protein: alpha1-antitrypsin clearance Carbs: hydrogen breath test (not a great test), stool pH \<5.5 (because carbs are acidic), D-xylose low = proximal defect Bile acids: fecal concentration, C14 glycocholic acid test Vitamins: individually

Answer 207

1) Impaired **luminal** hydrolysis/solubility 2) Impaired **mucosal** hydrolysis, uptake or packaging 3) Impaired **removal** of nutrients

Answer 208

**Pancreatic exocrine** insufficiency: alcohol, obstruction, CF, familial/hereditary **Bile acid** deficiency **Zollinger-Ellison syndrome** (gastrinoma--causes increased acid): bile acid precipitate, inactivation of enzymes, acid directly toxic to mucosa **Post-gastrectomy** malabsorption **Rapid** intestinal transit Small bowel **bacterial overgrowth** **Autoimmune polyglandular failure** (rare, but think of this if multiple endocrine abnormalities and malabsorption)

Answer 209

**TG** broken down by **lipase** (ie pancreatic lipase) into **FFA** and **monoglyceride** FFA constructed into **micelles** by **bile acids**?

Answer 210

Most bile acids absorbed in **ileum**

Answer 211

**Increased** amounts of **bile acids** delivered to colon following ileal damage or resection This causes profound **diarrhea**

Answer 212

**Fat** in stool, **clay** colored (or whitish or yellowish) stool If no pancreatic lipase (knocked out 90% pancreatic exocrine function), get steatorrhea Occurs in **late** **chronic** **pancreatic insufficiency** Low bicarb = **low pH** = inactivated enzymes Treatment: lots of **pancreatic enzymes** +/- medium chain TG diet True steatorrhea = malabsorption

Answer 213

**Brush border** or **metabolic** **diseases**: lactase deficiency, sucrase-isomaltase deficiency, glucose-galactose malabsorption, abetalipoproteinemia **Mucosal** diseases: **celiac**, **Crohn's**, Common Variable Immunodeficiency (**CVID**), lymphoma, radiation enteritis, amyloidosis, **microscopic colitis** (lymphocytic, collagenous) **Infectious** diseases: tropical sprue, Whipple's disease, parasitic diseases, mycobacterium avium-intracellulare, AIDS enteropathy **Post-intestinal resection**: IBD surgery, short bowel, etc

Answer 214

**Hydrogen** production is increased in lactase deficiency If don't have lactose then can't break down lactose to glucose and galactose to get absorbed across intestinal epithelium **Lactose + bacteria** in ileum/cecum create **H2** + **CO2** + short chain fatty acids (and acidic pH) --\> bloating and belching

Answer 215

1) **Congenital** (very rare, autosomal recessive) 2) **Hypolactasia** (complex genetics, onset delayed) 3) **Acquired** (usually after intestinal injury)

Answer 216

1) **Decreased** brush border **hydrolases** resulting in **unabsorbed CHO** 2) **Villous** **atrophy** (fluid, nutrient and electrolyte malabsorption) 3) **Crypt** **hyperplasia** (increased endogenous secretion) 4) **Inflammation**, induced secretion

Answer 217

Type 1 DM Autoimmune **thyroid** disorder **Addison's** disease Primary biliary cirrhosis Autoimmune **hepatitis** Autoimmune **cholangitis** **Anemia** Osteoporosis, **selective IgA deficiency**, **dermatitis herpetiformis**

Answer 218

Adherence: **poor palatability**, poor availability, high cost, social/cultural/peer pressures, lack of support group, inadequate info Response to diet: gluten ingestion, sequelae of sprue (refractory +/- clonal T cells, T cell lymphoma, collagenous sprue, small bowel cancer), wrong diagnosis (lactose intolerance, bacterial overgrowth, microscopic colitis, pancreatic insufficiency, IBD, IBS, incontinence, autoimmune enteropathy)

Answer 219

**Giardia** lamblia Coccidia **Microsporidia** **Strongyloides** stercoralis Capillaria philippinensis, Metagonimus yokogawai **Tapeworms**: T. saginata (beef), Hymenolepis nana (Dwarf tapeworm), D latum (fish)

Answer 220

Lymphangiectasia Chronic mesenteric ischemia

Answer 221

OTC laxatives, **sorbitol**, **olestra** (nonabsorbable carbohydrates can cause diarrhea/anal leakage!) Medications

Answer 222

Oral biology: **Waldeyer's** ring (**tonsil** tissue) Esophagus Gastric **acidity** and **bile salts** create hostile environment Mucosal **motility** reduces time in contact with epithelium **Mucoid** **glycocalyx** layer creates a barrier Generally, mucosal immunity refers to lymphoid tissues of GI, respiratory, UG tracts Liver has macrophages and NK T cells to filter everything that isn't killed by gut (not part of mucosal immune system)

Answer 223

Production of mucosal associated antibody **IgA** (dimer, connected by SC) Population of T cells with mucosa-specific regulatory properties **"Systemic ignorance"** activated lymphocytes home in on GI mucosa but ignore gut microbiota

Answer 224

**Smaller** size Smaller cecum **Decreased villous renewal** **Caloric requirements** higher Hypoplastic immune response With repletion, majority of body's leukocytes are in gut Germ-free animals get **more autoimmune disease** and **cancer**

Answer 225

Secreted by **paneth cells** in intestinal crypt Production induced by **normal flora**

Answer 226

1) Failure of **tolerance** (Treg) 2) Host **genetics** (MHC loci, HLA) 3) Revealed **autoantigens** 4) **Molecular mimicry** of foreign and self epitopes 5) **Infectious** trigger (bacterial, viral) 6) **Environmental** triggers

Answer 227

**IBD** **Celiac** **Common Variable Immunodeficiency (CVID)** **Microscopic colitis** **Scleroderma** **Eosinophilic esophagitis (EE) and gastroenteritis (EG)** **Autoimmune gastritis** **Autoimmune hepatitis (AIH)** **Primary biliary cirrhosis (PBC)** **Primary sclerosing cholangitis (PSC)** Autoinflammatory diseases (Familial Mediterranean Fever, Muckle-Wells) Vasculitis (Lupus, Microscopic polyarteritis) Infectious: HIV/AIDS, MALT lymphoma, immunoproliferative small intestinal disease (IPSID) Cancer (stomach, colon, pancreas, liver, lymphoma) Autoimmune pancreatitis Type I DM

Answer 228

Heterogeneous group of diseases where **IgG** levels are **decreased**, but also with variable **defects in Ig subclasses** and T cells **Primary immunodeficiency syndrome** Mean age of diagnosis 29-33 Recurrent **sinopulmonary** **infections** or **atypical bacterial infections** **Malabsorption**, nodular lymphoid hyperplasia, small bowel bacterial overgrowth (**SIBO**), small bowel **lymphoma**, Giardia, autoimmune diseases, splenomegaly Treatment: **IVIG**, manage malabsorption (budesonide, mesalamine, vitamin supplementation), vaccinations (?)

Answer 229

Non-bloody, watery, **secretory diarrhea** **Lymphocytic** colitis vs. **collagenous** colitis (physical barrier to absorption) Causes: **bacterial** **toxins**, **bile** **acids**, NSAIDs, statins, lansoprazole Therapies: bismuth, cholestyramine, 5-ASA compound (mesalamine), budesonide (steroids)

Answer 230

**3 feet**

Answer 231

H&P **Serum CBC** **Iron** panel **Carotene** (total, not beta; \<20 is malabsorption, \>100 is not) **Vitamin B12**, folate **Vitamin D,** Ca2+ IgG panel Bone density scan (indicates Ca2+ abnormalities)

Answer 232

Huge **selective pressure** on the **lactase gene** (breaks down lactose into glucose and galactose) This pressure exists because has to do with whether people can domesticate animals (drink cow's milk) In places where they drink lots of milk (Northern Europe?) don't have much hypolactasia because NEED lactose! In Africa and East Asia where don't drink milk, lots of hypolactasia

Answer 233

**Rare** genetic disorder **Malabsorption of fat nutrients**

Answer 234

**Inducible autoimmune disease** (triggered by **gliadin** which is a component of gluten which is in wheat products) Gliadin is deamidated then picked up by APCs, presented to T and B cells and get immune response that destroys intestines: **villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis** Symptoms: early **osteoporosis**, unexplained **anemia**, **weight loss**, vitamin deficiencies, relative **hyperphagia** (eating too much), **shorter** than same sex parent/sibling, **diarrhea/constipation**, abdominal **pain**, **bloating**, **gas**, **fatigue** 1 in 133 people have celiac!

Answer 235

First do **serologic** tests for **anti-TG2** (**antiendomysial**) antibody Also test **total IgA** because remember people with celiac might have IgA deficiency so this could lead to false negative if no IgA! Then do **intestinal biopsy** to look for histologic features of celiac Put on **gluten-free diet** and if clinical or histologic improvement then definitive diagnosis

Answer 236

**Fibrosis**, **vascular** alterations and **immune activation** **Limited** SSc: **"CREST syndrome"** (calcinosis cutis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) **Diffuse** SSc: "worst form" (GI, renal, cardiac, lung) Esophageal dilation, malformations of small vessels in fingernails, fibrosis in lung (telangectasias) Women more than men Polymorphism in **CTGF** promoter **Antibodies** in scleroderma: topoisomerase I (SCL-70), centromere antibodies, nucleolar **Environmental** stimuli: vinyl chloride, epoxy resins, pesticides, organic solvents, silicone implants

Answer 237

**Microstomia**: decreased food intake Difficulty swallowing: **sicca** syndrome **GERD**: LES non-functional **Esophageal** dysmotility and strictures **GAVE** (gastric antral vascular ectasias) and GI **bleeding** Small intestine bacterial overgrowth (**SIBO**) **Hypomotility** Stasis/pseudo-obstruction **Malabsorption**/steatorrhea Vitamin deficiency **Diarrhea**

Answer 238

Emerging disease spectrum of unknown cause EE yypically affects young men, peripheral eosinophilia (\>5%), increased IgE, allergic/atopic disease Eosinophilic **esophagitis** (EE): **GERD** symptoms, esophageal **strictures**, food impactions; rings Eosinophilic **gastroenteritis** (EG; rare): obstruction, bloating, abdominal pain

Answer 239

Acid suppression Dilation Fluticasone (swallowed steroid) Budesonide Montelekast Mepolizumab (IL-5 Ab)

Answer 240

Autosomal dominant Females more than males HLA B8 and DR3 Antibodies against parietal cell **H+/K+ ATPase** and **intrinsic factor** Associated with **Hashimoto's** thyroiditis and **vitiligo** More likely can cause: **pernicious anemia**, carcinoid tumors, gastric adenocarcinoma, esophageal squamous cell carcinoma Less likely can cause: H pylori infection

Answer 241

1) **R factors** in **saliva** bind B12 2) **Acid** and **pepsin** in **stomach** begin to liberate B12 from R factors 3) Secretion of **intrinsic factor** (IF) by gastric **parietal cells** 4) **Pancreatic** **proteases** complete the liberation of B12 from R factors. **Intrinsic factor** now bound to **B12** 5) **Ileum** takes up **B12-IF complexes** through receptor-mediated endocytosis

Answer 242

Primary biliary cirrhosis (**PBC**) Autoimmune hepatitis (**AIH**) Primary sclerosing cholangitis (**PSC**)

Answer 243

Chronic **necroinflammatory** disease of the liver **Periportal hepatitis** with **plasma** **cells** and **lymphocytic** infiltrate Female predominance **Hypergammaglobulinemia** (IgG) **Autoantibodies**: ANA, ASMA, LKM1, SLA Good response to immunosuppressants Common presentations: acute liver failure in 25%, fatigue, **RUQ pain**, **jaundice**, mild pruritus, arthralgias Mechanisms: autoantigens (CYP2D6, UGT1, ASGPR), HLA DR3, DR4, B8, molecular mimicry (virus), failure of tolerance (Treg), drugs (minocycline, diclofenac) Autoantibodies alone don't make diagnosis, usually need **liver biopsy**; must exclude other chronic liver diseases Treatment: **prednisone +/- azathioprine**; responds well to tx before cirrhosis or to transplant Absolute indications to treat: if **AST/ALT \>10x** upper normal limit; AST/ALT \>5x upper normal limit + **IgG \>2x** normal; **bridging necrosis** or multiacinar necrosis on biopsy Relative indications to treat: symptoms (fatigue, arthralgia, jaundice), serum AST/ALT and IgG less than absolute criteria, interface hepatitis on biopsy

Answer 244

Chronic **cholestatic** disease **Bile duct proliferation** with **inflammation** leading to **obliteration** and **fibrosis** Male predominance **Autoantibodies** (ANCA, ANA, SMA) "Onion skin" lesion on histology Heavily associated with IBD (**UC** \> Crohn's), but no correlation with IBD activity Usually **asymptomatic** but diagnosis made by **MRCP** (string of beads/pearls) 70% have underlying IBD but only 10% of IBD has PSC No proven effective medical therapy **Don't stent** multiple strictures: multiple **cancer** risks, **cholangiocarcinoma** (10-15%), **hepatocellular** **carcinoma** if cirrhotic, **colorectal** cancer (IBD related)

Answer 245

**AIDS cholangiopathy** **Bile duct neoplasms** **Prior biliary surgery** **Stone** disease **Ischemic** bile duct damage **Drug** (5-FU) **Congenital**

Answer 246

Chronic **cholestatic** disease **Loss of tolerance** to mitochondrial **pyruvate dehydrogenase** Genetic associations with IL-12/IL-12R Female predominance **Hyperlipidemia** (IgM) and **bone loss** Mitochondrial autoantibodies (AMA) Mechanism of **autoreactive** **antigen** in PBC: in biliary epithelial cell, **no glutathione** so get immunoreactive PDC-E2? and epitope presented to APC and get PBC Symptoms: spider angiomata, **jaundice**, pruritis, **varices**/portal HTN, "florid duct lesion" on histology Treatment: is very treatable; **ursodiol** 13-15mg/kg slows disease, manage lipids, **DEXA** scans, Ca2+, **Vit D**, bisphosphonates

Answer 247

Not enough defense against **microbiome** so can get **diarrhea** and **inflammation**

Answer 248

GE junction is anatomical: where stomach meets esophagus; just proximal to end of gastric rugae SC junction is histological: where squamous cells meet columnar cells

Weeks 5 and 6 (GI) Flashcards

(273 cards)