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
Is screening for Barrett's warranted?
- In the general population, no.
- In selective populations (men over 50 w/ heartburn), then maybe.
What's the 5 year survival for CRC?
- early-stage: >90%
- regional node: 68%
- widespread mets: <10%
What are some features of adenomas that correlate with an increased malignant potential?
- Large size (>1cm)
- More villous
- Higher degree of dysplasia
- multiple polyps
- first-degree relative with CRC
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
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
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
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
What does that Vibrio Cholera have?
- Cholera toxin: A-B
- Massive watery diarrhea (dehydration)
- Dx: stool culture on TCBS
- Rx: fluids!
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
What's typhoid fever?
- Survives in macrophages, Vi antigen protects in lysosome
- See Peyer's Patch ulcers (distal ileum)
- Chronic carriers in gallbladder
What does Yersinia Enterocolitica cause?
- Pseudoappendicitis in older kids and teens
- Cooler climates, cooler months (grows at 4C)
What's Whipple's Disease?
- Actinomycete-like 16S RNA
- Happens in men at 55
- Infects bowel wall--see PAS+ foamy macrophages
What are your food poisoners?
- Get cereus
- Clostridium perfringens: HL toxin, meats/gravys, small bowel perf, pig roasts, gas gangrene
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)
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)
Who's at risk for colonic ischemia?
- Constipation-inducing meds
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
What's the most common mechanism for pain in functional GI disorders?
Visceral hypersensation (esophageal spasm, functional dyspepsia)
Others: disordered GI motility, others...
What are the excitatory and inhibitory neurotransmitters of the enteric nervous system?
- Excite: Ach, Tachykinins
- Inhibit: NO, VIP
- slow emptying in the absence of mechanical outlet obstruction
- sx: early satiety, bloating, upper ab pain, n/v
- idiopathic (35%)
- DM!!! (30%) - d/t hyperglycemia
- post-gastric surgery
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
Abdominal pain or discomfort with altered bowel habits atleast 3 months long. Relieved by pooping
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%
What's Ogilvie's syndrome (acute colonic pseudo-obstruction)?
- acute dilation of the colon w/o mechanical obstruction
- risk factors:
- sick hospital ppl
- narcs, anti-ACh
What are your two types of gastric adenocarcinoma?
- H. pylori
- smoked stuff
- autoimmune gastritis
- CDH1 (E-cadherin)
- Signet ring cells
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
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
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
What's the definition of chronic diarrhea?
- greater than 250g/day
- more than 3 poops/day
- sx > 4 weeks
What are the most frequent diagnoses made in patients with chronic diarrhea?
- idiopathic IBD
- malabsorption syndrome
- chronic infections
- idiopathic secretory diarrhea
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
What characterizes osmotic/secretory diarrhea?
- osmotic: osmotic gaps >125
- Mg-containing laxatives and antacids are important causes
- secretory: <50
- always rule out infection
What are some causes of inflammatory diarrhea?
- invasive infections
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)
When can you see really big elevations in aminotransferases?
- Drug-induced hepatitis
- Acute viral hepatitis
- Autoimmune hepatitis
- choledocholithiasis (rare)
- muscle disease
What are some side effects of common HCV therapy?
- INF: bone marrow suppression
- Ribavirin: hemolytic anemia
What are the risk factors for gettin that drug-induced hepatitis?
- age >60
- previous hepatotoxicity
- *chronic liver disease does NOT increase the risk
What's the basis for D-I hepatitis?
phase I reaction-p450 metabolite
What's the treatment for amantia induced hepatitis?
- antidote=high dose PNG
What do you need for the diagnosis of autoimmune hepatitis?
- 1. autoantibodies
- 2. hypergammaglobulinemia (IgG)
- 3. interface hepatitis
- 4. portal plasma cell infiltration
- 40% mortality in 6 months if untreated, sx patient
What are the types of autoimmune hepatitis?
- Type 1: ANA/SMA, SLP/LP
- 10-20, 45-70
- Type 2: LKM-1, SLA/LP
What's the most common extrahepatic manifestation of AIH?
Thyroid disease (Hashimoto>Grave's)
then RA, DM1, Sjogren, vitiligo, addison, celiac
What causes drug-induced hepatitis?
Nitrofurantoin, methyldopa, dihydralazine
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
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
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
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)
What are some normal biochemical changes during pregnancy?
- Albumin: decrease by 20%
- Alk Phos: increase 2-3 fold
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)
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)
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%
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
- Elevated bili
- Elevated PT
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