Ch. 17 pt 2 Flashcards

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

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2
Q

what is the pathogenesis of ischemic bowel dz

what variables determine the severity of the dz

A

two phases:

  1. initial hypoxic injury
  2. reperfusion injury

severity:

  1. severity of vascular compromise
  2. time frame
  3. vessels affected (more proximal, more significant)
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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

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4
Q

What is the pathogenesis of colon CA

A
  1. APC/B-catenin/Wnt path –> classic adenoCA sequence (80% sporadic mutations)
  2. 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

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5
Q

which etiologies of colon CA cause sesile serated adenomas & mucinous adenocarinoma

A

DNA mismatch repair defect

  1. MYH-associated polyposis = AR
  2. Hereditary non-polyposis colorectal cancer - R-side = AD
  3. Sporadic CA (10-15%)- R side

&&&

hypermethylation = Sporadic CA (5-10%) - R side

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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

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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)

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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

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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

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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

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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

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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
  1. congenital: mutation in gene encoding lactase; _auto re_c; explosive diarrhea w/ watery, frothy stool & abd distention w/ milk ingestion
  2. aquired: downreg of lactsoe gene expression; native american, african american, chinese; may present after enteric viral/bacteral infxn

(Bx is unremarkable for biochem defect)

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13
Q

Which dz’s have defect of only transepithelial transport

A

carcionoid syndrome

Abetalipoproteinemia

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14
Q

what are the steps of MMR carinogenesis (10-15 % sporadic & HNPCC)

A
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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

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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)

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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

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18
Q

label this

A
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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)

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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

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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

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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

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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

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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
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25
Q

What are the characterisitics of Ascaris lumbricoides

A

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

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26
Q

What is the clinical presentation of Campylobacter enterocolitis

A

water/bloody diarrhea

(bloody - bacterial invasion; minority of Campylobacter strains)

enteric fever: when bacterial prolif w/i lamina propria & mesenteric LM

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27
Q

what are the clincal features of colon CA

A

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%

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28
Q

what genes are associated w/ Crohn’s dz & UC

A

Crohns: Th17 & Il-23(p40 & p19), IL-23 receptor complex, CCR6, TNFSF15, JAK2/STAT

UC: all EXCEPT TNFSF15

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29
Q

What are the difference of clinical presentation of crohns & UC

perianal fissures?

fat/vit malabs?

malignancy?

recurrence after SRG?

toxic megacolon?

A
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30
Q

what are the clinical manifestations of intestinal obstruction

A

Abd pain (localized or diffuse), abd distention

vomiting, constipation

*rmr these DO NOT tell etiology*

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31
Q

How do you confirm the Dx of Shigella

how do you treat

A

stool culture

Abx shorten the clincal course & duration of bacterial shedding

anti-diarrheal medications can prolong sxs & delay clearance

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32
Q

how can Yersinia present clinically

how does cause infxn

A

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

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33
Q

what are specifics about C. jejuni

A

MC bacterial enteric pathogen in developed countries

traveler’s diarrhea (food poisoning - chicken, unpasteurized milk, contaminated water)

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34
Q

Whipple dz

geography

epidemiology

GI site

symptoms

complications

A

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)

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35
Q

what is the immune response in pts w/ intestinal inflam

A

==> 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

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36
Q

define diarrhea

differentiate it from dysentery

A

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

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37
Q

Pseudomembranous colitis (C. Diff) - (aka ABx-associated colitis/diarrhea)

geography

transmision

epidemiology

GI site

reservoir

symptoms

complications

A

worldwide

ABx allow emergence

immunosuppressed, ABx-treated

colon

humans, hospitals

water diarrhea, fever

relapse, toxic megacolon

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38
Q

what category does shigella belong to

A

gram neg, unencapsulated, nonmotile, facultative anaerobe

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39
Q

what are characteristics of autoimmune enteropathy

how does it differ from celiac dz

A

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

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40
Q

What are characteristics of Strongyloides stercoralis

A

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

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41
Q

what are clinical features of IBS

A

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)

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42
Q

what is the presentaton of pseudomembranous colitis

A

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

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43
Q

What are juvenile polyps

A

<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

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44
Q

what are characteristics of Cryptosporidium spp

A

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

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45
Q

What is the pathogenesis/morphology of whipple dz

A

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 (-)

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46
Q

what is the distribution and morphology of UC

A

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

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47
Q

what is the fxn of Th17 cells in intestinal inflam

A

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

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48
Q
  1. which dz has a defect of only terminal digestion?
  2. which one is the only one w/ a defect in lymptic transport
A
  1. disaccharidase def
  2. whipple dz
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49
Q

what are hamarthomatous polyps

A

sporadic or due to genetic/acquired syndrome;

have underlying germline mutation in tumor suppressor gene/proto-oncogene

some increase risk for CA

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50
Q

how do you characterize E. coli

(what are specifics about each strain)

A

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

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51
Q

what are characteristics of Enterobius vermicularis (pinworm)

A

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

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52
Q

what is clinical presentation of crohns

A

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!)

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53
Q

what is the clinical presentation of Shigella

A

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
Q

what is the clinical presentation of UC

A

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
Q

what is the epidemiology of salmonella

A

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
Q

what is the most freq cause of intestinal obstruction world wide?

what are the associated characteristics & complications

A

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
Q

What is the MCC of acute gasteroenteritis requiring medical attn

what are its characterisitics

A

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
Q

Salmonella

geography

transmision

epidemiology

GI site

reservoir

symptoms

complications

A

worldwide

meat, poultry, eggs, milk

children, older adults (peak summer/fall)

colon & SI

poultry, farm animals, reptiels

watery/bloody diarrhea

sepsis, abscess

59
Q

What does UC look like grossly

A

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
Q

what is infectious enterocolitis

A

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
Q

what is the fxn of STK11 gene

A

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
Q

What are characteristics of hyperplastic polyps

A

L colon, single/multiple

60-70s- bc decreased epithelial cell turnover & delayed shedding of surface epithelial cells –> goblet cells & absorptive cells pile up

63
Q

what are the classic clinical presentations of a pt w/ ischemic bowel dz

A

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
Q

where are polyps most commonly located

what are possible characterisitics

A

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
Q

What are characteristics of Entamoeba histolytica

*know!!*

A

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
Q

what are causes of vascular lesions of the SI/LI

A

ischemic bowel dz

angiodysplasia

67
Q

What is the presentation of intussusception

A

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
Q

How does erythema nodosum present

A

type of skin inflam

located in part of the fatty layers of skin

reddish, painful, tender lumps/nodule

*front of legs, below knees*

69
Q

what is the outcome of acute compromise in ischemic bowel dz

A

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
Q

What are characterisitics of rotovirus

A

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
Q

what are diagnostic tests used for GI complaint

A

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
Q

what are types of polyps

A

hyperplastic

inflam

hamartomatous

adenoma

73
Q

What is Abetalipoproteinemia

A

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
Q

What is the presentation of angiodysplasia

A

= 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
Q

what are the extra-intestinal manifestations of IBD

A

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
Q

What are characteristics of internal cestodes

A

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
Q

What is FAP

A

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
Q

what is the relation of iron and Yersinia

A

iron enhances virulence –> stimulates systemic dissemination (occur w/ multiple transfusion)

==> greater risk for sepsis/death

non-heme related - chronic form of anemia/hemochromatosis

79
Q

what is ischemic bowel dz

A

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
Q

What is the morphology of colon CA

A

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
Q

Yersinia

geography

transmision

epidemiology

GI site

reservoir

symptoms

complications

A

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
Q

what dz’s have intraluminal digestion defects

A

chronic pancreatitis

CF –> pancreatitis

primary bile acid malabs (w/ defect in transepithelial transport)

IBD (w/ defect in terminal digetion & transepithelial transport)

83
Q

what is hereditary nonpolyposis colorectal CA?

A

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
Q

what is the DDx for malabs diarrhea

A

CF

celiac

environmental enteropathy/ enteric dysfxn

autoimmune enteropathy

lactase (disaccharidase) def

abetalipoproteinemia

infectious entercolitis

85
Q

what is the immune response in intestines of healthy ind

A

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
Q

What is a volvulus

A

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
Q

label this

A
88
Q

what are the 4 types of diarrhea

A
  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
Q

How do you treat pseudomembranous colitis

A

metronidazole & vancomycin

but prevalence of ABx resistant & hypervirulent C. diff is increasing

90
Q

what is diverticular Dz

A

acquired pseudodiverticular outpouching of colonic mucosa & submucosa

rare < 40 yo; but common > 60 yo

asia & africa: R. side diverticula ; japan 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
Q

What is the etiology of acute obstruction to flow in ischemic bowel dz

A

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
Q

what is caused by a mutation of the MTP gene

A

abetalipoproteinemia

gene is required for transfer of lipids to nascent apolipoprotein B polypeptide in the endoplasmic reticulum

w/o it –> lipids accumulate intacellularly

93
Q

What are the therapeutic approaches to IBD

A

=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
Q

what are adenomatous polyps

A

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
Q

what syndromes may present with hamartomatous polps & what are extra-GI manifestations for each

A
  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
Q

what is a fxnal bowel obstruction, aka paralytic ileus

A

=temporary disturbance of peristalsis (w/o mechanical prob)

=post-op ileus = MC etiology

also caused by metabolic probs, endocrinopathies, certain drugs

97
Q

What is the etiology of chronic/hypoperfusion states in ischemic bowel dz

A

=non-obstructive

cardiac failure

shock

dehydration

drugs (vasoconstict) - cocaine

98
Q

what are histological factors of Peutz-Jeghers syndrome

A

arborizing network of CT, Sm M, lamina propria & glands lined by normal appearing intestinal epithelium

99
Q

what is the presentation of guillain-barre syndrome

A

demyelinating polyneuropathy

paresthesias in hands & feet

M weakness (start in legs and ascend)

severe resp M weakness

absent/depressed deep tendon reflexes

100
Q

What is the function of APC

A

= 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
Q

What are characterisitics of giardia lamblia

A

MC parasitic pathogen in human; spread fecally contaminated water or food

cysts resistant to chlorine

flagellate protozoan decrease 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
Q

How do you diagnose celiac dz

A

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
Q

What is celiac dz

A

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
Q

what are virulence factors due to for C. jejuni

A

motility

adherece

toxin production

invasion (dysentery)

105
Q

Differentiate gastroschisis & omphalocele

A

gastroschisis: intestines protrude thru abd wall defect; but not covered by membrane
omphalocele: abd viscera herniate into base of umbilicus; covered by membrane

106
Q

which dz’s have a defect of both terminal digestion and transepithelial transport

A

celiac dz

environmental enteropathy

autoimmune enteropathy

viral/bacteral/parasitic gasteroenteritis

107
Q

what are the earliest lesions of crohns dz

& what are other morphological features

A

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
Q

which colon CA etiologies lead to tubular, villous, typical adenoCA

A

FAP = AD

Sporadic Colon CA (70-80%) - predom L side

both = APC/WNT pathway

109
Q

What is Peutz-Jeghers syndrome

A

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
Q

Shigellosis

geography

transmision

epidemiology

GI site

reservoir

symptoms

complications

A

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
Q

what are the macroscopic differences btn crohn’s & UC

bowel region

distribution

strictures?

wall appearance

A
112
Q

what is the morphology for ischemic bowel dz

A

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
Q

what is the most important characteristic that correlates w/ malignancy in polyps

A

SIZE

114
Q

where does environmental enteric dysfxn present? ( aka environmental enteropathy, tropical enteropathy, tropical sprue)

how does it present

A

poor sanitation/hygiene

sub-saharan africa (zambia), aboriginal pop in N. australia (travel or live there)

=malabs, malnutrition & stunted growth

115
Q

What is IBD

what is the epidemiology

A

=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
Q

what are watershed zones?

A

most vulnerable for ischemic bowel dz

splenic flexure btn SMA & IMA (= marginal A)

sigmoid colon & rectum - IMA, pudendal & iliac A circulation ends

117
Q

who is at risk for salmonella infxns

A

CA

immunosuppression

EtOH

CV

sickle cell (osteomyletis)

hemolytica anemia

118
Q

what is the pathogenesis of celiac dz

A

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
Q

how is IBS defined

what pop does it present in most

A

=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
Q

E. coli

geography

transmision

epidemiology

GI site

reservoir

symptoms

complications

A
121
Q

what are characterisitcs of inflammatory polyps

A

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
Q

what are causes of GI obstruction (which are most often in the SI, bc of the narrow lumen)

A

80%:

  1. hernia = MC worldwide
  2. adhesions
  3. volvulus
  4. intussuseption

tumors, infarctions, other strictures = 10-15%

123
Q

how does dermatis herpetiformis present

A

microabscess- papillae

subepidermal blisters

granular IgA deposits

(associated w/ celiacs)

124
Q

What is the morphology of salmonella

A

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
Q

What is the morphology of pseudomembranus colitis

A

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
Q

how does celiac dz present in adults

A

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
Q

How does celiac present in children

A

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
Q

what is malabsorption

what is the MC malabs disorder

A

= 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
Q

what are microscopic differences of crohns & UC

inflam:

pseudopolyps

ulcers

lymphoid rn

fibrosis

serositis

granulomas

fistulae/sinuses

A
130
Q

what are characteristic of CF

A

= 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
Q

what are the chances of getting colorectal adenoCA in pts w/ untreated FAP

A

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
Q

what is indeterminate colitis

A

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)