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37 Cards in this Set
- Front
- Back
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Intestinal Bowel Disease (IBD)
- definition - types - which two are most common? |
= chronic uncontrolled inflammation of intestinal mucoas
Types: - Ulcerative Colitis - Crohn's Disease (2 most common) - Microscopic Colitis (lymphocytic and collagenous) |
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What is the geographic distribution of IBD?
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Northern-hemisphere and industrialized countries > Southern-hemisphere, developing countried
(but rates increasing in both) |
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What is the age of onset of IBD?
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16-35
- possible "2nd peak" in later decades |
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What is the gender distribution of IBD?
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overall equal rates between M and F
- CD slight female predominance - UC: slight male predominance |
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What is the ethnic distribution of IBD?
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- caucasians > non-caucasians
- high in ashkenazi jews!!!!! - increasing rates among african-americans, hispanics, asians |
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Pathogeneses of IBD - what GENERAL factors are involved?
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Multifactorial!
- environmental - genetics - immunologic |
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Pathogenesis of IBD - What are the environmental factors involved??
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- Hygiene Hypothesis - less sanitary, crowded living conditions are possibly PROTECTIVE
- Appendectomy - pos protective in UC, but increased risk for CD - Microbial Flora = "flare inducer" - NSAIDS - Cigarettes - protective for UC, but doubles risk for CD |
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What is the role of Appendectomy in IBD? Why?
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- possibly protective in UC
- increased risk for CD - most common place for CD is terminal ileum and R colon, and that is right where the appendix is |
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Pathogenesis of IBD - what is the role of GENETICS?
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- 75% familial concordance of IBD subtype
- higher rates in Ashkenazi Jews - susceptibility genes: NOD2/CARD 15 and IL23R |
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NOD2/CARD 15
- location? - function? - assoc with IBD? |
- chrom 16q12
- 3 major risk alleles in/near leucine-rich repeat region (LRR) - 27-39% CD patients have mutation NOD2 encodes protein = intracellular (in macrophaes, dendritic cells, intestinal epith cells) sensor for bacterial muramyl-dipeptide (MDP) ---> Bacteria interact with NOD2 --> induces inflammatory pathways, production pf cytokines, secretion of antimicrobial substances into GI lumen Paradox in ppl with IBD - possible upregulation? possible less tolerance to microflor? possible decreased T-cells? |
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IL23R
- what is? - assoc with IBD? |
= common p40 and b1 receptor
- Mult independed risk alleles increase IBD susceptobility - stimulation --> perpetuation and expansion of Th17 --> mediates intestinal inflammation - Anti p40 Abs - therapeutic in mice |
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What are the immune dysregulations that play a role in IBD?
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1. T-cell problems
- Normally, Th1, Th2, Th17 respond to bacteria and Ags that break the intestinal mucosal barrier --> cause inflamm - Then, T-reg cells downregulate the Th response when the job is done (anti-inflammatory) - IBD - either too much Th-mediated inflammation; or too little anti-inflam T-reg response 2. Defects in Innate Immunity - intestinal barrier defect - increased permeability - neutrophil/macrophage defects - e.g., NOD2 mutation - paneth cell defects - impaired defensin production - therapeutic targets impaired - e.g., EGF enemas 3. Defects in Adaptive Immunity - overprodction of cytokines after innate immune response 4. Ineffective apoptosis of activated T-cells 5. Abnormal response to normal flora v. specific pathogens |
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Due to the dysregulation of the immune system in IBD, what are 3 broad therapeutic targets?
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1. Control secretion of cytokines and other products from activated immune cells, which damage the colon (via TNF)
2. Control activation if T-cells 3. Control leukocyte trafficking to the colon (which induces cytokine response) |
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Diagnosis of IBD
- suggested by? - supported by? - confirmed by? |
- suggested by clinical presentation
- supported by endoscopy and radiographs - confirmed by history |
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UC - sx??
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Sx from colon:
- hematochezia - diarrhea - (rarely constipation) - incontinence - tenesmus - abd cramps - urgency - nocturnal awakening |
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What is hematochezia?
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Passage of bright red bloody stools
- commonly associated with lower GI bleeding |
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CD - sx?
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**variable with disease location/subtyple
Sx similar to UC but also: - ileum (RLQ pain, diarrhea, fever) - perianal (pain, drainage) - FISTULAS- entero-enteric, rectovaginal, rectovesicular - STRICTURING- emesis, obstipation |
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What is obstipation?
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Severe constipation that prevents passage of both stool and gas
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What areas of the GIT are affected by UC and CD?
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UC - involves only the colon, extends continuously from the rectum proximally (ranges from proctitis to pancolitis)
- rectosigmoid 46% - L colon 37% - pancolitis 17% ** inflammation limited to mucosa CD - may involve any part of the GIT - most commonly terminal ileum and colon; spares rectum! - "Rule of thirds" - ileum 30%, colon 30%, il&col 30%, perianal <30% ** inflammation is transmural and patchy; "skip" lesions |
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What is the hallmark hiso finding for CD?
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noncaseating granulomas
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What are serious complications of CD and UC?
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CD - strictures, fistulas, abscesses
UC - toxic megacolon, hemorrhage, perforation, (if long-standing) colon carcinoma |
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What can lead to intraabdominal abscess?
What physical exam technique can discover this? |
*Abscess = complication of CD
- Psoas Sign!!! Indiates inflamm extending to psoas muscle |
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What MUST you do on a physical exam for CD?
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Examine rectum!!!
- might see skin tags, "elephant ears," fistulas, etc |
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What should you expect the vitals to be of someone with UC or CD?
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- high HR
- low BP - fever |
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What lab results might support UC/CD dx?
- what is it important to remember about these labs?? - what else can labs be useful for? |
NOT DIAGNOSTIC!!
**Also useful for IDing associated problems, sx UC: - iron deficient anemia - low K+, albumin - high CRP, WBC, ESR +pANCA CD: - iron and/or B12 deficiency anemia - low K+, albumin - high CRP, ESR - low fat sol vits (A, D, E, K) - elevated PT +ASCA, OmpC, CBir1 |
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What are specific serology markers that can differentiate between UC and CD?
- in what pop most useful? |
- especially useful in kids!
UC: +pANCA CD: +ASCA, OmpC, CBir1 |
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What are the subtypes of CD?
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1. Inflammatory - fever, weight loss, anorexia, diarrhea (+/- blood), abd pain, arthralgias, fatigue
2. Fibrostenotic - obstruction, diarrhea (bacterial overgrowth) 3. Fistulizing - enteroenteric, entorocutaneous, rectovaginal, perianal |
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What are endoscopic features of CD?
- mild? - moderate/severe? |
mild: apthoid ulcers, edema, hyperemic spots, loss of vascular pattern
moderate/severe: "bear claw" ulcers (deep, linear, stellate, coalescing ulcers), cobblestoning |
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What are the endoscopic signs of UC?
- mild - moderate - severe - chronic |
mild: erythema, edema, blunted vascular pattern
moderate: granularity, erosions, ulcers, friability severe: ulcer coalescence, mucopurulent exudate, spont bleeding, pseudopolyps chronic: featureless --> mucosal atrophy, muscular hypertrophy, loss of haustra, shortened/narrowed colon |
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What is the best way to distinguish acute from chronic UC?
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HISTO!!
- acute: mucosal infiltrate by neutrophils, lymphocytes, plasma cells, macrophages --> cryptitis and crypt abscesses - chronic: CRYPT DISTORTION/ATROPHY, paneth cell metaplasia, lymphoid aggregation, chronic inflamm infiltrate |
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What radiographs are used for UC? CD?
- findings? |
UC:
- barium enema (granylarity, ulcers, thickened folds, etc) - CT (diffuse thickening, dilation) - MR/CT colonography CD: - small bowel series/enteroclysis (lymphoid hyperplasia, granularity, thickening, cobblestoning, ulceration, polyps, fistulae, stricture (STRING SIGN) - CT (thickeinging, fat stranding, halo sign, abscess, obstruction - CT/MR enterography - MRI (perianal/rectovaginal fistulae) |
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What are some extraintestinal manifestations of IBD?
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- Rheumatologic
--- peripheral arthropathies --- axial arthropathies (e.g., ankylosis spondylitis) --- metabolic bone disease (osteopenia, osteoporosis, ostenecrosis) - Mucocutaneous --- pyoderma gangrenosum --- erythema nodosum (red nodules due to hypersensitivity of subQ fat) --- sweet's syndrome (sudden onset of fever, tender red nodules, leukocytosis, papillary neutrophil infiltrate) --- oral lesions (MOST COMMON) --- psoriasis - Ocular --- uveitis --- scleritis - Hematologic --- iron deficiency anemia (blood loss) --- B12 deficiency anemia (ilial CD) --- hypercoagulable states - Nephrolithiasis (Ca or Uric Acid) - Hepatobiliary --- Primary Sclerosis Cholangitis --- Gallstones --- Granulomatous Hepatitis - Other --- amyloidosis --- pericarditis/myocarditis --- pulmonary sx |
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What is 1st line med tx for UC??
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5-Aminosalicylates
(not great for CD) |
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IBD and colon cancer
- increased risk? - decreased risk - surveillance? |
Increased Risk of CC with...
- duration of disease (30% at 35 years) - extent of disease - PSC - severity of inflamm - pseudopolyps - fam hx - smoking ? young age at onset ? backwash ileitis Decreased Risk: - 5-ASAs Surveillance: begin colonoscopies every 8-10 yrs after onset of IBD (more frequently if more severe) |
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What are the goals of treatment of IBD?
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1. gain remission
2. maintenance of remission |
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What is important surgery for UC/CD? What are its effects?
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Total Proctocolectomy (TPC) --> curative in UC!!
- reserved for pts with medically-refractory disease or complications/neoplasm Surgery in CD is not curative, but up to 70% patients require >/= 1 operation (most common ileocecectomy) |
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What is the monozygotic twin concordance for UC and CD?
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UC = 15-20%
CD = 20-50% |
