S.I./Colon Key Concepts Flashcards
what is the most common site of gastrointestinal ischemia?
the colon
- lesions can be continuous but are most often segmental and patchy
- mucosa is hemorrhagic and may be ulcerated
- bowel wall is thickened by edema that may involve the mucosa or extend into the submucosa and muscularis propria
what is the main cause of transmural infarction?
acute arterial obstruction
initially the tissue in intensely congested and dusky to purple-red -> later, blood-tingued mucus or frank blood accumulates in the lumen and the wall becomes edematous, thickened and rubbery
- coagulative necrosis of the muscularis propria within 1-4 days, and perforation may occur
- serositis, with purulent exudates and fibrin deosition may be prominent
transmural infarction
arterial blood continues to flow for a time, resulting in a less abrupt transition from affected to normal bowel
- propagation may lead to secondary involvement of the splanchnic bed
- ultimate result is similar to that produced by acute arterial obstruction because impaired venous drainage eventually prevents oxygenated arterial blood from entering the capillaries
mesenteric venous thrombosis
crypts may be hypoproliferative
- inflammatory infiltrates are initially absent in acute ischemia, but neutrophils are recruited within hours of reperfusion
ischemic intestine
this is accompanied by fibrous scarring of the lamina propria, and uncommonly, stricture formation
chronic ischemia
in both acute and chronic ischemia, bacterial superinfection and enterotoxin release produces what?
- resembles C. diff-associated pseudomembranous colitis
pseudomembrane formation
biopsy specimens from the second portion of the duodenum or proximal jejunum (which are exposed to highest concentration of dietary gluten) are diagnostic in what?
celiac disease
increased numbers of intraepithelial CD8 T lymphocytes (intraepithelial lymphocytosis), crypt hyperplasia, and villous atrophy
- loss of mucosal brush-border most likely leads to malabsoprtion
- increased crypt mitotic activity may limit the ability of absorptive enterocytes to fully differentiate and express proteins necessary for terminal digestion and transepithelial transport
- increased numbers of plasma cells, mast cells, and eosinophils
celiac disease
what is a sensitive (NOT specific) serologic marker of celiac disease?
increase in the number intraepithelial lymphocytes, particularly in the villus (even in the absence of epithelial damage and villous atrophy)
NOTE: combination of histology and serology is the most specific diagnosis of celiac
may occur through any weakness or defect in the wall of the peritoneal cavity, including inguinal and femoral canals, the umbilicus and sites of surgical scars
abdominal hernias
a segment of intestine that telescopes into the immediately distal segment
- most common cause of intestinal obstruction in children younger than 2 years of age
intussusception
most common at the splenic flexure, sigmoid colon and rectum (watershed zones where two arterial circulations terminate)
ischemic bowel disease
malformation of submucosal and mucosal blood vessels
- common cause of lower intestinal bleeding in those older than 60
angiodysplasia
malabsorption associated with what disease, is the result of pancreatic insufficiency
- leading to inadequate pancreatic digestive enzymes, and deficient luminal breakdown of nutrients
cystic fibrosis
immune-mediated enterophathy, triggered by the ingestion of gluten-containing grains
- malabsorptive diarrhea is due to loss of brush border surface area, including villous atrophy, and possibly deficient enterocyte maturation as a result of immune-mediated epithelial damage
celiac disease
prevalent in areas with poor sanitation
- estimated to affect more than 150 million children worldwide, may contribute to a large number of deaths
environmental enterophathy
osmotic diarrhea due to inability to break down or absorb lactose
- AR form is rare and severe, acquired form usually presents in adulthood and is common
lactase deficiency
X-linked disorder characterized by severe persistent diarrhea and autoimmune disease that is caused by mutation in FOXP3 resulting in defective function of regulatory T cells
autoimmune enteropathy
rare AR disease due to a mutation in microsomal triglyceride transfer protein that is required for enterocytes to process and secrete triglyceride-rich lipoproteins
abetalipoproteinemia
comma-shaped, flagellated, gram-neg org
- dx by stool culture since biopsy findings are nonspecific
- acute self-limited colitis
- mucosal and intraepithelial meutrophil infiltrates are prominent, particularly within superficial mucosa
- cryptitis (neutrophil infiltration of crypts)
- crypt abscess (accumulation of luminal neutrophils)
- CRYPT ARCHITECTURE IS PRESERVED
Campylobacter
up to 40% of what syndrome are associated with campylobacter infection?
Guillain-Barre syndrome
most prominent in the left colon, but ileum may be involved (due to Peyer patches)
- mucosa is hemorrhagic and ulcerated
- pseudomembranes may be present
- tropism for M cells, so aphthous-appearing ulcers may occur, similar to those seen in Crohn’s disease
Sigella infection
this sickness causes infection of Peyer patches in the terminal ileum
- enlarged, sharply delineated, plateau-like elevations up to 8cm in diameter
- draining lymph nodes enlarged
- neutrophils accumulate within the superficial lamina propria
- macrophages containing bacteria, red cells, and nuclear debris mix with lymphocytes and plasma cells in the lamina propria
- mucosal damage creates oval ulcers, oriented along the axis of the ileum, that may perforate
Typhoid fever
this sickness causes an enlarged, soft spleen with uniformly pale red plump, follicular markings and prominent phagocyte hyperplasia
- liver shows small randomly scattered foci of parenchymal necrosis in which hepatocytes are replaced by macrophage aggregates, called typhoid nodules
typhoid fever
infection of this organism preferentially involves the ileum, appendix, and right colon
- organisms multiply extracellularly in lymphoid tissue, resulting in lymph node and Peyer patch hyperplasia and bowel wall thickening
- mucosa overlying lymphoid tissue may become hemorrhagic, and aphthous-like erosions and ulcers may develop, along with neutrophil infiltrates and granulomas
Yersinia
NOTE: can be confused with Crohn disease
adherent layer of inflammatory cells and debris at sites of colonic mucosal injury
- surface epithelium is stripped down, and the superficial lamina propria contains a dense infiltrate of neutrophils and occasional fibrin thrombi within capillaries
- superficially damaged crypts are distended by a mucopurulent exudate that forms an eruption reminiscent of a volcano
C. diff-associated colitis with pseudomembranes
dense accumulation of distended, foamy macrophages in the small intestinal lamina propria
- macrophages contain periodic acid-Schiff (PAS)-positive, diastase-resistant granules that represent lysosomes stuffed with partially digested bacteria
- intact rod-shaped bacilli can also be identified by electron microscopy
- villous expansion caused by dense macrophage infiltrate imparts a shaggy gross appearance to the mucosal surface
Whipple disease
when would you see macrophages accumulating within mesenteric lymph nodes, synovial membranes of affected joints, cardiac valves, and the brain?
Whipple disease
org that secretes a preformed toxin that causes massive chloride secretion
- water follows resulting is osmotic gradient -> secretory diarrhea
Vibrio cholerae
most common bacterial enteric pathogen in developed countries, also causes traveler’s diarrhea
- most isolates are noninvaside
Campylobacter jejuni
often triggered by antibiotic therapy that allows colonization by this organism
- releases toxins that disrupt epithelial function
- associated inflammatory response includes characteristic volcano-like eruptions of neutrophils from colonic crypts that spread to form mucopurulent pseudomembranes
C. difficile
very common cause of self-limited diarrhea both in adults and children
- spreads from person to person in sporadic cases and by water in epidemic cases
norovirus
most common cause of severe childhood diarrhea and diarrheal mortality worldwide
- diarrhea is caused by a loss of mature enterocytes, resulting in malabsorption as well as secretion
rotavirus
what are the most common sites involved in Crohn disease?
terminal ileum, ileocecal valve, and cecum
multiple, separate, sharply delineated areas of disease, results in skip lesions
- strictures are common
- aphthous ulcer may progress -> elongated, serpentine ulcers oriented along the axis of the bowel
- edema and loss of normal mucosal texture
- patchy distribution results in a coarsely textured COBBLESTONE appearance in which diseased tissue is depressed below the level of normal mucosa
- Fissures develop between mucosal folds and may extend deeply to become fistula tracts
Crohn disease
what is a hallmark of Crohn disease that is found in 35% of cases and may occur in areas of active disease, OR uninvolved regions in any layer of the intestinal wall
noncaseating granulomas
always involves the rectum and extends proximally in a continuous fashion to involve part or all of the colon
- NO skip lesions, NO mural thickening, serosal surface is normal, NO strictures, NO granulomas
- inflammation can damage the muscularis prorpia and disturb neuromuscular function -> TOXIC MEGACOLON
- colonic mucosa may be slightly red and granular or have extensive broad-based ulcers that are aligned along the long axis of the colon, but do NOT replicate the serpentine ulcers of Crohn’s
- pseudopolyps seen
- may lead to mucosal atrophy, with flat and smooth mucosal surface that lacks normal folds
- inflammatory process is diffuse and generally limited to the mucosa and superficial submucosa
UC
what is pancolitis?
UC that includes the entire colon
small, flask-like outpouchings (usually 0.5-1cm in diameter) that occur in a regular distribution alongside the teniae coli
- thin wall composed of flattened or atrophic mucosa, compressed submucosa and attenuated or absent muscularis propria
- hypertrophy of the circular layer of muscularis propria is common
- may cause segmental diverticular disease-associated colitis, fibrotic thickening in and around the colonic wall, or stricture formation (803)
colonic diverticula
chronic, relapsing abdominal pain, bloating, and changes in bowel habits without obvious gross or histologic pathology
- psychologic stress, diet, gut microbiome, abnormal GI motility, and increased enteric sensory responses to GI stimuli
IBS
umbrella term for UC and CD
- thought to arise from a combination of alterations in host interactions with intestinal microbiota, intestinal epithelial dysfunction, and aberrant mucosal immune responses
IBD
limited to the colon, is continuous from the rectum and ranges from only rectal disease to pancolitis
- neither skip lesions nor granulomas present
UC
most commonly affects the terminal ileum and cecum, but any site with gastrointestinal tract can be involved
- skip lesions and noncaseating granulomas are common
CD
risk of what increases in IBD patients who have had colonic disease for more than 8-10 years
epithelial dysplasia and adenocarcinoma
two forms of microscopic colitis, both of which cause chronic watery diarrhea
- intestines are grossly normal, and the diseases are identified by their characteristic histologic features
collagenous and lymphocytic colitis
common disease of the sigmoid colon, in western populations older than age 60
- causes include low fiber diets, colonic spasm, and unique anatomy of the colon
diverticular disease
most commonly found in the left colon, typically less than 5mm
- smooth nodular protrusions of the mucosa, often on the crests of mucosal folds
- may occur singly but are more frequently multiple, particularly in the sigmoid colon and rectum
- histo: composed of goblet cells and absorptive cells -> delayed shedding of these cells leads to crowding that creates the serrated surface architecture = hallmark
hyperplastic polyps
less than 3cm
- pedunculated, smooth-surfaced, reddish lesions with characteristic cystic spaces apparent after sectioning
- dilated glands filled with mucin and inflammatory debris
- remainder of polyp composed of lamina propria expanded by mixed inflammatory infiltrates
juvenile polyps
most common in the small intestine, but may occur in stomach, colon, bladder or lungs
- polyps are large and pedunculated with a lobulated contour
- histo: characteristic arborizing network of connective tissue, smooth muscle, lamina propria, and glands lined by normal-appearing intestinal epithelium
Peutz-Jeghers polyps
what is helpful in distinguishing polyps of Peutz-Jeghers syndrome from juvenile polyps?
the arborization and presence of smooth muscle intermixed with lamina propria (Peutz-Jeghers)
vary in size from .3-10cm, can be pedunculated or sessile (no peduncle), with the surface having a texture resembling velvet or a raspberry
- histo hallmark: nuclear hyperchromasia, elongation, and stratification
- prominent nucleoli, eosinophilic cytoplasm, and a reduction in the number of goblet cells
- epithelial cells fail to mature as they migrate from crypt to surface
epithelial adenoma
histologically similar to hyperplastic polyps, but are more commonly found in the right colon
- malignant, but lack cytologic features of dysplasia that are present in other adenomas
- serrated architecture throughout the full length of the glands, including crypt base, crypt dilation, and lateral growth
sessile serrated adenomas
occurs when dysplastic epithelial cells breach the basement membrane to invade the lamina propria or muscularis mucosae
- little or no metastatic potential (b/c no lymphatic channels in colonic mucosa)
- polypectomy is usually curative
- invasion beyond the muscularis mucosa -> invasive adenocarcinoma and carries risk of metastasis
intramural carcinoma
what is the “first hit” according to the Knudson hypothesis?
inactivation of APC at 5q21 in colonic epithelium
what does the “second hit” cause in colonic epithelium?
loss of the intact second copy of APC
what does mutation of KRAS at 12p12 lead to?
protooncogene mutations
mutations of:
- TP53 at 17p13
- LOH at 18q21
- SMAD 2 and 4
homozygous loss of additional cancer suppressor genes and over expression of COX-2
= EMERGENCE OF CARCINOMA
what is more critical to mutations than occurrence in a specific order?
accumulation of different mutations
what do mutations of telomerase and “many other” genes lead to?
additional mutations, gross chromosomal alterations
= full on carcinoma
distributed approximately equally over the entire length of the colon
- proximal colon: often grow as polypoid, exophytic masses that extend along the wall of the caliber cecum and ascending colon
- distal colon: tend to be annular lesions that produce “napkin ring” construction and luminal narrowing
adenocarcinoma
- some are poorly differentiated and form few glands
- others may produce abundant mucin that accumulates within the intestinal wall => poor prognosis
- some may also be composed of signet-ring cells that are similar to those in gastric cancer, or may display features of neuroendocrine differentiation
what is responsible for the characteristic firm consistency of colonic adenocarcinoma?
the invasive component of the tumor elicits a strong stromal desmoplastic response
mutations in what genes leads to sessile serrated adenoma?
MLH1, MSH2 (MSH6, PMS1, PMS2)
mutations in what genes leads to carcinoma (from adenoma)?
TGF-b, BAX, BRAF, TCF4, IGFR
benign epithelial proliferations most commonly found in the left colon and rectum
- no malignant potential, must be distinguished from sessile serrated adenomas
hyperplastic polyps
these form as a result of chronic cycles of injury and healing
inflammatory polyps
these occur sporadically or as part of a genetic disease (juvenile polyposis, Peutz-Jeghers Syndrome) -> associated with incrased risk of malignancy
hamartomatous polyps
benign epithelial neoplastic polyps of the intestines
- hallmark: cytologic dysplasia (precursors of colonic adenocarcinoma)
adenoma
in contrast to adenomas, these lack cytologic dysplasia and share morphologic features with hyperplastic polyps
sessile serrated adenomas
what are the two most common forms of familial colon cancer?
familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC)
caused by APC mutations
- patients typically have more than 100 adenomas and develop colon cancer before the age of 30
FAP
caused by mutations in DNA mismatch repair enzymes
- patients have far fewer polyps and develop cancer at older ages than FAP, but still younger than those with sporadic colon cancer
HNPCC
nearly all colonic cancers are what? what are the two most important prognostic factors?
adenocarcinomas
- depth of invasion and the presence/absence of lymph node metastases
sub-serosal vessels are congested and there is a modest perivascular neutrophilic infiltrate within all laters of the wall
- inflammatory reaction transforms the normal glistening serosa into a dull, granular, erythematous surface
acute appendicitis
what does the diagnosis of acute appendicitis require?
neutrophilic infiltration of the muscularis propria
as the process continues, focal abscesses may form within the wall
acute suppurative appendicitis
further compromise leads to areas of hemorrhagic ulceration and gangrenous necrosis that extends to the serosa, which can be followed by rupture and suppurative peritonitis
acute gangrenous appendicitis
collateral vessels that develop secondary to persistently elevated venous pressure within the hemorrhoidal plexus
- also occur in portal HTN
hemorrhoids
most common in children and adolescents
- thought to be initiated by increased intraluminal pressure and compromised venous outflow
acute appendicitis
what is the most common tumor of the appendix?
benign carcinoid
what can cause pseudomyxoma peritonei?
peritoneal dissemination of mucinous tumors
what is the cellular inflammatory response primarily composed of?
dense collection of neutrophils and fibrinopurulent debris that coat the viscera and abdominal wall
- serous or slightly turbid fluid begins to accumulate and become suppurative as infection progresses
