Path GI II Sml & Lrg Intestine (18)

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  1. Ischemic Bowel Disease
    • can be caused by anything that ↓ intestinal blood flow
    • an infarcted bowel is edematous & diffusely purple
    • extensive hemorrhage is seen in the mucosa & submucosa; is especially prominent in VENOUS occlusions
    • ischemic injury usually begins in the mucosa & spreads outward
    • within 18 to 24 hours there's a thin, fibrinous exudate over the serosa (most outer layer)
    • mucosal surface (most inner layer) shows irregular white sloughs, the wall becomes thin & distended, & bubbles of GAS may be present in the bowel wall & mesenteric veins
  2. After 24 hours of decreased blood flow to the bowl, what is taking place?
    • intestinal bacteria produce outright gangrene & sometimes perforation of the bowel
    • the serosal surface is cloudy & COVERED by inflammatory cells
  3. Adynamic Ileus
    • term for when the bowel proximal to the lesion is dilated & filled w/ fluid
    • it's smooth muscle cell function is compromised & therefore peristalsis is unable to occur
  4. Are the boundaries between infarcted & normal tissue more distinct when caused by arterial or venous occlusions?
    • boundaries are MORE distinct w/ arterial occlusion
    • it's more difficult to differentiate between the 2 tissue types when the ischemia is caused by a venous occlusion
  5. What is the most common cause/type of Ischemic Bowel Disease?
    • acute intestinal ischemia
    • occlusion of the Superior Mesenteric artery is the MOST common cause of acute intestinal ischemia
    • this is associated w/ injury ranging from mucosal necrosis to transmural bowel infarction
  6. Why might gradual or unnoticed loss of 1 of the 3 major vessels of the intestine not cause an effect (i.e. Ischemic Bowel Disease)?
    because rich anastomoses exist between the Celiac artery, Superior Mesenteric artery, or Inferior Mesenteric artery (the 3 vessels)
  7. What are the severity 3 levels of Ischemic Bowel Disease?
    • 1. mucosal infarction
    • 2. mural infarct
    • 3. transmural infarction
    • mucosal & mural infarcts are secondary to acute or chronic hypoperfusion
    • damage to the mucosa & submucosa are less severe in mural & mucosal infarctions
    • transmural infarction is generally caused by acute occlusion of a major mesenteric artery
  8. What are some conditions that can predispose acute arterial obstructions?
    • Atherosclerosis
    • Aortic aneurysms
    • hypercoagulable states
    • Oral contraceptive use
    • Embolization of cardiac vegetations
    • Aortic atheroma (plaques)
    • other conditions associated w/ hypoperfusion & bowel ischemia: cardiac failure, shock, dehydration, vasoconstrictive drugs, systemic vasculitides, portal hypertension, compression by masses such as tumors, etc.
  9. Possible Outcomes of Ischemic Bowel Disease
    • recovers w/ complete repair of the lesions OR granulation tissue & fibrosis
    • this second way eventually leads to stricture formation
  10. Celiac Disease (Celiac Sprue, Gluten-sensitive Enteropathy)
    • an immune response to gluten in cereals characterized by:
    • 1. Generalized malabsorption
    • 2. Small intestine mucosal lesions
    • 3. Prompt clinical & histopathologic response to the withdrawal of gluten-containing foods from the diet
    • found in 0.5–1% of Caucasians w/ European ancestry
  11. Cells of Celiac's
    • dense plasma cell infiltrates in the lamina propria
    • T lymphocyte infiltration of the surface epithelium
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  12. General Celiac Characteristics
    • blunting or total disappearance of villi
    • crypt hyperplasia
    • villous atrophy
    • leaky epithelium
    • ↑ in intraepithelial CD8+ T cells (lymphocytosis)
    • ↑ plasma cells, mast cells, & eosinophils in the lamina propria but NOT in deeper layers
    • full blown celiac's is characterized by malabsorption
  13. Major Histocompatibility Complex (MHC)
    • cell surface molecules that mediate interactions between T cells & antigens
    • also called human leukocyte antigens (HLA) & determine whether a donated organ is compatible for transplant
    • genes for the molecule found on the short arm of chromosome 6, Class II (DP, DQ, DR) & Class I (B, C, A)
  14. What HLA/MHC genes are found in 90% of patients with Celiac Disease?
    • HLA-B8
    • HLA-DR8
    • HLA-DQ2
    • these HLA molecules display gluten fragments (gliadin) to immune cells which then direct an attack on the intestinal lining where many of them are lodged
    • concordance (the presence of the same trait) in 1st-degree relatives ranges from 8–18%
  15. What contains most of the disease-producing components?
    • Gliadin, a fraction of gluten
    • gliadin particles interact w/ the immune system → killing of enterocytes & damage to the mucosal epithelium
  16. What is the hypothesis behind gluten's activation of an immune response against the small intestine mucosa?
    • 1. indigestible fragments of gluten induce enterocytes to release zonulin → LOOSENS tight junctions between mucosal cells
    • 2. gluten may move through now opened spaces between cells & accumulate underneath
    • 3. enterocytes secrete IL-15 in response to deposited gluten → intraepithelial leukocytes squeeze through mucosa to target area
    • 4. tissue transglutaminase (tTG) modifies the gluten, which is now picked up by APCs, presented to T cells, initiating an immune response
    • 5. T cell activation occurs, B cells make Ig's to gluten, & damage mucosal enterocytes in the destruction process
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    • both innate & adaptive immune mechanisms are involved in the tissue responses to gliadin
  17. Pseudomembranous Colitis
    • infection of the large intestine (colon) by an overgrowth of Clostridium difficile bacteria
    • is a type of infectious enterocolitis
    • cytotoxin-producing strains of C. diff may overgrow in the gut after use of antibiotics (eg. clindamycin) – is usually a normal gut organism
  18. leads/manifests as a bare surface epithelium & superficial lamina propria filled w/ NEUTROPHILS
    (+ the occasional capillary fibrin thrombi)
  19. When released, what do C. diff toxin proteins TcdA & TcdB cause?
    • disruption of the intestinal epithelial cytoskeleton
    • loss of tight junction barriers
    • cytokine release
    • apoptosis of intestinal epithelial cells
    • the production of a DISTINCTIVE PSEUDOMEMBRANE
  20. C. diff Pseudomembrane
    • superficially damaged crypts are distended by a mucopurulent exudate (MUCUS + NEUTROPHULS) that forms a volcano-like ‘eruption’
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    • the released exudate coalesces to form the pseudomembrane, a plaque-like adhesion of fibrinopurulent debris & mucus to the damaged superficial mucosa
  21. Diverticular Disease (Nutrition)
    • high intracolonic pressure can cause colonic outpouchings, called Diverticulosis
    • if in addition you have poor intestinal transit, things such as food, stool, or bacteria can get stuck in the outpouchings
    • DiverticuLITIS: infection & inflammation due to impaction of stool or food particle in colonic outpouchings
  22. DiverticulOSIS (Diverticular Disease)
    • an acquired herniation/diverticulum (outpouching) of the mucosa & submucosa through the muscular layers of the colon
    • are generally asymptomatic
    • ENVIRONMENTAL factors are primarily responsible for the disease, as shown by how varied its prevalence of is
    • ~10% of persons are affected in Western countries
    • it increases in frequency w/ age
  23. What part of the colon is affected in 90% of cases?
    • the SIGMOID colon
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  24. Layers of the Intestinal Wall (Inner → Outer)
    • 1. Mucosa (Epithelium, Lamina propria, Muscularis Mucosae)
    • 2. Submucosa
    • 3. Muscularis (Circular, Longitudinal Muscle)
    • 4. Serosa (Areolar CT, Epithelium)
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  25. What layers of the intestine are involved in the outpouchings (diverticulum)?
    • only the mucosa & submucosa are herniated through the muscle layer (should really be called a pseudodiverticula)
    • the base of the diverticulum is the serosal connective tissue
  26. DiverticuLITIS
    • inflammation of the BASE of a diverticulum
    • results from irritation caused by retained fecal materials
    • is seen in 10–20% of patients w/ diverticulosis
    • such infection increases the risk of outpouching perforation
  27. Crohn's Disease
    • chronic, segmental, transmural inflammation of the intestine
    • occurs mainly in the DISTAL SMALL INTESTINE but may involve any part of the digestive tract (eg. the colon, esp. the right colon)
    • appears in adolescents or young adults, most common among persons of European origin
    • has a higher frequency in the JEWISH population
    • slight female predominance (1.6 : 1)
    • a type of IBD (Inflammatory Bowl Disease, which is also a type IV hypersen rxn)
  28. What factors play a part in the pathogenesis of Crohn's Disease?
    1. Genetic: a family history of IBD, mutation of NOD2/CARD15 gene

    2. Immunologic: chronic/recurrent inflammation, mucosal immune response, immunosuppression

    3. Epithelial: defective trans-epithelial transport

    4. Microbial: not well understood
  29. What layers of the intestine wall are usually involves in Crohn's Disease?
    • it's a TRANSmural inflammatory disease, so inflammation usually involves ALL layers of the bowl wall
    • mucosal damage is SHARPLY delimited
  30. Is involvement of the intestine continuous or discontinuous with Crohn's Disease?
    • segments of inflamed tissue are separated by apparently normal intestine (SKIPPED lesions)
  31. The presence of what inflammatory processes is indicative of Crohn's Disease?
    • Non-caseating Granulomas
    • are present in 40–60% of cases
    • can be present anywhere in the GI tract, even if the disease is limited to one bowel segment
    • also Crohn's Disease can exist w/o granulomas present
  32. 4th Important Characteristic of Crohn's Disease
    fissuring (linear tear) & the formation of fistulae (abnormal connections between two epithelium-lined organs or vessels)
  33. Gross Description of Crohn's Disease
    • thickened bowl wall
    • edema & fibrosis of ALL (transmural) layers
    • “creeping fat”: mesenteric fat often wraps around the bowel
    • a NARROWED intestinal lumen due to the edema & fibrosis
    • “cobblestone” appearance b/c of the nodular swelling, fibrosis, & mucosal ulcerations
    • early lesions = aphthous ulcers (canker sores)
    • ulcers later become deeper & appear as linear clefts or fissures
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  34. Microscopic Description of Crohn's Disease
    • 1. NEUTROPHIL infiltration into epithelium & accumulation in crypts → crypt abscesses
    • 3. CHRONIC MUCOSAL CHANGE: distortion, atrophy, & metaplasia
    • 4. transmural, nodular LYMPHOID aggregates
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    • blue = lymphoid aggregates btwn the mucosa & submucosa
  35. Symptoms of Crohn's Disease
    • 1. Abdominal pain & Diarrhea: these are the MOST frequent symptoms (are in 75% of patients)
    • 2. Fever (50% of patients)
    • 3. Malabsorption
    • 4. Colonic Bleeding
    • are highly variable
  36. What are the most common complications of Crohn's Disease?
    • intestinal obstruction
    • fistulas (abnormal connections between two epithelium-lined organs or vessels)
  37. What types of cancers are people with Crohn's Disease prone to?
    • Small Bowel Cancer is 3x more common in people w/ Crohn's
    • Colorectal Cancer
  38. Ulcerative Colitis (AUTOIMMUNITY) UC
    • a chronic superficial inflammation of the colon & rectum
    • characterized by chronic diarrhea & rectal bleeding
    • presents as a pattern of exacerbation & remission
    • can have serious local & systemic complications
    • cause is UNKNOWN but most of the factors implicated in Crohn's Disease are implicated in UC
  39. What 3 major pathologic features characterize UC & help differentiate it from other inflammatory conditions?
    • 1. it's a diffuse disease: extends from the distal part of the rectum for a variable distance proximally
    • • it almost always involves the rectum
    • • therefore it rarely only involves the right side of the colon ALONE
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    • 2. inflammation is generally limited to the colon & rectum
    • • it rarely involves the small intestine, stomach, or esophagus

    • 3. it's essentially a mucosal disease
    • • deeper layers are rarely involved (only in EXTREME cases or w/ Toxic Megacolon)
  40. General UC Symptoms
    • most patients (70%) have intermittent attacks w/ partial or complete remission in between
    • symptoms are VERY variable
  41. Clinical Features of Mild Ulcerative Colitis
    • rectal bleeding
    • rectal pressure
    • discomfort
    • 50% of patients w/ UC have mild colitis
  42. Clinical Features of Moderate Ulcerative Colitis
    • loose bloody stools
    • some anemia (from the chronic fecal blood loss)
    • crampy abdominal pain
    • low-grade fever lasting days or weeks
    • 40% of patients w/ UC have moderate colitis
  43. Clinical Features of Severe Ulcerative Colitis
    • severe or fulminant episodes, often during a flare of activity
    • may be more than 6 & sometimes more than 20 bloody bowel movements daily, often w/ fever and other systemic manifestations
    • dehydration, anemia, & electrolyte depletion from blood and fluid loss
    • massive hemorrhage may be life threatening
    • 10% of patients w/ UC have severe colitis
  44. Toxic Megacolon
    extreme dilation of the colon & an associated risk of perforation that is a dangerous complication of Ulcerative Colitis
  45. Fulminant Ulcerative Colitis
    • a medical emergency that requires immediate intensive therapy & possible colectomy
    • affects the entire colon
    • ~15% of patients w/ Fulminant UC die of the disease
  46. People with long-standing (Advanced) Ulcerative Colitis have a higher risk of what disease than the general population?
    Colorectal Cancer :(
  47. Early Ulcerative Colitis
    • a raw, red, & granular mucosal surface that's frequently covered w/ a yellowish exudate & bleeds easily
    • superficial erosions or ulcers may be present
    • mucosal congestion
    • edema
    • microscopic hemorrhages
    • diffuse chronic inflammatory infiltrate in the lamina propria
    • damage & distortion of the colorectal crypts, which are often surrounded & infiltrated by NEUTROPHILS
    • suppurative necrosis of the crypts → crypt abscess: appear as dilated crypts filled w/ NEUTROPHILS
  48. Crypt Abscess
    • typical of Ulcerative Colitis (& mentioned in Crohn's Disease)
    • a collection of pus in in the mucosa of the large intestine
    • causes swelling & inflammation around it
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  49. Progressive Ulcerative Colitis
    • Inflammatory Polyps: formed from crypt abscesses joining (this undermines the mucosa leaving areas of ulceration adjacent to hanging fragments of mucosa)
    • NO strictures
    • granulation tissue develops in denuded (bare) areas
    • loss of mucosal folds; atrophic mucosa
    • tortuous & branched colorectal crypts
  50. Advanced (Long-standing) Ulcerative Colitis
    • shortened large bowel, esp. the LEFT side
    • mucosal folds are indecipherable → have been replaced by a granular or smooth mucosa
    • the mucosa is atrophied & there's a chronic inflammatory infiltrate in the mucosa + superficial submucosa
    • Crohn's: lesions skip around, don't affect a part of the colon uniformly
    • also inflammation is TRANSMURAL (affecting ALL layers of the intestine), includes ulcerations & fissures
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    • Colitis: there is continuous, chronic involvement that starts in the rectum → proceeds up the left (descending) colon
    • inflammation manifests as pseudopolyps (b/c not all layers are involved) & also ulcers
  52. Crohn's v. Ulcerative Colitis Distribution Pattern
    • Crohn's
    • • distr. pattern: lesions happen discontinuously/non-uniformly throughout the small or large intestine & cause STRICTURES
    • • ulcer conformation: LINEAR (fissures through most layers)
    • • wall thickenings: transmural inflammation (all layers thicken)

    • Ulcerative Colitis
    • • distr. pattern: lesions happen continuously starting in the rectum & are generally in the large (left) colon
    • • ulcer conformation: SUPERFICIAL (only in mucosa mostly)
    • • wall thickenings: pseudopolyps that only really involve the mucosa (& submucosa if advanced)
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  53. Non-neoplastic Polyps of the Small & Large Intestine
    most of intestinal polyps occur sporadically, particularly in the colon, & ↑ in frequency w/ age
  54. What percentage of all epithelial polyps in the large intestine are non-neoplastic?
    • 90%
    • are found in more than half of all people 60 or older
    • are found in more than half of all people 60 or older
    • MOST are hyperplastic polyps, small (<5mm dia.), nipple-like, hemispherical, smooth protrusions of the mucosa found in the rectosigmoid region
    • these generally have no malignant potential
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  55. However what kind of hyperplastic polyps may HAVE malignant potential?
    • Sessile Serrated Adenomas
    • these tend to be found on the Right side of the colon & may be precursors of Colorectal Carcinomas
  56. Adenomatous Polyps
    • premalignant lesions that arise from the mucosa
    • 50% are found in the RECTOSIGMOID region
    • appearance varies from a barely visible nodule, a small, pedunculated adenoma, or a large, sessile (flat) adenoma
    • classified as Tubular, Villous, or Tubulovillous
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  57. Tubular Adenomas
    • smooth-surface lesions, often have a stalk covered by normal colonic mucosa
    • head is composed of neoplastic epithelium, forming branching glands lined by tall, hyperchromatic, somewhat disorderly cells, which may or may not show mucin secretion
    • DYSPLASIA may be encountered, ranging up to cancer confined to the mucosa (intramucosal carcinoma) or invasive carcinoma extending into the submucosa of the stalk
    • risk of invasive carcinoma is correlated to the size of the tubular adenoma
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  58. Villous Adenomas
    • are large, broad-based, elevated lesions w/ a shaggy, cauliflower-like surface found predominantly in the rectosigmoid region
    • most are larger than 2 cm in diameter
    • 10% of colonic adenomas belong to these type
    • composed of thin, tall, finger-like processes that superficially resemble the villi of small intestines
    • there can be variable degrees of dysplasia
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  59. Which contains foci of carcinomas more often, Tubular or Villous adenomas?
    • VILLOUS adenomas do
    • more than 1/3 of all resected villous adenomas contain invasive cancers
  60. Tubulovillous Adenomas
    • have both tubular & villous features (duh)
    • polyps w/ more than 25% & less than 75% villous architecture are termed tubulovillous
    • such polyps have an intermediate risk of developing invasive carcinoma between tubular & villous adenomas
  61. Risk Factors for Colorectal Cancer
    • increasing age
    • chronic Inflammatory Bowel Disease
    • prior colorectal cancer
    • diet
    • genetics: persons w/ 2 or more 1st or 2nd degree relatives w/ colorectal cancer constitute 20% of all patients that develop the disease
  62. What percentage of all colorectal cancers are inherited as autosomal dominant traits?
    5 – 10%
  63. Adenocarcinomas of the colon & rectum are an example of what type of carcinogenesis?
    • Image Upload
    • APC = tumor suppressor gene (makes Adenomatous polyposis coli proteins)
    • DCC = Deleted in Colorectal Carcinoma, a protein encoded by the DCC gene
  64. Colorectal Cancers
    • tend to be polypoid & ulcerating or infiltrative and may be annular & constrictive
    • majority of cases are adenocarcinomas
    • 10 – 15% secrete large amount of mucin & are called Mucinous Adenocarcinomas
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    • adenocarcinoma of the colon presents as an ulcerated mass w/ enlarged, firm, rolled borders
    • can also present w/ malignant glands that have prominent cribriform pattern & frequent central necrosis
    • these can infiltrate into the muscle wall
  65. How is Colorectal Cancer spread?
    • by direct extension or vascular/lymphatic invasion
    • the LIVER is involved in its metastasis in most patients
  66. What is the MOST common sign of Colorectal Cancer?
    • occult (hidden) blood in the feces
    • there also may be obstructive symptoms, especially w/ cancers on the left side of the colon
    • cancers on the right side can grow to a large size W/O causing symptoms
    • also due to the chronic asymptomatic bleeding, Iron-deficiency Anemia* can be a first indication of colorectal cancer
  67. Appendicitis
    • inflammatory disease of the wall of the vermiform appendix → transmural inflammation & perforation w/ peritonitis (if untreated)
    • acute = obstruction of its orifice w/ secondary distention of the lumen & bacterial invasion of the wall
    • the organ is congested, tense, & covered by a fibrinous exudate
    • its lumen often contains purulent material
    • a fecalith (hardened feces) may be present
    • the entire wall becomes infiltrated w/ NEUTROPHILS, which eventually reach the Serosa
    • perforation of the wall releases the luminal contents into the peritoneal cavity
Card Set:
Path GI II Sml & Lrg Intestine (18)
2014-03-10 16:55:23
MBS Pathology
Exam 3
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