03-04 IBD Overview Flashcards
• Describe the major clinical and pathohysiologic features of IBD. Discuss the similarities and differences between Crohn's disease and Ulcerative colitis • Describe the clinical and pathological characteristics of microscopic and collagenous colitis • Discuss the genetic predisposition and environmental factors role in the etiology of IBD • Describe the presenting symptoms and signs of Crohn's disease and ulcerative colitis (compare and contrast). Explain how the severity and ext
<p>
OBJECTIVE: Describe the major clinical and pathophysiologic features of IBD.</p>
<ul>
<li>
Discuss the similarities and differences between Crohn's disease and Ulcerative Colitis.</li>
</ul>
<p>
<u>Ulcerative Colitis</u></p>
<ul>
<li>
Diffuse mucosal inflammation</li>
<li>
<strong>only colonic</strong> involvement</li>
<li>
Starts in rectum</li>
<li>
Continuous proximal extension (No skip lesions)</li>
<li>
Surgery curative (w/ colectomy)</li>
</ul>
<p>
<u>Crohn's Disease</u></p>
<ul>
<li>
<strong>Transmural</strong> inflammation</li>
<li>
May involve <strong>any part of GI tract</strong></li>
<li>
Complications: strictures, fistulas, abscesses</li>
<li>
Perianal disease</li>
</ul>
<p>
Normal Histo of Small Bowel vs. Colon</p>
<p>
What do you see here?</p>
<ul>
<li>
Dx?</li>
</ul>
<p>
intense, diffuse inflam infiltrate; complete ulceration of the surface epithelium; and widespread distortion and destruction of colonic glands (crypts not lined up like little test tubes like they should be)</p>
<ul>
<li>
Many of the crypt lumens—esp. one in middle of pic—are filled with inflammatory cells and necrotic debris (crypt abscesses and cryptitis), which are a prominent (though not a specific feature of ulcerative colitis)</li>
<li>
Note that even when the inflammation is severe, it typically r<u>emains limited to the mucosa</u>. In fact, the base of the crypts fall abnormally short of the muscularis mucosae and the intervening space is filled with chronic inflammatory cells</li>
<li>
Dx =active ulcerative colitis</li>
</ul>
<p>
Epidemiology of IBD</p>
<ul>
<li>
Geography</li>
<li>
Time of Onset</li>
</ul>
<div>
Geographic Distribution</div>
<ul>
<li>
Occurs worldwide</li>
<li>
Higher rates in "Westernized" countries</li>
<li>
North-South: more pole-ward countries (north in our hemisphere) </li>
</ul>
<p>
Time of onset</p>
<ul>
<li>
Can be any age</li>
<li>
But peak is 15-30 y/o</li>
</ul>
<p>
There are three proposed overlapping categories of IBD-causing factors: genetics, environmental triggers, luminal stimuli</p>
<p>
1st Cause: Genetics</p>
<p>
Genetics</p>
<ul>
<li>
Inhereitance seen in both U.C. and Crohn's</li>
<li>
but Crohn's has much stronger genetic presentation
<ul>
<li>
> 70 Crohn's-related loci isolated thus far</li>
<li>
(50% of monozygotic twins both affected vs. 8% in U.C.)</li>
</ul>
</li>
</ul>
<p>2nd Cause: IBD Environmental Triggers</p>
<p>Environemental Triggers</p>
<ul>
<li>Smoking
<ul>
<li>Smoking is <strong>protective in U.C.</strong>
<ul>
<li>Quitting smoking may actually cause first presentation or a flare!</li>
</ul>
</li>
<li>Smoking is very <strong>exacerbating in Crohn's</strong></li>
</ul>
</li>
<li>Appendectomy Prior to Onset
<ul>
<li>Decreases risk in UC but no Crohn's</li>
</ul>
</li>
<li>Hygiene Hypothesis
<ul>
<li>Evidence in Crohn's but not UC</li>
</ul>
</li>
<li>Altering Gut Flora</li>
<li>
<ul>
<li>Abx</li>
<li>Diet</li>
</ul>
</li>
<li>Altering barrier functions
<ul>
<li>Acute infx</li>
<li>NSAIDs</li>
<li>Smoking</li>
<li>Stress</li>
</ul>
</li>
</ul>
<p>
2rd Cause: Diseases that may trigger IBD (environmental)</p>
<p>
<strong>Disease Triggers</strong></p>
<ul>
<li>
Measles
<ul>
<li>
Measles epidemics had higher rates of Crohn’s</li>
<li>
—Live measles vaccine has RR = 3!</li>
</ul>
</li>
<li>
Mycobacterium paratuberculosis
<ul>
<li>
May cause Crohn's b/c causes Yo-naise (sp?) dz in cows</li>
<li>
Transmitted by milk (even pasteurized milk)</li>
<li>
No definitive data to show good outcomes w/ treating Crohn's dz w/ course of anti-TB abx</li>
</ul>
</li>
<li>
Normal Flora
<ul>
<li>
Byproducts of normal flora (e.g. proteoglycans from gut bacteria) may be pathogenic in susceptible individuals</li>
</ul>
</li>
</ul>
<p>
3rd Cause: Luminal Stimulus</p>
<p>
Data suggest that the microbiome of the gut plays a significant role in the pathogenesis of IBD</p>
<ul>
<li>
Mouse study
<ul>
<li>
Injecting mouse guts w/ different mix of bacteria caused either horrible colitis (cecal bacteria) or protection (cecal bacteria + Lactobact)</li>
</ul>
</li>
<li>
Surgery study:
<ul>
<li>
if you connect people's colons directly to ostomy bag, they don't recur</li>
<li>
If you re-anastomose their small bowel to their colon, they have a recurrence</li>
</ul>
</li>
</ul>
<p>
**bacteria near ileo-cecal junction seem to be culprits</p>
<p>
Pathogenesis models</p>
<ol>
<li>
Dysregulated immune response (current favorite hypothesis)
<ul>
<li>
abnormal response to normal gut flora/contents</li>
</ul>
</li>
<li>
Dysbiosis
<ul>
<li>
altered balance of flora</li>
</ul>
</li>
<li>
Defective mucosal integrity
<ul>
<li>
could lead to bacteria getting through normal defenses</li>
</ul>
</li>
</ol>
<p>
We all have insults that cause acute inflammation</p>
<ul>
<li>
Normal pts get over it even in the presence of all that bacteria</li>
<li>
IBD pts develop chronic dz</li>
</ul>
<p>
U.C.</p>
<ul>
<li>
Presentating S/Sx</li>
<li>
Severity</li>
<li>
Extent of the colon affected?</li>
<li>
How to dx?</li>
<li>
<strong>DDx?</strong></li>
<li>
Natural hx of U.C.</li>
<li>
Complications</li>
</ul>
<ul>
<li>
Presentation
<ul>
<li>
common presenting sx: rectal bleeding, diarrhea, passing mucopus, abd pain and tenesmus.</li>
<li>
may present w/ sudden onset (like infectious colitis) but usu slow onset:
<ul>
<li>
stools gradually looser, mixing w/ blood and increasing frequency over weeks </li>
</ul>
</li>
<li>
Diarrhea present 80% of the time ~always w/ blood (hematochezia)
<ul>
<li>
small volume and high frequency.</li>
<li>
Large volume watery diarrhea w/o bleeding should call the diagnosis of ulcerative colitis into question.</li>
</ul>
</li>
<li>
Urgency and tenesmus (rectal dry heaves) common</li>
<li>
Abd pain may not be dominant sx
<ul>
<li>
when present usu in LQs.</li>
<li>
severe dz presents w/ significant abd pain and signs of toxicity and even megacolon.</li>
</ul>
</li>
<li>
<u>continuous</u> (vs skipping in Crohn's) symmetrical distribution from rectum (almost always rectal involvement) to all or part of colon</li>
<li>
Systemic symptoms (low grade fever and night sweats)</li>
<li>
Extraintestinal manifestations</li>
</ul>
</li>
<li>
Severity—Truelove and Witts Classification
<ul>
<li>
Mild Disease
<ul>
<li>
< 4 stools per day</li>
<li>
No fever, tachycardia or anemia. Nl ESR</li>
</ul>
</li>
<li>
Moderate Disease
<ul>
<li>
> 4 stools per day, min systm disturbance</li>
</ul>
</li>
<li>
Severe Disease
<ul>
<li>
>6 stools per day, with blood</li>
<li>
Systemic disturbance: fever, HR . 90, anemia</li>
</ul>
</li>
<li>
<em>Can also grade severity based on colonoscopy findings</em></li>
</ul>
</li>
<li>
Extent of colon affected?
<ul>
<li>
Proctitis ~50% of cases</li>
<li>
Proctosigmoiditis</li>
<li>
Left-sided</li>
<li>
Extensive (mid transverse)</li>
<li>
Pancolitis</li>
</ul>
</li>
<li>
How to dx?
<ul>
<li>
Clinical story</li>
<li>
Colonoscopy + biopsy</li>
<li>
Exclude others (infx, Crohn's)</li>
<li>
Remains chronic</li>
</ul>
</li>
<li>
DDx
<ul>
<li>
a. Crohn's</li>
<li>
b. Infectious colitis</li>
<li>
c. Ischemic colitis</li>
<li>
d. Collagenous colitis</li>
<li>
e. Microscopic colitis</li>
<li>
f. Sexually transmitted diseases
<ul>
<li>
GC, Syphilis, Herpes Simplex, Cytomegalovirus</li>
</ul>
</li>
<li>
g. Radiation colitis/proctitis</li>
<li>
h. Solitary Rectal Ulcer Syndrome</li>
<li>
i. Vasculitis
<ul>
<li>
SLE, Polyarteritis nodosa</li>
</ul>
</li>
<li>
j. Diverticulitis</li>
<li>
k. Eosinophilic gastroenteritis</li>
</ul>
</li>
<li>
Natural Hx
<ul>
<li>
Recurring episodes of mild-to-mod severity (majority cases)</li>
<li>
Fulminating (severest)
<ul>
<li>
at risk for perforation</li>
<li>
often need surgery</li>
</ul>
</li>
<li>
Chronic active (disease smoulders along w/o remission)
<ul>
<li>
often need surgery</li>
</ul>
</li>
<li>
Proctitis (remains localized and may be difficult to treat)</li>
</ul>
</li>
<li>
Complications
<ul>
<li>
Massive hemorrhage
<ul>
<li>
May need transfusion, surg</li>
</ul>
</li>
<li>
Toxic megacolon
<ul>
<li>
Thumb-printing</li>
</ul>
</li>
<li>
Perf (15-20% mortality once perf'd)</li>
<li>
Colon ca
<ul>
<li>
Have incr risk of colon ca after 8-10 yrs</li>
<li>
increased risk w/:
<ul>
<li>
extent of dz</li>
<li>
severity of dz</li>
<li>
duration of dz</li>
<li>
sclerosing cholangitis (highest risk of cancer)</li>
</ul>
</li>
</ul>
</li>
</ul>
</li>
</ul>
<p>
Cancer in IBD vs/ control pts</p>
<p>
Control pts:</p>
<ul>
<li>
normal → adenomatous polyp → cancer</li>
</ul>
<p>
U.C. Patients:</p>
<ul>
<li>
colitis → dysplasia → cancer</li>
<li>
do colos w/ bx q few years</li>
<li>
if dysplasia found, refer for colectomy</li>
</ul>
<p>OBECTIVE: Describe the clinical and pathological characteristics of microscopic colitis (a.k.a. Lymphocytic Colitis)</p>
<p><u><strong>Microscopic Colitis</strong></u> (a.k.a. Lymphocytic Colitis)</p>
<ul>
<li>watery, non-bloody diarrhea w/ microscopic inflammation</li>
<li>but <strong>colonic mucosa usually appears normal on endoscopy</strong></li>
<li>two subtypes
<ul>
<li>collagenous colitis</li>
<li>lymphocytic colitis</li>
</ul>
</li>
</ul>
<p>
Collagenous Colitis</p>
<ul>
<li>
Clinical Presentation</li>
<li>
Biopsy findings</li>
</ul>
<p>
Clincal Presentation</p>
<ul>
<li>
sudden profuse, chronic, watery diarrhea</li>
<li>
predominantly: women > 50</li>
<li>
diarrhea is not bloody and the endoscopic appearance is usually normal</li>
</ul>
<p>
Biopsy</p>
<ul>
<li>
but colonoscopic biopsies will reveal an infiltration of lymphocytes and plasma cells in the lamina propria as well as a marked excess of intraepithelial lymphocytes.</li>
<li>
thickened subepithelial layer of collagen</li>
</ul>
<p>
Crohn's</p>
<ul>
<li>
Clinical Presentation</li>
<li>
Biopsy</li>
<li>
Severity</li>
<li>
Extent of the colon affected?</li>
<li>
<strong>How to dx?</strong></li>
<li>
<strong>DDx</strong></li>
<li>
<strong>Natural hx of U.C.</strong></li>
<li>
Complications</li>
</ul>
<ul>
<li>
Clinical Presentation
<ul>
<li>
transmural inflamm all throughout GIT (not just colon as w/ UC)</li>
<li>
ileocecal region is the most common, involved in at least 2/3 of patients.
<ul>
<li>
resection of terminal ileum → malabs of bile salts → bile salt diarrhea and steatorrhea + B12 malabs = megaloblastic anemia</li>
</ul>
</li>
<li>
pain, tenderness, low-grade fever, anorexia</li>
<li>
diarrhea often presents w/ out bleeding</li>
<li>
rectum usu. spared (vs. almost always affected in UC)</li>
<li>
peri-anal fistulas/abcesses</li>
</ul>
</li>
<li>
Biopsy
<ul>
<li>
Transmural</li>
<li>
<strong>cobblestoning</strong> of mucosa</li>
<li>
non-caseating granulomas
<ul>
<li>
nail the dx for you</li>
</ul>
</li>
</ul>
</li>
<li>
Severity
<ul>
<li>
?</li>
</ul>
</li>
<li>
Extent of GIT affected?
<ul>
<li>
often affects small bowel</li>
<li>
can just be colon alone (difficult to ddx vs. U.C.)</li>
<li>
can go all the way to the upper GI tract rarely</li>
</ul>
</li>
<li>
How to dx?
<ul>
<li>
clinical picture/course</li>
<li>
endoscopy/colo/capsul</li>
<li>
radiographic (CT)</li>
<li>
path findings.</li>
</ul>
</li>
<li>
Natural Hx?
<ul>
<li>
?</li>
</ul>
</li>
<li>
DDx?
<ul>
<li>
a. Acute appendicitis or appendiceal abscess</li>
<li>
b. R-sided diverticulitis</li>
<li>
c. Ileocecal TB</li>
<li>
d. Intestinal infections such as Yersinia enterocolitica</li>
<li>
e. Small bowel lymphoma</li>
<li>
f. Amebiasis</li>
<li>
g. Cecal carcinoma</li>
<li>
h. Lymphosarcoma</li>
<li>
i. Vasculitis</li>
<li>
j. NSAID-induced ulceration</li>
<li>
k. Ischemia</li>
</ul>
</li>
<li>
Complications
<ul>
<li>
Strictures/scarring down → Chronic obstruction
<ul>
<li>
looks like chain of sausages</li>
<li>
post-prandial cramps (60 mins s/p food)</li>
<li>
borborygmi</li>
<li>
vomiting</li>
<li>
distention</li>
</ul>
</li>
<li>
fistulization: connection of ileum to sigmoid colon, e.g.
<ul>
<li>
enteroenteric</li>
<li>
eneterovesical</li>
<li>
retroperitoneal</li>
<li>
eneterocutaneous</li>
<li>
perianal</li>
<li>
rectovaginal</li>
</ul>
</li>
<li>
confined perforation often in RLQ causing abscess mimicking appendicitis</li>
<li>
perirectal disease
<ul>
<li>
Just awful</li>
<li>
crypts of Morgagni fistulize</li>
<li>
entero-cutaneous fistulas much more common than in U.C.</li>
</ul>
</li>
<li>
Malignancy</li>
<li>
Malabsorption: Interrupted entero-hepatic circulation of bile salts.
<ul>
<li>
B12: loss of terminal ileum.</li>
<li>
Kidney stones: oxalate hyperabsorption and dehydration.</li>
</ul>
</li>
<li>
Protein-losing enteropathy</li>
<li>
Systemic complications: see ulcerative colitis (much the same).</li>
<li>
Growth retardation: in children</li>
<li>
Bone loss and osteoporosis are common in patient with Crohn’s disease. Exacerbated by long term corticosteroid usage but can occur independent of steroid use.</li>
</ul>
</li>
</ul>
<p>
Childhood Crohn's Presentation</p>
<p>
Systematic sx often predominate</p>
<ul>
<li>
Fever, anemia, and arthritis are three of the most common non-GI sx</li>
<li>
Retardation of growth and development, including sexual maturatlon (35% of IBD kids)
<ul>
<li>
This complication may precede any other s/sx by months or even years; it is appreciated only over long-term observation, and it carries a high risk of becoming irreversible if not detected and treated promptly. </li>
</ul>
</li>
</ul>
