1. What are the risk factors for esophageal SCC?
    Dietary factors: dominant factor in high and intermediate risk countries.

    ETOH and tobacco: dominant factor for low-risk countries.

    Diseases: achalasia, strictures, caustic, Plummer-Vinson, partial gastrectomy, SCC head/neck
  2. Is screening for Barrett's warranted?
    • In the general population, no.
    • In selective populations (men over 50 w/ heartburn), then maybe.
  3. What's the 5 year survival for CRC?
    • early-stage: >90%
    • regional node: 68%
    • widespread mets: <10%
  4. What are some features of adenomas that correlate with an increased malignant potential?
    • Large size (>1cm)
    • More villous
    • Higher degree of dysplasia

    • and...
    • multiple polyps
    • first-degree relative with CRC
  5. What are the three pathways to colon carcinogenesis?
    • 1. chromosomal instability
    • gain of function mutations
    • K-ras: most frequent mutated oncogene in CRC
    • APC (5q): tumor suppressor: The most critical gene in the EARLY development of CRC
    • DCC, SMAD4,2 (18q)
    • p53(17p): 50-70% of CRC occurs LATE, except in IBD
    • 2. microsatellite instability (germline in HNPCC, sporadic in 15% of CRC)
    • MMR genes: hMSH2, hMLH1, hPMS1,2, hMLH3
    • 3. methylation pathway (MSI-/LOH-)
    • MMR defects and inactivation
  6. What are the bacterial diarrheal syndromes?
    • Enteritis- watery diarrhea, non-inflammatory, upper small bowel, toxins (Cholera)
    • Enterocolitis- watery to inflammatory, S and L bowel, invasion, +/- toxins (Salmonella/Shigella)
    • Colitis/Dysentery- colon, invasion or cytotoxins (Shigella, EHEC)
    • Enteric fever- diarrhea and bacteremia (Typhoid)
    • Food poisoning- toxins
  7. What does that ETEC do?
    • Traveler's diarrhea.
    • Heat labile toxin (like cholera)- ADP ribosylation
    • Heat stable toxin: a-activates cGMP, b-non cyclic nucleotide and HCO3 secretion
  8. What does that EHEC do?
    • -Shiga-like toxin, A-B: messes with adenine from 28S ribosome to EF-2
    • -HUS in 10% of kids
    • -Dx: sorbitol-MacConkey (doesn't ferment sorbitol)
    • -Tx: none! druge increase risk for HUS
  9. What does that Vibrio Cholera have?
    • Cholera toxin: A-B
    • Massive watery diarrhea (dehydration)
    • Dx: stool culture on TCBS
    • Rx: fluids!
  10. What do Shigella do?
    • Invades mucosa and superficial mucosa of colon
    • Shiga and neurotoxins-->seizures
    • Cramps, watery diarrhea then dysentery
    • Fever, ab pain, leukocytosis with bands
    • Dx: routine stool culture, PMNs in stool
    • Rx: antibiotics
  11. What's typhoid fever?
    • Survives in macrophages, Vi antigen protects in lysosome
    • See Peyer's Patch ulcers (distal ileum)
    • Chronic carriers in gallbladder
  12. What does Yersinia Enterocolitica cause?
    • Pseudoappendicitis in older kids and teens
    • Cooler climates, cooler months (grows at 4C)
  13. What's Whipple's Disease?
    • Actinomycete-like 16S RNA
    • Happens in men at 55
    • Infects bowel wall--see PAS+ foamy macrophages
    • Malabsorption
  14. What are your food poisoners?
    • Staph
    • Get cereus
    • Clostridium perfringens: HL toxin, meats/gravys, small bowel perf, pig roasts, gas gangrene
  15. What's your collateral circulation in the mesentery?
    • Celiac and SMA
    • superior and inferior pancreaticoduodenals
    • SMA and IMA
    • middle colic and left colic through marginal of Drummond
    • IMA and Circulation
    • superior and middle rectal vessels (internal iliac arteries)
  16. What are the major causes of acute mesenteric ischemia?
    • 1. SMA embolism (50)
    • 2. SMA thrombosis (15-25)
    • 3. Venous thrombosis (5)
    • 4. Nonocclusive mesenteric ischemia (20-30)

    mortality >60%!!!
  17. Who's at risk for colonic ischemia?
    • 60
    • Hemodialysis
    • HTN
    • Hypoalbuminemia
    • DM
    • Constipation-inducing meds
  18. What are a couple potential genetic factors for developing Crohn's?
    • NOD2/CARD15 in 30%
    • More likely to make fistulas/fibrostenosis, ileal disease

    TNF-alpha activation: infliximab, adalimumab, certolizumab pegol
  19. What's the most common mechanism for pain in functional GI disorders?
    Visceral hypersensation (esophageal spasm, functional dyspepsia)

    Others: disordered GI motility, others...
  20. What are the excitatory and inhibitory neurotransmitters of the enteric nervous system?
    • Excite: Ach, Tachykinins
    • Inhibit: NO, VIP
  21. What's gastroparesis?
    • slow emptying in the absence of mechanical outlet obstruction
    • sx: early satiety, bloating, upper ab pain, n/v

    • causes:
    • idiopathic (35%)
    • DM!!! (30%) - d/t hyperglycemia
    • post-gastric surgery
    • other
  22. What's functional dyspepsia?
    • symptoms from the gastroduodenal region in the absence of an organic cause.
    • sx: early satiety, postprandial fullness, bloating, discomfort, n/v
  23. What's IBS?
    Abdominal pain or discomfort with altered bowel habits atleast 3 months long. Relieved by pooping
  24. How do you classify constipation?!?!
    • Normal transit (functional) - 60%
    • Colonic inertia (beads get spread all throughout) - <15%
    • Functional ano-rectal outlet obstruction (2* pelvic floor dysfunction) - 25%
  25. What's Ogilvie's syndrome (acute colonic pseudo-obstruction)?
    • acute dilation of the colon w/o mechanical obstruction
    • risk factors:
    • sick hospital ppl
    • post-op
    • narcs, anti-ACh
    • immobile
  26. What are your two types of gastric adenocarcinoma?
    • Intestinal:
    • H. pylori
    • smoked stuff
    • autoimmune gastritis
    • Diffuse:
    • CDH1 (E-cadherin)
    • Signet ring cells
  27. What's a GI stromal tumor?
    • stomach is the most common site
    • c-KIT gain of function mutation (tyrosine kinase) gleevec
    • arise from interstitial cells of Cajal
    • spindled/epithelioid
  28. How do you get that MALT lymphoma in the stomach?
    • 5% of all gastric malignancies
    • B cell type
    • slow grower
    • H. pylori: antibiotics will lead to tumor regression at the point where a monoclonal b cell line is still dependent on antigen-stimulated T-helpers for growth!!!
    • Later: killing the bug won't matter
    • BCL-1 or MALT-1:constitutive activation of NF-kappaBeta
    • Dx: stain for monoclonal kappa-lambda light chains
  29. What cancers are P-Jers at risk for?
    pancreas, breast, lung, ovary

    also see melanotic oral mucosal/cutaneous pigmentation

    hamartomas show smooth muscle bundles and proliferation
  30. What's the definition of chronic diarrhea?
    • greater than 250g/day
    • more than 3 poops/day
    • sx > 4 weeks
  31. What are the most frequent diagnoses made in patients with chronic diarrhea?
    • IBS
    • idiopathic IBD
    • malabsorption syndrome
    • chronic infections
    • idiopathic secretory diarrhea
  32. What is the purpose of the D-xylose test?
    • Differentiate between pancreatic and small bowel disease (does not require pancreatic enzymes to be absorbed)
    • Collect pee for 5 hours...it should be there if small bowel is good

    Celiac or Whipple's, massive bacterial overgrowth
  33. What characterizes osmotic/secretory diarrhea?
    • osmotic: osmotic gaps >125
    • Mg-containing laxatives and antacids are important causes
    • secretory: <50
    • always rule out infection
  34. What are some causes of inflammatory diarrhea?
    • UC
    • Crohn's
    • invasive infections
    • Whipple's
    • Lymphoma
  35. What's the Rome criteria for IBS?
    • Pain/discomfort 3 days/month in the last 3 months associated with two or more of the following:
    • better on pooping
    • onset associated with change in frequency of stool
    • '' '' '' change in form of stool
    • Tx: hydrophilic bulk-forming agents: psyllium (Metamucil)
  36. When can you see really big elevations in aminotransferases?
    • Drug-induced hepatitis
    • Acute viral hepatitis
    • Ischemia
    • Autoimmune hepatitis
    • choledocholithiasis (rare)
    • muscle disease
  37. What are some side effects of common HCV therapy?
    • INF: bone marrow suppression
    • Ribavirin: hemolytic anemia
  38. What are the risk factors for gettin that drug-induced hepatitis?
    • age >60
    • female
    • fat
    • malnurished
    • booze
    • poly-pharm
    • previous hepatotoxicity
    • *chronic liver disease does NOT increase the risk
  39. What's the basis for D-I hepatitis?
    phase I reaction-p450 metabolite
  40. What's the treatment for amantia induced hepatitis?
    • charcoal
    • antidote=high dose PNG
  41. What do you need for the diagnosis of autoimmune hepatitis?
    • 1. autoantibodies
    • 2. hypergammaglobulinemia (IgG)
    • 3. interface hepatitis
    • 4. portal plasma cell infiltration
    • Women
    • 40% mortality in 6 months if untreated, sx patient
  42. What are the types of autoimmune hepatitis?
    • Type 1: ANA/SMA, SLP/LP
    • 10-20, 45-70
    • Type 2: LKM-1, SLA/LP
    • kids
  43. What's the most common extrahepatic manifestation of AIH?
    Thyroid disease (Hashimoto>Grave's)

    then RA, DM1, Sjogren, vitiligo, addison, celiac
  44. What causes drug-induced hepatitis?
    Nitrofurantoin, methyldopa, dihydralazine
  45. What's that about PBC?
    • interlobular disease (in the liver)
    • women, not kids
    • pruritis, fatigue, jaundice
    • Increased alp phos, AMA titer
    • Associated conditions: KC sicca, RTA, GS, arthritis
    • tx: ursodiol
  46. What's that about PSC?
    • affects whole biliary tree
    • men <45, can happen in kids
    • association with IBD (80%)
    • jaundice, pruritis
    • dx: MR cholangiography, ERCP if symptomatic
    • at risk for cholangiocarcinoma
    • tx: medical therapy-UDCA not effective, stricture dilatation, LT
  47. What extrahepatic complications do you need to be worries about with cholestatic disease?
    • Osteopenia: give Vit D and Ca!!!
    • Pruritis: bile acid sequesterants, ursodiol
    • Sicca syndrome
  48. What's up with that Wilson's disease?
    • patho=copper overload
    • p-type ATPase (ATP7B on 13)
    • decreased bile copper, serum ceruloplasmin
    • Neurological features, personality changes, tremor, dystonia, choreic movements, drooling
    • K-F rings, sunflower deals (anterior chamber)
    • tx: chelators (D-penacilamine)
  49. What are some normal biochemical changes during pregnancy?
    • Albumin: decrease by 20%
    • Alk Phos: increase 2-3 fold
  50. What are the liver diseases specific to pregnancy?
    • 1. Intrahepatic cholestasis of pregnancy (ICP)
    • 2. HELLP (hemolysis, elevated liver enzymes, low platelets)
    • 3. Acute fatty liver of pregnancy (AFLP)
  51. What's the pathogenesis, diagnosis, and treatment for intrahepatic cholestasis of pregnancy?
    • Patho: unknown, thought to be due to increased estrogen levels.
    • Dx: clinical symptoms, fasting serum bile acids >3x normal, exclude other causes of jaundice and pruritis, NO duct dilation on US, don't need biopsy
    • Tx: monitor LFTs, fetal assessment, ursodiol
    • Mom is usually OK, high risk of recurrence. Preterm labor=most common fetal manifestation (then distress, then stillbirth)
  52. What does HELLP look like and how do you manage?
    • Associated with preeclampsia
    • Most cases occur later in pregnancy and can happen after birth
    • Presenting symptoms include nausea and abdominal pain
    • Unknown etiology
    • Manage: deliver. DIC in 20%, abruptio placenta, ARF, maternal mortality = 1-4%, perinatal mortality = 10-20%
  53. What characterizes AFLP?
    • Similar to HELLP, but severe progression to hepatic failure w/o prompt delivery.
    • These happen commonly in AFLP but NOT in HELLP
    • Encephalopathy
    • Elevated bili
    • Elevated PT
  54. What's the pathogenesis of AFLP?
    • Association with fetal enzymatic deficiency in mitochondrial trifunctional protein.
    • Catalyzes last 3 steps in mito long chain fatty acid oxidation
    • hydratase, dehydrogenase (LCHAD), thiolase
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