Ch. 17 pt 2 Flashcards
(132 cards)
1
Q
how does salmonella present clinically
A
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
2
Q
what is the pathogenesis of ischemic bowel dz
what variables determine the severity of the dz
A
two phases:
- initial hypoxic injury
- reperfusion injury
severity:
- severity of vascular compromise
- time frame
- vessels affected (more proximal, more significant)
3
Q
What is the morphology of shigella
A
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
4
Q
What is the pathogenesis of colon CA
A
- 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
5
Q
which etiologies of colon CA cause sesile serated adenomas & mucinous adenocarinoma
A
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
6
Q
How does salmonella cause infection
A
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
7
Q
what are characteristics of Schistosoma
*know!!!*
A
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)
8
Q
what are freq abnormalities in the SI an LI
what are the causes
A
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
9
Q
Campylobacter spp.:
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
A
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
10
Q
when do you begin regular surveillance colonoscopies
A
age 50
younger is african american or FHx
polyp removal reduce the incidence of colorectal adenocarcinoma
11
Q
What are diagnostic tests used infectious enterocolitis
A
selective serologic testing (giardia Ag)
fecal leukocytes (evidence of invasion)
fecal lactoferrin
stool culture
assays for toxins (C. diff toxin)
stool for ova & parasites
12
Q
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
A
- 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)
13
Q
Which dz’s have defect of only transepithelial transport
A
carcionoid syndrome
Abetalipoproteinemia
14
Q
what are the steps of MMR carinogenesis (10-15 % sporadic & HNPCC)
A
15
Q
what are characteristics of intestinal hookworm
A
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
16
Q
neoplasia in IBD are related to..
A
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)
17
Q
What are characterisitics of V. cholerae
A
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
18
Q
label this
A
19
Q
what is the epidemiology of Colon Cancer
A
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)
20
Q
What are characterisitics of obstructions due to adhesions
A
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
21
Q
When/How do the SI and LI form embryonically
A
=4th & 5th wk
quickly outgrow the space –> entire midgut herniate into the umbilical cord - form loop
rotate –> pulled back for midline closure
22
Q
Wht are characterisitics of adenovirus
A
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
23
Q
what are other causes of chronic colitis
what are characteristics of each
A
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
24
Q
what is the distinction between UC and Crohns primarily based on?
what are these characterisics for crohns dz
A
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
25
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**
26
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_
27
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%
28
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
29
What are the difference of clinical presentation of crohns & UC
perianal fissures?
fat/vit malabs?
malignancy?
recurrence after SRG?
toxic megacolon?
30
what are the clinical manifestations of intestinal obstruction
**Abd pain (localized or diffuse), abd distention**
**vomiting, constipation**
\*rmr these DO NOT tell etiology\*
31
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_**
32
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
33
what are specifics about C. jejuni
**MC bacterial enteric pathogen in developed countries**
**traveler's diarrhea** (food poisoning - chicken, unpasteurized milk, contaminated water)
34
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)
35
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
36
# 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
37
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**
38
what category does shigella belong to
**gram neg, unencapsulated, nonmotile, facultative anaerobe**
39
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
40
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**
41
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)
42
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
43
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**
44
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
45
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 (-)_
46
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_**
47
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
48
1. which dz has a defect of only terminal digestion?
2. which one is the only one w/ a defect in lymptic transport
1. disaccharidase def
2. whipple dz
49
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_
50
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_
51
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
52
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!)
53
what is the clinical presentation of Shigella
incubation up to 1 wk
**self limited dz**
7-10 days of diarrhea, fever, abd pain
_watery diarrhea --\> dysenteric phase_ (50%)
persist as long as 1 month (**shorter in children; but more severe**)
adults: uncommon subacute weeks of waxing/waning diarrhea - **mimic new-onset of UC**
54
what is the clinical presentation of UC
inital attack may be severe --\> medical/SRG emergency
**bloody diarrhea w/ stringy, mucoid material** & abd pain
triggers = infectious enteritis, psych stress, **STOP smoking** (smoking may relieve symps.....)
55
what is the epidemiology of salmonella
typhoid fever (enteric fever) - worldwide incidence of 30 mil
S. enterica; 2 subtypes (**typhi** -endemic countries & **paratyphi**-travelers)
children/teens - endemic areas
no age preference - non-endemic areas
infxn associated w/ travel to **india, mexico, philippines, pakistan, el salvador, haiti**
**gallbladder colonization w/ S. typhi/paratyphi may be assocaited w/ gallstones & chronic carrier state**
56
what is the most freq cause of intestinal obstruction world wide?
what are the associated characteristics & complications
**hernias = 3rd MC in USA**
**most freq = inguinal (narrow orifice & large sac)**
complications = pressure at the neck of the pouch may _impair venous drainage of entrapped viscus_ --\> _stasis & edema_ --\> increase bulk of herniation --\> _permanent entrapment --\> strangulation --\> infarcture_
57
What is the MCC of **acute gasteroenteritis requiring medical attn**
what are its characterisitics
**norovirus=** ssRNA
fecal-oral
spreaad w/i schools, hospital, nursing homes, cruise ships
significant prob in immunocompromised pts
**villous shortening, loss of brush borders, crypt hypertrophy, lymphocytic infiltration**
58
Salmonella
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
worldwide
meat, poultry, eggs, milk
**children, older adults (peak summer/fall)**
colon & SI
poultry, farm animals, reptiels
watery/bloody diarrhea
sepsis, abscess
59
What does UC look like grossly
colonic mucosa - _slightly red & granular or w/ extensive, broad based ulcers_
**abrupt transition-** btn dz & uninvolved colon
ulcers along _long axis of colon_
**isolated islands of regenerating mucosa** bulge into lumen ==\> **pseudopolyps** w/ _tips_ that _can fuse_ and create _mucosal bridges_
chronic --\> mucosal atrophy w/ Sm. mucosal surface that lacks normal folds
60
what is infectious enterocolitis
presents w/ broad range of symps
=diarrhea, abd pain, urgency to defecaate, perianal discomfort, incontinence & hemorrhage
**global problem w/ 2,000 deaths per DAY in kids & 10% of death worldwide by age 5**
61
what is the fxn of STK11 gene
instruction for making Ser/Thr kinase 11
= tumor suppressor - help determine the amounf of energy a cell uses
promotes apoptosis
required for normal development in birth
62
What are characteristics of hyperplastic polyps
**L colon**, single/multiple
**60-70s**- bc decreased epithelial cell turnover & delayed shedding of surface epithelial cells --\> goblet cells & absorptive cells pile up
63
what are the classic clinical presentations of a pt w/ ischemic bowel dz
**MC \> 70 yo,** slightly more F
acute --\> sudden _cramps LLQ_, desire to defecate, _passage of blood/bloody diarrhea_ (BRB, hematochezia)
may progress to _shock and vascular collapse_ w/i hrs in several cases
_SRG_ needed if evidence of _infarction_ --\> _paralytic ileus_ (decrease bowel sounds), gaurding/rebound tenderness
(CMV & radiation enteritic mimic ischemic bowel dz)
64
where are polyps most commonly located
what are possible characterisitics
**colon & rectum**
most begin as **small elevations** of mucosa **= sessile (w/o stalk)**
--\> can enlarge, prolif into mass and the effects of traction of the luminal protrusion may create a stalk --\> **pedunculated**
_classification: neoplastic or not_
65
What are characteristics of Entamoeba histolytica
\*know!!\*
fecal-oral; **india, mexico, columbia**
--\> liver abscesses and dysentery; abdpain, *_bloody_* diarrhea, or wt loss
penetrate splanchnic vessels and **embolize to liver producing abscesses**
acute necrotizing colitis & megacolon -- both = significant mortality
cysts w/ chitin wall and 4 nuclei and **resistant to gastric acid**
flask shaped ulcer with narrow neck and broad base
LACK mitochondria/Krebs cycles enzymes = obligate fermenters of glucose
66
what are causes of vascular lesions of the SI/LI
ischemic bowel dz
angiodysplasia
67
What is the presentation of intussusception
**MC obstruction of kids \<2 yo** (spontaneous/viral infxn/**rotovirus vaccine; lymphoid hyperplasia --\> lead point**; Peutz-Jegher) ==\> Tx: contrast enema, air enema
adults: due to intraluminal mass/tumor (usually malignant) --\> Tx: SRG
=segment telescopes into the immediately distal segment
68
How does erythema nodosum present
type of skin inflam
located in part of the fatty layers of skin
reddish, painful, tender lumps/nodule
\*front of legs, below knees\*
69
what is the outcome of acute compromise in ischemic bowel dz
mucosal & non-transmural infarct - may NOT be fatal
transmural ==\> 10% mortality w/i 30 days bc **full thickness necrosis** (_NEC - MC aquired GI in neonates can cause transmural necrosis)_
_worst outcome = SMA occlusion_
70
What are characterisitics of rotovirus
**MCC severe childhood diarhea & diarrheal mortality worldwide**
= encapsulated dsRNA
**6-24 months = most vulnerable** (probably bc Ab in breast milk confer protection during 1st 6 months)
outbreak _hostpital & daycare centers_
enterocyte damage ==\> loss of absorptive fxn & new secretion of water & electrolytes --\> incomplete abs of nutrients --\> osmotic diarrhea
71
what are diagnostic tests used for GI complaint
imaging: XR, barium, CT scan, US, angiography, **CTE (best for SI)**/MRE (enterography)
endoscopy: video capsule/ colonoscopy
labs: CBC, CMP, Micro, Genetics (malignancy/syndromes)
Bx: endoscopic, fine needle aspiration/core Bx, SRG, autopsy
72
what are types of polyps
hyperplastic
inflam
hamartomatous
adenoma
73
What is Abetalipoproteinemia
**rare auto rec dz = inablity to assemble triglyceride-rich lipoprotein**
**infancy-** FTT, diarrhea & steatorrhea
plasma = complete devoid of lipoprotein containing apolipoprotein B
fail to abs essential FA --\> def in fat-soluble vits
lipid membrane defects --\> **acanthocytes in peripheral blood smear**
74
What is the presentation of angiodysplasia
= malformed **tortuous** submucosal & mucosal blood vessels = **dilated & thin**
**MC - cecum or R. colon; \>60 y/o**
anemia b/c slow GI bleed _(= 20% of major lower GI bleeds in older pts)_
chronic/intermittent/massive hemorrhage
75
what are the extra-intestinal manifestations of IBD
Mouth: _aphthous ulcers_
Eyes: uveitis
Biliary tract: **_sclerosing cholangitis 2.5-7.5% pt w/ UC_**, gallstones
Joints: migratory polyarthritis, sacroilitis, ankylosing spondylitis,
Skin: erythema nodosum, _pyogerma grangrenosum_
amyloidosis, finger clubbing
76
What are characteristics of internal cestodes
_exclusively in intestinal lumen_
does NOT penetrate intestinal mucosa --\> NO peripheral eosinophilia
**raw meat** contain encysted larvae
_proglottids & eggs are shed in the feces_
Sxs: diarrhea, abdominal pain, nausea
3 primary species:
1. Diphyllobothrium latum (fish tapeworm) ==\> _B12 def_ & megaloblastic anemia
2. taenia solium (pork tapeworm)
3. hymenolepis nana (dwarf tapeworm)
77
What is FAP
familial adenomatous polyposis
= _AD_ disorder - pt develops _numerous colorectal adenomas_ as **TEENAGER**
= somatic mutation in APC gene (75% inherited) --\> may have biallelic mutation of MYH
associated w/ variety of extraintestinal manifestations - including _congenital hypertrophy or the retinal prigment epithelium_ - detect @ birth
78
what is the relation of iron and Yersinia
iron enhances virulence --\> stimulates systemic dissemination _(occur w/ multiple transfusion)_
==\> greater risk for sepsis/death
non-heme related - chronic form of anemia/hemochromatosis
79
what is ischemic bowel dz
interconnection btn arcades (as well as collateral vessels of proximal celiac & distal pudendal/iliac circulation) allow _slow, progressive blood loss_
chronic - progressive hypoperfusion, acute (abrupt) compromise --\> infarction of several meters of intestine
80
What is the morphology of colon CA
_proximal_ colon tumors - grow as _polypoid, exophytic mases_ --\> extend along one wall of large-caliber _cecum & ascending colon_ ==\> rarely obstruct
_distal_ colon tumors - _annular lesions - make **"napkin ring"** constriction & lumincal narrowing_ --\> sometimes obstruct
both invade bowel wall over time
81
Yersinia
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
N & central europe
pork, milk, water
clustered cases
**ileum, appendix, R colon**
pigs, cows, puppies, cats
Abd pain, fever, diarrhea
**reactive arthritis w/ urethritis, conjunctivits, myocarditis, erythema nodosum & kidney dz**
82
what dz's have intraluminal digestion defects
chronic pancreatitis
CF --\> pancreatitis
primary bile acid malabs (w/ defect in transepithelial transport)
IBD (w/ defect in terminal digetion & transepithelial transport)
83
what is hereditary nonpolyposis colorectal CA?
HNPCC = Lynch syndrome
= AD ; younger age \*look for FHx\*
**MC syndromic form of colon CA**
R-sided (_ascending colon)_
MSH2/MLH1 affected by DNA mismatch repair
84
what is the DDx for malabs diarrhea
CF
celiac
environmental enteropathy/ enteric dysfxn
autoimmune enteropathy
lactase (disaccharidase) def
abetalipoproteinemia
infectious entercolitis
85
what is the immune response in intestines of healthy ind
goblet cells --\> mucus --\> limit exposure to bacteria
antimicrobial peptides (a-defensins) by Paneth cells & IgA ==\> protect luminal microbiota
innate sensing by TOL-R and NOD proteins --\> dendritic cells present Ag to CD4 T cell in 2ndary lymphoid organ (peyer's patches & mesenteric LNs) --\> TGF-B & IL-10 modulate differentiation of CD4 T cells subgroups (Treg, Thelpers)--\> induce enterotropic molecules
CD4 cells circulate intestinal lamina propria --\> effector fx
86
What is a volvulus
feature of obstruction & infarction
most often = _large redundant loops of **sigmoid colon**_
(also by cecum, small bowel, stomach, transverse colon)
= rare; but seen in pts _w/ mental deficits/in institutionalized facilities_
**can lead to gangrenous sigmoid colon --\> rupture --\> peritonitis & toxic megacolon**
-emergency laprotomy w/ clinical signs/sxs of colonic ischemia, failed decpression & clinical features suggestive of colonic ischemia at colonoscopy
87
label this
88
what are the 4 types of diarrhea
1. **secretory**: isotonic stool, _persist during fasting_
2. **osmotic:** excess osmotic forces by luminal solutes; lactase def; _stops w/ fasting_
3. **malabs**: general failure to abs nutrients; steatorrhea, _stops w/ fasting_
4. **exudative**: due to inflam dz = purulent, bloody; _persists w/ fasting_
89
How do you treat pseudomembranous colitis
metronidazole & vancomycin
but prevalence of ABx resistant & hypervirulent C. diff is increasing
90
what is diverticular Dz
**acquired** pseudodiverticular outpouching of colonic **mucosa & submucosa**
rare \< 40 yo; but _common \> 60 yo_
**_asia & africa_: R. side** diverticula ; **_j_**apan LESS common
**_western countries_ = L side**
= intermittent cramping, continuous low abd discomfort, constipation, distention or sensation of never being able to completely empty rectum
can cause abscess, fistula or perforation
91
What is the etiology of acute obstruction to flow in ischemic bowel dz
thrombosis or embolism
_severe athreosclerosis_ (likes to start in ostium)
AAA
cardiac mural thrombi - Afib or hypokinesia --\> stasis
vasculitis
mesenteric venous thrombosis: _hypercoag state_, tumors, trauma, _cirrhosis_
92
what is caused by a mutation of the MTP gene
abetalipoproteinemia
gene is required for transfer of lipids to nascent apolipoprotein B polypeptide in the endoplasmic reticulum
w/o it --\> **lipids accumulate intacellularly**
93
What are the therapeutic approaches to IBD
=**focus on (-) proinflam cytokines, inhibit entry of cells into intestinal tissues & inhibit T-cell activation & prolif**
block co-stimulatory signals that increase interaxn btn innate & adaptive cells
administer EGF
enhance tolerance
94
what are adenomatous polyps
**MC neoplastic polyps**
**=** _intraepithelial neoplams that range from small pedunculated to large sessile_
30% by age 60, M slightly more
**hallmarks of epithelial dysplasia are nuclear hyperchromasia, elongation & stratification**
**_sessile serrated lesions lack typical cytologic features of dysplasia_**
95
what syndromes may present with hamartomatous polps & what are extra-GI manifestations for each
1. **Cowden syndrome, Bannayan-Ruvalcaba-Riley syndrome:** _GI-lipomas, ganglioneuromas;_ benign skin tumors, benign/malignant thyroid/breast leions; _NO increase in GI CA_
2. **Cronkhite-Canada:** _GI: polyps in stomach, SI; abn nonpolypoid mucosa_; nail atrophy, hair loss, abn skin pigmentation, cachexia and anemia
3. **tuberous sclerosis:** mental retardation, epilepsy, facial angiofibroma, cortical tubers, renal angiomyolipoma
96
what is a fxnal bowel obstruction, aka paralytic ileus
=temporary disturbance of peristalsis (w/o mechanical prob)
=**post-op ileus = MC etiology**
also caused by metabolic probs, endocrinopathies, certain drugs
97
What is the etiology of chronic/hypoperfusion states in ischemic bowel dz
=non-obstructive
cardiac failure
shock
dehydration
drugs (vasoconstict) - cocaine
98
what are histological factors of Peutz-Jeghers syndrome
**arborizing network of CT, Sm M, lamina propria & glands lined by normal appearing intestinal epithelium**
99
what is the presentation of guillain-barre syndrome
demyelinating polyneuropathy
paresthesias in hands & feet
M weakness (start in legs and ascend)
severe resp M weakness
absent/depressed deep tendon reflexes
100
What is the function of APC
= one of tumor suppressors
degrade B-catenin --\> **downreg- growth promoting signaling paths**
APC is a component of WNT signaling path --\> major role in controlling cellular growth & differentiation during embryonic development
**BOTH copies** must be lost for adenoma to form
defect = b-catenin accumulate --\> form complex w/ DNA binding factors TCF --\> activate myc and cyclin D1 --\> proliferate
101
What are characterisitics of giardia lamblia
**MC parasitic pathogen in human; spread fecally contaminated water or food**
cysts resistant to chlorine
flagellate protozoan **d****ecrease expression of brush border enzymes, including lactase**
secretory IgA and mucosal IL-6 responses -important for clearance
= continuous modification of major surface Ag
Trophozoites = pear shape w/ 2 equal size nuclei
secretions damage brush border = malabs
102
How do you diagnose celiac dz
**IgA Ab _tTG_ or endomysial =** _sensitive & specific (95%)_
**_tTG Ab = recommended single serologic test for celiac screening_**
test for **gliadin Ab** NOT recommended bc low sensitivity/specificity
intraepithelial lymphocytes & villous atrophy in histology not specifi, so combo of serolgy and histolgy = most specific dx
103
What is celiac dz
aka celiac sprue/ gluten-sensitive enteropathy
gluten (wheat, rye, barley) --\> **immune mediated** enteropathy in genetically predisposed pts
**autoimmunity arises from a combo of inheritance of susceptiblity of genes --\> contribute to breakdown of self-tolerance, environmental triggers (infxn/tissue damage) --\> activation of self-reactive lymphocytes**
104
what are virulence factors due to for C. jejuni
motility
adherece
toxin production
invasion (dysentery)
105
Differentiate gastroschisis & omphalocele
gastroschisis: intestines protrude thru abd wall defect; but _not covered by membrane_
omphalocele: abd viscera herniate into base of umbilicus; _covered by membrane_
106
which dz's have a defect of both terminal digestion and transepithelial transport
celiac dz
environmental enteropathy
autoimmune enteropathy
viral/bacteral/parasitic gasteroenteritis
107
what are the earliest lesions of crohns dz
& what are other morphological features
_aphthous ulcers_
may progress --\> multiple lesions often coalesce into elongated, serpentine ulcers along _the axis_ of the bowel
common: edema & loss of normal mucosal folds
ulcerations w/ sparing of interspersed mucosa --\> **irregular, cobblestone appearance**
develop _fissures_ & may become fistula tracts/perforation
108
which colon CA etiologies lead to tubular, villous, typical adenoCA
FAP = AD
Sporadic Colon CA (70-80%) - predom L side
both = APC/WNT pathway
109
What is Peutz-Jeghers syndrome
AD syndrome- _LOF in STK11 50% pt_
(_10-15 yo)_
**multiple GI hamartomatous polyps & mucocutaneous hyperpigmentation**
MC: SI (but can occur in stomach, colon, and less freq bladder/lungs)
intusussusception often fatal
_pigmented macles; risk for colon, breast, lung, pancreatic and thyroid CA_
110
Shigellosis
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
worldwide, endemic developing countries (_poor sanitation_)
**fecal-oral, food, water**
_children, migrant workers, travelers, nursing homes_
L colon, ileum
humans
**MCC: bloody diarrhea - worldwide**; death (limited to \< 5 yo)
**reactive arthritis, urethritis, conjunctivitis** (**HLA-B27** men 20-40 yo), **HUS, toxic megacolon**
111
what are the macroscopic differences btn crohn's & UC
bowel region
distribution
strictures?
wall appearance
112
what is the morphology for ischemic bowel dz
lesions = patchy
mucosa = hemorrhagic/ulcerated
_transmural infarct_ --\> large portion affected; sharp line btn infarct & healthy tissue
chronic: fibrous scarring of lamina propria; _pseudomembrane_ resembles c. diff
113
what is the most important characteristic that correlates w/ malignancy in polyps
**_SIZE_**
114
where does environmental enteric dysfxn present? ( aka environmental enteropathy, tropical enteropathy, tropical sprue)
how does it present
poor sanitation/hygiene
**sub-saharan africa (zambia), aboriginal pop in N. australia** (travel or live there)
=malabs, malnutrition & stunted growth
115
What is IBD
what is the epidemiology
=chronic; **inappropriate mucosal immune response to normal gut flora = crohns & UC**
_teens/ early 20's_ (**UC** slightly more _F & 2nd peak 60s-70s_)
_white, ashkenazi jews_
_n. america, europe, australia_
116
what are watershed zones?
most vulnerable for ischemic bowel dz
**splenic flexure** btn SMA & IMA _(= marginal A)_
sigmoid colon & rectum - IMA, pudendal & iliac A circulation ends
117
who is at risk for salmonella infxns
CA
immunosuppression
EtOH
CV
**sickle cell (osteomyletis)**
hemolytica anemia
118
what is the pathogenesis of celiac dz
triggered by ingestion of gluten --\> _gliadin (alc soluble fraction) = most of dz-producing component_ (**resistant to breakdown by proteases)**
_innate response_= induce IL-15 --\> (+) CD8 - express NKG2D --\> attack enterocytes w/ MIC-A --\> _damage increases chance of gliadin to enter lamina propria_ --\> deaminated by **tTG**
--\> interact w/ **HLA-DQ2 & HLA-DQ8 --\>** _(+) adaptive response_ --\> CD4 make cytokines --\> _tissue damage_
119
how is IBS defined
what pop does it present in most
=chronic relapsing abd pain, bloating & changes in bowel habits **w/o obvious gross/histological features**
3 types: diarrhea predom, constipation predom & mixed
pathogenesis = psychologic stressors, diet, gut microbiome, abn GI motility & increased enteric sensory response
_Female, 20-40 yo, high income countries_
120
E. coli
geography
transmision
epidemiology
GI site
reservoir
symptoms
complications
121
what are characterisitcs of inflammatory polyps
may be part of **solitary rectal ulcer syndrome (SRUS)**
triad = **rectal bleeding, mucus discharge, inflam lesions on anterior rectal wall**
--\> chronic cycles of injury/healing
histology: mixed inflam infiltrates, erosion & epithelial hyperplasia w/ prolapse induced lamina propria firbomuscular hyperplasia
122
what are causes of GI obstruction (which are most often in the SI, bc of the narrow lumen)
80%:
1. **hernia = MC worldwide**
2. adhesions
3. volvulus
4. intussuseption
tumors, infarctions, other strictures = 10-15%
123
how does dermatis herpetiformis present
microabscess- papillae
subepidermal blisters
granular IgA deposits
(associated w/ celiacs)
124
What is the morphology of salmonella
**peyer patches in the terminal ileum** - enlarge into sharply delinated, _plateau-like elvation_
enlarge mesenteric LN
acute/chronic inflam cell recruited to lamina propria --\> necrotic debris & overlying mucosal ulcers along the axis of the ileum (may perforate)
spleen = enlarged & soft w/ uniform pale red pulp & obliterated follicular markings
**typhoid nodules**: focal hepatocyte necrosis w/ macrophage aggregates
125
What is the morphology of pseudomembranus colitis
associated w/ C.diff
pseudomembrane - made up of an adherent layer of inflam cells & debris are non specific & may also be present in ischemia/necrotizing infxn
histopath = **damaged crypts** - distended by _mucopurulent exudate that form an eruption-like volcano --\> form membrane_
126
how does celiac dz present in adults
Females (autoimmune)
30-60 yo
silent or symptomatic
chronic diarrhea, bloating, chronic fatigue, anemia (chronic iron and vitamin malabsorption)
**Dermatitis herpetiformis: itchy, blistering skin lesion (10%)**
127
How does celiac present in children
M=F
6-24 months: irritable, abd distention, chronic diarrhea, FTT, wt. loss, M. loss
older = abd pain, N/V, bloating, constipation
_extraintestinal:_ arthritis/joint pain, aphthous ulcers, stomatitis, anemia, delayed puberty, short stature
128
what is malabsorption
what is the MC malabs disorder
= defective abs of fats, h2o-soluble vits, proteins, carbs, electrolytes, minerals & water
**hallmark = steatorrhea -excessive fecal fat** -bulky, frothy, greasy, yellow, clay colored stool
**pancreatic insufficiency, celiac dz & crohns dz MC chronic malabs prob in USA**
129
what are microscopic differences of crohns & UC
inflam:
pseudopolyps
ulcers
lymphoid rn
fibrosis
serositis
granulomas
fistulae/sinuses
130
what are characteristic of CF
= inherited; dysfxn ion transport --\> affect fluid secretions in _exocrine glands & epithelial lining of resp, GI, reproductive tract_
=thick secrtions obstruct organs:
1. **infant: _meconium ileus_**
2. _chronic lung dz_ 2ndary to recurrent infxn
3. **_pancreatic insufficiency_ - 85-90 % pt; severe --\> completely plugged glands --\> atrophy of gland & fibrosis==\> impair fat abs (avitaminosis A --\> dermatitis, glossitis, squamous metaplasia)**
4. _steatorrhea_
5. _malnutrition_
6. _hepatic cirrhosis_
7. _intestinal obstuction_
8. _male infertility_
131
what are the chances of getting colorectal adenoCA in pts w/ untreated FAP
**_100%_**- before 30 & nearly all by age 50
**common site = ampulla of vater & stomach**
adenomatous polyps = known precursors to majority of colorectal adenoCA
**_adenoCA of colon = MC malignancy of GI (10% CA deaths worldwide)_**
132
what is indeterminate colitis
unable to make definitive dx bc overlap of UC and crohns
serologic studies useful in finding overlapping features (75% UC - antineutrophil cytoplasmic Ab & only 11% crohns)
