Intestine Pathophys Flashcards Preview

GI2 > Intestine Pathophys > Flashcards

Flashcards in Intestine Pathophys Deck (64):
1

Crohns pathophysiology

causative agent (pathogen), modifying factors (env, genetic - predisposed) - lumenal factors 

immune response

inflammation

tissue injury

TH1!!!!!!

2

When does surgery for rectal cancer fail? 

usuall local reccurrance or distant metastases 

confined space - hard to get good margins 

3

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 

4

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.

5

Side effects of steroids in IBD

greatest predictor of infection! 

lots of side effects

need slow taper (2-3 months) 

must have exit strategy

6

What kind of T cell response is Chrons? 

TH1

7

phases of IBD treatment

induce remission

maintain remission

 

reduce need for surgery and reduce risk of cancer development

8

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! 

9

Location of CD lesions

any part of the GI tract 

rectum in 10% 

transmural injury

skip lesions 

insidious onset (belly pain, anemia) 

10

histo of IBD

crypt distortion

granulomas (CD) 

inflammatory cells in lamina propria 

plasma cells near crypt base

crypt abscesses 

11

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

12

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)

13

CRC screening if no risk factors? 

50 years of age (45 for african americans?)

14

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

15

symptosm seen more in UC than CD? 

rectal bleeding (hematochezia) 

16

Bevacizumab

humanized ab vs VEGF - best data for metastatic disease 

perforation risks 

delays wound healing

17

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.

18

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

19

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

20

UC Pathophysiology

changed gut epithelial imparment effecting tight junctions

antigens come through - present - cascade 

mostly in lamina propria 

increased permeability and antigen uptake 

21

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.

22

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 

23

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 

24

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

25

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.

26

CD on colonoscopy

cobblestoning 

thickened wall 

fissure

fat wrapping

27

5-ASA

first line for inducing and maintaining remission in UC, no evidence to support use in Crohn's but can be used for mild disease - •If patients have disease in their small bowel or the peri-anal area, this medication will not work

reduce inflammation in the local environment

best when oral and topical - •5-ASA pills are given, but patients who have UC have disease in their distal bowel, in the rectum, and tend to do best either when you give them a suppository and a pill, or an enema and a pill

side effects: headache, nausea, rash, hypersensitivity

28

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.

29

Gold standard fo diagnosing CRC? 

Colonoscopy or flexible sigmoidoscopy

30

Colonoscopy vs flexible sigmoidoscopy?

Endoscopy is the gold standard.

  Colonoscopy or flexible sigmoidoscopy. Colonoscopy is done with a longer tube, but it’s the same instrument. Flexible sigmoidoscopy – only see about half of your colon.

31

top down therapy

anti-TNF

AZA/MTX 

Combo

steroids 

(if high risk for complications) 

32

Risk factors for CRC

age (rare before 40) 

hereditary syndromes (i.e. FAP, Lynch) 

Family history 

IBD 

Diabetes, alchol, S bovis 

33

ileal pouch anal anastomosis

most common surgery for UC patients (30%)

refractory disease, dysplasia, hemorrhage 

ileum pulled into pelvis and anastamose 

•They can get what is called a J-pouch

•The ileum is pulled down into the perineum, and they get a reservoir

•They can get a normal bowel movement out of the anus

•This can work for many patients, but many patients will get inflammation in their pouch

•They can develop Crohn’s in their pouch after removing what was thought to be UC previously

•End ileostomy is absolutely curative

•A pouch can work for people, but there are consequences

34

appendectomy and IBD 

•History of an appendectomy, primarily in a young male for the true indication of appendicitis

Uncertain for CD

•May actually have protective effects in the development of UC

35

symptoms seen more in CD than UC? 

fever 

malaise

weight loss fatigue 

36

UC on colonoscopy 

ulceration

pseudopolyps = surviving mucosa 

crypt distortion

loss of haustra 

 

37

Progression of crohn's disease

1. inflammation 

2. stenosis - from scarring and fibrosis! obstruction and narrowing

3. 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

38

Anti-TNF

mod-severe IBD! 

infliximab, adalimumab, golimumab

monoclonal antibodies that bind TNFalpha 

must check TB and HBV status 

side effects: infusion reaction, hep, infection, malignancy

39

step up therapy 

5ASAs 

steroids 

AZA/MTX 

Anti-TNF

40

Antibiotics in Crohns

some postiive data for use in inducing and maintaining remission in crohn's 

no specific class! 

risk of c. diff and resistance combined w poor quality of evidence has lead to lack of rec

41

IBD

Chronic, systemic, inflammatory process with a relapsing and remitting course affecting various parts of the GI tract 

not always limied to the bowel

a disease of the developed world 

42

Combonation therapy

azathioprine (immunomodulator) + infliximab (anti-TNF ab)

diminish infusion reaction and increase efficacy!

boosts drug 

43

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 

44

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 

45

fecal calprotectin

best marker for neutrophil degredation 

46

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

47

tobacco use and IBD

•Shown to increase, as well as worsen, Crohn’s disease course

•Can improve UC

•Or when someone stops smoking, their UC can present or flare

48

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]

49

C reactive protein

 inflammatory marker

increased more in crohn's because it's transmural 

50

video capsule endoscopy (VCE) 

in CD - no role in UC! (worried about perforation)

pill camera - 8-10 hours

NSAIDs can produce similar lesions 

capsule can be retained or obstruct in those with stricuturing disease!! 

 

51

Radiation therapy in CRC? 

Best in stage II and III 

52

CRC Screening of HNPCC? 

Every 2 years beginning at age 20-25 until 40, then annually

53

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 

 

54

Steroid use in IBD

used in UC with 5-ASA failure or need for urgent respponse (not for maintenence) 

used in Crohns for severe inflammatory 

oral, parenteral, topical 

hard to use!! 

55

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.

56

surgical management of CD

80% will require 

abscesses, stricture, relief of obstruction

post-op recurrence always in neoterminal ileium 

57

Most frequent CRC mets? 

regional lymph nodes 

liver - Because of portal drainage – colon drains into the portal system, which go to the liver first, which acts as a sieve for cancer cells and they implant there and then they metastasize. 

lungs - In distal colon cancers near the rectum, that part of the colon has drainage through the vertebral veins. Not through the portal system, but through the systemic system, so bypass the liver and end up in the lungs.

peritoneum

58

S. bovis

It’s a bacteria that has been associated with the presence of colon cancer. People don’t know if its caused by it or not, it doesn’t seem like it is, but the recommendations right now, if you have ever had S. bovis in your blood stream, the recommendation is to get a colonoscopy to look for a malignancy there.

maybe just colonizes cancer tissue 

59

Common pathway of CRC stepwise mutations

APC - KRAS - p53

60

CRC Screening of FAP? 

Annula flexible sigmoidoscopy r colonoscopy starting at age 12 or until colectomy

100% of developing! 

61

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.

62

Barium studies for IBD

determine location of disease and extent of inflammation and changes to lumen caliber 

may show aphthous ulcers, coarseed villous folds or thickening 

may also see fistulas and strictures 

also perforations and anscesses

falling out of favor!! 

63

Location of UC lesions

colon and rectum - rectum ascending prox

rectum universally involved 

mucosal and submucosal injury 

continuous pattern of inflammation 

acute onset! bleeding, obvious 

64

carcionembryonic antigen (CEA)

antigen that is elevated in certain people who have colon cancer (about 30%). Useful if you have an elevated CEA at diagnosis, and then resected successfully, your CEA should drop.  Usually use as follow up, if it starts to elevate again, you are worried it’s a recurrence of the tumor.

  If there is a metastasis, CEA will be elevated as well.