This document summarizes various gastrointestinal disorders including small and large bowel diseases, hernias, intestinal obstructions, ischemic bowel disease, malabsorption, and more. It describes signs and symptoms, pathogenesis, clinical presentation, and microscopic findings for each condition. Key points covered include Meckel's diverticulum, Hirschsprung's disease, celiac disease, ischemic colitis, angiodysplasia, and necrotizing enterocolitis. Images are also included showing gross and microscopic pathology.

1. GASTROINTESTINAL DISORDERS Fe A. Bartolome, MD, FPASMAP Department of Pathology Our Lady of Fatima University

6. Meckel Diverticulum The specimen is a portion of small intestine with a diverticulum protruding out 25 mm in length.

7. 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.

10. Extensive diverticulosis of sigmoid colon with segmentation and shortening of bowel. Openings of diverticula can be clearly seen. Circular muscle is thick and corrugated.

11. Whole mount of colon with diverticular disease. Whole-mount view of colonic diverticulosis. One of the diverticula shows marked chronic peridiverticulitis. Note hypertrophy of the muscle wall.

13. Hirschsprung Disease

16. 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.

22. Route of a direct hernia. The hernia sac passes directly through Hesselbach's triangle and may disrupt the floor of the inguinal canal.

27. Umbilical hernia exacerbated by refractory ascites. Advanced liver disease precluded operative repair in this case.

31. Incarcerated umbilical hernia Strangulated inguinal hernia

35. A volvulus is a twisting of the bowel on itself. It is one cause of intestinal obstruction.

55. 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

57. Autopsy of infant showing abdominal distension, intestinal necrosis and hemorrhage, and peritonitis due to perforation.

58. 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.

60. An angiodysplasia in the cecum, explaining the patients iron deficiency anaemia

64. Malabsorption: Cystic Fibrosis Absent epithelial cystic fibrosis transmembrane conductance regulator Defective intestinal chloride ion secretion Impaired bicarbonate, sodium, and water secretion Defective luminal hydration Formation of intraductal concretions in pancreatic ducts Exocrine pancreatic insufficiency Failure of intraluminal phase of nutrient absorption

66. 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

68. 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.

69. The surface epithelium of this biopsy contains numerous intraepithelial lymphocytes.

74. Dermatitis herpetiformis on the forearm

78. 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.

79. 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.

80. 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

82. Tropical sprue showing lymphoplasmacytic infiltrate and villous blunting

90. 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

92. Infectious Enterocolitis: Shigellosis MOT M (microfold) cells Intracellular proliferation Escape into lamina propria Phagocytosed by macrophages Induce apoptosis and inflammation

96. 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

97. Infectious Enterocolitis: Salmonellosis Salmonella Induce epithelial release of eicosanoid hepoxilin A3 Attract neutrophils into intestinal lumen Mucosal damage

98. 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

99. 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

101. Infectious Enterocolitis: Typhoid Fever Seen here: Salmonella, isolated from infected macrophages. (Mildly color-enhanced.)

103. Infectious Enterocolitis: Typhoid Fever Histopathology of a lymph node in a case of Typhoid Fever. Typhoid nodules (microgranulomas) in ileal wall.

106. Infectious Enterocolitis: Escherichia coli – EHEC Lethal enterohemorrhagic E. coli O-157 infection (8 y-o F). Massive and diffuse hemorrhage in the autopsied colon (gross findings)

107. Infectious Enterocolitis: Escherichia coli – EHEC Lethal enterohemorrhagic E. coli O-157 infection (8 y-o F). Marked hemorrhagic destruction of the autopsied colonic mucosa (HE)

110. 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)

112. 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

114. 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).

115. Pseudomembranous Colitis Fully developed pseudomembrane

119. Viral Gastroenteritis: Rotavirus Marked infiltration of lymphoid cells both in the lamina propria and within the surface epithelium (HE)

123. 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

124. 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

125. Ulcerative colitis. Chronic form, showing mucosal ulceration with residual foci of elevated and hyperemic mucosa. Ulcerative colitis. Acute form with marked hyperemia.

126. Pseudopolyps in ulcerative colitis.

128. 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.

129. Gross appearance of Crohn's disease. Example of cobblestone appearance.

130. 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.

133. Acute inflammatory infiltrates near the base of the diverticulum Acute diverticulitis

137. Gross appearance of inflammatory fibroid polyp. Inflammatory fibroid polyp showing myofibroblast-like cells, eosinophils, and other inflammatory cells in a sclerotic background.

141. Juvenile polyposis. The markedly hyperemic quality is a characteristic feature of these lesions. Whole-mount view of a juvenile (retention) polyp.

143. 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.

145. 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.

149. 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.

150. 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.

152. Tubulovillous adenoma

154. 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.

157. Familial polyposis The colon is covered in a carpet of adenomatous polyps.

161. This low power section shows the typical histologic appearance of a submucosal carcinoid tumor. Histologically, carcinoids typically grow as multiple solid nests of tumor cells.

164. The malignant transformation is evident through different grades of cellular alterations (dysplasia).

172. 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.

173. 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

178. Swollen appendix due to acute appendicitis

185. Gross appearance of carcinoma of anal canal. The tumor involves the dentate line and is exophytic with a central ulceration.

186. Invasive well-differentiated squamous cell carcinoma of the anal canal. Low-power view of basaloid carcinoma of the anal canal.