Ch. 17 pt 2 Flashcards
how does salmonella present clinically
acute - anorexia, abd pain, bloating, N/V, bloody diarrhea w/ short asymp phase –> bacteremia & fever w/ flu-like symp
abd pain may mimic appendicitis
erythematous maculopapular rash (Rose spots)
systemic- extraintestinal complication = septic arthritis, abscess, osteomyelitis, encephalopathy, meningitis, seizures, endocarditis, myocarditis, pneumonia & cholecystitis
what is the pathogenesis of ischemic bowel dz
what variables determine the severity of the dz
two phases:
- initial hypoxic injury
- reperfusion injury
severity:
- severity of vascular compromise
- time frame
- vessels affected (more proximal, more significant)
What is the morphology of shigella
L colon (but ileum may be involved)
abundance of M cell in dome epithelium overlying Peyers Patches
mucosa = hemorrhagic, ulcerated & pseudomembrane
histology of early cases similar to self-limited colitides (like Campylobacter colitis)
tropism for M cells, aphthous ulcers similar to Crohns dz
What is the pathogenesis of colon CA
- APC/B-catenin/Wnt path –> classic adenoCA sequence (80% sporadic mutations)
- Microsatellite instability (MSI) path –> defect in DNA mismatch repair
both paths = accumulation of multiple mutations but differ in genes involved & mechanism by which mutations accumulation
epigentic events - MC = methylation induced gene silencing –> enhance progression along either path
which etiologies of colon CA cause sesile serated adenomas & mucinous adenocarinoma
DNA mismatch repair defect
- MYH-associated polyposis = AR
- Hereditary non-polyposis colorectal cancer - R-side = AD
- Sporadic CA (10-15%)- R side
&&&
hypermethylation = Sporadic CA (5-10%) - R side
How does salmonella cause infection
very few vaible strains cause infxn
= absence of gastric acid, in ind w/ atrophic gastritis or those on acid-suppressive therapy
penetrates SI mucus layer –> transverses the intestinal epithelium thru M cell on Peyer’s patches –> causes Peyers patches in terminal ileum to enlarge & elevations –> hyperplasia –> points of intussusception Mesenteric LN =enlarged
what are characteristics of Schistosoma
*know!!!*
from snail –> ingested
adult worms residing w/i mesenteric veins
sxs by trapped eggs w/i the mucosa and submucosa
granulomatous immune rxn –> bleeding and obstruction
–> SCC bladder
–> cirrhosis (2nd MCC)
what are freq abnormalities in the SI an LI
what are the causes
malabs & diarrhea: disrupt normal h2o and nutrient transport
infectous & inflam disorders: intestinal bacteria 10x # of eukaryotes in the body
Colon = MC site of GI neoplasia in the Western pop
Campylobacter spp.:
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
high income countries
poultry, milk, contaminated water, other foods - food poisoning
sporadic__, children, travelers
colon
farm animals
water/bloody diarrhea- (travelers diarrhea)
reactive arthritis (pt w/ HLA-B27), guillain-barre syndrome, erythema nodosom
when do you begin regular surveillance colonoscopies
age 50
younger is african american or FHx
polyp removal reduce the incidence of colorectal adenocarcinoma
What are diagnostic tests used infectious enterocolitis
selective serologic testing (giardia Ag)
fecal leukocytes (evidence of invasion)
fecal lactoferrin
stool culture
assays for toxins (C. diff toxin)
stool for ova & parasites
Lactose def = lactose cant be broken down to glu and galac, so it stays in lumen and exerts osmotic forces to attract fluid & cause diarrhea
what are the 2 types of lactose def
- congenital: mutation in gene encoding lactase; _auto re_c; explosive diarrhea w/ watery, frothy stool & abd distention w/ milk ingestion
- aquired: downreg of lactsoe gene expression; native american, african american, chinese; may present after enteric viral/bacteral infxn
(Bx is unremarkable for biochem defect)
Which dz’s have defect of only transepithelial transport
carcionoid syndrome
Abetalipoproteinemia
what are the steps of MMR carinogenesis (10-15 % sporadic & HNPCC)
what are characteristics of intestinal hookworm
penetrate skin –> develop lungs –> migrate to trachea & swallowed
suck blood & reproduce in the duodenum –> multiple superficial erosions, focal hemorrhage, and inflammatory infiltrates
Chronic infxn leads to iron deficiency anemia
neoplasia in IBD are related to..
duration of dz - > 8-10 yo
extent of dz - pancollitis > chance than if only L side dz
neutrophilic response: active inflam
(acquired conditions predispose to CA; chronic inflam, DALM = dysplasia associated lesions or mass (aka precursor lesions) & immune def)
What are characterisitics of V. cholerae
comma-shaped, gram (-)
India & Bangladesh, areas of natural disaster
cause cholera
transmitted in shellfish, contaminated H2O (fecal-oral)
Severe cases: ‘rice water diarrhea’ with fishy odor ==> dehydration
label this
what is the epidemiology of Colon Cancer
highest incidence = North america - bc dietary factors = low fiber, high fat/refined carbs
USA- 2nd MC cause of cancer death
peak incidence = 60-70 yo (rarely under 50 UNLESS HNPCC!)
use of ASA & NSAID –> prevention (inhibit COX-2)
What are characterisitics of obstructions due to adhesions
MC obstrution in USA
most often = acquired (surgery, trauma, intra-abd infxn, endometriosis)
healing –> fibrous bridge that creates loops where material can get lodges btn the bowel & adhesion
When/How do the SI and LI form embryonically
=4th & 5th wk
quickly outgrow the space –> entire midgut herniate into the umbilical cord - form loop
rotate –> pulled back for midline closure
Wht are characterisitics of adenovirus
common cause peds diarrhea & immunocompromised diarrhea
droplet/close contact transmission
SI bx show epithelial degeneration but more often non specific villous atrophy & compensatroy crypt hyperplasia
nonspecific sxs - resolve after 10 days
what are other causes of chronic colitis
what are characteristics of each
diversion colitis: blind colon segment bc of SRG resulting in ostomy; develop numerous mucosal lymphoid follicles; cure = re-anastamonsis
microscopic colitis: both types = watery diarrhea w/o wt loss; collagenous-in mid-age F; lymphocytic- in celiac dz & auto immune dz
graft-vs-host dz: after allogenic hematopoietic stem cell transplantation; crypts severely destroyed; watery diarrhea may become bloody in severe cases
what is the distinction between UC and Crohns primarily based on?
what are these characterisics for crohns dz
distribution & morphology
- MC: terminal ilieum, ileocecal valve, cecum (40% limited to SI & 30% SI & LI); multiple, sharply delineated areas (skip lesions)
- intestinal wall = thickened/rubbery bc transpural edema, inflam, submucosal fibrosis & hypertrophy of muscularis propria
- extensive transmural dz –> creeping fat - mesenteric adipose tissue extend over the serosal surface
What are the characterisitics of Ascaris lumbricoides
ingest eggs hatch in intestines –> larvae penetrate mucosa –> migrate to systemic circulation –> enter the lungs & grow w/i alveoli –> cough up and swallowed –> mature into worms –> eosinophilic-rich inflam rxn –> physical obstruction/the intestine/biliary tree
eggs in stool
fecal-oral
What is the clinical presentation of Campylobacter enterocolitis
water/bloody diarrhea
(bloody - bacterial invasion; minority of Campylobacter strains)
enteric fever: when bacterial prolif w/i lamina propria & mesenteric LM
what are the clincal features of colon CA
screening colonoscopy does not equal staging
R vs L sided CA
- R side = fatigue, weak bc Fe def anemia; older M or postmenopausal F
- L side= occult bleeding, changes in bowel habits, cramping & LLQ discomfort
prognostic factors depth of invasion & presence of LN metastasis
metastasis MC to liver
5 yr survival - 65%
what genes are associated w/ Crohn’s dz & UC
Crohns: Th17 & Il-23(p40 & p19), IL-23 receptor complex, CCR6, TNFSF15, JAK2/STAT
UC: all EXCEPT TNFSF15
What are the difference of clinical presentation of crohns & UC
perianal fissures?
fat/vit malabs?
malignancy?
recurrence after SRG?
toxic megacolon?
what are the clinical manifestations of intestinal obstruction
Abd pain (localized or diffuse), abd distention
vomiting, constipation
*rmr these DO NOT tell etiology*
How do you confirm the Dx of Shigella
how do you treat
stool culture
Abx shorten the clincal course & duration of bacterial shedding
anti-diarrheal medications can prolong sxs & delay clearance
how can Yersinia present clinically
how does cause infxn
in ileum, R colon, appendix – abd pain, fever, bloody diarrhea (can mimic appendicitis)
prolif extracellularly in lymphoid tissue –> regional LN & Peyer path hyperplasia as well as bowel wall thickening
mucosa overlying lymphoid tissue –> become hemorrhagic & aphthous erosions & ulcers ; may appear w/ neutrophil infiltrates & granuloma
(may be confused w/ crohns dz (like shigella))
reactive arthritis, with urethritis, conjunctivitis, myocarditis, erythema nodosom, and kidney dz
what are specifics about C. jejuni
MC bacterial enteric pathogen in developed countries
traveler’s diarrhea (food poisoning - chicken, unpasteurized milk, contaminated water)
Whipple dz
geography
epidemiology
GI site
symptoms
complications
rural > urban
rare, white men (particularly farmers)
SI
Malabs- triad: diarrhea, wt. loss, arthralgia
arthritis, arthralgia, fever, LAD, neurologic, cardiac or pul dz, CNS dz (may present before malabs by mon-yrs)
what is the immune response in pts w/ intestinal inflam
==> increased bacterial exposure - disruption of mucus layer, dysreg of tight jxns, increased intestinal permeability, increased bacterial adherence to epithelial cells
innate cells –> increase leves of TNF-a, IL-1B, 6, 12, 23 and chemokines –> expansion of lamina propria w/ increased CD4 cells (esp pro-inflam T subgroup) –> secrete cytokines & chemokines –> recruit leukocytes –> cycle of inflam
define diarrhea
differentiate it from dysentery
increase in stool mass, freq, fluidity
typically > 200 gm/day
severe cases- stool vol can exceed 14 L/day
w/o fluid resuscitation –> Death
dysentery = painful, bloody, small volume diarrhea
Pseudomembranous colitis (C. Diff) - (aka ABx-associated colitis/diarrhea)
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
worldwide
ABx allow emergence
immunosuppressed, ABx-treated
colon
humans, hospitals
water diarrhea, fever
relapse, toxic megacolon
what category does shigella belong to
gram neg, unencapsulated, nonmotile, facultative anaerobe
what are characteristics of autoimmune enteropathy
how does it differ from celiac dz
X-linked (germline LOF FOXP3)- severe diarrhea & autoimmune dz in children
severe familal form = IPEX = immune dysreg, polyendocrionpathy, enteropathy & X-linkage
autoAb of enterocytes & goblet cells & some have autoAb to parietal/islet cells
neutrophils infiltrate intestinal mucosa (unlike celiac!)
=give immunosuppressive drugs
What are characteristics of Strongyloides stercoralis
penetrate unbroken skin –> migrate thru lungs –> induce inflam infiltrates –> reside in the intestines maturing into adult worms
autoinfection: eggs can hatch w/i the intestine and release larvae that penetrate the mucosa
infection can persist for life
larvae stage is OUTSIDE human host strong tissue rxn and induce peripheral eosinophilia
what are clinical features of IBS
abd pain 3 days/month over 3 months
improves w/ defecation
chronic, relapsing abd pain, bloating, changes in bowel habits without changes in the gross pathology or histology
dx based on clinical critera (Rome criteria)
what is the presentaton of pseudomembranous colitis
fever, leukocytosis, abd pain, cramps, water-diarrhea & dehydration
protein loss–> hypoalbuminemia
fecal leukocytes & occult blood
toxic megacolon - marked dilation of colon - marked injury to the colonic wall
What are juvenile polyps
<5 yo; sporadic or syndromic (AD)
rectal location (SB and stomach if syndromic)
dysplasia present –> risk of gastic, SI, colonic, pancreatic adenocarcinoma
can be associated w/ rectal bleeding intussusception, intestinal obstruction or polyp prolapse
congenital malformations, digit clubbing
mutation: SMAD4 –> affect TGF-B signaling
what are characteristics of Cryptosporidium spp
Chronic diarrhea- AIDs pts
oocysts resistant to chlorine - need to freeze/filter
ENTIRE life cycle in a single host
attach brush border & damage enterocyte –> malabs of sodium, chloride secretion, an increased tight junction permeability – non-bloody watery diarrhea
terminal ileum and proximal colon
present thru GIT, biliary tree, and the resp tract of immunodeficient hosts
diagnosis == oocysts in the stool
What is the pathogenesis/morphology of whipple dz
dense accumulation of distended foamy macrophages in small intestine lamina propria & many argyrophilic rods in LN
PAS-positive bacteria, diastase-resistant granules that represent partially digested bacteria w/i lysosomes
H&E stain- normal lamina propria by distended macrophages; micrograph of macrophase show bacilli w/i cell -seen at higher magnification
==> look similar to TB; acid fast stain help you differentiate TB (+) and Whipple dz (-)
what is the distribution and morphology of UC
ALWAYS involved rectum & extends proximally in contninous fashion
if entire colon = pancolitis –> backwash ileitis- mild inflam of distal ileum in pancolitis
limited = descriptive (ie ulcerative proctitis or proctosigmoiditis)
NOT transmural –> so colon wall = THIN, surface serosa normal & no strictures
what is the fxn of Th17 cells in intestinal inflam
express CCR6 & IL-23 receptors (include IL-23 receptor complex & IL-12 receptor B1)
APC secrete IL-23 (p19 & p40)
interact w/ receptor –> (+) JAK2 signal transducers –> (+) STAT3 –> regulate transcriptional activation
IL-23 –> contribute to Th-17 cell prolif, survival or both
actions of IL-23 enhanced by TNFS15
- which dz has a defect of only terminal digestion?
- which one is the only one w/ a defect in lymptic transport
- disaccharidase def
- whipple dz
what are hamarthomatous polyps
sporadic or due to genetic/acquired syndrome;
have underlying germline mutation in tumor suppressor gene/proto-oncogene
some increase risk for CA
how do you characterize E. coli
(what are specifics about each strain)
gram (-) bacilli; colonize healthy GI tract;most are nonpathogenic but subset cause human dz
ETEC: principal cause of traveler’s diarrhea, secretory, non-inflam diarrhea
EPEC: produce attaching/effacing lesions in which bacteria attach tightly to the enterocyte apical membrane & cause local loss
EHEC: O157:H7 –> HUS
EIEC: invade epithelial cells causing nonspecific, acute self-limited colitis
what are characteristics of Enterobius vermicularis (pinworm)
do NOT invade host tissue
entire life w/i the intestinal lumen == rarely cause illness
fecal oral
female migrates to anal orifice –> deposits eggs on perirectal mucosa –> lot of irritation, leads to itching
scotch tape test
what is clinical presentation of crohns
20% pt present w/ acute RLQ pain, fever, bloody diarrhea (mimic appendicitis/bowel perforation)
dz onset associated w/ initiation of smoking
malabs –> malnutrition, hypoalbeminemia, Fe def anemia
increased risk fo adenocarcinoma
Ab to saccharomyces cervisiae (not in UC!)