B7PBLWeeks4-7

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

• In the general population, no.
• In selective populations (men over 50 w/ heartburn), then maybe.

• early-stage: >90%
• regional node: 68%
• widespread mets: <10%

• Large size (>1cm)
• More villous
• Higher degree of dysplasia

• and...
• multiple polyps
• first-degree relative with CRC

• 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

• 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

• Traveler's diarrhea.
• Heat labile toxin (like cholera)- ADP ribosylation
• Heat stable toxin: a-activates cGMP, b-non cyclic nucleotide and HCO3 secretion

• -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

• Cholera toxin: A-B
• Massive watery diarrhea (dehydration)
• Dx: stool culture on TCBS
• Rx: fluids!

• 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

• Survives in macrophages, Vi antigen protects in lysosome
• See Peyer's Patch ulcers (distal ileum)
• Chronic carriers in gallbladder

• Pseudoappendicitis in older kids and teens
• Cooler climates, cooler months (grows at 4C)

• Actinomycete-like 16S RNA
• Happens in men at 55
• Infects bowel wall--see PAS+ foamy macrophages
• Malabsorption

• Staph
• Get cereus
• Clostridium perfringens: HL toxin, meats/gravys, small bowel perf, pig roasts, gas gangrene

• 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)

• 1. SMA embolism (50)
• 2. SMA thrombosis (15-25)
• 3. Venous thrombosis (5)
• 4. Nonocclusive mesenteric ischemia (20-30)

mortality >60%!!!

• 60
• Hemodialysis
• HTN
• Hypoalbuminemia
• DM
• Constipation-inducing meds

• NOD2/CARD15 in 30%
• More likely to make fistulas/fibrostenosis, ileal disease

TNF-alpha activation: infliximab, adalimumab, certolizumab pegol

Visceral hypersensation (esophageal spasm, functional dyspepsia)

Others: disordered GI motility, others...

• Excite: Ach, Tachykinins
• Inhibit: NO, VIP

• 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

• symptoms from the gastroduodenal region in the absence of an organic cause.
• sx: early satiety, postprandial fullness, bloating, discomfort, n/v

Abdominal pain or discomfort with altered bowel habits atleast 3 months long. Relieved by pooping

• Normal transit (functional) - 60%
• Colonic inertia (beads get spread all throughout) - <15%
• Functional ano-rectal outlet obstruction (2* pelvic floor dysfunction) - 25%

• acute dilation of the colon w/o mechanical obstruction
• risk factors:
• sick hospital ppl
• post-op
• narcs, anti-ACh
• immobile

• Intestinal:
• H. pylori
• smoked stuff
• autoimmune gastritis
• Diffuse:
• CDH1 (E-cadherin)
• Signet ring cells

• stomach is the most common site
• c-KIT gain of function mutation (tyrosine kinase) gleevec
• arise from interstitial cells of Cajal
• spindled/epithelioid

• 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

pancreas, breast, lung, ovary

also see melanotic oral mucosal/cutaneous pigmentation

hamartomas show smooth muscle bundles and proliferation

• greater than 250g/day
• more than 3 poops/day
• sx > 4 weeks

• IBS
• idiopathic IBD
• malabsorption syndrome
• chronic infections
• idiopathic secretory diarrhea

• 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

• osmotic: osmotic gaps >125
• Mg-containing laxatives and antacids are important causes
• secretory: <50
• always rule out infection

• UC
• Crohn's
• invasive infections
• Whipple's
• Lymphoma

• 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)

• Drug-induced hepatitis
• Acute viral hepatitis
• Ischemia
• Autoimmune hepatitis
• choledocholithiasis (rare)
• muscle disease

• INF: bone marrow suppression
• Ribavirin: hemolytic anemia

• age >60
• female
• fat
• malnurished
• booze
• poly-pharm
• previous hepatotoxicity
• *chronic liver disease does NOT increase the risk

phase I reaction-p450 metabolite

• charcoal
• antidote=high dose PNG

• 1. autoantibodies
• 2. hypergammaglobulinemia (IgG)
• 3. interface hepatitis
• 4. portal plasma cell infiltration
• Women
• 40% mortality in 6 months if untreated, sx patient

• Type 1: ANA/SMA, SLP/LP
• 10-20, 45-70
• Type 2: LKM-1, SLA/LP
• kids

Thyroid disease (Hashimoto>Grave's)

then RA, DM1, Sjogren, vitiligo, addison, celiac

Nitrofurantoin, methyldopa, dihydralazine

• 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

• 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

• Osteopenia: give Vit D and Ca!!!
• Pruritis: bile acid sequesterants, ursodiol
• Sicca syndrome

• 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)

• Albumin: decrease by 20%
• Alk Phos: increase 2-3 fold

• 1. Intrahepatic cholestasis of pregnancy (ICP)
• 2. HELLP (hemolysis, elevated liver enzymes, low platelets)
• 3. Acute fatty liver of pregnancy (AFLP)

• 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)

• 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%

• 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

• Association with fetal enzymatic deficiency in mitochondrial trifunctional protein.
• Catalyzes last 3 steps in mito long chain fatty acid oxidation
• hydratase, dehydrogenase (LCHAD), thiolase