Path GI II Sml & Lrg Intestine (18)

• 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

• intestinal bacteria produce outright gangrene & sometimes perforation of the bowel
• the serosal surface is cloudy & COVERED by inflammatory cells

• 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

• 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

• 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

because rich anastomoses exist between the Celiac artery, Superior Mesenteric artery, or Inferior Mesenteric artery (the 3 vessels)

• 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

• 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.

• recovers w/ complete repair of the lesions OR granulation tissue & fibrosis
• this second way eventually leads to stricture formation

• 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

• dense plasma cell infiltrates in the lamina propria
• T lymphocyte infiltration of the surface epithelium
• 

• 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

• 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)

• 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%

• Gliadin, a fraction of gluten
• gliadin particles interact w/ the immune system → killing of enterocytes & damage to the mucosal epithelium

• 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
• 
• both innate & adaptive immune mechanisms are involved in the tissue responses to gliadin

• 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

(+ the occasional capillary fibrin thrombi)

• disruption of the intestinal epithelial cytoskeleton
• loss of tight junction barriers
• cytokine release
• apoptosis of intestinal epithelial cells
• the production of a DISTINCTIVE PSEUDOMEMBRANE

• superficially damaged crypts are distended by a mucopurulent exudate (MUCUS + NEUTROPHULS) that forms a volcano-like ‘eruption’
• 
• the released exudate coalesces to form the pseudomembrane, a plaque-like adhesion of fibrinopurulent debris & mucus to the damaged superficial mucosa

• 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

• 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

• the SIGMOID colon
• 

• 1. Mucosa (Epithelium, Lamina propria, Muscularis Mucosae)
• 2. Submucosa
• 3. Muscularis (Circular, Longitudinal Muscle)
• 4. Serosa (Areolar CT, Epithelium)
• 

• 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

• 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

• 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)

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

• it's a TRANSmural inflammatory disease, so inflammation usually involves ALL layers of the bowl wall
• mucosal damage is SHARPLY delimited

• DISCONTINUOUS
• segments of inflamed tissue are separated by apparently normal intestine (SKIPPED lesions)

• 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

fissuring (linear tear) & the formation of fistulae (abnormal connections between two epithelium-lined organs or vessels)

• 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
• 

• 1. NEUTROPHIL infiltration into epithelium & accumulation in crypts → crypt abscesses
• 2. ULCERATION
• 3. CHRONIC MUCOSAL CHANGE: distortion, atrophy, & metaplasia
• 4. transmural, nodular LYMPHOID aggregates
• 5. GRANULOMAS
• 
• blue = lymphoid aggregates btwn the mucosa & submucosa

• 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

• intestinal obstruction
• fistulas (abnormal connections between two epithelium-lined organs or vessels)

• Small Bowel Cancer is 3x more common in people w/ Crohn's
• Colorectal Cancer

• 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

• 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
• 

• 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)

• most patients (70%) have intermittent attacks w/ partial or complete remission in between
• symptoms are VERY variable

• rectal bleeding
• rectal pressure
• discomfort
• 50% of patients w/ UC have mild 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

• 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

extreme dilation of the colon & an associated risk of perforation that is a dangerous complication of 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

Colorectal Cancer :(

• 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

• 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
• 

• 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

• 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
• 
• 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

• 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)
• 

most of intestinal polyps occur sporadically, particularly in the colon, & ↑ in frequency w/ age

• 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
• 

• Sessile Serrated Adenomas
• these tend to be found on the Right side of the colon & may be precursors of Colorectal Carcinomas

• 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
• 

• 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
• 

• 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
• 

• VILLOUS adenomas do
• more than 1/3 of all resected villous adenomas contain invasive cancers

• 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

• 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

5 – 10%

• MULTISTEP
• 
• APC = tumor suppressor gene (makes Adenomatous polyposis coli proteins)
• DCC = Deleted in Colorectal Carcinoma, a protein encoded by the DCC gene

• 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
• 
• 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

• by direct extension or vascular/lymphatic invasion
• the LIVER is involved in its metastasis in most patients

• 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

• 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