Diseases of Lower GI (SI/colon) Flashcards
Celiac disease aka…
Gluten-Sensitive enteropathy
Celiac disease pathogenesis
gluten digested by luminal/brush border enzymes – exposure to alpha-gliaden peptide leads to autoAb formation –> inflammation(increased T lymphs) –> villous atrophy –> tissue damage –> loss of mucosal/brush border surface area –> malabsorption, diarrhea
Clinical features of celiac dz
- Classical: bulky fat diarrhea, flatulence, weight loss, anemia, nutritional deficiencies, growth failure in kids
- atypical: minor GI complaints, anemia, dental enamel defects, infertility, arthritis
Host factors for celiac dz
Class II HLA-DQ2 or HLA-DQ8 allele; northern european
- association w/other autoimmune dz: type I DM, thyroiditis, Sjogren syndrome
Celiac dz diagnosis
- probs serology first
- Endoscopy–loss of surface villi
- Serology: IgA Ab to tissue transglutaminase; auto-endomysial Ab
**may have false negative if IgA deficiency
Celiac dz biopsy findings
- *3 characteristic findings
- villous blunting
- increased intraepithelial lymphocytes – percolating in epithelium
- lymphoplasmacytosis of lamina propria (lamina propria expanded)
Does histologic severity correlate with symptoms?
not always
Endoscopy buzz word for celiac disease
“scalloped”, cracked mud appearance
Pathogenesis of Whipple dz
caused by gram + intracellular bacilli (Tryopheryma whippelii) taken up by macrophages in lamina propria that then obstruct lymphatics –> malabsorptive diarrhea
Triad of Whipple dz
diarrhea, weight loss, malabsorption
Typical presentation of whipple dz
middle-aged or elderly white male
Diagnosis of Whipple dz
tissue biopsy shows organisms (see swollen macrophages)
Infectious enterocoliitis Giardiasis cause
protozoan parasite Giardia
- causes sporadic/epidemic diarrhea
- waterborne (especially in US)/foodborne
incubation pd for giardia
7-14 days
symptoms of Giardiasis
chronic watery diarrhea, malabsorption, flatulence, weight loss, may cause intermittent symptoms
can chlorine kill giardia
cysts resistant – need filter
Pseudomembranous colitis cause
most often from C difficile after antibiotics (third gen cephalosporins)
cause of most self-limited food borne/waterborne illness
viral
Important Extraintestinal manifestation in ulcerative colitis
Primary sclerosing manifestations
Celiac extra-intestinal complaints
- fatigue, Fe deficiency anemia, short stature, pubertal delay, aphthous stomatitis
- dermatitis herpetiformis (blistering skin dz)
- lymphocytic gastritis/colitis
celiac-associated malignancies
- enteropathy associated T-cell lymphoma (EAT lymphoma)
- small intestinal adenocarcinoma
other common sxs in Whipple dz
arthritis, lymphadenopathy, neurologic disease
teardrop shaped organism with sucker
Giardia
“schools of fish”
Giardia
where in GI is Giardia most often found
duodenum
2 main classes of colitis
infectious causes, noninfectious
Infectious causes of colitis
bacterial enterocolitis, pseudomembranous colitis, viral gastroenteritis, parasitic enterocolitis
causes of noninfectious colitis
microscopic colitis, ischemic colitis
Bacterial infectious enterocolitis
mostly related to contaminated water/food, foreign travel
- typically acute, self-limited colitis
- typically present several weeks after sxs onset
types of infectious bacterial enterocolitis
Cholera, campylobecter jejuni, shigellosis, salmonellosis, Enteric (typhoid) fever, Yersinia spp., E coli, mycobacterial infection
Campylobacter spp
- major cause of worldwide diarrhea
- gram (-)
- leading cause of foodborne illness in US
campylobacter species commonly associated with food-borne bastroenteritis
C. jejuni
infection more often seen in immunosuppressed pts
Campylobacter fetus
sxs of Campylobacter infection
watery diarrhea +/- blood
source of Campylobacter spp
contaminated meat (poultry), water, unpasteurized dairy
Infectious Salmonella enterocolitis
Gram (-) bacillus, important cause of food poisoning/traveler’s diarrhea
Salmonella transmission
food water
Sxs of non-typhoid salmonella species
mild, self-limiting gastroenteritis
- endoscopy: mucosal redness, ulceration, exudates
E coli Enterocolitis species
Enterotoxigenic Enteropathic Enteroinvasive Enterohemorrhagic (0157H7) Enteroadherent
Enterohemorrhagic E coli
(O157H7)=most common strain
- non-invasive, toxin-producing, contaminated hamburgers
- deadly outbreaks
E coli O157H7 sxs
- according to infectious diarrhea lecture, it can be variable from asymptomatic to extreme
- this lecture: bloody diarrhea, severe cramps, mild or no fever, sometimes renal failure (HUS)
E coli O157H7 on endoscopy
edema, erosions, ulcers, hemorrhage (right colon mostly)
E coli with nonbloody diarrhea
- Enterotoxigenic, enteropathic, enteroinvasive, enteroadherent
Major cause of traveler’s diarrhea
Enterotoxigenic E coli
infection in infants/neonates
Enteropathogenic E coli
Invasive e coli similar to shigella
Enteroinvasive
- non-bloody diarrhea, dysentery-like illness, bacteremia
- cause of traveler’s diarrhea
Transmitted via contaminated cheese, water, person-person contact
Enteroinvasive e coli
Non-invasive, nonbloody diarrhea
enteroadherent e coli
forms coating of adherent bacteria on surface epithelium of enterocytes
Enteroadherent e coli
chronic diarrhea and wasting in AIDS
enteroadherent e coli
similar to enteropathogenic e coli
enteroadherent e coli
antibiotic-associated colitis
pseudomembranous colitis; often after antibiotic therapy
most common cause of pseudomembranous colitis
C. difficile
antibiotics most commonly causing pseudomembranous colitis
third generation cephalosporins (clindamycin)
Pseudomembranous colitis commonly found where
in hospitalized pts (up to 30%)
sxs of pseudomembranous colitis
fever, leukocytosis, abdominal pain, cramps, watery diarrhea (can have bloody)
pathogenesis of pseudomembranous colitis
disrupted bacterial microbiota in intestine by antibiotics allows C diff overgrowth –> toxin release disrupts epithelium cytoskeleton, Tight junction barrier loss, cytokine release, and apoptosis
Pseudomembranous colitis histology
pseudomembranes (adherent layer of inflammatory cells and mucinous debris at sites of colonic mucosal injury)
- surface epithelium denuded, mucopurulent exudates
What is pseudomembrane
“volcano-like” eruption of neutrophils/mucinous debris attached to surface epithelium
Infectious enterocolitis - viral causes
Cytomegalovirus, Herpes, Enteric Viruses (Rotavirus)
most common cause of severe diarrhea as child/diarrheal mortality worldwide
rotavirus
population most vulnerable to rotvirus
children 6-24 months
location of CMV enterocolitis
mouth - anus
location of herpesvirus enterocolitis
esophagus, anorectum
pathogenesis of rotavirus
infects/destroysmature enterocytes –> villus surface repopulated by immature secretory cells –> lose absorptive function –> net secreiton of water/electrolytes –> osmotic diarrhea –>DEHYDRATION
how to avoid rotavirus infection
VACCINATE
Parasitic causes of infectious Enterocolitis
protozoa, esp Entamoeba histolyktica
diagnosis of protozoal infections
examine stool
prevalent pathogens in tropic/subtropic areas
protozoa
how common is E. histolytica
10% of world’s population infected
sxs of E. histolytica
severe dysentery-like fulminant colitis; can disseminate to other sites (liver)
If you have E. histolytica infection, where else an it disseminate beyond GI
Liver
Area most commonly affected by E. histolytica
cecum
what might you see on mucosa of E histolytica infections
“flask-shaped” ulcers in mucosa (thicker bottom part with thinner “neck” )
Other parasite causing enterocolitis besides E. histolytica
Helminth infections
diagnose helminth infection
examine stool for ova/parasites
what types of places have prevalent heliminth infections
places with deficient sanitation, poor SEC and hot, humid climate
side effect of helminth infection
nutritional problems can be severe or life-threatening, esp in children
common helminth
Ascaris lumbricoides (roundworm)–
where are Ascaris most commony ound
tropics
one of most common parasites in humans
Ascaris lumbricoides (roundworm)
transmission of Ascaris
ingested from soil contaminated with feces
complications of ascaris infection
obstruction, perforation, growth retardation
Ischemic colitis
lack of blood flow due to low cardiac output or occlusive disease of vascular supply to bowel
Who are more likely to have ischemic colitis
older individuals with co-existing cardiac or vascular disease(however I think most don’t have preexisting issue?)
- Young patients: long distance runners, women on oral contraceptives
- Mechanical obstruction: hernia, volvulus
Clinical presentation of ischemic colitis
- acute transmural infarction: severe abdominal pain, tenderness, N/V, bloody diarrhea, blood instool
- Peristaltic sounds disappear, rigid abdomen shock, sepsis
histology of ischemic colitis
varies from focal acute mucosal necrosis to full thickness necrosis
watershed areas
splenic flexure and sigmoid colon
what might early ischemic colitis look grossly
small red dots scattered on surface
what does regeneration in ischemic colitis look like
Yes; fibrosis, withered, atrohpic crypts
microscopic colitis
chronic, nonbloody watery diarrhea without weight loss
biopsy appearance of microscopic colitis
mucosal inflammation
2 types of microscopic colitis
collagenous colitis, lymphocytic colitis
microscopic colitis presents mostly in what population
middle aged and older women; NSAID implicated
Diagnosis of microscopic colitis
endoscopy will appear normal so have to do biopsy
- biopsy shows lymphocytic inflammation (intraepithelial lymphocytes) +/- thickened subepithelial collagen layer
lymphocytic colitis shows strong association with what disease
celiac disease, lymphocytic gastritis, and other autoimmune diseases
IBD
chronic condition from inappropriate mucosal immune activation
2 disorders of IBD
Crohn’s and Ulccerative colitis
Cause of colitis
- host interactions with intestinal microbiota
- intestinal epithelial dysfunciton
- aberrant mucosal immune responses
Mucosal immune response in IBD
T-cell mediated
- Crohns = TH1 type
- UC = TH2 type
- have dysregulation of immunoregulation: pro and anti-inflammatory cytokines
Epithelial defects in IBD
defects in of tight junction barrier function,
- Crohns: NOD2 polymorphisms
- UC: ECM2 polymorphisms
Crohn’s Genetics
NOD2 (chr 16), IBD5 (chr 5), IL23R (chr 1)
Genetics of UC
HLA-A11, HLA-A7,
- HLA-DR2 (Japanese), DRB103, DRB12 (Western)
Bacteria in IBD?
recent studies indicate antibiotics reduce severity of disease, although specific org not identified
Characteristics of Crohn’s
Skip lesions, Ileal involvement, transmural chronic inflammation, inflammatory strictures, fissuring ulcers, sinus tracts, fistulae
Clinical features in Crohn’s
intermittent attacks of relatively mild diarrhea, fever, abdominal pain
- diarrhea tends to be non-bloody
- relapsing/remitting disease
Extraintestinal Crohn’s features
Uveitis, migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythemia nodosum
Crohn’s gives increased risk of what
colonic adenocarcinoma
Ulcerative Colitis sxs
Bloody diarrhea or loose stools with lower abdominal pain, cramps
- sxs relieved by defecation
Ulcerative colitis extraintestinal manifestations
Primary sclerosing cholangitis
UC has increased risk of
colonic adenocarcinoma
Characteristics of UC
rectal involvement with retrograde continuous diffuse disease, no ileal involvement (except with “backwash ileitis”), disease worse distally, Mucosal inflammation not transmural, no fissures, sinuses, fistula tracts
Cancer risk in IBD
adenocarcinoma risk similar in UC/Crohn’s
cancer risk in IBD related to
duration of dz, extent of disease (pancolitis vs localized), fam hx, extra-intestinal manifestations (i.e. pSC)
Endoscopic surveillance for IBD
assess disease activity and dysplasia, that can become adenocarcinoma
Wall appearance in Crohn’s vs UC
Crohn's = thickened UC= thinned
Ulcers in Crohn’s vs UC
Crohn's = deep, knife-like UC = superficial, broad based
pseudopolyps in CD vs UC
CD: moderate
UC: marked
Granulomas in IBD
Crohn’s - 35%
UC - no
fibrosis in UC vs CD
CD: marked
UC: mild to none
serositis in CD vs UC
CD: marked
UC: mild to none
Diverticulum
outpouching/herniation of mucosa and submucosa
pathogenesis of diverticulum
decreased dietary fiber –> decreased stool bulk –> elevated intraluminal pressure –> mucosal herniation through focal defects in the bowel wall
most common place fo diverticula
sigmoid colon
prevalence of diverticula
approaches 60% in adult populations over 60
sxs of diverticula
asymptomatic or intermittent cramping, lower abdominal discomfort
diverticulosis
presence of diverticula
diverticulitis
inflammation of diverticula, usually secondary to obstruction
diverticulosis microscopic findings
diverticular oupouching lined by mucosa, submucosa, and variable amounts of muscularis propria
- compressed/flattened mucosa
diverticulitis microscopic findings
diverticulum becomes infiltrated with acute, then chronic inflammatory cells
- as inflammation extends, mucosa ulferates and pericolonic abscesses or sometimes fistula form
diverticula complicaitons
obstruction, perforation, abscess, bleeding
appendix
small outpouching at end of ileium
- “true diverticulum of colon”
Appendicitis pathogenesis
luminal obstruction by stone-like mass of stool “fecalith” –> ischemic injury and stasis of luminal contents –> inflammatory response
Microscopic findings of appendicitis
mucosal ulceration, transmural acute and chronic inflammation, extension of inflammation into mesoappendix (mesentery connecting ileum to appendix)
lifetime risk of appendicitis
7%
Appendicitis more common in males or females
M>F
Population most commonly affected by appendicitis
adolescents nad young adults
classic appendicitis findings
McBurney’s sign (tenderness 2/3 of distance from umbilicus to right anterior superior iliac spine)
appendicitis treatment
appendectomy; often laparoscopic
how does appendicitis often present
acute abdomen (distended)
acute abdomen
sudden onset of severe abdominal pain – etiology unknown
