Ectopic pancreatic or gastric tissue may be present result in peptic ulceration of adjacent small intestinal mucosa
Present with occult bleeding or abdominal pain
Meckel Diverticulum The specimen is a portion of small intestine with a diverticulum protruding out 25 mm in length.
Meckel Diverticulum Meckel diverticulum. Photomicrograph (original magnification, ×16; hematoxylin-eosin [H-E] stain) shows the diverticulum composed of all layers of the intestinal wall. Normal small intestinal mucosa and a focus of gastric mucosa (arrow) line the diverticulum.
Diagnosis requires documenting absence of ganglion cells within the affected segment
Rectum always affected most cases limited to rectum and sigmoid colon
(+) megacolon stretch and thin the colonic wall to the point of rupture (usually cecum)
Hirschsprung Disease Gross specimen of Hirschsprung's disease. The proximally dilated segment of bowel has been resected. Colonic mucosa stained for acetylcholinesterase from a patient with Hirschsprung's disease. There is a marked increase in the number of nerve fibers in the lamina propria.
Atherosclerotic narrowing of SMA or IMA (+) mesenteric angina
Severe pain in splenic flexure shortly after eating
Weight loss due to fear of eating
Accompanied by bloody diarrhea due to mucosal or mural infarction
Common site of strictures and obstruction
Ischemic colitis. The lesion is typically located in the splenic flexure. The mucosa is markedly hyperemic and covered by a fibrinopurulent exudate. Ischemic colitis with hyalinized lamina propria and gland dropout
Most common acquired GI emergency of neonates (premature and LBW)
Acute disorder of small & large intestines
Occurs most often at time of feeding
Autopsy of infant showing abdominal distension, intestinal necrosis and hemorrhage, and peritonitis due to perforation.
Necrotizing enterocolitis. Gross appearance. The mucosa is necrotic. Numerous small gas-filled cysts are present in the wall. Low-power microscopic appearance showing extensive ulceration, necrosis, and hemorrhage.
Also known as celiac sprue or gluten-sensitive enteropathy
Immune-mediated triggered by ingestion of gluten-containing cereals (eg, wheat, rye, or barley) in genetically-predisposed individuals
Gliadin – alcohol-soluble fraction of gluten; contains the disease-producing components
Malabsorption: Celiac Disease Some gliadin peptides Induce epithelial cell expression of IL-15 Activation and proliferation of NKG2D+ CD8+ intra-epithelial T lymphocytes No recognition of gliadin Cross the epithelium Deaminated by tissue trans-glutaminase Interact with HLA-DQ2 or HLA-DQ8 on APCs Presented to CD4+ T cells (+) Immune reaction
Second portion of duodenum or proximal jejunum exposed to highest concentration of dietary gluten biopsy specimens diagnostic
Intraepithelial lymphocytosis (CD8+ T cells)
Inc. plasma cells, mast cells, and eosinophils within upper part of the lamina propria
This is an endoscopic biopsy of celiac disease that shows total crypt hyperplastic villous atrophy with complete flattening of the mucosal surface. Note the intense lymphoplasmacytic inflammation in the lamina propria.
The surface epithelium of this biopsy contains numerous intraepithelial lymphocytes.
Morphologic hallmark: distended, foamy macrophages in small intestinal lamina propria
(+) villous expansion due to dense macrophage infiltrates shaggy gross appearance to mucosal surface
Whipple Disease Outer aspect of mesenteric lymph nodes massively involved by Whipple's disease. Cut surface of mesenteric lymph nodes massively involved by Whipple's disease.
Whipple Disease Jejunal mucosa in Whipple's disease. The lamina propria is packed with histiocytes and empty round spaces. The latter contained lipid material that has been extracted during tissue processing.
Celiac Disease Whipple Disease Characteristic Clinical Autoimmune: Abs vs gliadin Female dominant; usually begins in infancy Primarily involves duodenum & jejunum Flattened villi Hyperplastic glands w/ chronic inflammation Strong association with dermatitis herpetiformis (autoimmune vesicular disease) May produce T-cell lymphoma of stomach and/or small intestines Restrict or eliminate gluten from diet Best screening test: anti- gliadin antibodies Male dominant disease Caused by Tropheryma whippelii bacilli (only visible by EM) Blunting of villi Foamy PAS-positive macrophages in lamina propria obstruct lymphatics & reabsorption of chylomicrons Fever, recurrent polyarthritis, generalized LAD, increased skin pigmentation Treat with antibiotics
Most common pathogens vary with age, nutrition, host immune status, and environmental influences
Pediatric infectious diarrhea
Result in severe dehydration and metabolic acidosis
Most commonly caused by enteric viruses
Infectious Enterocolitis: Cholera Cholera Toxin B subunit A subunit Binds GM1 ganglioside (surface of epithelial cells) Carried to ER (retrograde transport) Endocytosis Reduced by protein disulfide isomerase in ER Cytosol Unfolding Refolding Interact with cytosolic ADP ribosylation factors Activate G protein Stimulate adenylate cyclase Inc. cAMP Open CFTR Cl released in lumen; secretion of HCO 3 , Na + & water MASSIVE DIARRHEA
Non-typhoid Salmonella – usually due to Salmonella enteritidis
Infection most common in young children and the elderly
MOT: ingestion of contaminated food, particularly raw or undercooked meat, poultry, eggs, and milk
Infectious Enterocolitis: Salmonellosis Salmonella Virulence genes Encode type III secretion system Transfer of bacterial proteins into M cells and enterocytes Activation of host cell Rho GTPases (+) actin rearrangement and bacterial uptake Bacterial growth within phagocytes
Infectious Enterocolitis: Salmonellosis Salmonella Induce epithelial release of eicosanoid hepoxilin A3 Attract neutrophils into intestinal lumen Mucosal damage
Infectious Enterocolitis: Salmonellosis Salmonella Flagellin Activation of TLR4 in host cells Bacterial LPS Acute Inflammation + ulceration PG synthesis Enterotoxins Cytokines Activation of adenyl cyclase Inc. cAMP Fluid production (SI and LI) DIARRHEA
Infectious Enterocolitis: Typhoid Fever Salmonella typhi Small intestines Engulfed by mononuclear cells in underlying lymphoid tissue M cells Blood and lymphatic dissemination Reactive hyperplasia of phagocytes and lymphoid tissue
Aided by dispersin – bacterial surface protein neutralizes the negative surface charge of LPS
Non-bloody diarrhea – prolonged in individuals with AIDS
Infectious Enterocolitis: Escherichia coli – EAEC Numbers of rods attached to the crypt epithelium in the region of active inflammation (HE, high power) Numbers of rods attached to the crypt epithelium (HE, oil immersion)
Antibiotic-associated colitis or antibiotic-associated diarrhea
Generally caused by Clostridium difficile but may also be caused by Salmonella, C. perfringens type A or S. aureus
Any antibiotic may be responsible most commonly implicated are 3 rd generation cephalosporins
Pseudomembranous Colitis Antibiotic intake Disruption of normal colonic flora Overgrowth of C. difficile Toxin release Ribosylation of small GTPAses (Rho) Disruption of epithelial cytoskeleton Tight junction barrier loss Cytokine release Apoptosis
Pseudomembranes made up of an adherent layer of inflammatory cells and debris at sites of colonic mucosal injury
Denuded surface epithelium
Dense neutrophilic infiltrates in lamina propria
Occasionally with fibrin thrombi in capillaries
Pseudomembranous Colitis There are multiple, discrete white plaques of purulent exudate on the mucosal surface. The patient was taking ampicillin. (Courtesy of Dr. RA Cooke, Brisbane, Australia; from Cooke RA, Stewart B: Colour Atlas of Anatomical Pathology. Edinburgh, Churchill Livingstone, 2004).
Pseudomembranous Colitis Fully developed pseudomembrane
Chronic condition resulting from inappropriate mucosal immune activation
May involve any area of GIT; typically transmural
Severe ulcerating inflammatory disease
Limited to colon and rectum extends into mucosa and submucosa
Fever Ulcerative colitis Crohn’s disease Epidemiology Whites > black Americans No sex predilection Young adults Whites > black Americans; Jews > non-Jews Women > men Young adults Extent Mucosal & submucosal Transmural Location Mainly rectum Extends continuously into left colon (may involve entire colon) Does not involve other areas of GIT 30% - terminal ileum alone 50% - ileum and colon 20% - colon alone Involves other areas of GIT (mouth to anus) Gross feature Bowel region Distribution Stricture Wall appearance Colon only Diffuse Rare Thin Ileum + colon Skip lesions Yes Thick
Fever Ulcerative colitis Crohn’s disease Microscopic Inflammation Pseudopolyps Ulcers Lymphoid rxn Fibrosis Serositis Granulomas Fistula/sinus Limited to mucosa Marked Superficial, broad-based Moderate Mild to none Mild to none No No Transmural Moderate Deep, knife-like Marked Marked Marked Yes (~35%) Yes Clinical findings Perianal fistula Malabsorption Malignant potential Recurrence after surgery Toxic megacolon No No Yes No Yes Yes (in colonic disease) Yes With pancolitis, early age onset, duration > 10 years Common No Radiography “ Lead pipe” appearance in chronic disease “ String” sign in terminal ileum from luminal narrowing by inflam-mation, fistulas
Ulcerative colitis. Chronic form, showing mucosal ulceration with residual foci of elevated and hyperemic mucosa. Ulcerative colitis. Acute form with marked hyperemia.
Gross appearance of Crohn's disease. Note the segmental nature of the inflammation, and rigidity of the wall, and flattening of the mucosa are characteristic. So-called ‘aphthous ulcers’, an early feature of Crohn's disease.
Gross appearance of Crohn's disease. Example of cobblestone appearance.
Whole mount specimen of Crohn's disease showing transmural inflammation with predominance of the inflammation in the mucosa and submucosa. Crohn's disease showing marked inflammatory changes and the formation of a fissure.
Multiple GI hamartomatos polyps + muco- cutaneous hyperpigmentation
Can initiate intussusception
Increased risk of malignancies (colon, pancreas, breast, lung, ovaries, uterus, and testicles
Loss-of-function mutations in the gene LKB1/STK11 (tumor suppressor gene)
Duodenal polyp in a Peutz-Jeghers syndrome patient. Medium power microscopic view of a PJS-type jejunal polyp with pseudo-invasion. Arrows indicate hamartomatous small intestine mucosa in the intestinal wall.
Most common type in adults (6 th and 7 th decades); majority in sigmoid
Result from decreased epithelial cell turnover & delayed shedding of surface epithelial cells “piling up” of goblet cells and absorptive cells
No malignant potential or polyposis syndromes
Histologic: “sawtooth” appearance
Gross appearance of multiple hyperplastic polyps. The lesions are characteristically small, sessile, and pale. Microscopic appearance of hyperplastic polyp. The individual glands show a typical serration of their mid portion.
Small, pedunculated – looks like a mushroom; section shows complex branching of glands (adenomatous change)
A small adenomatous polyp (tubular adenoma) is seen here. This lesion is called a "tubular adenoma" because of the rounded nature of the neoplastic glands that form it. It has smooth surfaces and is discreet. Such lesions are common in adults. Small ones are virtually always benign. Those larger than 2 cm carry a much greater risk for development of a carcinoma, having collected mutations in APC, DCC, K-ras, and p53 genes over the years.
A microscopic comparison of normal colonic mucosa on the left and that of an adenomatous polyp (tubular adenoma) on the right is seen here. The neoplastic glands are more irregular with darker (hyperchromatic) and more crowded nuclei. This neoplasm is benign and well-differentiated, as it still closely resembles the normal colonic structure.
Greatest risk for developing colon cancer (30% - 40% risk)
May cause hypoproteinemia and hypo- kalemia
Gross appearance of villous adenoma. The lesion is characteristically large and flat and has an arborescent architecture. Low-power microscopic appearance of villous adenoma. Long villi are arranged in parallel, perpendicularly to the mucosa.
Sites of metastasis: liver (most common), lungs, bone, and brain
Shortness of breath (lung metastasis)
Jaundice (liver metastasis)
Duke’s Staging: Stage A tumors - limited to the wall (not extending beyond muscularis propria), stage B - extending through the wall (into subserosa and/or serosa, or extra-rectal tissues), and stage C - those having lymph node metastasis (C1 when only perirectal nodes were positive and C2 when nodes at the point of mesenteric blood vessel ligature, called apical nodes, were involved.
Astler-Coller Staging: The original scheme had five stages, A was limited to the mucosa, B1 involved muscularis propria but did not penetrate it, B2 penetrated the muscularis propria, and C1 and C2 were counterparts of B1 and B2 with nodal metastases. Since then, later modifications have added three more stages. B3 represents involvement of adjacent structures, C3 is B3 with nodal metastasis, and D signifies presence of distant metastasis. 6