• villi increase the surface area as they project into lumen
  • emptying into crypts at their base which extends into muscularis mucosa
  • core of villi filled with supportive CT
  • villi covered by apical brush border and mucous containing goblet cells
• crypts are site of regeneration of epithelial cell layer and release of GI
  • contain eosinophilic Paneth cells
• lymphoid tissue found as aggregates and follicles in mucosal layer and superficial submucosa
  • macroscopically, may be seen as Peyer's patch
  • immune cells (M cells) in epithelium overlying lymphoid tissue to transport/present Ag's to lymphocytes
• duodenum contents
  • submucosal glands
  • Brunner's glands
  • contain cells similar to those found in stomach pylorus

• only crypts that extend into muscularis mucosa
• crypts lined by absorptive cells and mucus producing goblet cells, some neuroendocrine cells

• rule of 2's
  • 2% of normal adults
  • 2 feet from ileocecal valve
  • 2 inches long
  • commonly presents in first two years of life
• definition- congential vestige of vitelline duct
• clinical presentation
  • usually asymptomatic
  • but can present with complications of intussuseption or incarceration

• primary/congenital
• secondary/toxic

• epidemiology- male predominance
• pathogenesis
  1. abnormal neurological development of colon
  2. causes aganglionic segments of colon where no ganglionic cells can be seen in muscle wall
  3. means no VIP
  4. constricted portion of colon
• clinical presentation- dysmotility and dystension of colon in infants

• most common causes in US population
  • ulcerative colitis
  • ischemic colitis
• pathogenesis
  1. inflammation
  2. results in destruction of intestinal wall integrity
• infectious etiologies- T. cruzi (chagas disease)
  • cause damages to nerves and muscle

• pathogenesis
  1. foci of submucusal venous ectasias (focal relaxation and dilation of small veins)
  2. extension of venous walls into lamina propria where the weakend wall
  3. results in intestinal hemorrhage
• location- cecum, ascending colon

• pathogenesis
  1. dilation of perianal submucosal veins (due to straining at stool or portal HTN)
• clinical presentation
  • rectal pain with bowel movements
  • blood staining
  • persistent pain or itching
  • if advanced, hemorrhage may occur

• pathogensis
  1. caused by increase in intraluminal pressure and focal weakness in colonic wall
  2. leads to outpouching from alimentary tract into lumen of gut (often, uninvolved surrounding muscle is hypertrophied)
  3. if infected, can obstructed and perforated, associated with an acute inflammation
• common location- sigmoid colon (although can occur anywhere)
• false diverticula- only mucosa and subucosa outpouching with attenuated muscle layer

• acquired contortions of bowel loops that can result in obstruction or vascular compromise leading to infarction
  • intusception- infolding/telescoping of bowle lumen on itself
  • adhesion- caused by previous invflammation or surgery that entraps loops of bowel in internal herniations

• disaccharide deficiency
• abetalipoproteinemia

1. lack of enzyme necessary to cleave lactose
2. allows lactose to accumulate
3. results in osmotic diarrhea

• pathogenesis
  1. congenital disease charactized by hypolipoproteinemia due to lack of beta lipoprotein
  2. prevents synthesis of apoproteins required to export chylomicrons out of mucosal epithelial cells
• histopathology
  • accumulation of lipid vacuoles which occurs in mucosal epithelial cells

• histopathology
  • variable acute neutrophilic inflammation
  • fibropurulent exudate (can include abscess formation or necrosis)
• epidemiology- young adults
• clinical presentation
  • periumbilical to right lower quadrant pain
  • tenderness
  • nausea
  • vomiting with fever and leukocytosis
• potential pathogenesis
  • obstruction of appendix by fecalith or worms causing ischemic injury, inflammation, and perforation

• etiology
  • vascular occlusion/insufficiency most commonly due to atherosclerosis or hypotension
• gross pathology- watershed areas between mesenteric circulations such as occurs at splenic flexure
• histopathology
  • vascular insufficiency-
    • acute or chronic inflammatory cells
    • usually confined to lamina propria with possible superficial mucosal erosions acutely or fibrosis if chronic
  • occlusions/severe insufficiency- transmural infactrs

• infectious
  • viral
  • bacterial
• Pseudomembranous colitis
• Whipple's disease
• tropical sprue
• metabolic etiology
  • celiac sprue or gluten sensitive enteropathy
• idiopathic etiologies
  • IBD
  • Crohn's
  • ulcerative colitis

• etiology- usually secretory diarrhea
  • Rotavirus
  • Norwalk
• histopathology- small intestinal mononuclear inflammation in lamina propria of small intestines and possible blunting of villi

• Vibreo cholera
• S. aureus
• E coli (EHEC, ETEC, EPEC)

Due to ability to produce secretion stimulatory toxins

• E coli (EIEC)
• Sigella
• Salmonella
• Yersinia enterocolitica

Due to ability of tissue injury caused by direct invasion of epithelial cells. (if extensive, usually comes with hemorrhage and exudative diarrhea)

• variable evidence of mucosal injury
• neutrophilic inflammatory infiltrate
• congestion and edema
• damage to epithelial cells
• erosion of epithelium
• fibrinopurulent exudate
• extensive bowel injury with infarction can occur in some cases
  • esp. with infants when infection is coupled with immature bowel development aka necrotizing enterocolitis

extent of injury depens largely on

• tendency of organism to invade epithelial cells
• bacterial load

• pathogenesis
  1. use of antibiotic therapy
  2. induce elaboration of C. difficile toxin
     • can also occur in setting of ischemic injury or enteroinvasive infection
• histopathology
  • fibrinopurulent exudate that overlies and adheres to inflammed mucosa
  • otherwise shows neutrophils, edema, congestion, superfical erosion
  • usual DONT see inflammation extend below lamina propria

• histopathology
  • clusters of foamy macrophages with little other inflammation in the small intestines lamina propria
  • TEM- rod shape bacilli in thiese macrophages and in macrophages in LN's and elsewhere in body
• epidemiology- middle aged white men
• causative agent- infection attributed to an Actinomycte
• clinical presentation
  • malabsorption
  • diarrhea
  • fever
  • migratory arthritis

• causative agent- ETEC (causes malabsorptive syndrome)
• common location- distal small bowel
• histopathology
  • variable inflammation in lamina propria, includes infiltrates, edema, or blunting of villi

• epidemiology- whites
• clinical presentation
  • often sublcliical OR
  • abdominal cramping,
  • diarrhea,
  • wt loss
• pathogenesis
  1. sensitive acquired as neonaten in reaction to gliandin in proteins containing gluten (grains)
  2. cause serum Ab to gluten and high levels of IgA anti-endomysial autoAb's
  3. Ab's to transglutaminase which deamidates gialdin peptides to expose them in a way that will stimulate immune HS
• common location- most marekd in proximal SI
• histopathology
  • lymphoplasmacytic inflammation in lamina propria
  • associated with lymphocytes as well in epithelial layer

• familial disposition
• clinical presentation
  • cramping adbdominal pain
  • diarrhea
  • GI bleed
  • other signs of systemic inflammation
• associated with extra intestinal autoimmune type Ab's

• epidemiology
  • white predominance
  • female predominace
  • peak age at 20-40 yrs
• extraintestinal associations
  • cholangitis
  • polyarthritis

Mild increased risk of intestinal cancer

• location- small and large intestines, perianal area
• gross pathology
  • skip lesions (multiple defined areas are common with intervening normal bowel)
  • ulcerations extending deep into wall producing fissures and fistulae, causing "cobblestone" appearance to mucosa on gross exam
• histopathology
  • transmural inflammation
    • neutrophils
    • destruction of epithelial cells
    • addition mononuclear inflammatino within lamina propria and extending into submucosa
    • mucosal injury cause canse villous blunting in SI, ulceration, or metaplastic change
  • non-caseating granuloma
  • transmural fibrosis and thickening of wall
    • result in strictures and obstruction

• epidemiology
  • young adults (peak at 20-25 yrs)
  • white females predominant
• extraintestinal manifestations (inflammation)
  • cholangitis
  • angiosarcoma

• location- confined to large intestines
• histopathology
  • continuous area of inflammation extend retrograde from rectum (no SKIP AREAS)
  • inflammation remain superficial to mucosa
    • neutrophilic infiltration and crypt abscesses or ulceration confined to mucosa and perhaps submucosa without deeper extension into wall
  • inflammatory polyps (due to ulceration of mucosa), leaving tags of residual regenerative mucosal epithelial aka pseudopolyps
  • mucosa becomes atrophic and thin
    • predispose to toxic megacolon and perforation

• characteristics
  • mucosal tags of overgrowing epithelial mucosa in area of erosion and exuberant repair
  • usually mutliple
• composition
  • mucosal epithelium with an inner core of muscularis mucosa that has lifted off of underlying ulcerated mucosa
• prognosis- no malignant potential

• prognosis- no malignant potential
• epidemiology- comprise most of intestinal polyps
• pathogenesis- delayed shedding of epithelial cells
• histopathology
  • extrusion of mucosa containing well formed glands and crypts lined by crowded cells
  • saw tooth pattern

• genetics
  • AD syndrome associated with melanotic spots on lips and skin and increase risk of non-intestinal cancer
  • could also occur sporadically
• composition
  • normal glands surrounding by disorganized and branching smooth muscle fibers
  • hamartomous polyps

• genetics
  • can be sporadically
  • can be part of AD syndrome which has an increased risk of intestinal cancer
• composition
  • hamartomatous polyps
  • large polpys
  • consist of normal but distorted cystic

• may have growth pattern of neoplastic tissue that describs them as tubular adenomas or villous adenomas, or tubulovillous adenomas
• clinical consequences
  • polpys can erode leading to blood in stool
  • obstruction or intussusception of bowle
  • potential malignant focus
  • increase risk of developing carcinomas

• tubular adenomas (most common type)- 20% increase risk of developing carcinoma
• villous adenomas- 40% increase risk of developing carcinoma
• tubulo-villous
  • pathologic features of tubular and villous adenomas, with similar increase risk of developing carcinoma

• pedunculated growth (berry like head) on a stalk with a fibrovascular core
• tubules extend down from luminal surface (into the berry-like head)
• neoplastic epithelium lines the tubules (cells appear normal, but crowded)

• sessile growth in most cases
• epithelium arranged in villi
• villi extend out toward the lumen from inner aspect of polyp
• neoplastic epithelium lines the epithelium (appears normal)
• appear crowded

• theory- progression from adenomatous polyp to cancer
• risk of cancer increase in relation to:
  • size
  • predominance of villous pattern
  • evidence of cellular dysplasia (ex: back to back glands without intervening stroma, increase N/C ratio, loss polarity)

• genetics
  • AD inherited germline mutation (chromosome 5q) in APC tumor suppressor gene leads to multiple small polyps ("carpet")
• prognosis- inevitable progression to cancer
• tx- colectomy

associated with adenomatosis coli with malignant tumos of CNS and cafe au lait pigmentation spots

• mainly in loarge intestines
• second highest cancer death rate in US
• relatively greater incidence in US than other industrialized contries
• increased risk with low fiber, high fat diets

• APC mutation (chromomsome 5q)
• HNPCC
  • auto-D in genes that allow for DNA mismatch
  • this result in many uDNA replication errors and rapid progression from adenoma to cancer
• RAS oncogene
• p53 (chromosome 17p)

• gross pathology
  • occur as polypoid gorwth into lumen of right colon
  • more infiltrative and encircling (napkin ring) in the left colon
• staging strongly correlates strongly with resectability (the only hope for cure) and prognosis

• stage A- carcinoma in situ (severe dysplasia of polyp confined to mucosa with 100% 5 yr survival)
• stage B- extend into muscularis mucosa
  • B1- into, not through muscularis (T1-2, N0, M0)
  • B2- through muscularis to serosa, no lymph nodes (T3, N0, M0)
• stage C- B criteria with LN involvement
  • N1 is less than 3 regional LN's
  • N2 is greater than 3 regional LN's
• stage D- distant metastases

• pathogenesis
  1. neuroendocrine tumor arising in intestines (or, lung, pancreas, or hepatobiliary tree)
  2. produces many biogenic amines, especially serotonin
  3. causes syndrome of flushing and diarrhea
  4. produces other amines causing gastrinoma or insolinoma
• prognosis- if arise in apendix or rectum, could (rarely) metastasize even when locally invasive, but tumors in other areas of

If arise in liver (which cant metabolize serotonin), it causes increase serotonin in the blood, and its metabolite (5-HIAA) in the urine

• small uniform cells
• pink cytoplasm and round oval stippled nucleus
• frequently in clusters or islands that may be surrounded by desmoplastic (fibrous) reactive tissue