Intestine Pathophys Flashcards
Crohns pathophysiology
causative agent (pathogen), modifying factors (env, genetic - predisposed) - lumenal factors
immune response
inflammation
tissue injury
TH1!!!!!!
When does surgery for rectal cancer fail?
usuall local reccurrance or distant metastases
confined space - hard to get good margins
classic features of crohn’s disease
abdominal pain
diarrhea with nocturnal stools
weight loss
fever
can have a palpable mass on exam
children may present with failure to thrive, failure to develop secondary sex characteristics, growth retardation
MLH1 and MSH2
There are other mutations that occur, MLH1 and MSH2 lead to microsatellite instability. Those are also associated with cancer, but slightly different than the adenoma pathway.
Side effects of steroids in IBD
greatest predictor of infection!
lots of side effects
need slow taper (2-3 months)
must have exit strategy
What kind of T cell response is Chrons?
TH1
phases of IBD treatment
induce remission
maintain remission
reduce need for surgery and reduce risk of cancer development
CRC screening if family history of colon cancer?
40 years of age or 10 years before index case
also if family history of large or high grade adenoma
even polyp w high grade adenoma!
Location of CD lesions
any part of the GI tract
rectum in 10%
transmural injury
skip lesions
insidious onset (belly pain, anemia)
histo of IBD
crypt distortion
granulomas (CD)
inflammatory cells in lamina propria
plasma cells near crypt base
crypt abscesses
Physical Exam signs for IBD?
abdomen (tender)
perineum/rectal (skin tags, abcesses, fistula)
apthi in mouth (common in CD
- Skin-tag – Has a shiny surface with a waxy appearance at the anus [middle]
- Skin tags are a very common feature
- Can also see a fistula [left]
- Opening right here
- If you were to probe it, you would track it back into the colon
- This is nice clean, not bad looking one
- It can be really mean and angry looking
- Sometimes if you push it, it can express either purulent material because they can get an abscess, or stool will leak out of these areas
- Can imagine what this does for patient’s QoL
How does CRC present?
Abdominal pain (partial obstruction, peritoneal involvement)
change in bowel habits (especially in distal colon, stool is really thin This is seen more often in cancers of the distal colon because on the right side of the colon (proximal colon) it still has to be liquid. so even if you have a blockage, don’t really feel it because its liquid so it still goes by the obstruction. But if there is a lesion that is blocking in the distal colon, you see more bowel changes because its solid forming there)
hematochezia (ulcerate and bleed easily)
CRC screening if no risk factors?
50 years of age (45 for african americans?)
low anterior resection
Surgeries in the rectum are often dictated by how low the cancer is. If there is enough room from the cancer to the anal verge, they can reconnect the colon, which is called a low anterior resection
symptosm seen more in UC than CD?
rectal bleeding (hematochezia)
Bevacizumab
humanized ab vs VEGF - best data for metastatic disease
perforation risks
delays wound healing
Fecal occult blood test
put stool on a card, put droppers on it and see if it turns blue – just tells you if there is a bleed in the GI tract, not necessarily colon cancer.
when to use immunomodulators?
in mild-moderate crohn’s and moderate UC
take 12 wks to take effect
side effects = infection, hepatitis, pancreatitis, bone marrow suppression
cyclosporine - when to use?
severe, steroid refractory UC
in IV formed then tansitioned to oral to induce remission
NOT for maintence
majority of patients require colectomy
side effects: hypertension, renal failure, seizures, infection
UC Pathophysiology
changed gut epithelial imparment effecting tight junctions
antigens come through - present - cascade
mostly in lamina propria
increased permeability and antigen uptake
Barium enema
“apple-core” lesions
you have to prep yourself. Then they inject barium through the rectum which coats the colon. Look for things called apple core lesions.
CRC chemo mainstay
5-fluorouracil is backbone of treatment
post surgical adjuvant therapy:
When you look at the data, the adjuvant therapy has the most benefit with patients with Stage III disease.
Stage 3 – beyond the colon (into the nodes) but don’t have distant metastasis.
not sure if it’s worth it at lower stages
CRC repeat intervals for various tests
colo
flex sigmoidoscopy
barium enema
fecal occult blood
colo - 10 years
flex sigmoidoscopy - 5 years
barium enema - 5 years
fecal occult blood - every year
repeat in shorter intervals if fine things! every 3 years if one or more adenomatous polyp >1 cm, 3 or more of any size
Mot common locations fo crohns?
right colon and distal ileum!
- The most common area of involvement is going to be the small bowel, the distal/terminal ileum, and the right colon
- So ileocolonic disease is the most common areas here
- About 35% patients have distal ileum disease and 35% of patients have right colonic disease
- 20% of patients will just have colonic disease
- That being said, almost all patients who have CD do not have the rectum involved
- Rectal sparing is a big important feature of CD
- Only 10% of patients will have inflammation in the rectum
- This can help you tease out UC and CD
Again, not everybody reads the book
abdominal perineal resection.
some colon cancers are very distal and extend right to the anal verge, so don’t have enough room to stitch the colon together, so have to have a colostomy bag forever. This is an abdominal perineal resection. Resect the entire distal rectum and perineum.
CD on colonoscopy
cobblestoning
thickened wall
fissure
fat wrapping
Staging of CRC
Think of stage 1,2,3, and 4.
Stage 0 hasn’t invaded. mucosa only
Stage 1, invaded into the muscularis
Stage 2 has invaded through the muscularis, propria, or through the colon itself but doesn’t have anything in the nodes.
Stage 3 – once you have nodes
Stage 4 – Metastasis.
top down therapy
anti-TNF
AZA/MTX
Combo
steroids
(if high risk for complications)
UC on colonoscopy
ulceration
pseudopolyps = surviving mucosa
crypt distortion
loss of haustra
Progression of crohn’s disease
- inflammation
- stenosis - from scarring and fibrosis! obstruction and narrowing
- fistula - develop to relieve pressure in scarred areas - to adjacent organs or skin, inflammed, tunnel to skin
can have all sep
- The inflammatory portion is just where you see transmural inflammation of the bowel wall (Image B)
- Stenosis is when you basically can describe as a scar in your intestines (Image A)
- It becomes fibrostenotic
- There is no medication you can give a fibrostenotic scar
- If it is causing symptoms, it has to come out surgically
- There is nothing you can do to reverse it
- It is unclear if you catch it in the inflammatory phase whether you can avoid this scar formation
- In theory yes, but we do not know
- Patients can present with what seems like a stenotic area, they come in obstructed
- You think that maybe they have a scar, but you give them some steroids or rest their bowel and it resolves
- Suggests that maybe it was just an inflammatory process and you can avoid surgery
- Important to tease that out
- There are clinical factors, lab factors, patient history and all those kinds of things that can help you work it out
- Other important type of CD is that of a fistulizing CD (Image C)
- A fistula is an abnormal connection between two organs
- You can develop fistulas between two portions of the bowel as seen here as an enteroenteric fistula
- Here you are seeing a fistula develop between in the distal ileum in the sigmoid colon
- You can also have enterocutaneous fistula where the bowel fistulizes to the skin
- Can see enterovesicular where it fistulizes to the bladder
- The most common area where we see fistulas is the peri-anal area, which is basically eneterocutaneous fistula making an abnormal connection between the rectum and the skin around the rectum
- See this in up to a 1/3 of our patients with CD
- Can be very difficult to manage
- Often a palliative management as an opposed to a definitive management
step up therapy
5ASAs
steroids
AZA/MTX
Anti-TNF
Combonation therapy
azathioprine (immunomodulator) + infliximab (anti-TNF ab)
diminish infusion reaction and increase efficacy!
boosts drug
peri-appendiceal patch
may be seen in UC
•You can get an inflammatory patch right here [right above the appendix] even though this portion of the colon is spared [pointing to ascending colon]
backwash ileitis may occur
vedolizumab
anti-integrin
for **maintanence of UC or CD
monoclonal ab that binds alpha4bta7 integri and inhibits t cell movement across the endothelium to inflammed GI tissue
infusion based
nasopharyngitis, headache
enterography
taking over for barium imaging
CT or MR based studies
consume a large volume of water soluble contrast to distend the small bowel prior to scanning
exposed to radiation!!
- The area of interest that we really need to focus on is the small intestines
- Our upper endoscope goes to the proximal small intestines
fat wrapping around!!
•Our colonoscope goes to the bottom of our small intestines
There is a whole segment in between that is less easy to gain info on
classic features of UC
usually more acute presentation
always involves the rectum and ascends in a continuous pattern
can have disease limited to the rectum, left colon, or entire colon
inflammation is localizedto the mucosa or submucosa
- This disease starts in the rectum and ascends up
- Can have a condition where you also have a clear delineation of the end of the colitis, somewhere distal to the right side of the colon [pointing to where the start of the word transverse], and have what is called an isolated cecal patch or a periappendiceal patch
- See the little tail of the appendix
- You can get an inflammatory patch right here [right above the appendix] even though this portion of the colon is spared [pointing to ascending colon]
immunomodulators in IBD
6-MP, methotrexate, azathioprine
•Can be used both in moderate CD and 5-ASA refractory UC
halt DNA replication and interfere with purine synthesis
TPMT level required prior to initiating treatment - •TPMT levels helps predict if patients will have bone marrow toxicity from this drug
tons of scary side effects
Volgermer
Colon cancers develop through a stepwise accumulation of somatic mutations and so this diagram is called the Volgermer after him, and it describes the stepwise mutations that occur through an adenoma pathway.
Common pathway of CRC stepwise mutations
APC - KRAS - p53
primary anastamoses
Top- want to reconnect the two sides of the colon after you have taken out some of it.
Might not want to do it immediately after surgery:
Inflammation
Anastomosis might not hold very well.
But do want to reconnect. Called a primary anastomosis because do it in one step.
Bottom pictures: Sometimes can’t do that: can’t prep, too much inflammation, other complications. Instead, take out the part with the cancer, seal it off for a little bit, then bring the distal end of the colon to the abdominal wall and they end up with a colostomy bag. Sometimes can later reconnect, sometimes not.
