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Flashcards in P- Small and Large Intestines Deck (139):

What are the layers of the small bowel from the lumen out?

1. mucosa
2. lamina propria
3. muscularis mucosa
4. submucosa
5. muscularis propria
6. serosa


Describe the mucosa of the small bowel.

It consists of crypts and villi line by simple columnar epithelium.

the villi is: enterocytes(absorptive), Goblet cells (mucus), and enteroedocrine

the crypts are Paneth cells (secrete lysozomal enzymes and factors) and stem cells


What are the 3 sections of the small intestine and what are the distinguishing features of each part?

1. Duodenum - Brunner's glands (submucousal glands that secrete bicarb, pepsinogen, glycoproteins)

2. Jejunum (no special features. longest part)

3. Ileum - Peyer's patches - increased mucosal lymphoid tissue which clusters into nodules


What are the layers of the colon and rectum from lumen out?

Lamina Propria
Muscularis mucosa
muscularis propria


Describe the mucosa of the colon and rectum.

The absorptive simple columnar epithelium has crypts and glands arranged in parallel in the lamina propria. There are no VILLI.

The cells of epithelium are :endocrine, Goblet cells, undifferentiated stem cells and columnar cells


Describe the proliferative zone of the colon mucosa.

It is located in the bottom of the crypts and scattered mitotic figures go 1/3 to 1/2 up the crypt.

As the cells move up the crypt they:
1. increase cytoplasm
2. decrease N/C ratio
3. maintain proper polarity (nucleus at the base of the cell)


Ischemic injury can occur anywhere in the GI tract, but what are the 2 places it occurs most frequently?

It occurs most frequently at watershed areas where the collaterals are small and narrow.

1. rectosigmoid junction - terminal branches of IMA
2.** splenic flexure - terminal branches of SMA


Why is the small intestine much more vulnerable to ischemia than the colon?

Because the colon can get some accessory supply and drainage from the retroperitoneal portions (ascending/descending)


What typically causes acute enterocolitis? What kind of infarct would occur?
What typically causes chronic enterocolitis?

Acute- thrombus/embolism in the celiac, SMA or IMA which can cause hemorrhagic infarct {hemorrhagic infarct is seen in organs with dual blood supply}

Chronic- gradual build up of atherosclerosis in vessels supplying the bowel


What patient population is most likely to be affected by ischemic enterocolitis?

Incidence increases with:
1. age
2. cardiovascular disease
3. DM


What are the 3 major variables in ischemic bowel disease?

1. severity of the vascular compromise
2. period over which the compromise developed
3. vessel involved


Why are the splenic flexure and rectosigmoid junction considered "watershed areas"?

Splenic flexure- termination of SMA, IMA
Rectosigmoid- termination of IMA, pudendal, iliac

Because the blood supply terminates here, these areas are most suceptible to injury by hypotension or hypoxemia


In addition to the major arteries to the intestines, what other blood supply is involved in intestinal circulation?

Intestinal capillaries run from the crypts alongside the glands to the surface and empty into postcapillary venules.

This protects the stem cells of the crypt so they can repopulate the surface.
The epithelium is more susceptible to ischemic injury because they are last to receive blood supply


What is a morphological signature of ischemic intestinal disease?

1. surface epithelium atropy
2. sloughing/necrosis of epithelium
3. normal or hyperproliferative crypts


What are predisposing conditions to bowel infarcts due to arterial thrombus?

1. atherosclerosis
2. vasculitis
3. dissecting aneurysm
4. hypercoagulable states
5. angiography procedures/surgery accidents


What are predisposing conditions to bowel infarcts due to arterial embolism?

1. cardiac vegetations
2. angiographic procedures
3. aortic atheroembolism


What are predisposing conditions to bowel infarcts related to venous thrombosis?

1. hypercoagulable state
2. sepsis
3. post-op
4. vascular-invasive cancer (hepatocellular carcinoma)
5. cirrhosis
6. abdominal trauma


What are predisposing factors to bowel infarct related to NON-occlusive ischemia?

Anything that gives low flow
1. cardiac failure
2. shock
3. dehydration
4. vasoconstrictive drugs (cocaine)


What is the difference between a mucosal, mural and transmural infarct?

Mucosal - does not go below the muscularis mucosa (due to acute/chronic hypoperfusion)

Mural- mucosa AND submucosa (due to acute/chronic hypoperfusion)

Transmural- all layers of the wall (due to occlusion of major mesenteric artery)


Describe what you would see with transmural infarct due to an acute arterial obstruction.

What is occuring in the mucosal layer? Muscularis propria? Serosa?

1. sharp demarcation between normal/ ischemic bowel
2. infected bowel is intensely congested, purple/red and hemorrhagic
3. wall becomes thick, edematous, rubbery
4. Coag necrosis of muscularis propria in 1-4 days with the potential for perforation
5. serositis- purulent exudate and fibrin deposition


A patient presents with sudden, severe abdominal pain and tenderness. They have nausea, vomiting, melena. They are progressing to shock/vascular collapse. Peristaltic sounds have diminished and they have rigidity of the abdomen. What are 4 potential things this could be?

1. acute transmural infarction
2. acute appendicitis
3. perforated ulcer
4. acute cholecystitis


Describe the difference in margins between arterial occlusion and venous occlusion causing transmural infarction of the bowel.

Arterial - sharply defined borders of ischemic area
Venous- margins are less distinct


Describe the lesions associated with mucosal and mural infarcts. What layers are involved? What parts of the bowel? What forms at the edges of the segments?

They can affect anywhere from the stomach to the anus.
The lesions can be continuous but are most often patchy and segmental.

Mucosa- hemorrhagic and ulcerated
Bowel wall is thickened with edema and can involve just the mucosa or extend down into the submucosa.
Serosa hemorrhage and serositis are ABSENT.

At the edges of the affected segments, pseudomembranes form. They are necro-inflammatory exudates overlying the mucosa.


As long as the ______________ is spared, mucosal and mural infarct lesions are completely reversible.

Muscularis propria


What is the difference between congenital and acquired diverticulosis? What are examples of each?

1. Congenital -involves all three layers of bowel INCLUDING the muscle
- Meckel diverticulum
- normal appendix

2. Acquired- lack or have attenuated muscularis propria due to focal weakness or increased intraluminal pressure (80% in the sigmoid colon)
- Zenker diverticulum
- colonic diverticulum


What are the 2 influences that lead to the genesis of a diverticula?

1. exaggerated peristaltic contractions (elevated intraluminal pressure)
2. inherent anatomy - incomplete longitudinal muscle layer gathered in tenia coli and neurovascular bundles penetrating the inner circular muscle alongside tenia coli

Western diets lead to diverticula because the low fiber diet increased transit time, thus increasing #1)


Describe the gross morphology of diverticulosis.

1. multiple small, flask-like envaginations along the tenia coli filled with mucus or stool
2. bulging into the serosa or omental appendices
3. thickened circular muscle of the colon with "accordion" mucosal folds


Describe diverticulosis microscopically?

there will be an absence of muscle except for some random bundles of muscularis mucosa.

Inflammation may be present if there is obstruction or perforation. This can extend into the pericolic fat and give the appearance of colon carcinoma


A patient presents with cramping, discomfort, sensation of the inability to completely empty rectum. They have alternating constipation and diarrhea. What are you suspicious of and what are some of the complications associated?


1. diverticulitis - inflammation/infection
2. peritonitis
3. hemorrhage
4. perforation with abscess resembling a mass or forming a sinus tract
5. adhesions
6. obstruction
7. fistula to bowel/bladder


What is treatment for diverticula?

1. High fiber diet
2. if diverticulitis--> antibiotics
3. if peritonitis/perforation--> resection


What are 80% of SBO due to?

Mechanical obstructions due to:
1. adhesions
2. hernia
3. volvulus
4. itussusception


What is the leading cause of SBO in industrialized nations? What is most closely associated with the formation?

Post-op adhesions- fibrous bridges between bowel loops when peritonitis (due to surgery, infection, endometriosis) heals.

Surgeries most closely related with formation are:
- appendectomy
- colorectal surgery
- gynocologic procedures
- GI precedures


What is the most common form of SBO associated with post-op adhesions? How does it occur?

It is most associated with strangulated SBO and it occurs when distended loops of bowel twist on the mesenteric pedicle causing arterial occlusion--> bowel ischemia/necrosis.


What are hernias? What are the locations where they are most likely to occur? When do they become medical emergencies?

A hernia is when the contents of a body cavity bulge out of the area where they should be contained. Usually it is bowel or abdominal fatty tissue.
Usually they are asymptomatic, but can cause emergency if they get "incarcerated" and strangulated.

Usual sites:
1. inguinal
2. femoral
3. umbilicus
4. surgical scars (incisional)


In children, intussusception is a common cause of abdominal pain. In adults, what does it point to?

Intraluminal tumor


What is a volvulus?

It is when the bowel twists completely on its mesenteric attachment site


What is the pathological process for SBO?

1. venous drainage is impaired
if the process continues
2. arterial inflow is cut off
3. infarction ensues
4. mucosa gets ischemic first and sloughs off leading to currant jelly stool (blood, mucus, mucosa)

If untreated
5. transmural gangrene and perforation


When must surgery be done for a strangulated bowel to drastically reduce the mortality rate?

36 hours or less


A patient presents with abdominal pain and nausea. Two days ago he was having diarrhea, but now he is constipated. He is developing fever and tachychardia.
When ascertaining his history you discover he has had prior appendectomy. What are you concerned about?

A small bowel obstruction- and you should be exceptionally concerned because fever/tachycardia is an indication of possible strangulation


What is Hirschprung disease?
Who does it affect? What is treatment?

It is congenital aganglionic megacolon.
A segment of the colon (short segment disease) or the entire colon (long segment disease) is missing the myenteric (aucher) and submucousal (meissners) plexuses.

The portion of the colon missing innervation is narrowed and the proximal portion is dilated .

Because it is congenital it is frequently seen in infants and children.
Infants- alternating diarrhea/constipation
Children- constipation

Treatment is surgery to remove the aganglionic portion of the colon


What genes are though to be mutated in Hirschprung disease? What is the penetrance?

It is thought to be a mutation in the RET gene that inactivates RET receptor kinase activity.
RET promotes survival of neurites and provides directions to migrating neural crest cells.

The penetrance is variable and dependent on environmental factors.


What is the epidemiology of Hirshprung?
Are male or female children more affected?

1/5000 live births
4 to 1 male to female predominance but females more freq get long segment disease


What is the official definition of diarrhea?

Increased stool weight of 250-300 g/day but a good working definition is:
3 or more watery stools/day Or a definite decrease in consistency of increase in frequency


Who is most negatively affected by diarrheal disease?

It is the leading cause of death in children in developing countries and is greatest in children under 1

This is because diarrhea can lead to dehydration and hypokalemia


What is the basic pathogenesis of all forms of diarrhea?

There is a reversal of normal net absorptive processes of water and electrolytes to secretion.

1. osmotic force to drive water into the gut
2. active secretory state induced by enterocytes


What is the difference between acute diarrhea and chronic diarrhea in terms of time frame? causes?

Acute -lasts days to a week.
Infectious causes - virus, parasite, bacterial
Non-infectious- IBS, drugs, food, thyrotoxicosis, carcinoid

Chronic- lasts atleast 3 weeks
IBS, IBD (Crohn's, ulcerative colitis), intestinal bacterial overgrowth, chronic bacteria (Giardia), colon cancer, fat/carb malabsorption, lax abuse, endocrine (addison's )


A patient presents with abdominal bloating/cramps. There is increased borborygmi (rumbling) and abdominal pain. The stool is loose and watery. They have increased sense of urgency for the restroom and nausea/vomiting. Is this likely to be uncomplicated or complicated diarrhea?



A patient presents with blood, mucus and undigested food in the stool. They have weight loss, fever, electrolyte loss, dehydration and vascular collapse. Is this uncomplicated or complicated diarrhea?



What is the mechanism by which secretory diarrhea occurs?
Does it abate with fasting?
What are common causes?

In secretory diarrhea, there is prolonged increase in enterocyte levels of cAMP which secretes Cl and water follows. This occurs by increased activation of adenyl cyclase.

This form of diarrhea persists with fasting!!

vibrio cholerae, E. coli heat labile toxin, laxatives, hormone-producing tumors, drugs, metals


What is the mechanism by which osmotic diarrhea occurs?
Does it abate by fasting?
What are the 2 usual causes?

If there is excessive solute retained in the intestinal lumen water will not be absorbed--> osmotic diarrhea.

This will abate by fasting.

It usually occurs by:
1. ingestion of a poorly absorbed substrate (carbs-mannitol, sorbitol), epson salts, MgOH2
2. malabsorption - ex. lactose intolerance


What is the mechanism of exudative diarrhea?
How does it have components of secretory and osmotic diarrhea?
Does it abate with fasting?
What are the usual causes?

Bacterial or viral infection:
1. increase serum/blood exudation into the lumen with WBC inciting cytokines to increase secretion (secretory) and leukocytes using ROS to destroy cells and grow new ones that are deficient in brush border enzymes/transporters (malabsorption/osmotic)

2. destroy enterocytes so there is reduce absorption of water and solutes

It does NOT abate with fasting


Describe the pathology of malabsorption diarrhea.

It can be just one nutrient (lactase deficiency--> lactose diarrhea)
Or it can be diffuse disorder (celiac sprue) where there is a general malabsorption which increases stool output and causes high volume diarrhea.

It will abate with fasting


What are the functions of the small bowel? How does this contribute to the symptoms of diarrheal disease?

It absorbs nutrients and secretes enzymes and fluid. Dysregulation due to infection can lead to:

large volume diarrhea/ NO fever/NO blood or inflammatory cells
abdominal cramping
bloating, gas, weight loss


What are the functions of the colon? How does this contribute to the symptoms of diarrheal disease?

It absorbs water and electrolytes (Na) and secretes K and Cl. Dysregulation leads to:

Frequent, small volume diarrhea/FEVER/blood and inflammatory cells


Viruses are usually the cause of acute infectious gastroenteritis in the US, however, what are the top 5 bacterial/protozoa causes?

1. salmonella
2. camylobacter
3. shigella
4. E. coli O157:H7
5. cryptosporidium


What are the 3 leading causes of viral gastroenteritis?
What is the pathogenesis of all 3?

They all 3 destroy the epithelial lining of the small intestine and wreck absorption capacity.

1. Rotovirus- fecal oral, children
2. Norovirus- fecal-oral, person-person, contaminated surfaces, food/water
3. Adenovirus- contact, fecal-oral, waterborne


What are the 3 mechanisms by which enteropathogenic bacteria can elicit GI disease?

1. ingestion of pre-formed toxins (no bacterial replication in the gut)
2. ingestion of toxigenic organisms (replicate in the gut and elaborate enterotoxins)
3. enteroinvasive organisms (invade and replicate in the gut destroying mucosal epithelial cells)


What 3 virulence factors do all bacteria (toxigenic or enteroinvasive) have that allow them to replicate/proliferate in the gut?

1. Adherence to epithelial cells via plasmid-encoded adhesions
2. elaborate enterotoxins (secretagogues, cytotoxins)
3. Invade (virulence plasmid)


What are the 4 types of E coli? Which are invasive?

1. ETEC - enterotoxigenic NO invasion
2. STEC/EHEC (shigatoxin-like) - NO invasion
3. EPEC - no toxin OR invasion
4. EIEC- enteroinvasive - INVASION


What toxin is in ETEC? What is the clinical presentation and likely source?

It is cholera-like toxin.
The clinical presentation is traveler's diarrhea.
The source: food/water


What toxin is in STEC/EHEC?
What is the clinical presentation?
What is the likely source?

It is a shiga-like toxin and is associated with O157:H7.

It causes hemorrhagic colitis and HUS.

Source: undercooked beef


What toxin is in EPEC?
What is the clinical presentation?
What is the source?

There is no toxin, or invasion.
This strain attaches to the small bowel villi and blunts them (like sprue).

Source- water, weaning fluids for infants


What toxin is in EIEC?
What is the clinical presentation?
What is the source?

This strain invades epithelial cells and multiply intracellularly watery diarrhea by raising camp levels (Shigella-like).

Source: cheese, water, person-to-person


What bacteria can you get from milk, beef, eggs, poultry and pet turtles? What is the mechanism by which this bacteria works? What is the presentation?

Salmonella is the likely bacteria. It invades cells, translocates, causes lymphoid proliferation and then disseminates.

Typhoid: enteric fever, asymptomatic carriers
non-typhoid: gastroenteritis, bacteremia, localized tissue infections


How does shigella enter the host cells? What determines the infectivity?

It takes a very small inoculum of shigella to cause disease. Shigella produces an enterotoxin like Shiga and O157:H7 E. coli
It enters through the M cells associated with Peyer's patches and lymphoid follicles.


What bacteria can you get from undercooked, contaminated poultry? What is the clinical presentation?

you can get bloody stool (colon) or water stool (small intestine) as well as systemic disease


What bacteria is currently causing a pandemic in Asia, Africa and Latin America? It is acquired via shellfish, water and person-to-person. It infects the proximal small intestine preferentially and causes watery diarrhea without tissue damage due to its lack of ability to invade.

Vibrio cholera


What bacteria is responsible for antibiotic-associated diarrhea and colitis?
What is the presentation?
What is the gross pathology?
What is the microscopic pathology?
What is the mode of virulence?

Clostridium dificile is responsible for pseudomembranous colitis.
It presents as mild-to-moderate diarrhea.

Grossly: yellow-white pseudomembranous plaques form on the mucosa.
Microscopically: inflammatory exudate with mucinous finbrinous material with neutrophils

Mode of virulence: disrupts normal bacterial flora, colonizes and releases exoA and exoB that cause inflammation and damage.


What are the 3 main protozoa that cause intestinal illness in humans?

1. Giardia lamblia- water, fecal-oral [duodenum]
2. Entamoeba histolytica- water, f-o, food [colon]
3. Cryptosporidium parvum -water, swimming pools, f-o [small bowel]


What are the 3 major phases of digestion and absorption where disruption could cause malabsorption?

1. intraluminal hydrolysis of fats, carbs, proteins [bile salts solubolize fats in this phase]

2. brush border enzymes digest and uptake end-products

3. lymphatic transport of nutrients


If a person if having a malabsorption problem, what are 4 very common clinical presentations?
What is the most common symptom?

1. steatorrhea
2. diarrhea [chronic diarrhea is most common]
3. abdominal bloating
4. gas


What vitamin deficiency is associated with the following descriptions:
1. bone pain, deformity, ease of fracture, muscle spasms, tooth discoloration
2. fatigue, weakness, anemia (2 nutrients)
3. muscle spasms
4. diarrhea, confusion, sore tongue
5. edema, dry skin, hair loss
6. night blindness
7. fatigue and weakness, anemia, pins-and-needles, confusion
8. tendency to bruise

1. calcium
2. folate, iron
3. magnesium
4. niacin
5. protein
6. vit A
7. B12
8. vit K


What are the 3 main causes of malabsorption?

1. defective intraluminal digestion
2. mucosal cell abnormalities
3. reduced small bowel SA


If a patient has pancreatic insufficiency or ZE syndrome, what are they not able to digest/absorb?

Proteins and fats


If a patient has disruption of bile flow or ileal dysfunction, what are they likely to malabsorb?

They won't be able to complete fat solubilization


What is the effect of Crohn's, Celiac sprue and short gut syndrome (due to resection) on absorption?

There will be malabsorption due to small bowel surface area


What is the pathology of Celiac sprue?

There is an inappropriate immune response to gluten controlled by CD4 T cells in the lamina propria.

Genetic: HLA DQ2 and DQ8


When will severe celiac sprue manifest?

When infants make the transition to cereal (introduction of gluten) and they will have failure to thrive, diarrhea, light, fatty stool


How is diagnosis of celiac sprue made?

1. clinical suspicion
2. lab tests consistent with malabsorption
3. anti-TTG and anti-EMA (endomysial antibody)

If either of the serological tests are + ------>
4. biopsy of second part of the duodenum


What are the 3 classic histological signs of celiac sprue?

1. shortened or absent villi
2. hyperplastic crypts
3. intraepithelial lymphocytes


What is the cause of Whipple disease?
What is the usual patient population?
Besides GI, what else can be affected?
What is the treatment?

It is causes by the bacteria tropheryma whippelii.
It usually affects white men 30-60.
It causes arthritis, weight loss and diarrhea and can affect heart, brain, serous cavities.

Treatment is 1 year minimum of trimethaprim/sulfamethoxazole


What is the histologic appearance consistent with Whipple disease?

In the proximal small bowel there will be an abundance of PAS+ filled macrophages in the lamina propria along with lipid pools


How do you differentiate between T. whippelii and mycobacterium avium intracellulare (MAI) even though they have similar histologic appearance?

MAI stains + with Zehl-Nielson acid fast stain


What are the 2 microscopic colitides? What are the 3 characteristics that apply to both?
How do they differ on biopsy?

Collagenous and lymphcytic colitis both:
1. produce watery diarrhea
2. normal colonoscopy
3. characteristic histopathology

Collagenous- thickened collagenous band under the epithelium
Lymphocytic- increased intra-epithelial and lamina propria lymphocytes


What is the etiology of Crohn disease?

It is is an abnormally and chronically activated immune system in the absence of an identifiable invader. There seems to be environmental, immunologic and bacterial factors at play.

It can lead to persistant transmural inflammation and mucosal ulceration.


What MHCII alleles have recently been linked with Crohn disease?

DR7 and DQ4


What mutation is thought to play a role in Crohn disease considering it is found in 25% of people with Crohn?

NOD2 - a gene though to either:
1. promote excessive host response to intestinal bacteria
2. is defective in responding to bacteria


A patient presents with abdominal pain, weight loss and diarrhea. They have had recurrent perianal fistulae and abscesses. What is your suspicion?

Crohn disease


What 3 mechanical complications can arise with Crohn disease?

1. obstruction
2. abscesses
3. fistula :
-bowel to bowel
-bowel to skin
-bowel to vagina
-bowel to bladder


What is the risk of colon cancer is a person with Crohn related to?

The amount of colon affected by the disease


Is ulcerative colitis or Crohn more associated with diarrhea?
Which is more likely to lead to colon cancer?

UC is more associated with diarrhea AND more likely to lead to colon cancer


What are the extra-intestinal manifestations of Crohn disease?

1. dermal- erythema nodusum (red bumps on shins), pyoderma gangrenosum (leg ulcerations)

2. ocular- uveitis, episcleritis

3. joints/spine- inflammatory seronegative arthropathies

4. liver- hepatitis, PSC (not as strongly related as UC)


What 3 radiographic and endoscopic tests are done for suspicion of Crohn? What is seen on each?

1. Xray w/o barium can show obstruction of dilated loops and strictures. W/ barium can show mucosal detail like ulcers, strictures, filling defects.

2. CT can show bowel wall edema, fistulas, engorged ileal vasa recta, abscesses, dilation etc. With IV and oral contrast= better than barium

3. Colonoscopy- shows patchy "cobblestone" appearance in the colon and ileum but NOT rectum. Cobblestone means ulcerated areas separated by narrow areas of healthy tissue


What are the key features you see on gross examination of ileum and colon with Crohn disease? What feature is great for differentiating it from UC?

1. rigid thickening of involved segment
2. "creeping fat/wrapping fat" (hyperplasia of subserosal/mesenteric fat)
3. adhesions
4. strictures in the terminal ileus
5. aphthous ulcers- periphery of involved segment
6. patchy disease
7. linear, serpiginous mucousal ulcers with intervening edematous mucosa (cobblestoning)
8. vertical fissures ** great for differentiation from UC.


What chronic inflammatory changes are seen with Crohn disease?

1. lyphoplasmacytic infiltrate in the lamina propria
2. architectural distorsion (gland drop-out/atrophy)
3. mild to severe acute inflammation (neutrophilic cryptitis)


You do a patient biopsy and notice chronic inflammatory changes in the mucosa. There seem to be skip lesions where there are areas of normal mucosa next to areas of inflamed mucosa. The sample is from the same section and same region of the colon.
There appears to be transmural inflammation with multiple lymphoid aggregates in the subserosal fat.

There are longitudinal fissures surrounded by granulation tissue. There is also non-caseating epitheliod granulomas.
The submucosa is fibrous and has neuromuscular hyperplasia.
What is the likely diagnosis?
What helps differentiate this from another similar disorder?

This appears to be Crohn disease.
The non-caseating epitheliod granulomas helo differentiate it from UC.

You cannot be definitive with the diagnosis however and need to make sure history, and radiologic data supports.


What is treatment for Crohn disease when it is active and when it is in remission?
When should surgery be considered?

Treatment for active Crohn disease is:
1. antibiotics
2. medications to reduce inflammation like
- immunomodulators (azathioprine, mercaptopurine, methotrexate)
- biologics (infliximab)

For remission:
1. avoid recurrence of symptoms

Steroids can push Crohn to remission but should NOT be used in remission as it can lead to long term effects (diabetes, bone disease, cataracts)

Surgery cannot cure Crohn but it may be necessary if there is obstruction, abscess or fistula as a result of Crohn.


What MCHII is associated with UC?



How does smoking affect the epidemiology of Crohn disease? UC?

Smoking increases the risk of Crohn and decreases the risk of UC


What is the age distribution for Crohn and UC?

Both are bimodal with peaks in the teens/twenties and then at the 50-70 age group


What is the defining histological finding of ulcerative colitis?

Superficial mucousal ulcerations that begin at the rectum (ulcerative proctitis) and extend up the colon. If the whole colon is involved it is pancolitis.


What are the extra-intestinal manifestations of UC disease?

The majority of symptoms are limited to the colon, however, they CAN present with the same manifestations as seen in Crohn disease:
skin, ocular, joint/spine, liver



What are the 3 major complications of UC?

1. Anemia (iron deficient and anemia of chronic disease) due to the blood loss from inflamed colon/rectum

2. toxic megacolon - inflammation dilates the colon to a larger size *(more prone to rupture, potential surgical emergency). These people will have fever, pain/distension, dehydration, malnutrition

3. colon cancer- risk is increased if it involves more of the colon, has been around longer, and is more severe. Colonoscopy/biopsy every 1-2 years to look for dysplasia


What are the classic radiographical findings of UC from early to late?

1. mucosal granularity on air contrast BE
2. spiculations/serrated bowel from tiny ulcers
3. collar button ulcers
4. thumbprinting (bowel wall edema)
5. pseudopolyps- sea of ulceration with polyp/edematous mucosa islands
6. shortening of the colon (longitudinal muscle rigidity, fibrosis)
7. loss of haustra on the left colon


What are the earliest endoscopic findings for ulcerative colitis?

erythema, edema, and abnormal vascular pattern of the mucosa


Describe the mucosa of UC with increasing inflammation?

There are extensive ulcerations with mucopurulent exudate.
The mucosa is friable and easily bleeds.


What are the colonoscopic characteristics of chronic UC?

"featureless colon"
1. mucosal atrophy
2. muscular hypertrophy
3. loss of haustral folds --> shortening and increased rigidity of the colon


What 2 specific lesions allow differentiation of UC and Crohn?

1. Crohn is transmural lesions, UC is limited to the mucosa
2. Crohn has fissuring which is NOT seen in UC.


Describe the gross appearance of UC.

1. lesions are limited to the mucosa
2. RARE stenosis, fistulas, and thickening of the walls (different from crohn)
3. wet mucosa due to blood and mucus
4. varying size ulcers but NOT fissuring
5. sessile nodules "pseudopolyps"


What are the microscopic features of UC?

1. chronic inflammation in mucosa and submucosa
2. shallow ulcerations (not past muscularis propria_
3. lack of fibrosis (diff from Crohn)
4. neutrophilic infiltrate
5. no epithelioid granules
6. Architectural changes - crypt distortion, irregular glands, gland dropout, bifid glands, shortened glands
7. fulminant colitis (destruction of mucosal and submucosal layers, fissures and inflammation of the muscularis propria)


What is the most common cancer arising in the GI tract, and specifically the colon?

Adenocarcinomas account for 70% of GI malignancies and 98% of colon malignancies


What are the 4 MALIGNANT tumors of the colon?

carcinoid tumor


What is the gross and clinical presentation of hyperplastic polyps?

They are
1. small (<5mm) smooth surfaced protrusions in rectosigmoid
2. pedunculated or sessile


What is the histology of a hyperplastic polyp?

1. crypts lined by goblet cells
2. star-like pattern to crypts
3. scant intervening lamina propria


Adenomas are by definition ____________. What are the 2 shapes they can be? What are the 3 types of architecture?

By definition, adenomas are dysplastic.

They can be pedunculated (stalked) or sessile (no-stalk).

They can be tubular, tubulovillous or villous.


Where in the colon are the majority of adenomas found?

In the rectosigmoid


If a patient is discovered to have an adenoma, what are the next steps?

The patient will be followed by colonoscopy. The surveillance intervals depend on:
1. size and number of adenoma polyps
2. family history


What 3 features of adenoma correlate with malignant risk? Which is the chief determinant?

1. size of the polyp (max diameter)*** key
2. architecture
3. severity of the dysplasia (low, high-grade, intramucosal carcinoma)


How do adenomas appear histologically?

They will appear bluer than adjacent non-adenoma tissue because of :
1. mucin loss/goblet cell loss
2. nuclear hyperchromasia, pseudostratified, rounder nuclei
3. mitotic figures


Why doesn't high grade dysplasia or intramucousal carcinoma have a risk of metastases?

In these states there cells are dysplastic and LOOK like adenocarcinoma. However, they only are in the mucosa and do not extend beyond the muscularis mucosa.
Because the tumor does not go into the submucosa (where lymphatic vessels are) there is no potential for metastases.


What is the clinical phenotype of FAP?
What is the lifetime risk of CRC?
What gene is mutated? What is the inheritance pattern?

In FAP there are adenomas throughout the GI tract.
There are >500 colonic polyps.

The lifetime risk of CRC is 100%

The APC gene on chromosome 5q21 is mutated and passed on in an autosomal dominant fashion


What is the genetic problem in HNPCC/Lynch syndrome?
What is the clinical phenotype
What are the precursor lesions?
What are the cancers?

In HNPCC, there is a DNA mismatch repair gene mutation resulting in microsatellite instability.

Clinical presentation :
1. precursor lesions = sessile serrated adenoma, large right sided hyperplastic polyps, mucinous carcinomas

2. Cancers- endometrial, ovarian, hepatobiliary tract


What is sporadic colorectal cancer?

It has the presentation of FAP (>500 colonic polyps throughout the GI tract) but without the family history


Mutations in hMLh1, hMSh2, hPMS2, hPMS1 and MSH6 are associated with what?

HNPCC/Lynch syndrome


What are the 3 parts of the Amsterdam criteria for characterizing something as HNPCC?

1. 3 family members (atleast 2 first degree relatives)
2. 2 successive generations
3. one family member diagnosed before 50


What age group and regional areas are associated with CRC?
What is believed to be a substantial contributor to CRC?

It affects people 60-70 in developed countries. (30% less incidence in developing countries)

Groups who migrate from low risk to high risk areas develop the disease so DIET is supposed to be a big contributing factor.


What 4 dietary factors are associated with CRC?

1. decreased unabsorbable vegetable fiber
2. increased refined carbs
3. increased fat intake (red meat)
4. decreased vit. A, C, E


What are the 3 protective features of fiber for reducing the risk of colorectal carcinoma?

1. increases stool bulk which decreases transit time
2. dilutes the concentration of other colonic substances so there is reduced exposure of the colonic epithelium to carcinogens
3. fiber is not digested/absorbed but undergoes fermentation in the presence of colonic flora. This reduces fecal pH and generates SCFA (protective)


What is the effect of NSAIDs on the development of CRC?

They offer a protective effect (mechanism is unknown, but probably connected to COX2)


What are the 2 pathogenetically distinct pathways for the development of CRC?

1. APC/B-catenin (chromosome instability, adenoma->carcinoma sequence)

2. DNA mismatch repair (microsatellite instability)


The APC/b-catenin pathway accounts for ____% of sporadic CRC.
It is associated with large genome alterations like _________ or __________________.


1. aneuploidy
2. gain or loss of chromosomal region


How many genetic mutations are required to make a malignant phenotype?



What is usually the first mutation to occur in APC/b-catenin pathway?

APC gene gets a mutation (APC is a tumor suppressor)
-germline mutation for FAP
- somatic mutation in 50% of sporadic adenomas, 80% of sporadic CRC


After the APC gene mutation, what 5 other genes can cause the second "hit" to the cell?

1. K-ras (large polyps only, predictor of effectiveness of EGFR biologics bc it is downstream)
2. p53 (occurs in high grade dysplasia. failure to respond to chemo/radiation)
3. DPC4/DCC/SMAD4 (advanced phenotype, poor response to surgery)
4. EGFR- poor prognosis
5. DCC - deleted in colon cancer


How is high freqency microsatellite instability (H-MSI) detected?
Where are these microsatellites located?
What is the most common phenotype and colonic area for the DNA mistmatch repair pathway?

They are detected by immunocytochemistry.

The microsatellites are located in coding regions of genes that regulate cell growth like:
1. TGFb - which normally inhibits cell growth
2. BAX - normally initiates apoptosis

MSI pathway will present with sessile serrated adenomas and right sided CRC


Is APC or MSI pathway going to have more right-sided carcinomas?
How do right sided carcinomas grow?
What are 2 reasons why they do not cause obstruction?
What are presenting symptoms?

MSI is going to have more right sided cancers.

Right sided CRCs grow as exophytic masses along one wall.

Obstruction is uncommon because :
1. ascending colon is wider then descending colon allowing more growth of tumor before symptoms
2. exophytic growth instead of into the lumen

1. iron-deficient anemia****
2. SOB, fatigue, weakness


What are the growth features of left-sided CRC?
How does this contribute to the symptoms?
What is treatment?

They grow into the lumen, obstructing the flow of feces.

This leads to "napkin ring" or "apple core" lesion on radiology images with contrast.

Because the tumor obstructs feces, the primary symptom is change in bowel habits. Other symptoms are ab pain, constipation, distension.

This is a surgical emergency.


What are the microscopic features of adenocarcinoma in the colon?

1. stratified, pleiomorphic, hyperchromatic epithelial cells
2. glands with multiple lumens (cribriforming)
3. back -to -back architecture
4. Mucinous (colloid) cells with signet ring pattern
5. geographic necrosis (necrosis that is scalloped and interfaced with viable gland/tissue)


What are the 3 main uses for CEA tumor marker?

1. determine pre-op prognosis (higher levels, adverse)
2. detect recurrent colorectal cancer
3. detect liver metastasis from colorectal cancer *** most useful application