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Small bowel (small intestine)

Superpage - Nontumor

Revised: 8 January 2013
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

Normal anatomy


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Extends from gastric pylorus to ileocaecal valve
● 6 meters long, divided into duodenum, jejunum, ileum

Duodenum:
● 25 cm long, from pyloric sphincter to ligament of Treitz, mostly retroperitoneal, fixed in position
● Common bile duct (CBD) and pancreatic duct enter second part of duodenum posteromedially at ampulla of vater (eMedicine)

Jejunum:
● 240 cm long, 40% of remainder of bowel, begins at ligament of Treitz
● Has prominent circular mucosal folds (folds of kerckring) that increase absorptive surface

Ileum:
● 360 cm long, distal 60% of post-duodenal bowel
● Mucosa has transverse folds, prominent in proximal ileum, flat/absent at terminal ileum

Ileocecal valve:
● At end of small bowel
● 2 lip structure containing adipose tissue and lymphoid tissue

Lymph nodes:
● Duodenum drains to portal and pyloric nodes
● Jejunum and proximal ileum drain to mesenteric nodes and nodes around superior mesenteric artery, terminal ileum drains to ileocolic nodes
Lacteals are lymphatic channels in villi for chylomicrons

Intestinal immune system consists of:
● Peyer’s patches in ileum (ovoid lymphoid follicles, partly mucosal and partly submucosal, in antimesenteric side of terminal ileum)
● Small intestinal goblet cells, which deliver low molecular weight soluble antigens from intestinal lumen to CD103+ lamina propria dendritic cells, which regulates development of T cells (Nature 2012;483:345)
● M (membranous) cells, part of follicle associated epithelia (MALT) in small bowel and colon, which transfer antigen macromolecules from lumen to lymphocytes
● T cells, usually CD8+ and scattered in surface epithelium
● Lamina propria contains CD4+ T cells and B cells
● Mucosa associated lymphoid tissue: lymphoid nodules, mucosal lymphocytes, appendiceal lymphoid follicles and mesenteric nodes (Annu Rev Cell Dev Biol 2000;16:301, RIKEN Research Center for Allergy and Immunology

Neuromuscular function:
● Anterograde and retrograde peristalsis mixes food and promotes maximal contact of nutrients with mucosa
● Colonic peristalsis prolongs contact with mucosa
● Peristalsis is mediated via myenteric plexus and autonomic innervation (sympathetic-thoracolumbar, parasympathetic-vagal)
● Also through interstitial cells of Cajal (pacemaker cells) and smooth muscle cells
● Vagal receptors are abundant in duodenum and scattered throughout wall

Diagrams
=========================================================================



Duodenum


M cells

Gross images
=========================================================================



Ileum and terminal ileum

Micro images
=========================================================================



Peyer's patches


Lymph nodes: lacteals



Normal histology


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 8 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

Layers:
● Mucosa, submucosa, muscularis propria (externa), subserosa, serosa

Mucosa:
● Contains villi with central blood vessels, lymphatics
● Layers are epithelium, lamina propria, muscularis mucosa

Villi:
● Short and stubby in duodenum, very tall in jejunum, intermediate height in ileum
● Contain microvilli
● Villus to crypt length is 3-5:1
● Lined by primarily columnar absorptive cells and goblet cells
● Usually 1 lymphocyte per 5 enterocytes
● Villi may be short and distorted next to lymphoid aggregates
● 4 normal villi in a row in a biopsy suggests normal villous architecture
● Each villus contains an arteriole with capillary network, veins and a central lymphatic with numerous nerve fibres

Absorptive cells:
● Have microvilli on luminal surface (brush border) and underlying mat of microfilaments (terminal web)

Microvillus:
● 1.5 to 2 µm in length and 100 nm in diameter
● PAS positive, actin-myosin complexes

Goblet cells:
● Occur in crypts and surface absorptive cells
● Decrease towards villus tip, increase in frequency along small intestine (most numerous in lower ileum)
● Columnar in shape, mucus droplet in supranuclear area, secretes mucus, ions and water

Crypts of Lieberkuhn:
● Lower 20% of epithelium, contain undifferentiated (immature) crypt cells, Paneth cells (have large, apical eosinophilic granules containing antimicrobial proteins), scattered goblet cells and endocrine cells
● Are surrounded by pericrypt fibroblast sheath
● Secrete ions, water, IgA, antimicrobial peptides into lumen
● Crypt cells take 3-8 days to migrate to surface
● Allows for rapid repair, but also causes these cells to be sensitive to radiation therapy and chemotherapy

Lamina propria:
● Contains loose connective tissue, lymphocytes, plasma cells, occasional eosinophils, macrophages, mast cells, neutrophils

Submucosa:
● Contains connective tissue, blood vessels, lymphatics, submucosal (Meissner’s) plexus
● Also Brunner’s glands in duodenum

Brunner glands:
● Submucosal mucous glands in duodenum, secrete bicarbonate ions, glycoproteins, pepsinogen II
● Resemble gastric pylorus mucous glands

Muscularis propria (externa):
● Inner circular and outer longitudinal layer, with myenteric (Auerbach’s) plexus between these layers
● Plexus also contains interstitial cells of Cajal (Am J Surg Pathol 2003;27:228), ganglion cells, fibroblasts

Serosa:
● Contains mesothelial lining, loose connective tissue

Endocrine cells:
● Similar to cells in pancreas, biliary tree, lung, thyroid, urethra
● Contain fine eosinophilic granules with secretory proteins
● Nuclei on luminal side of granules, not basal

Micro images
=========================================================================



Brunner glands


Crypts of Lieberkuhn


Enterocyte


Serosa


Villi



Duodenum


Jejunum



Congenital anomalies

Atresia/stenosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

Atresia: imperforate mucosal diaphragm or string like segment of bowel
Stenosis: narrowing of lumen; less common
Complications: perforation, meconium peritonitis, brown bowel syndrome

Etiology
=========================================================================

● Developmental failure, intrauterine vascular accidents, intussusceptions

Case reports
=========================================================================

● 46 day old male infant with multiple areas of jejunal atresia with apple peel deformity (twisted around an artery) associated with 22q11 abnormality (Arch Pathol Lab Med 2000;124:880)

Additional references
=========================================================================

World J Gastroenterol 2010;16:5716



Congenital anomalies

Diverticula (other than Meckel’s)


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

Duodenal:
● Present in 1-2%, usually solitary and congenital, may cause obstructive jaundice, pancreatitis, fistulas, hemorrhage, perforation
● Usually penetrate the pancreas
● May project into lumen like a polyp

Jejunal:
● Present in 0.3% to 1.4% of autopsies
● Three times less frequent than duodenal, but four times more likely to develop complications
● Usually proximal jejunum along mesenteric border
● Often multiple with thin wall
● Associated with diverticula elsewhere in GI tract
● Some are congenital but most are acquired
● Usually asymptomatic but may cause obstruction, hemorrhage, perforation, abscess, malabsorption or Vitamin B12 deficiency, possibly due to bacterial overgrowth in the diverticula

Case reports
=========================================================================

● 88 year old man with acute ulcerative jejunal diverticulitis (World J Gastroenterol 2008;14:6265)

Clinical images
=========================================================================



Jejunal diverticula



Congenital anomalies

Duplication


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Saccular to long, cystic structures which usually have shared muscular wall (so incomplete duplication)
● More common in ileum, near ileocaecal valve; rare in duodenum, where choledochocele (cystic or diverticular dilatation of terminal intramural portion of the common bile duct) is more common
● Present with abdominal mass, pain, vomiting and chronic rectal bleeding
● Associated with gastric heterotopia, but not associated with vertebral body abnormalities

Case reports
=========================================================================

● 51 year old man with adenocarcinoma arising in a cystic duplication (World J Surg Oncol 2012 Apr 10;10:55)

Treatment
=========================================================================

● Resect entire duplication and segment of normal bowel attached to it



Congenital anomalies

Ehlers-Danlos syndrome


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Defect of collagen synthesis, commonly causes hyperelasticity of skin and joints
● May cause spontaneous intestinal perforation and hemorrhage
● Perforations are most common in recto-sigmoid, small bowel perforations (normal or diverticulae) are less common
● Colonic perforation may be associated with abnormal myogenic activity and

Case reports
=========================================================================

● 53 year old woman with occult perforation of distal ileum (Cases J 2010;3:57)

Clinical images
=========================================================================



: Occult small bowel perforation in patient with Ehlers Danlos syndrome



Congenital anomalies

Enterogenous cysts


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Found in wall of small bowel, mesentery, posterior mediastinum or rectorectal space
● May be associated with vertebral body abnormalities

Micro description
=========================================================================

● Lined by respiratory, small intestinal or gastric epithelium
● Wall composed of irregularly oriented smooth muscle

Additional references
=========================================================================

J Indian Assoc Pediatr Surg 2012;17:68, J Pediatr Surg 2004;39:e5



Congenital anomalies

Gastroschisis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Congenital defect characterized by defect in anterior abdominal wall through which abdominal contents freely protrude (Wikipedia)
● Associated with younger mothers, alcohol and tobacco use, ibuprofen use during pregnancy (eMedicine #1, #2)



Congenital anomalies

Heterotopic gastric mucosa


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Mature gastric tissue in location where normally not found (i.e. small bowel)
● Discrete small nodules or sessile polyps, usually in duodenum (first and second part)
● May cause obstruction, diarrhea, ulceration, bleeding, perforation, intussusception, pain (Pediatr Dev Pathol 2000;3:277)
● Presence in duodenum is associated with H. pylori infection and is probably not congenital (Hum Pathol 2003;34:156)

Case reports
=========================================================================

● 50 year old man with duodenal polyp (Case of the Week #124)
● 52 year old woman with jejunal mass (Arch Pathol Lab Med 2003;127:506)
● 67 year old woman with gastric type adenoma (Virchows Arch 1999;435:452)

Gross images
=========================================================================



Case of the Week #124


Figure 1

Micro description
=========================================================================

● Mature gastric tissue, usually fundic type mucosa with chief and parietal cells, lined by foveolar epithelium, with a full mucosal thickness, forming a mucosal island
● Divided into two subtypes, one lined by foveolar epithelium only and another foveolar epithelium along with fundic glands
● The former may be congenital or acquired (metaplasia) and latter is only congenital (Int J Clin Exp Pathol 2012;5:46)

Micro images
=========================================================================



Case of the Week #124


Various images

Differential diagnosis
=========================================================================

● Gastric metaplasia: associated with chronic inflammation, duodenitis and H. pylori, only occupies part of mucosal thickness, typically no gross findings, no parietal cells (Braz J Med Biol Res 2007;40:897, Dig Liver Dis 2002;34:16)
Peptic ulcer disease: no goblet cells



Congenital anomalies

Heterotopic pancreas


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called adenomyoma, myoepithelial hamartoma (although without pancreatic tissue)
● Incidence of 1-14%, affects all ages but peaks in 4-6th decade
● Most common near ampulla of Vater; also stomach, jejunum
● May cause blockage of duct, leading to infection, cystic dilation and fat necrosis
● Usually incidental finding at surgery submitted for frozen section, but carcinoma may arise from pancreatic heterotopia (Arch Pathol Lab Med 1999;123:707)

Case reports
=========================================================================

● 39 year old woman with duodenal polyp (Case of the Week #226)

Gross description
=========================================================================

● Submucosal nodule, intramural mass
● Yellow-white, lobulated, 0.2 cm to 4 cm
● May have central mucosal dimple

Micro description
=========================================================================

● Widely separated pancreatic acini with minimally developed ducts, well formed acini may be seen (JOP 2007;8:588, Mod Pathol 2003;16:530)
● Pancreatic heterotopia may be total, only ducts, only acinar cells (exocrine heterotopia), only islet cells (endocrine heterotopia)
● Adenomyoma: predominance of pancreatic ducts with proliferation of thick smooth muscle bundles of the muscularis around the ducts (seen in periampullary region of the duodenum)

Micro images
=========================================================================



Various images


With acinar cell carcinoma


With ductal adenocarcinoma

Differential diagnosis
=========================================================================

● Well-differentiated adenocarcinoma
● Neuroendocrine tumor from endocrine heterotopia
● Cystic change in pancreatic heterotopia from duplication

Additional references
=========================================================================

Arch Pathol Lab Med 2010;134:378



Congenital anomalies

Hirschsprung’s disease


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Originates in colon, but may extend into small bowel, causing enterocolitis and high mortality (see Colon-nontumor chapter)
● Also absence of ganglion cells in small intestine, a rare form of Hirschsprung's disease; found in newborns and associated with increased morbidity and mortality (Gastroenterol Nurs 1999;22:164)



Congenital anomalies

Malrotation


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● From improper embryologic rotation of gut
● Small bowel is found predominantly on right side of abdomen (Wikipedia)

Drawings
=========================================================================



Normal rotation and malrotation



Congenital anomalies

Meckel’s diverticulum


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Most prevalent congenital abnormality of GI tract, in 2% of normal population
● Usually asymptomatic, but also abdominal pain of unknown etiology (Rev Esp Enferm Dig 2011;103:250)
● Due to persistence (failure to involute) of proximal vitelline duct (also called omphalomesenteric duct, connects lumen of fetal intestine to yolk sac)
● Normally, vitelline duct atrophies and becomes fibrous cord connecting umbilicus and bowel, which is subsequently absorbed
● 63% occur in males
● Usually 20 cm proximal to ileocecal valve on antimesenteric side of bowel, 1-8 cm long (Clin Anat 2011;24:416)
● Associated with other congenital anomalies
Complications: perforation, enteroumbilical fistula, peptic ulceration (usually in adjacent ileum and not in diverticulum), hemorrhage (often massive in children), intussusception, obstruction, carcinoid and other tumors

Case reports
=========================================================================

● 22 year old woman with Crohn’s disease within Meckel's diverticulum (Arch Pathol Lab Med 2003;127:E99)

Treatment
=========================================================================

● Remove if found at surgery, even if incidental

Gross images
=========================================================================



Meckel's diverticulum

Micro description
=========================================================================

● Usually small intestinal mucosa, but 50% have gastric or pancreatic heterotopia
● Contains all 3 layers of bowel wall

Micro images
=========================================================================



With pancreatic heterotopia



Congenital anomalies

Meconium peritonitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare prenatal complication in 1 per 30K live births
● GI perforation releases meconium into abdominal cavity, inducing sterile inflammatory reaction and calcium deposition
● Perforation may be due to anoxia leading to bowel ischemia, atresia, congenital bands, Hirschprung’s disease, internal hernia, meconium ileus, stenosis, volvulus or idiopathic
● Presents with fetal distress, maternal polyhydramnios, abdominal distention or a mass
● Newborns with perforation should be evaluated for cystic fibrosis (Pediatr Surg Int 2003;19:75)

Radiology
=========================================================================

● Prenatal ultrasound shows dilated bowel, ascites, polyhydramnios, intra-abdominal calcifications (Prenat Diagn 2005;25:676)
● Ultrasound findings have prognostic value (Fetal Diagn Ther 2003;18:255, Prenat Diagn 2007;27:960)

Case reports
=========================================================================

● 35 week old female with intrauterine distress (Case of the Week #106)

Treatment
=========================================================================

● Surgical
● Gestational age at diagnosis does not predict postnatal outcome (J Pediatr Surg 1995;30:979)

Gross description
=========================================================================

● Organized peritonitis with fibrosis, calcifications, dense intestinal adhesions
● Meconium pseudocyst (fibrous wall) may form

Gross images
=========================================================================



Abdominal cavity


Small intestine

Micro description
=========================================================================

● Peritoneal surface shows fibrinous exudate with microcalcifications, bile pigment-like debris, histiocytes, chronic inflammatory cells

Micro images
=========================================================================



Peritoneal surface

Differential diagnosis
=========================================================================

● Vernix caseosa peritonitis: cheesy white exudate coats the visceral organs after cesarean section (J Obstet Gynaecol 2007;27:660)



Congenital anomalies

Omphalocele


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Infant born with herniated abdominal contents into ventral membranous sac because abdominal musculature fails to form

Clinical images
=========================================================================



Ruptured omphalocele

Differential diagnosis
=========================================================================

● Gastroschisis: similar, but umbilical cord is not involved

Additional references
=========================================================================

Hum Genet 2012;131:739



Patterns of abnormal small bowel architecture

Severe villous abnormality


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Flat intestinal mucosa with no villi seen
● Usually diffuse, with epithelial lymphocytosis, crypt hyperplasia, numerous mitotic figures
● Mucosa actually of normal villous thickness
● Due to celiac sprue, refractory or unclassified sprue, other protein allergies, lymphocytic enterocolitis



Patterns of abnormal small bowel architecture

Variable villus abnormality and crypt hypoplasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Villi focally flat or mild/moderate villus shortening
● Also increased intraepithelial lymphocytosis, decreased crypt mitotic figures

Etiology
=========================================================================

● Marasmus: severe protein-calorie malnutrition
● Kwashiorkor: protein malnutrition but adequate caloric intake
● Megaloblastic anemia: vitamin B12 or folate deficiency, no increased inflammatory cells
Chemoradiation effect: apoptosis, atypical cells
Microvillus inclusion disease



Patterns of abnormal small bowel architecture

Nonspecific variable villus abnormality


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Various villus abnormalities, usually not flat mucosa
● Usually due to partial treated celiac sprue



Malabsorption

Malabsorption-general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Standard site for biopsies is proximal jejunum, just distal to ligament of Trietz
● Mount specimen mucosal side up on solid substance, then embed perpendicular to mounting material; then step section or serial section
● Small bowel is important for absorption of fats, fat-soluble vitamins, proteins, carbohydrates, electrolytes, minerals, water
● In US, most common malabsorption disorders are celiac sprue, pancreatic insufficiency and Crohn’s disease
● Steatorrhea: bulky, greasy stools associated with weight loss, anorexia, muscle wasting

Symptoms associated with specific deficiencies
=========================================================================

● Diarrhea, flatus, abdominal pain, weight loss, mucositis, anemia (iron, folate, Vitamins B6, B12)
● Bleeding / purpura (Vitamin K)
● Osteopenia, tetany (calcium, magnesium, vitamin D)
● Amenorrhea / impotence / infertility (generalized malnutrition)
● Hyperparathyroidism (calcium, vitamin D)
● Edema (albumin)
● Dermatitis (zinc, vitamin A, fatty acids, niacin)
● Peripheral neuropathy (vitamins A, B12)

Physiologic classification of malabsorption
=========================================================================

Disturbances related to:
● (a) Intraluminal digestion: saliva, gastric peptic digestion, small bowel, bile salts
● (b) Terminal digestion: hydrolysis of carbohydrates and peptides by disaccharidases and peptidases in brush border of small bowel
● (c) Transepithelial transport: across small bowel epithelium to intestinal vasculature; fatty acids to triglycerides, cholesterol to chylomicrons

(a) Causes of defective intraluminal digestion
● Digestion of fats/proteins: pancreatic insufficiency due to pancreatitis or cystic fibrosis, Zollinger-Ellison syndrome
● Defective bile secretion (fat solubilization): ileal dysfunction or resection with decreased bile salt uptake, cessation of bile flow (obstruction, hepatic dysfunction), nutrient preabsorption or modification by bacterial overgrowth

(b/c) Causes of abnormalities in terminal digestion or transepithelial transport
● Disaccharidase deficiency (lactose intolerance), bacterial overgrowth, abetalipoproteinemia, defects in ileal bile acid transporter



Malabsorption

Abetalipoproteinemia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare; due to mutations in MTP gene encoding microsomal triglyceride transfer protein (MTP); autosomal recessive (Ann Hepatol 2011;10:221)
● Causes defect in synthesis and export of apoprotein B from intestinal mucosal cells
● As a result, free fatty acids and monoglycerides cannot be assembled into chylomicrons and become triglycerides stored within cells, causing lipid vacuolization
● Symptoms: failure to thrive, diarrhea, steatorrhea

Laboratory
=========================================================================

● Lipid profile shows no chylomicrons, no VLDL, no LDL
● CBC smear shows acantholytic red blood cells (Burr cells) due to lipid membrane abnormalities

Micro description
=========================================================================

● Marked fat vacuoles in apical villous cytoplasm, normal villi

Positive stains
=========================================================================

● Fat stains highlight lipid vacuoles

Differential diagnosis
=========================================================================

● Megaloblastic anemia
Celiac sprue
Tropical sprue



Malabsorption

Acrodermatitis enteropathica


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Autosomal recessive, linked to zinc deficiency, affects children
● Genetic defect mapped to SLC39A4 gene at 8q24, encodes zinc transporter Zip4 (J Am Acad Dermatol 2007;56:116)
● Cutaneous lesions (perioral and extremity skin lesions, alopecia, nail dystrophy), diarrhea, malabsorption

Treatment
=========================================================================

● Zinc sulfate

Micro description
=========================================================================

● Severe villus abnormality in some; normal in others

Electron microscopy description
=========================================================================

● Rodlike fibrillar inclusions in Paneth cells



Malabsorption

Agammaglobulinemic sprue


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare; no plasma cells in lamina propria



Malabsorption

Celiac sprue


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Major cause of malabsorption - almost all adults in North America with severe villous abnormality and crypt hyperplasia have celiac sprue
● Also called nontropical sprue, gluten-sensitive enteropathy, celiac disease

Pathophysiology
=========================================================================

● Individuals with genetic predisposition have increased immunological responsiveness to prolamins such as dietary wheat gliadin and similar proteins in barley, rye, possibly oats
● Gluten is an alcohol soluble, water insoluble protein component in wheat, oat, barley, rye
● Gluten is mostly made up of 2 groups of proteins: ethanol-soluble gliadins and ethanol-insoluble glutenins
● Gliadin contains chiefly proline and glutamine amino acids
● αGliadin is most toxic to celiac patients
● Gliadin serves as a substrate for transglutaminase (85-kDa enzyme) and becomes cross-linked to it creating a neoantigen – induces immune response
● Disease is due to abnormal cell mediated immunity - gluten exposure causes accumulation of intraepithelial cytotoxic T cells and helper T cells in lamina propria

Clinical features
=========================================================================

● Affects 1 per 200-300 whites in Western countries, onset typically in childhood, rare in Africa, Japan, China
● HLA DQ alpha/beta heterodimer appears to confer susceptibility (90% have DQw2 HLA on #6), linked to HLA B8 (80%)
● Also associated with lymphocytic gastritis / colitis, selective IgA deficiency, type 1 diabetes, Sjogren’s syndrome, autoimmune thyroiditis
● Does not appear to be associated with H. pylori gastritis (Am J Gastroenterol 2006;101:1880)

Symptoms:
● Newborns: diarrhea and failure to thrive
● Symptoms of episodic diarrhea, flatulence, weight loss, fatigue begin as late as age 40; also abdominal pain and distention, weight loss (Clin Med Res 2004;2:71)
● Clinical and microscopic improvement after dietary changes

Late onset:
● 40’s and 50’s
● Symptoms of short stature, infertility, peripheral neuropathy, iron or folate deficiency, osteoporosis, indigestion, dental enamel defects

Complications:
● Long term risk of malignant disease is 2x normal, usually T cell intestinal lymphomas
● Also GI or breast carcinomas or esophageal squamous cell carcinoma

Seronegative celiac disease
=========================================================================

● Individuals lack serum autoantibodies, have normal villous architecture or mild atrophy
● Increased intraepithelial lymphocytes (IEL)
● Tissue transgultaminase IgA immune deposits are detectable in lamina propria

Classification
=========================================================================

Old Marsh-Oberhuber classification (5 states of small-intestinal mucosal injury (types 0–4)):
● Type 0: Preinfiltrative: normal small-intestinal mucosa with less than 30 IELs per 100 enterocytes
● Type 1: Infiltrative type: normal villous and crypt architecture ( >3 1) and an increased IELs (>30 IELs per 100 enterocytes)
● Type 2: Infiltrative-hyperplastic type: normal villous architecture and crypt hyperplasia with an increased number of IELs-rare
● Type 3: Destructive (flat mucosa) type of CD lesion: 3 different subgroups depending on the degree of villous atrophy
  ● Type 3a: Mild villous atrophy with villous to crypt ratio of <3 1 or 2 1, and increased IELs
  ● Type 3b: Marked villous atrophy with villous to crypt ratio of <1 1, and increased IELs
  ● Type 3c: Total villous atrophy with completely flat mucosa and increased IELs
● Type 4: Atrophic type (hypoplastic); very rare pattern, flat mucosa with only a few crypts and near-normal IEL counts

New classification (Corazza and Villanacci):
● Grade A: Nonatrophic, with normal crypt and villous architecture and increased IELs (>25 IELs per 100 enterocytes)
● Grade B1: Atrophic, with villous to crypt ratio <3 1, but villi are still detectable and IELs are increased (>25 IELs per 100 enterocytes)
● Grade B2: Atrophic and flat, villi are not detectable and increased IELs are noted (>25 IELs per 100 enterocytes)


Comparison of classification systems

Diagnosis
=========================================================================

● Antitransglutaminase, antigliadin or antiendomysial antibodies plus clinical malabsorption plus typical histologic findings plus improvement in symptoms and histology after gluten withdrawal

Laboratory
=========================================================================

● Elevated serum IgA except in those with IgA deficiency (more common in these patients than normals)
● Also IgA anti-transglutaminase, antiendomysial, antireticulin and antigliadin antibodies


Sensitivity of various antibodies

Serum IgA:
● Used to monitor compliance with gluten-free diet

Antitransglutaminase antibody:
● Sensitive marker of disease

IgA anti-endomysial antibody:
● Detect with monkey esophageal tissue
● Sensitive and specific, although also positive in dermatitis herpetiformis

IgA and IgG anti-gliadin antibody:
● Less sensitive than antitransglutaminase and antiendomysial antibodies

Anti-reticulin antibody:
● In 40%, but nonspecific
● Also seen in Crohn's disease, myasthenia gravis, Sjogren’s, other

Case reports
=========================================================================

● 56 year old woman with long history of untreated celiac sprue (Case of the Week #127)

Treatment
=========================================================================

● Improves clinically and microscopically after dietary withdrawal of wheat gliadins and related grain proteins

Gross description
=========================================================================

● Usually flat, scalloped mucosa
● May be normal

Micro description
=========================================================================

Note: diagnosis requires clinical correlation - pathology report can only state "consistent with celiac sprue"
● Increase in intraepithelial lymphocytes, most sensitive marker is 40+ lymphocytes per 100 surface or upper crypt enterocytes
● Early-clustering of 12+ lymphocytes at tip of villi and extending evenly down the sides of the villus (Mod Pathol 2003;16:342)
● Diffuse enteritis with marked atrophy or total loss of villi
● Fat globules in surface epithelium, enterocytes have stratified nuclei, lose their brush border, increased crypt mitotic figures
● Crypts are elongated and hyperplastic, but overall mucosal thickness is the same
● Also increase in plasma cells in lamina propria
● Changes more marked in proximal small bowel (greater exposure) and abnormalities recede last here after gluten withdrawal
● Significant duodenal neutrophilia often noted in children, associated with more active disease
● Disease activity is proportional to eosinophilic infiltration and foveolar metaplasia (Am J Surg Pathol 2012;36:1339)
● Do not overdiagnose on biopsy based on minimal and nonspecific histologic changes, as diagnosis has lifelong implications (Arch Pathol Lab Med 2008;132:1594)

Micro images
=========================================================================



Marsh-Oberhuber classification


Marsh Type I & III lesions


Various images


Case of the Week #127

Virtual slides
=========================================================================



Small intestine

Differential diagnosis
=========================================================================

● Autoimmune enteropathy: crypt injury or destruction, anti-enterocyte antibodies, typically in first 6 months of life
● Common variable immunodeficiency: no plasma cells, marked lymphoid hyperplasia, often Giardia infection
Crohn’s disease
Dermatitis herpetiformis: associated with gluten-sensitive enteropathy but also has skin lesions
● Duodenal intraepithelial lymphocytosis with normal villous architecture: associated with H. pylori infection, but no other features of celiac disease (Mod Pathol 2005;18:1134)
● Infectious enteritis: prominent neutrophils, normal intraepithelial lymphocytes
● Kwashiorkor
● Morbid obesity: intraepithelial lymphocytosis in architecturally normal small intestinal mucosa (Arch Pathol Lab Med 2007;131:344)
● Other protein allergies: sprue symptoms disappear and reappear if offending substance is withdrawn / reintroduced
Tropical sprue, severe: no antiendomysial antibodies, responds to antibiotics and folate

Differential diagnosis of intraepitheliial lymphocytes
=========================================================================

H.Pylori associated gastroenteritis, nongluten food hypersensitivity, infections (giardia, cryptosproridia), bacterial overgrowth, drugs (NSAID’s), IgA deficiency, common variable immunodeficiency, Crohn’s disease, small bowel allograft rejection (Arch Pathol Lab Med 2010;134:826)


Table

Additional references
=========================================================================

J Clin Pathol 2005;58:573, Arch Pathol Lab Med 2012;136:735



Malabsorption

Collagenous sprue


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 13 November 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Subtype of refractory sprue with patchy, excessive subepithelial collagen deposits (5 of 10 patients in one study, Am J Surg Pathol 2000;24:676)
● May eventually respond to gluten-free diet (Mod Pathol 2010;23:12), but disease may also be fatal

Micro description
=========================================================================

● Small intestinal villous and crypt atrophy, subepithelial collagen deposit thicker than 12 µm that entraps lamina propria cellular elements (Arch Pathol Lab Med 2011;135:803)

Micro images
=========================================================================





Various images



Malabsorption

Dermatitis herpetiformis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Skin-nontumor chapter

General
=========================================================================

● Usually present with skin manifestations only and are not aware of the underlying small-bowel problems ● Resembles celiac sprue - both respond to gluten free diet (skin lesions improve), both associated with HLA-B8 and HLA-DR3, both associated with lymphoma
● Pruritic, papulovesicular lesions symmetrically distributed on scalp, buttocks, extremities, with granular deposition of IgG at epidermal-dermal junctional
● Diagnosis: circulating IgA antibodies against epidermal transglutaminase (eTG) and tissue transglutaminase (tTG) (J Invest Dermatol 2008;128:332, J Am Acad Dermatol 2009;61:39)

Micro description
=========================================================================

● Severe mucosal lesion on small bowel biopsy
● May be patchy with variable villus abnormality



Malabsorption

Disaccharidase (lactase) deficiency


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Disaccharidases are located in apical cell membrane of villous absorptive epithelial cells

Congenital deficiency:
● Rare; malabsorption evident with milk feeding, which causes explosive, watery, frothy stools and abdominal distention

Acquired deficiency:
● Common in North American blacks
● Causes osmotic diarrhea
● Acquired deficiency of lactase also occurs in duodenal mucosa of children with celiac disease (J Gastroenterol Hepatol 2008;23:348)

Diagnosis
=========================================================================

● Increased hydrogen in breath test due to bacterial fermentation of undigested lactose

Treatment
=========================================================================

● Dietary elimination of milk and milk products



Malabsorption

Lymphangiectasia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 22 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Primary intestinal lymphangiectasia is rare disorder of dilated intestinal lacteals resulting in lymph leakage into the small bowel lumen, causing protein-losing enteropathy leading to lymphopenia, hypoalbuminemia and hypogammaglobulinemia (Orphanet J Rare Dis 2008;3:5, eMedicine)
● Dilation of lymphatics in mucosa, submucosa or subserosa
Primary: children, due to congenital obstructive defective in lymphatics
Secondary: due to constrictive pericarditis, Crohn’s (Virchows Arch 2008;452:57), intestinal malignancy, myocardial disease, pancreatitis, retroperitoneal fibrosis, sarcoidosis, Waldenström macroglobulinemia

Treatment
=========================================================================

● Resection, treatment of underlying conditions

Clinical images
=========================================================================




Markedly dilated lymphatics

Micro images
=========================================================================



Markedly dilated lymphatics



Malabsorption

Microvillus inclusion disease


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called congenital or familial microvillous atrophy
● Disorder of intestinal brush border that causes intractable watery diarrhea with steatorrhea in infants
● Patients require total parental nutrition, and rarely live beyond age 2 years
● Villous atrophy may be due to apoptotic cell loss (Hum Pathol 2000;31:1404)

Treatment
=========================================================================

● Small bowel transplant

Micro description
=========================================================================

● Severe villous abnormality with crypt hypoplasia, resembling celiac sprue but without lymphocytosis
● Increased enterocyte apoptosis and proliferation, bubbly vacuolated apical cytoplasm with extensive or patchy absence of brush border, absence of inflammation (Ultrastruct Pathol 2010;34:327)

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● CD10 (Am J Surg Pathol 2002;26:902), PAS, polyclonal CEA, alkaline phosphatase (cytoplasmic staining vs. linear brush border staining in normals)
● Vacuoles - PAS, CEA
● Cytoplasmic CD10 staining of absorptive colonocytes can aid in the diagnosis in situations where only colonic biopsy could be obtained (Am J Surg Pathol 2010;34:970)

Electron microscopy description
=========================================================================

● Abnormal microvillus structures at luminal border of enterocytes
● Apical intracytoplasmic inclusions lined by microvilli

Electron microscopy images
=========================================================================



Neonatal congenital microvillus atrophy



Malabsorption

Refractory sprue


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called unclassified sprue
● Celiac sprue that does not respond to gluten free diet of 6-12 months (note: wheat is present in many foods, so must verify that diet is actually gluten free), and is not due to other disorders
● Must rule out gluten contamination, microscopic colitis, bacterial overgrowth, pancreatic insufficiency, lactose intolerance, inflammatory bowel disease, lymphoma (Gut 2010;59:547)

Clinical features
=========================================================================


● Two subtypes: Type 1 (normal intraepithelial lymphocyte phenotype) and type 2 (presence of abnormal clonal intraepithelial lymphocyte phenotype)
● Often associated with thromboembolic events, coexisting autoimmune disorders, cavitation of mesenteric lymph nodes and hyposplenism, lymphoma


Table

Micro images
=========================================================================



Various images



Malabsorption

Tropical sprue


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 14 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called post-infectious sprue
● Affects people living in or visiting the tropics, particularly Caribbean (not Jamaica), Africa, India, SE Asia, Central/South America (Case Rep Gastroenterol 2010;4:168)
● Has endemic and epidemic features
● May be due to E. coli or Haemophilus
Symptoms: malabsorption within weeks of acute diarrheal enteric infection

Treatment
=========================================================================

● Broad-spectrum antibiotics (tetracycline), folic acid, vitamin B12
● No increased risk of intestinal lymphoma

Micro description
=========================================================================

● Variable villous atrophy (none, partial, total)
● Injury to entire small bowel (not proximal as in celiac sprue), inflammatory infiltrate, crypt hyperplasia

Micro images
=========================================================================



Various images


40 yr old man with chronic diarrhea who improved after antibiotics; marked villous atrophy in duodenal biopsy but no increase in intraepithelial lymphocytes (courtesy of Dr. Hanni Gulwani)

Additional references
=========================================================================

Gastrointest Endosc 2007;66:377, Dig Dis Sci 2011;56:161



Ulcers

Duodenal peptic ulcer


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Decreasing incidence, but still common (Int J Clin Exp Pathol 2012;5:46)
● Imbalance between gastric acid production and protective factors of intact epithelium and bicarbonate production
● Increased gastric acid production requires intact fundic mucosa
● Associated with duodenal Helicobacter pylori and gastric metaplasia
● Not associated with malignancy

Treatment
=========================================================================

● H2 blockers
● 80% heal within a month
● Surgery if hemorrhage, perforation, obstruction or failure to respond to medical treatment
● Ulcers located posteriorly bleed easily due to pancreaticoduodenal and gastroduodenal arteries in the vicinity

Gross description
=========================================================================

● Usually single lesion within 2 cm of pylorus
● Multiple lesions throughout duodenum suggest Zollinger-Ellison syndrome
● Margins well defined
● No heaped up edges
● May have large vessel with open lumen at ulcer base
● Also fibrosis and shortening of duodenum

Micro description
=========================================================================

● Ulcer usually < 1 cm, circular, small
● Brown ulcer base (digested blood), no induration of margins of ulcer
● Abrupt lesions with normal adjacent mucosa
● No scarring or blood vessel thickening
● Gastric foveolar cell metaplasia and chronic duodenitis common
● Various villus abnormalities in proximal duodenum with active duodenitis
● Also Brunner’s gland hyperplasia
Helicobacter pylori often present

Micro images
=========================================================================



Various images

Additional references
=========================================================================

World J Gastroenterol 2010;16:5496



Ulcers

Marginal ulcer


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Most common abnormality found among symptomatic patients after gastric bypass surgery on flexible upper endoscopy examination
● Usually in jejunum distal to stoma

Clinical images
=========================================================================



Various images



Ulcers

Small bowel ulcer


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Nonspecific small bowel ulcers are rare diagnoses of exclusion (BMC Gastroenterol 2011 May 10;11:51)
● Almost always related to other gastroduodenal disease, including celiac disease, congenital anomalies, drugs (NSAID, Korean J Gastroenterol 2008;52:134), endometriosis, enteric-coated potassium and hydrochlorothiazide, mechanical disorders, radiation, specific inflammations, tumors, vascular occlusion
● Cause obstruction, perforation, hemorrhage

Clinical images
=========================================================================



Endoscopic image

Gross description
=========================================================================

● Ulcer with adjacent hemorrhage, congestion, edema

Micro description
=========================================================================

● Nonspecific changes

Micro images
=========================================================================



Various images



Inflammatory disorders

Autoimmune enteropathy


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Severe and intractable watery diarrhea syndrome in infants associated with antibodies to intestinal epithelial cells
● Includes IPEX syndrome, an X linked recessive disorder due to mutations in FOXP3 gene (Mod Pathol 2009;22:95)
● Usually requires total parenteral nutrition
● Similar condition in adults associated with variable immunodeficiency and type I diabetes, rheumatoid arthritis, hemolytic anemia

Treatment
=========================================================================

● Immunosuppressive agents

Micro description
=========================================================================

● Variable villus abnormality, few intraepithelial lymphocytes
● May have colitis, increased expression of MHC class II antigens

Micro images
=========================================================================



IPEX syndrome



Inflammatory disorders

Behcet’s disease


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare immune-mediated systemic vasculitis that often presents with mucous membrane ulceration and ocular problems (Wikipedia)
● GI involvement in 10% of cases, usually ileum and cecum
● Punched out ulcers that may perforate
● Perivascular inflammation, necrotizing and nonnecrotising lymphocytic vasculitis affecting small veins and venules is often present
● Also aphthous stomatitis, genital ulcers, relapsing iritis

Case reports
=========================================================================

● 30 year old man with massive GI bleeding (Korean J Gastroenterol 2007;49:400)

Gross images
=========================================================================



Various images

Micro images
=========================================================================



Ulcers-site unspecified



Inflammatory disorders

Collagenous enterocolitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● May be associated with collagenous colitis, collagenous gastritis or collagenous sprue
● High intraepithelial lymphocyte count in terminal ileum biopsies of affected patients (Mod Pathol 2003;16:115, Am J Surg Pathol 2002;26:1484, Am J Surg Pathol 2011;35:1151)
● Lymphocytes are mostly suppressor T cells
Symptoms: chronic nonbloody diarrhea, relatively normal endoscopy

Micro description
=========================================================================

● Subepithelial collagen deposition in terminal ileum, partial villous atrophy

Micro images
=========================================================================



Terminal ileum with increase in subepithelial collagen

Positive stains
=========================================================================

● Trichrome highlights collagen



Inflammatory disorders

Crohn’s disease


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Relapsing, discontinuous, transmural granulomatous disease from oral cavity to anus, usually involves small intestine and colon (eMedicine)
● Also called terminal ileitis, regional enteritis, granulomatous colitis

Epidemiology
=========================================================================

● Affects primarily Western populations, equal gender incidence
● 3 per 100,000, peaks in teens/twenties and 50/60’s
● RR: Whites 2-5:1, Jews 3:1
● Associated with smoking
● Monozygotic twins have 30-50% concordance

Sites
=========================================================================

● Small bowel only (particularly terminal ileum) in 40%, colon only in 30%
● Rarely other sites in GI tract

Etiology
=========================================================================

● Cause unknown, although Yersinia DNA in 30% of cases by PCR (Am J Surg Pathol 2003;27:220)
● May be due to alteration in steady state between immune system activation by microbes, antigens, endogenous inflammatory stimuli and host defenses that maintain integrity of mucosa and down-regulate inflammation
● Unclear if mucosal pathology is primary or secondary (Inflamm Bowel Dis 2010;16:896)

Clinical features
=========================================================================

Symptoms:
● Variable, including episodic mild diarrhea, fever, pain
● May be precipitated by stress
● If colon affected, may have anemia
● 20% have abrupt onset, resembling acute appendicitis or bowel perforation

Extraintestinal symptoms:
● Migratory polyarthritis, sacroiliitis, ankylosing spondylitis, erythema nodosum, clubbing of fingertips, primary sclerosing cholangitis (not as common as with ulcerative colitis)
● Occasionally uveitis, pericholangitis, renal disorders secondary to periureteral fibrosis

Complications:
● Fibrosing strictures (common in terminal ileum), fistulas to loops of bowel, bladder, vagina, perianal skin
● Also protein losing enteropathy, generalized malabsorption, vitamin B12 deficiency, bile salt malabsorption with steatorrhea, perforation, abscesses
● 5x risk for GI carcinoma, usually adenocarcinoma of ileum

Course:
● Progressive
● Only rarely regresses

Crohn's related carcinoma
=========================================================================

Small bowel:
● Mean 20 years after onset of Crohn’s, usually ileum or site of active disease
● Often in strictures, 25% in bypassed bowel loops
● Poorly differentiated, poor prognosis
● Dysplasia in adjacent epithelium

Colon:
● Mean 20 years after diagnosis, usually gross intraluminal lesion, 20% in bypassed rectum
● Better differentiated and better prognosis than small bowel carcinomas
● Dysplasia near and distant from tumor

Treatment
=========================================================================

● Medical (immunosuppressive therapy), surgical

Clinical images
=========================================================================



Endoscopy

Gross description
=========================================================================

● Serosa dull and granular with creeping fat (mesenteric fat wraps around bowel surface), thick/rubbery intestinal wall (due to edema, inflammation, fibrosis, hypertrophy of muscularis propria), narrow lumen (string sign on barium enema), sharp demarcation of affected from uninvolved bowel, fistulas
● No rectal involvement
Early - aphthous mucosal ulcers that coalesce into long, serpentine linear ulcers along bowel axis with cobblestone appearance
Late - shortened and fibrotic mesentery; prominent reactive lymph nodes

Clinical images
=========================================================================



Terminal ileum: mucosal pseudopolyps (inflammatory pseudopolyps)


Terminal ileum: cobblestone change


Thickened bowel wall and fat wrapping

Micro description
=========================================================================

● Sharply delimited and typically transmural involvement of bowel by an inflammatory process with mucosal damage, noncaseating, non-confluent, sarcoid-like granulomas (60%) in involved and non-involved bowel, fissuring (30%) deep into muscularis propria with formation of fistulas and strictures
● Focal neutrophils in epithelium early on, particularly overlying lymphoid aggregates
● Also plasmacytosis, cryptitis, crypt abscesses
● Superficial or deep ulceration, edema, lymphatic dilation, hyperplasia / duplication of muscularis mucosa
● May have prominent nerve plexuses (submucosal, myenteric), fibrosis, muscularization (Histopathology 2012;60:1034)
● Often serositis and thickened bowel wall
Late - architectural distortion (villus blunting), crypt atrophy, particularly in colon, pyloric or Paneth cell metaplasia in distal colon, rarely cystically dilated glands (enteritis cystica profunda)
● Areas of stricture may have thick and continuous muscle layer from mucosal base to muscularis propria 1 cm or more in length, called “obliterative muscularization of submucosa" (Arch Pathol Lab Med 2001;125:1331)
● Isolated colonic Crohn’s may mimic ulcerative colitis – involve younger patients, only mucosal involvement and with fewer major microscopic features (Mod Pathol 2012;25;295)

Micro images
=========================================================================


 
Deep fissuring ulcers


Crypt abscess


Obliterative muscularization


Granulomatous enteritis


Lymphoid follicles


Comparison with ulcerative colitis

Virtual slides
=========================================================================



Small intestine

Differential diagnosis
=========================================================================

● Ischemic bowel disease
Tuberculosis



Inflammatory disorders

Diaphragm disease


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Small bowel pathology related to NSAID use, first described in 1988 (J Clin Pathol 1988;41:516)

Treatment
=========================================================================

● Cessation of NSAID use
● Often surgery (Colorectal Dis 2012;14:804) or endoscopic balloon dilation (Gastrointest Endosc 2006;64:1014)

Case reports
=========================================================================

● 46 year old woman with chronic aspirin use (Case of the Week #240)

Gross description
=========================================================================

● Segmentation of ileum by incomplete mucosal diaphragms, defined as thin circumferential membranes resembling the plica circularis, composed of mucosa and submucosa with accompanying fibrosis
● Also ulceration, strictures, perforation

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Thin circumferential membranes resembling plica circularis, composed of mucosa and submucosa with accompanying fibrosis
● Neuromuscular and vascular hamartoma-like changes, eosinophilic enteritis and acute inflammation (Am J Clin Pathol 2008;130:518).

Micro images
=========================================================================


           

       
Top row: H&E; bottom row: trichrome

Differential diagnosis
=========================================================================

● Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE): small intestinal strictures and ulcerations of unknown origin (World J Gastroenterol 2011;17:2873), characterized as atypical vasculitis presenting with unexplained stricture and ulceration of the small bowel in young and middle-aged patients, but without systemic inflammation; treated with steroids



Inflammatory disorders

Duodenitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Inflammation of duodenum due to various causes, associated with dyspepsia

Micro description
=========================================================================

● Increased plasma cells, edema, intraepithelial neutrophils
● Severe cases have villous atrophy, more neutrophils but fewer plasma cells
● Gastric metaplasia, Helicobacter pylori may be present

Micro images
=========================================================================



Various images



Inflammatory disorders

Enterocolic (lymphocytic) phlebitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

Clinical features
=========================================================================

● Venous lesions with lymphocytic infiltration of venular wall, necrotizing phelibitis, granulomatous phlebitis and endothelial and myointimal hyperplasia (Am J Surg Pathol 2000;24:824, Arch Pathol Med Lab 2007;131:1130)
● Also called lymphocytic or granulomatous or necrotizing phlebitis, myointimal venous hyperplasia
● Also ischemia and necrosis of ileum or colon due to localized phlebitis associated with fresh or organized thrombus of intramural mesenteric veins
● No systemic vasculitis
● Associated with hydroxyethyl rutozide, also other drugs
● Does not recur after surgery

Diagnosis
=========================================================================

● Predominantly lymphocytic infiltration of intramural tributaries of mesenteric veins

Case reports
=========================================================================

● 53 year old man with coexisting lymphocytic colitis, lymphocytic enteritis, and lymphocytic appendicitis (Am J Surg Pathol 2004;28:542)
● 66 year old woman with isolated mesocolic vasculitis (Am J Surg Pathol 2001;25:827)
● 68 year old man with chronic antral ulcer associated with gastroduodenal lymphocytic phlebitis (Am J Surg Pathol 2004;28:1659)
● 74 year old woman with ischemic colitis (Mod Pathol 2000;13:897)

Micro description
=========================================================================

● Lymphocytic infiltrate of venules

Micro images
=========================================================================






Inflammatory disorders

Eosinophilic enteritis / gastroenteritis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare disease that may present as obstruction, associated with peripheral eosinophilia and allergic symptoms in children or young adults (Rev Esp Enferm Dig 2004;96:279, Ann Acad Med Singapore 2011;40:379, Ital J Pediatr 2011;37:18)
● Nausea, vomiting, diarrhea, steatorrhea, protein-losing enteropathy
● Symptoms are related to site of infiltration: mucosa of stomach/small bowel-diarrhea and malabsorption; submucosa and muscularis propria-obstruction; subserosa-ascites

Micro description
=========================================================================

● Marked eosinophilic infiltration of bowel wall (>20 eosinophils/HPF in at least one focus), prominent vessels, occasionally necrotizing granulomas and vasculitis
● Eosinophils typically not associated with other inflammatory cells
● Infiltration may be patchy

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

Ancylostoma caninum infection
● Collagen vascular disease
● Inflammatory bowel disease
● Lymphoma
● Sarcocystis infection



Inflammatory disorders

Graft versus host disease


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Apoptotic cells and fibrosis commonly associated with allogeneic bone marrow transplant (Dig Dis Sci 2012;57:720)
● Recommended to delay biopsies until week 4 of immunosuppressive therapy or later
● Symptoms include severe watery diarrhea, changes in skin and liver

Case reports
=========================================================================

● 22 month old girl with AML and small bowel obstruction post bone marrow transplant (Korean J Hematol 2012;47:142)

Gross images
=========================================================================



Severe chronic GVHD involving small intestine, leading to obstruction of terminal ileum

Micro description
=========================================================================

● Acute: epithelial crypt apoptosis with minimal inflammation; severe cases have sloughing of mucosa
● Chronic: lamina propria fibrosis and submucosal fibrosis extending up to serosa

Micro images
=========================================================================



Severe loss of mucosal epithelium, many basal single cell apoptotic bodies, crypt dropout, submucosal/subserosal fibrosis



Inflammatory disorders

Ileal pouch / pouchitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Pouch is formed from connecting loops of terminal ileum for patients requiring total colectomy; used to create continence in an ileostomy or to preserve anal sphincter function
● Pouches are contraindicated in Crohn’s disease, because they are associated with fistulas and abscess
Complications: fistula, obstruction, incontinence, leaks, pouchitis

Pouchitis
=========================================================================

● Incidence 8% to 46%
● Some cases are due to initially undiagnosed Crohn’s disease
● Nausea, vomiting, malaise, fever, cramping
● Increased ileal stool that is bloody, watery, foul smelling
● Often with altered bacteria

Treatment
=========================================================================

● Antibiotics, pouch excision

Micro description
=========================================================================

● Decreased epithelial cell mucin, few/no lymphoid follicles
● Ulcers with granulation tissue, cryptitis, crypt abscesses and patchy neutrophils
● Rarely dysplasia
● CD10 staining confirms biopsy site - terminal ileum (CD10+) versus colon (CD10-), although negative staining also occurs in active enteritis (Mod Pathol 2011;24:1627)

Micro images
=========================================================================



CMV pouchitis: biopsy of post-colectomy pouch in 38 year old man with ulcerative colitis (courtesy of Dr. Hanni Gulwani)


CD10 staining



Inflammatory disorders

Jejunitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called acute phlegmonous jejunitis
● Rare, men and women age 55+ years

Case reports
=========================================================================

● 61 year old man with phlegmonous jejunitis associated with relatively mild strep infection (Scand J Infect Dis 2000;32:421)

Gross description
=========================================================================

● Sharply demarcated bowel mucosal inflammation, often with serosal pus
● Edematous bowel wall, glassy mesentery, enlarged lymph nodes

Micro description
=========================================================================

● Lymphangitis, regional lymphadenitis, abscesses within mesentery

Micro images
=========================================================================



Various images



Inflammatory disorders

Lymphocytic enterocolitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Refractory spruelike condition associated with colonic mucosal abnormalities (Can J Gastroenterol 2008;22:771)

Micro images
=========================================================================



Lymphocytic ileitis,: ileal biopsy from 28 year old man with chronic diarrhea shows marked increase in intraepithelial lymphocytes (Courtesy of Dr. Hanni Gulwani)


Lymphocytic colitis related

General
=========================================================================

● High intraepithelial lymphocyte count in terminal ileum biopsies (Mod Pathol 2003;16:115, Am J Surg Pathol 2002;26:1484)
● Normal range of ileal lymphocytes is 0-9 lymphocytes / 100 enterocytes, decreases with age (Am J Clin Pathol 2007;127:816)
● Lymphocytes are mostly suppressor T cells
Symptoms: chronic nonbloody diarrhea, relatively normal endoscopy

Micro images
=========================================================================



Terminal ileum with villous atrophy and increase in intraepithelial lymphocytes



Inflammatory disorders

Malakoplakia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare in small bowel; most likely secondary to bacterial infection (Gastroenterol Clin Biol 2003;27:655, Arch Pathol Lab Med 2010;134:378)

Case reports
=========================================================================

● 70 year old woman with Crohn's disease (Internet Journal of Gastroenterology 2007;5(2))

Micro description
=========================================================================

● Histiocytes contain calcospherites (Michaelis-Gutmann bodies)

Micro images
=========================================================================



Multiple von Hansemann cells and Michaelis-Gutmann bodies in ileum (PAS stain)


Michaelis-Gutmann bodies are calcium+ (von Kossa stain)



Inflammatory disorders

Necrotizing enterocolitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Acute, necrotizing inflammation of small bowel and colon in patients with myelosuppression
● Also called typhlitis, neutropenic enterocolitis, ileocecal syndrome
● Most common acquired GI emergency of neonates (eMedicine)
● Common in premature or low birth weight infants, particularly when they start on oral foods at 2-4 days
● Also adults with various myeloproliferative disorders, solid malignancies, post-transplant immunosuppression (eMedicine)
● Affects terminal ileum, ascending colon

Etiology
=========================================================================

● Intestinal bacteria invade immature intestinal epithelium, causing subsequent inflammation and tissue necrosis
● Bacteria in food produce more cytokines and injure mucosa
● May be due to TNF receptor 1 dependent depletion of mucus which occurs in immature small intestine (Am J Physiol Gastrointest Liver Physiol 2011;301:G656)
● May also be due to deranged intestinal blood flow (J Pediatr Surg 2011;46:1023)


Drawing

Clinical features
=========================================================================

Symptoms: mild GI disturbance or fulminant illness with intestinal gangrene, perforation, sepsis, shock
Complications: short bowel syndrome, malabsorption (due to ileal resection), strictures, recurrence

Treatment
=========================================================================

● Fluids and surgery if gangrene/perforation

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Early: mucosal edema, hemorrhage, necrosis
● Late: hemorrhagic and gangrenous bowel wall, fibrous strictures;often pneumatosis cystoides intestinalis
● After recovery, Paneth cell hyperplasia; colon also shows metaplastic Paneth cells (Pediatr Res 2011;69:217)

Micro images
=========================================================================



Various images

Additional references
=========================================================================

Pediatr Res 2011;69:183, J Pediatr Gastroenterol Nutr 2011;52:140



Inflammatory disorders

Radiation enterocolitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Observed acutely or years after radiation therapy for cervical carcinoma, Wilm’s tumor, lymphoma or other peritoneal tumors

Clinical features
=========================================================================

● Acute: anorexia, cramps, diarrhea due to mucosal injury and malabsorption
● Chronic: may present as inflammatory colitis or indolent; also vascular injury, ischemic fibrosis, stricture
● Treatment: resection if severe

Gross description
=========================================================================

● Thickened bowel wall

Micro description
=========================================================================

Acute:
● Varies from mild epithelial damage to massive necrosis and ulceration (BMC Surg 2004;4:10)
● Loss of columnar shape and nuclear polarity of enterocytes, nuclear pyknosis, bizarre nuclei, mucin depletion and decreased mitoses
● Also fibroblasts and endothelium with submucosal edema but low nuclear to cytoplasmic ratio, preservation of architecture
● No desmoplasia, no infiltrative pattern

Chronic:
● Atrophic and ulcerated mucosa, ectatic blood vessels, fibrosis of submucosa and muscular wall, vascular wall thickening, vascular stenosis
● Possible fistula formation, atherosclerosis-like changes of vasculature (subintimal lipid-laden macrophages, calcification, thrombosis), hyalinization of lamina propria

Micro images
=========================================================================



Acute changes (mice)



Inflammatory disorders

Sarcoidosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 15 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Multisystemic disorder of unknown cause characterized by noncaseating granulomas in involved organs (Orphanet J Rare Dis 2007 Nov 19;2:46); usually does NOT involve the small bowel (QJM 2010;103:60)
● Must rule out Crohn’s disease before making this diagnosis
● Presents with malabsorption, protein losing enteropathy and lymphangiectasia secondary to lymphatic obstruction

Case reports
=========================================================================

● 36 year old woman with 10 kg weight loss (Rev Med Interne 2010;31:262)

Clinical images
=========================================================================




Gastrocopy shows duodenal granulomatous involvement

Micro description
=========================================================================

● Compact bland noncaseating granulomas that involve bowel wall and regional nodes
● Must rule out Crohn's disease
● Negative stains / PCR for fungi, AFB

Micro images
=========================================================================



Various images



Inflammatory disorders

Ulcerative colitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Severe UC is associated with contiguous backwash ileitis and appendix involvement
● UC also associated with postcolectomy pouchitis
● Rarely diffuse duodenitis is associated with ulcerative colitis, but it does not behave as Crohn’s disease (Am J Surg Pathol 2000;24:1407)
● Diffuse chronic duodenitis in ulcerative colitis patients who have colectomy is a strong predictor of pouchitis (Am J Surg Pathol 2010;34:1672)

Backwash ileitis
=========================================================================

● Recommended to restrict use of term to active enteritis involving ileum contiguously from cecum that has a similar or greater degree of active inflammation; mild cases predominantly involves the superficial mucosa in a contiguous pattern
● Focal isolated ileal erosions, mucous gland metaplasia, or patchy edema with mild active inflammation are features of Crohn's disease (Am J Clin Pathol 2006;126:365)

Micro images
=========================================================================



Mild backwash ileitis in moderately active cecal chronic ulcerative colitis resection specimen; mucosa of distal ileum is edematous, and villi are slightly wider and flatter than norma; most of the active colitis stops abruptly at transition point between the 2 mucosae; the two most distal villi have the greatest degree of injury, including blunting, edema, and neutrophils in the lamina propria and surface epithelium


Moderate (left) and severe (center, right) backwash ileitis


Terminal ileum inflammation: (A) grade 1, cryptitis; (B) grade 2, scattered crypt abscesses
(C) grade 3, numerous crypt abscesses; (D) grade 4, ulcer




Infectious disorders

Diarrhea and dysentery


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Usual fluid input into intestines is 9 liters/day (oral intake-2, saliva-1, gastric-2, pancreatic-2, intestinal-1, other-1)
● Most reabsorbed in small bowel and colon
Diarrhea: increase in stool mass, frequency or stool fluidity (3 or more loose stools/day, eMedicine)
Dysentery: low volume, painful, bloody diarrhea
Exudative disease: purulent bloody stools, persists with fasting: due to bacteria (Salmonella, Shigella, Campylobacter), Entamoeba histolytica, idiopathic inflammatory bowel disease, typhlitis
Malabsorption: bulky stools, abates with fasting, due to defective intraluminal digestion, primary mucosal cell abnormalities, reduced small bowel surface area, lymphatic obstruction, Giardia lamblia

Secretory diarrhea:
● >500 ml of fluid stool per day, isotonic with plasma, persists during fasting
● Infectious (viral damage to epithelium): rotavirus, Norwalk virus, enteric adenoviruses, calicivirus, astrovirus
● Infectious (enterotoxin): Vibrio cholera, E. coli, Bacillus cereus, Clostridium perfringens
● Neoplastic: tumor production of peptides, villous adenoma in distal colon
● Excessive laxatives

Osmotic diarrhea:
● Due to luminal solutes, abates with fasting, stool osmolality > electrolyte concentration by 50 mOsm
● Associated with lactase deficiency, lactulose therapy, gut lavage, antacids, primary bile acid malabsorption

Deranged motility:
● Improper gut neuromuscular function causes decreased transit time
● Due to surgical resection of gut, irritable bowel syndrome (neural dysfunction), hyperthyroidism, diabetic neuropathy, carcinoid syndrome
● Decreased motility due to small bowel diverticula, blind loop, bacterial overgrowth

Epidemiology
=========================================================================

● 12,000 deaths/year from dehydration in developing countries - 50% of all deaths before age 5
● Affects 40% of US population - #2 in attack rates in US after common cold

Micro description
=========================================================================

● Patchy lesions with variable villus abnormality, rarely severe
● Increased chronic and acute inflammatory infiltrate in epithelium and lamina propria
● Small intestinal bacterial overgrowth: common cause of chronic diarrhea and malabsorption with either villous blunting or normal duodenal biopsy (Arch Pathol Lab Med 2010;134:264)

Micro images
=========================================================================




Small intestinal bacterial overgrowth



Infectious disorders

Bacterial enterocolitis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Bacterial related disease due to either ingestion of pre-formed toxin (Staphylococcus aureus, Vibrio cholera, Clostridium perfringens), infection by toxigenic organisms or infection by enteroinvasive organisms which invade and destroy mucosal epithelium cells (eMedicine)
● Bacterial adhere to mucosal epithelial cells, elaborate enterotoxins, have capacity to invade
● Adhere by plasmid-mediated adhesins (E. coli, V. cholera), fimbriae or pili
● Adhesion destroys microvilli brush border

Clinical features
=========================================================================

● Complications due to massive fluid loss and loss of mucosal barrier include dehydration, sepsis, perforation
Salmonella: invades via transcytosis with minimal epithelial damage
Yersinia enterocolitica: penetrates ileal mucosa, multiplies in Peyer’s patches and regional lymph nodes
Insidious infection: Yersinia and Mycobacterium tuberculosis
Cytotoxins: Shiga toxin, enterohemorrhagic E. coli

Enterotoxins:
● Bind to cell membrane, enter cell, activates massive electrolyte secretion (cholera toxin, E. coli heat-labile and heat-stable toxins produce travelers diarrhea)
● No white blood cells in stool

Bacterial invasion:
● Enteroinvasive E coli and Shigella have plasmid that mediates epithelial cell invasion via microbe-simulated endocytosis; then intracellular proliferation, cell lysis, cell to cell spread

Patients ingest preformed toxins:
● Symptoms within hours
● Explosive diarrhea and acute abdominal distress
● 1-2 days
C. botulinum may produce rapid, fatal respiratory failure

Infection with enteric pathogens:
● Incubation of hours-days
● Diarrhea and dehydration (secretory enterotoxin) or dysentery (cytotoxin or enteroinvasive)

Travelers diarrhea:
● Fecally contaminated water/food
● Begins abruptly, subsides in 2-3 days

Micro description
=========================================================================

● Decreased epithelial cell maturation, increased mitotic figures, hyperemia and edema of lamina propria, variable neutrophils, modest villus blunting of small bowel
Late - lymphocytes, plasma cells, regenerative change

Differential diagnosis
=========================================================================

Inflammatory bowel disease



Infectious disorders

AIDS / HIV


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Small bowel infections are associated with Kaposi’s sarcoma, lymphoma, smooth muscle tumors, other infectious disorders (must look for them / rule them out)
● 30-60% with HIV infection historically had diarrhea and either malabsorptive symptoms with villus atrophy or colitis resembling ulcerative colitis
● Even with HAART therapy, small bowel infections may still include cytomegalovirus, cryptosporidia, Mycobacterium avium complex (MAC) infections and Microsporidia (Hum Pathol 2010;41:1777, Rev Inst Med Trop Sao Paulo 2012;54:89)

Micro images
=========================================================================



Histopathologic features of HIV-associated GI pathology (small bowel and other GI sties)



Infectious disorders

Anisakis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Larvae of Ascarids (Anisakidae) are found in sea animals
● After ingesting contaminated raw fish or other sea food, larvae attach to mucosa of stomach or small intestine and cause ulceration, penetration or perforation


Life cycle

Case reports
=========================================================================

● 37 year old woman with epigastric pain two hours after ingesting fried hake and fish ova, and 200 larvae obtained by endoscopy (J Investig Allergol Clin Immunol 2010;20:437)
● 50 year old man with abdominal pain and peripheral eosinophilia after eating raw salmon from Pacific Ocean (Am J Surg Pathol 2003;27:1167)

Clinical images
=========================================================================



Larvae in terminal ileum


Larvae in fish


Larvae in a herring

Micro description
=========================================================================

● Serositis, mucosal edema, submucosal abscess with eosinophils surrounding parasite with unpaired excretory gland (renette cell), Y-shaped lateral epidermal cords, no apparent reproductive system, and a ventriculus (glandular esophagus)
● No lateral alae, no ventricular appendage, no intestinal cecum

Micro images
=========================================================================



Larva in submucosa with eosinophils and lymphocytes


Larva in jejunum; note its intestinal lumen (L), the large lateral chords (LC) with a butterfly-like shape and many somatic muscle cells (MC); also a marked eosinophilic infiltrate with neutrophils and lymphocytes



Infectious disorders

Campylobacter


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

Campylobacter jejuni is found in milk or poultry or transmitted from animal contact
● Invades small bowel and colon, causes dysentery or diarrhea

Micro description
=========================================================================

● Villous blunting, purulent exudates

Electron microscopy images
=========================================================================



Chacteristic corkscrew appearance



Infectious disorders

Capillariasis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Infection by nematode Capillaria philippinensis
● Described in Philippines, Thailand, Iran, Korea, Egypt
● May cause protein-losing enteropathy; worms infest jejunum and upper ileum
● Resembles trichuriasis


Life cycle

Diagnosis
=========================================================================

● Worms, eggs, larvae in stool

Case reports
=========================================================================

● 40 year old woman from India with diarrhea (Indian J Med Microbiol 2012;30:236)

Micro images
=========================================================================



Ovum (left, center) and adult female (right)



Infectious disorders

Clostridium


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 16 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

Clostridium difficile
● Causes bloody diarrhea after antibiotics (antibiotic associated colitis)
● Other risk factors include inflammatory bowel disease, colectomy with ileostomy or other bowel surgery (Anaerobe 2011;17:52)
● Due to cytotoxin, but locally invasive only
● Nosocomial spread

Clostridium perfringens
● Causes watery diarrhea
● Produces enterotoxin, and usually noninvasive
● Transmitted from meat, poultry, fish

Clostridium perfringens, type C strain
● Produces severe necrotizing enterocolitis of jejunum and ileum (enteritis necroticans) with perforation, also called pigbel, a pidgin English term for abdominal pain after a pig feast, reflecting a 1963 cluster of cases
● Occurred after World War II in previously starved children/adults after eating large meals of meat and vegetables
● Currently associated with severe protein malnutrition in Asia, Africa, South Pacific
● Rarely occurs in developed countries in patients with diabetes
● High mortality rate unless diagnose early and treat with antibiotics or surgical excision of necrotic bowel
● Preventative vaccine is available for toxin

Case reports
=========================================================================

● 66 year old woman with Type 2 diabetes mellitus who developed severe abdominal pain and bloody diarrhea from cooked turkey sausage (Mod Pathol 2002;15:66)

Clinical images
=========================================================================



Clostridium difficile enteritis 9 years after total proctocolectomy

Gross description
=========================================================================

● Segmental necrosis of proximal jejunum

Micro description
=========================================================================

● Ischemic changes with necrotic villi, inflammatory cells and fibrinoid necrosis of vessel

Micro images
=========================================================================



Various images


Crypt eruption and pseudomembranes



Infectious disorders

CMV


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● CMV infections associated with immunosuppression, HIV; usually reflects disseminated infection if present in gut
● May cause necrotizing injury and perforation
● CMV duodenitis may present with bleeding or ulceration

Micro description
=========================================================================

● Inclusions in endothelial cells, fibroblasts, smooth muscle cells
● Necrosis and granulation tissue associated with moderate/marked lymphoplasmacytic infiltrate (Scand J Gastroenterol 2011;46:1228 )
● Small bowel allografts: circumscribed area of mucosal injury with few eosinophils (Transplant Proc 2010;42:2671)

Micro images
=========================================================================



Various images




38 year old man with CMV pouchitis, post-surgery for ulcerative colitis; note nucleomegaly with intranuclear inclusions (courtesy of Dr. Hanni Gulwani)

Additional references
=========================================================================

Endoscopy 2007;39:E23, J Clin Pathol 2006;59:1133



Infectious disorders

Cryptosporidium parvum


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Acid fast protozoa which causes self-limited disease in immunocompetent, but severe watery diarrhea resistant to most therapy in immunocompromised (J Biomed Res 2012;25:1)

Diagnosis
=========================================================================

● Acid-fast infective oocyst in stool

Micro description
=========================================================================

● 2-5 micron basophilic spherical structures attached to microvillus surface of epithelium
● Variable villus abnormality, may have eosinophils infiltrating mucosa

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Giemsa, silver stains, PAS

Differential diagnosis
=========================================================================

● Mucin
● Cellular debris



Infectious disorders

Cyclospora cayetanensis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Coccidian parasite associated with municipal water systems, first report in late 1970's, causes protracted diarrhea (Clin Microbiol Rev 2010;23:218)

Diagrams
=========================================================================



Life cycle

Diagnosis
=========================================================================

● Oocyst in stool with modified acid-fast stain

Micro description
=========================================================================

● Resembles isospora

Micro images
=========================================================================



Various images

Electron microscopy images
=========================================================================



Several acid fast stained oocysts



Infectious disorders

Escherichia coli


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Causes traveler’s diarrhea (watery diarrhea, hemorrhagic colitis / hemolytic-uremic syndrome)

Different types of E. coli infection:
Enterotoxigenic: cholera like, not invasive, from food or water, toxins activate adenylate cyclase and guanylate cyclase
Enterohemorrhagic: shiga-like toxin, not invasive, from undercooked beef
Enteropathogenic: enterocyte effacement, no invasion, from weaning foods, water; fatal diarrhea in newborns, colonize proximal small intestine
Enteroinvasive: invasion and local spread, from cheese, water, person-to-person spread
Enteradherent: noninvasive, adherent to epithelial brush border; chronic prolonged diarrhea, villous atrophy



Infectious disorders

Entamoeba histolytica


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Dysentery causing protozoa that can also cause fulminant colitis; causes up to 100,000 deaths per year (Trop Biomed 2011;28:194)
● Increased incidence in homosexual men and AIDS patients

Pathophysiology
=========================================================================

● Fecal-oral spread
● Amoeba invade colonic crypts, burrow into lamina propria, create flask shaped ulcer with broad base
● 40% invade portal vessels, embolize to liver and cause abscesses up to 10 cm
● May activate apoptosis in target cells (Trends Parasitol 2011;27:254)
● Rare abscesses in lung, heart, kidneys, brain


Life cycle

Micro images
=========================================================================



Various images


Amoebic colitis, numerous trophozoites of amoeba are noted (courtesy of Dr. Hanni Gulwani)


Amoebic colitis, PAS stain (courtesy of Dr. Hanni Gulwani)



Infectious disorders

Giardia lamblia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Protozoan infection associated with malabsorption, chronic diarrhea
● Spreads by fecally contaminated water, common in underdeveloped countries
● Affects 1/3 of homosexual men in urban communities
● Attaches to mucosa but does not invade
● May cause endoscopic duodenal nodularity (Indian J Pathol Microbiol 2011;54:312)
● Causes epithelial barrier dysfunction by down regulating claudin 1 and increasing epithelial apoptoses (Gut 2007;56:328)


Life cycle

Diagnosis
=========================================================================

● Detect cysts, trophozoites or antigens in stool

Micro description
=========================================================================

● Variable villous blunting, increased inflammatory cells, organisms are teardrop (pear) shaped with paired nuclei in lumen between villi
● Size of organism is similar to enterocyte nuclei

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Trichrome with iron hematoxylin counterstain, Giemsa stain



Infectious disorders

Isospora belli


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Coccidian parasite that infects epithelial cells of small intestine
● Causes chronic diarrhea and acalculous cholecystitis in AIDS patients (Indian J Med Res 2011;134:878)


Life cycle

Diagnosis
=========================================================================

● Cysts in stool, biopsy (H&E or EM)

Case reports
=========================================================================

● 35 year old HIV+ man (Indian J Pathol Microbiol 2010;53:824)

Micro description
=========================================================================

● Cysts present in parasitophorous vacuole in lamina propria (Hum Pathol 2001;32:500)
● Ovoid developmental forms are identified in and beneath epithelial cells near villus tip

Micro images
=========================================================================



Various images


Isospora belli (20-30 µm long by 10-19 µm wide) - immature oocyst (Modified acid fast stain)

Positive stains
=========================================================================

● Giemsa



Infectious disorders

Leishmaniasis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Intracellular protozoa that infects macrophages and may disseminate throughout reticuloendothelial system

Case reports
=========================================================================

● 27 year old man with intermittent night fever and abdominal pain (Iran Red Crescent Med J 2011;13:348)
● 33 year old man with AIDS, visceral leishmaniasis and mycobacterial infection (Arch Pathol Lab Med 1999;123:835)

Micro images
=========================================================================



Numerous foamy macrophages packed with microorganisms

Electron microscopy images
=========================================================================



Submucosal macrophage containing intracellular bacilli (long arrows) and protozoa



Infectious disorders

Microsporidia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Caused by Enterocytozoon bieneusi, an obligate intracellular protozoan that affects only enterocytes and Encephalitozoon intestinalis, which infects macrophages, fibroblasts, endothelial cells, enterocytes
● Both cause chronic diarrhea in patients with immunosuppression, HIV

Diagnosis
=========================================================================

● Stool examination, PCR

Case reports
=========================================================================

● 33 year old woman with myeloma, post-autologous stem cell transplant and chemotherapy for relapse (Emerg Infect Dis 2012;18:1155)
● 43 year old man with pancreas/kidney transplant recipient and mullti-organ system dissemination (Arch Pathol Lab Med 2004;128:e41)

Treatment
=========================================================================

● Albendozole for E. intestinalis, nothing for E. bieneusi

Micro description
=========================================================================

● Minimal/no changes in mucosa but can find development spores as 1.5 mm dots in enterocytes
● May be surrounded by halos
● Also nucleated sporont present as 3-5 micron, rounded, basophilic structure often surrounded by a halo

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Giemsa

Electron microscopy description
=========================================================================

● Often helpful for diagnosis



Infectious disorders

Mycobacteria


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

See also Tuberculosis

General
=========================================================================

● Aerobic and nonmotile bacteria without endospores or capsules that typically cause small bowel disease only in immunosuppressed or HIV+, usually as part of disseminated infection

Case reports
=========================================================================

● 31 year old woman with HIV and upper GI bleeding (Clin Infect Dis 2009;48:321, answer to quiz)

Micro description
=========================================================================

● Foamy macrophages fill lamina propria
● Usually patchy, no fat vacuoles

Micro images
=========================================================================



Disseminated Mycobacterium avium intracellulare complex (MAC) with nodular infiltration of duodenum


Acid-fast stain: site unspecified

Positive stains
=========================================================================

● PAS (faintly positive bacillary forms), acid-fast stains

Differential diagnosis
=========================================================================

Whipple’s disease



Infectious disorders

Salmonella


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Bacterial causing food poisoning and typhoid fever (S. typhi)
● Typhoid fever: systemic dissemination with bacteremia, fever, chronic infection of joints, biliary tree, bones and meninges
● From contaminated milk, eggs, beef, poultry
● Usually affects terminal ileum

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Ulcers overlying Peyer’s patches with minimal inflammatory cells, chiefly mononuclear (plasma cells, histiocytes and lymphocytes)
● Often histiocytes with erythrophagocytosis
● May lead to perforation or toxic megacolon

Micro images
=========================================================================



Lymph node


Various images

Additional references
=========================================================================

Science 2010;330:390, Gut 1985;26:935



Infectious disorders

Strongyloides stercoralis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 20 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Nematode with complex life cycle that alternates between free-living and parasitic cycles, with potential for autoinfection and multiplication within host

Life cyclel
=========================================================================

● Larvae burrow into mucosa of duodenum and jejunum, where they mature into adults
● Females lay eggs, which develop into larvae that pass into stool, where they mature and become infective
● Infective larvae in soil penetrate intact skin, usually through feet
● Larvae enter circulatory system, are transported to lungs, enter alveolar spaces, are carried to trachea and pharynx, are swallowed and enter intestinal tract, where process is repeated
● If larvae become infective before leaving body, they may invade intestinal mucosa or perianal skin, causing autoinfection


Life cycle

Clinical features
=========================================================================

● Symptoms: none, diarrhea, malabsorption
● Severe/fatal infections in immunocompromised, due to worms moving from GI tract into other organs (WormBook. 2007 May 23:1-15.)

Diagnosis
=========================================================================

● Larvae in stool
● Adult female or eggs in small bowel mucosa, often with eosinophilic or granulomatous inflammation

Case reports
=========================================================================

● 43 year old Honduran man with diarrhea and abdominal pain (Case of the Week #133)
● 66 year old man with weakness and epigastric pain (Int J Prev Med 2012;3:370)

Treatment
=========================================================================

● Antihelminths such as thiabendazole (Ann Pharmacother 2007;41:1992)
● Prevent by wearing shoes in endemic areas

Micro images
=========================================================================



Case of the Week #133


Various images

Virtual slides
=========================================================================



Small intestine

Additional references
=========================================================================

Arq Gastroenterol 2011;48:225



Infectious disorders

Tuberculosis


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Disease occasionally seen in less developed countries
● Small intestinal disease may be transmitted via contaminated milk
Symptoms: abdominal pain, malabsorption, strictures, perforation, fistula

Sites
=========================================================================

● Terminal ileum, cecum, appendix

Gross description
=========================================================================

● Multiple and circumferential ulcers and strictures

Micro description
=========================================================================

● Confluent granulomas with central necrosis and peripheral lymphocytosis
● Destruction of muscularis propria, scarring

Micro images
=========================================================================



Granulomas in mucosa and submucosa


Ileocecal tuberculosis in 45 year old woman; epithelioid granulomas with Langhan’s giant cells in lamina propria (courtesy of Dr. Hanni Gulwani)


Ileocecal tuberculosis and adjoining draining lymph node (courtesy of Dr. Hanni Gulwani)

Positive stains
=========================================================================

● Acid-fast stains

Differential diagnosis
=========================================================================

Crohn’s disease: linear and serpiginous ulcers; no bacteria identified (World J Gastroenterol 2011;17:433, BMJ Case Rep 2009;2009.1729)



Infectious disorders

Vibrio


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

Vibrio cholerae, O1 or O139 serogroup, is noninvasive bacteria which produces enterotoxin causing watery diarrhea and cholera (Lancet 2012;379:2466)
● Transmitted via water, shellfish, person-to-person
● Spreads via pandemics

Electron microscopy images
=========================================================================



Various images



Infectious disorders

Whipple’s disease


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare systemic infection due to Tropheryma whippelii, a gram positive intracellular actinomycete (World J Gastroenterol 2009;15:2078)
● Usually affects proximal intestine, mesenteric lymph nodes
● Also called intestinal lipodystrophy
● Usually white males ages 30-49 years

Symptoms:
● Malabsorption with diarrhea, weight loss, abdominal pain
● Occasionally polyarthritis, CNS complaints, lymphadenopathy, hyperpigmentation
● Cardiac involvement less common
● Fatal without antibiotics

Pathophysiology
=========================================================================



Pathophysiology of Whipple's disease

Diagnosis
=========================================================================

● PCR, immunohistochemistry, PAS stain

Treatment
=========================================================================

● Antibiotics
● Relapses are common

Gross description
=========================================================================

● Shaggy mucosa, edematous bowel wall

Micro description
=========================================================================

● Distended macrophages in lamina propria containing PAS+ granules and rod shaped bacilli by EM
● Dilated lymphatics or fat vacuoles
● Often multinucleated giant cells; rarely epithelioid granulomas in minority
● In mesentery or retroperitoneal nodes, resembles lipogranulomatous inflammation with round empty spaces

Note:
● After treatment, macrophages decrease in lamina propria but remain present elsewhere for years; cytoplasmic inclusions become tissue-paper like with PAS, resembling Gaucher’s cells

Micro images
=========================================================================





Various images (contributed by Drs. Derek Mathis and Rosemarie Rodriguez, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas)


PASD images (contributed by Drs. Derek Mathis and Rosemarie Rodriguez, San Antonio Uniformed Services Health Education Consortium, San Antonio, Texas)

Positive stains
=========================================================================

● PAS, anti-T Whippelii immunostain (Hum Pathol 2003;34:589)

Electron microscopy description
=========================================================================

● Rod-shaped bacteria

Differential diagnosis
=========================================================================

Histoplasmosis: faint blue dot-like inclusions surrounded by a clear halo, PAS or silver stain shows budding yeast
● Mineral oil ingestion
Mycobacterium avium-intracellulare infection: immunocompromised patients, patchy infection, no lipid vacuoles, PAS shows faintly positive bacillary forms



Infectious disorders

Yersinia


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Common cause of bacterial enteritis in US, Canada, Australia, Western Europe, Northern Europe (eMedicine)
● Infection due to Y. enterocolitica, Y. pseudotuberculosis, gram negative invasive rods
● Bacteria present in infected milk, pork, water supplies, domestic pets and farm animals
● Causes enterocolitis, acute appendicitis, mesenteric lymphadenitis in children and adolescents
● Pathogenic strains invade small intestinal mucosa via M cells overlying Peyer’s patches, multiply there and within regional nodes, then spreads hematogenously and via lymphatics
● Patients homozygous for Thalassemia major are at risk of Y. enterocolitica, because they have iron overload and the bacteria require iron for growth

Sites
=========================================================================

● Ileum, right colon, appendix

Diagnosis
=========================================================================

● Culture

Case reports
=========================================================================

● 4 year old boy with intussusception due to Y. enterocolitica infection (Arch Pathol Lab Med 2001;125:1486)

Micro description
=========================================================================

● Elongated ulcerations overlying lymphoid hyperplasia
● Also small aphthoid ulcers overlying colonies of gram negative rods and with neutrophils at ulcer base
● Also necrotizing granulomas (particularly with Y. pseudotuberculosis)
● Mesenteric nodes show follicular hyperplasia with variable scattered microabscesses and epithelioid granlomas

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

Crohn’s disease
Mycobacteria
Typhoid fever



Obstruction

Obstruction-general


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Mechanical causes: adhesions, atresia, bands, congenital stricture (children), fecaliths, foreign bodies, gallstones, hernias, inflammation, intussusception, mesenteric ossification (Am J Surg Pathol 1999;23:1464), systemic disease (diabetes, scleroderma), tumors, volvulus
● Disturbances in peristalsis: Hirschsprung’s, ileus-postoperative paralytic, myopathy
● 80% due to hernias, intestinal adhesions, intussusception, volvulus
● May cause stasis, with resulting malabsorption
● Symptoms: distension, failure to pass flatus, pain, vomiting

Treatment
=========================================================================

● Dietary changes, medication (octreotide), surgery, intestinal transplantation

Micro description
=========================================================================

● Patchy mucosal changes of variable villus abnormality, increased chronic inflammatory cells in epithelium and lamina propria, occasional neutrophils



Obstruction

Adhesions


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 12 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Adhesions develop between bowel segments or abdominal wall and operative site
● May create internal herniations (closed loops through which viscera slide)
● Rarely adhesions are congenital

Etiology
=========================================================================

● Post-operative, infections, endometriosis

Clinical images
=========================================================================



Adhesions between loops of small intestine



Obstruction

Chronic idiopathic intestinal pseudo-obstruction


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Symptoms of intestinal obstruction without mechanical obstruction
● Attributed to abnormal physiology of gut propulsive system

Etiology
=========================================================================

● Local manifestation of generalized disease: diabetes, hypoparathyroidism, Parkinson’s disease, SLE
● Diseases with intestinal pathology: amyloidosis, Chagas’ disease, dermatomyositis/polymyositis, Duchene’s muscular dystrophy, myotonic dystrophy, myxedema, scleroderma
● Also drugs (anti-Parkinson, clonidine, mushroom poisoning), pheochromocytoma, psychosis,
● May be due to marked reduction in interstitial cells of Cajal (Am J Surg Pathol 2003;27:228)
● By definition, excludes known mechanical causes of obstruction: cathartic colon, ceroidosis, Hirschsprung’s disease, visceral myopathies (muscle cell degeneration/loss, fibrosis of muscularis propria), visceral neuropathies (familial-Am J Surg Pathol 2010;34:1528, sporadic; require special techniques to demonstrate)



Obstruction

Hernias


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Protrusion of pouchlike, serosa-lined sac of peritoneum (hernia sac) through weakness or defect in wall of peritoneal cavity
● Usually inguinal and femoral canals, umbilicus and surgical scars
● Rarely around ligament of Trietz
● Viscera may protrude and become trapped in hernias, including bowel loops and omentum
Complications: incarceration, strangulation, infarction

Gross images
=========================================================================



Various images



Obstruction

Scleroderma


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 18 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called progressive systemic sclerosis
● GI manifestations in 50-90% (Rheumatology (Oxford) 2009;48:iii36)
● May cause malabsorption syndrome (related to bacterial overgrowth), intestinal pseudo-obstruction (Presse Med 2006;35:1952)

Micro description
=========================================================================

● Dense fibrosis replacing entire muscularis propria or accentuated in inner layer
● No vacuolar change



Obstruction

Volvulus


Reviewer: Hanni Gulwani, M.D. (see Reviewers page)
Revised: 17 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
=========================================================================

● Complete twisting of a loop of bowel about its mesenteric base of attachment
● Produces intestinal obstruction and infarction
● Usually in redundant loops of bowel

Case reports
=========================================================================

● 4 year old boy with midgut volvulus (Int J Emerg Med 2010;3:523)
● 17 year old boy with 10 year history of nonspecific GI symptoms, and midgut malrotation (N Am J Med Sci 2012;4:196)

Diagrams
=========================================================================



Volvulus

Gross images
=========================================================================



Small bowel volvulus and necrotic bowel

End of Small bowel (small intestine) > Superpage > Nontumor


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