Small bowel (small intestine) - Printer Friendly Version
Last revised 29 April 2007
Copyright © 2003-2007, PathologyOutlines.com, Inc.
See also Ampulla of Vater
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Table of Contents
Primary references, normal anatomy, normal histology
Congenital anomalies: atresia/stenosis, diverticula (not Meckel’s), duplication, Ehlers-Danlos, enterogenous cysts, gastroschisis, heterotopic gastric mucosa, heterotopic pancreas, Hirschsprung’s, malrotation, Meckel’s diverticulum, omphalocele
Patterns of abnormal architecture: severe villous, variable villus, nonspecific variable villus
Malabsorption: general, abetalipoproteinemia, acrodermatitis enteropathica, agammaglobulinemic sprue, celiac sprue, dermatitis herpetiformis, disaccharidase deficiency, intestinal lymphangiectasia, microvillus inclusion disease, refractory sprue, tropical sprue
Ulcers: duodenal peptic ulcer, marginal ulcer, small bowel ulcer
Inflammatory disorders: autoimmune enteropathy, Behcet’s disease, collagenous enterocolitis, Crohn’s disease, duodenitis, enterocolic (lymphocytic) phlebitis, eosinophilic enteritis, graft vs. host disease, ileal pouch/pouchitis, jejunitis, lymphocytic enterocolitis, malakoplakia, necrotizing enteritis, radiation enterocolitis, sarcoidosis, Torkelson syndrome, ulcerative colitis
Infectious disorders: diarrhea and dysentery, bacteria, AIDS, Anisakis, Campylobacter, Capillariasis, Clostridium, CMV, Cryptosporidium, Cyclospora, Entamoeba histolytica, E coli, Giardia, Isospora, Leishmaniasis, Microsporidiosis, Mycobacteria, Salmonella, Strongyloides, Vibrio, Whipple’s disease, Yersinia
Obstruction: general, adhesions, chronic idiopathic pseudo-obstruction, hernias, scleroderma, volvulus
Other/benign tumors or tumor-like conditions: adenoma, amyloidosis, barium granuloma, blue rubber bleb nevus syndrome, brown bowel syndrome, Brunner’s gland hamartoma, Brunner’s gland nodule, clofazimine, colchicine toxicity, common variable immunodeficiency syndrome, Cowden’s syndrome, Cronkite-Canada syndrome, endometriosis, enteritis cystica profunda, fibromatosis, gangliocytic paraganglioma, ganglioneuroma, hemangioma, hemorrhagic necrosis, hereditary telangiectasia, hyperplastic Pacinian corpuscle, idiopathic retractile mesenteritis, idiopathic retroperitoneal fibrosis, inflammatory fibroid polyp, inflammatory myofibroblastic tumor, inflammatory polyp, intussusception, ischemia, kayexelate, Klippel-Trenaunay-Weber syndrome, leiomyoma, lipoma, lymphangiectasia, lymphangioma, lymphoid hyperplasia, mastocytosis, myxoma, neurofibroma, neuromuscular and vascular hamartoma, Peutz-Jeghers polyp, pneumatosis cystoids intestinalis, pseudomelanosis duodeni, radiation effect, reactive nodular fibrous pseudotumor, sclerosing peritonitis, selective IgA deficiency, transplantation, tufting enteropathy, Turner’s syndrome, vascular disease, vasculitis
Carcinoma: general, adenocarcinoma, adenosquamous, anaplastic, neuroendocrine, signet ring, small cell
Lymphoma: general, Burkitt’s, diffuse large B cell, follicular, histiocytic, Hodgkin’s, lymphoplasmacytic, MALT, mantle cell, Mediterranean, natural killer cell (NK), post-transplant, primary effusion, sprue-associated, Waldenström macroglobulinemia
Other malignancies: carcinoid tumor, carcinoid syndrome, duodenal endocrine tumors, follicular dendritic cell sarcoma, GANT, GIST, granulocytic sarcoma, Kaposi’s sarcoma, leiomyosarcoma, metastases, mullerian adenosarcoma, Zollinger-Ellison syndrome
Miscellaneous: staging, features to report
American Journal of Surgical Pathology (AJSP), Jan 2000 to Sep 2003
Archives of Pathology and Lab Medicine (Archives), Jan 1999 to Sep 2003
Human Pathology (Hum Path), Jan 2000 to July 2003
Modern Pathology (Mod Path), Jan 2000 to Aug 2003
AJCC Cancer Staging Manual (6th Ed)
Rosai, J: Ackerman’s Surgical Pathology (8th Ed); Mosby-Year Book, Inc., 1996
Sternberg, S: Diagnostic Surgical Pathology (3rd Ed); Lippincott Williams & Wilkins, 1999
Please refer to these primary references for more detailed discussions and photographs
6 meters long, divided into duodenum, jejunum, ileum
Duodenum: 25 cm long, from pyloric sphincter to ligament of Treitz, mostly retroperitoneal, fixed in position
Jejunum: 240 cm long, 40% of remainder of bowel, begins at ligament of Treitz
Ileum: 360 cm long, distal 60% of post-duodenal bowel
Mucosa has transverse folds, prominent in proximal ileum, flat/absent at terminal ileum
Peyer’s patches: oval, in antimesenteric side of terminal ileum, represent lymphoid follicles
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 drains to mesenteric nodes and nodes around superior mesenteric artery, terminal ileum drains to ileocolic nodes
Intestinal immune system
Peyer’s patches in ileum
M cells (membranous) in small bowel and colon, which transfer antigen macromolecules from lumen to lymphocytes
T cells, usually CD8+ are 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
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
top
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; contain 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
Absorptive cells: have microvilli on luminal surface (brush border) and underlying mat of microfilaments (terminal web)
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 cell of Cajal, 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
Reference: AJSP 2003;27:228
Congenital anomalies
Atresia: imperforate mucosal diaphragm or string like segment of bowel
Case report of multiple areas of jejunal atresia with apple peel deformity (twisted around an artery) associated with 22q11 abnormality, Archives 2000;124:880
Stenosis: narrowing of lumen; less common
Causes: developmental failure, intrauterine vascular accidents, intussusceptions
Complications: perforation, meconium peritonitis, brown bowel syndrome
Diverticula (other than Meckel’s)
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; 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
Saccular to long, cystic structures; duplication usually is incomplete due to shared muscular wall
More common in ileum
Rare in duodenum, choledochocele is more common
Not associated with vertebral body abnormalities
Treatment: resect entire duplication and segment of normal bowel attached to it
Defect of collagen synthesis, may cause spontaneous intestinal perforation and hemorrhage; also hyperelasticity of skin and joints
Found in wall of small bowel, mesentery, posterior mediastinum or rectorectal space
May be associated with vertebral body abnormalities
Micro: lined by respiratory, small intestinal or gastric epithelium; wall composed of irregularly oriented smooth muscle
Portion of abdominal wall fails to form together, with extrusion of intestines
Discrete small nodules or sessile polyps, usually in duodenum
Fundic mucosa usually present
May cause obstruction, ulceration, bleeding, perforation, intussusception, pain
Case report at Archives 2003;127:506
Presence in duodenum is associated with H. pylori infection and is probably not congenital, Hum Path 2003;34:156
DD: pyloric gland metaplasia, peptic ulcer disease (no goblet cells)
Also called adenomyoma, myoepithelial hamartoma (although without pancreatic tissue)
Incidence of 1-14%
Most common near ampulla of Vater; also stomach, jejunum
May cause blockage of duct, leading to infection, cystic dilation and fat necrosis
Usually encountered incidentally at surgery, submitted for frozen section
Case reports of associated carcinoma, Archives 1999;123:707, acinar cell#1, #2, ductal adenocarcinoma
Gross: submucosal nodule, intramural mass; yellow-white, lobulated, 0.2 cm to 4 cm; may have central mucosal dimple
Micro: pancreatic ducts and acini with smooth muscle proliferation but without islets
Originates in colon, but may extend into small bowel, causing enterocolitis and high mortality
See complete discussion under colon
From improper embryologic rotation of gut
Persistence (failure to involute) of proximal vitelline duct (aka 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
Found in 2% of normal population, usually asymptomatic, 63% males
Usually 20 cm proximal to ileocecal valve on antimesenteric side of bowel, 1-8 cm long
Associated with other congenital anomalies
Case report with involvement of Crohn’s disease and pancreatic heterotopia, Archives 2003;127:E99
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
Treatment: remove if found at surgery, even if incidental
Micro: usually small intestinal mucosa, but 50% have gastric or pancreatic heterotopia; contains all 3 layers of bowel wall
Abdominal musculature fails to form
Infant born with herniated abdominal contents into ventral membranous sac
Patterns of abnormal small bowel architecture
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
Variable villus abnormality and crypt hypoplasia
Villi focally flat or mild/moderate villus shortening
Also increased intraepithelial lymphocytosis, decreased crypt mitotic figures
Causes: marasmus (severe protein-calorie malnutrition), kwashiorkor (protein malnutrition but adequate caloric intake), megaloblastic anemia (vitamin B12 and folate deficiency, no increased inflammatory cells), chemoradiation effect (apoptosis, atypical cells), microvillus inclusion disease
Nonspecific variable villus abnormality
Various villus abnormalities, usually not flat mucosa
Usually due to partial treated celiac sprue
Malabsorption
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
Symptoms, due to deficiency in ( ): 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)
Steatorrhea: bulky, greasy stools associated with weight loss, anorexia, muscle wasting
In US, most common malabsorption disorders are celiac sprue, pancreatic insufficiency and Crohn’s disease
Physiologic classification of malabsorption - due to disturbances of:
(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
Rare inborn error of metabolism, autosomal recessive
Due to defect in synthesis and export of apoprotein B from intestinal mucosal cells; free fatty acids and monoglycerides cannot be assembled into chylomicrons and become triglycerides stored within cells, causing lipid vacuolization
Laboratory: lipid profile shows no chylomicrons, no VLDL, no LDL; CBC smear shows acantholytic red blood cells (Burr cells) due to lipid membrane abnormalities
Symptoms: failure to thrive, diarrhea, steatorrhea
Micro: marked fat vacuoles in apical villous cytoplasm, villi normal
Positive stains: fat stains highlight lipid vacuoles
DD: megaloblastic anemia, celiac sprue, tropical sprue have similar vacuolar change
Autosomal recessive, linked to zinc deficiency, affects children
Cutaneous lesions (perioral and extremity skin lesions, alopecia, nail dystrophy), diarrhea, malabsorption
Treatment: zinc sulfate
Micro: severe villus abnormality in some; normal in others
EM: rodlike fibrillar inclusions in Paneth cells
No plasma cells in lamina propria
Also called nontropical sprue, gluten-sensitive enteropathy, celiac disease
Individuals with a 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
Disease is due to abnormal cell mediated immunity, perhaps associated with adenovirus infection (cross reactivity to E1b protein of type 12 adenovirus); gluten exposure causes accumulation of intraepithelial cytotoxic T cells and helper T cells in lamina propria
Major cause of malabsorption; almost all adults in North America with severe villous abnormality and crypt hyperplasia have celiac sprue
Improves clinically and microscopically after withdrawal of wheat gliadins and related grain proteins from diet
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
Symptoms: diarrhea and failure to thrive in newborns; or symptoms of diarrhea, flatulence, weight loss, fatigue beginning as late as age 40
Late onset: 40’s and 50’s; symptoms of short stature, infertility, peripheral neuropathy, iron or folate deficiency, osteoporosis, indigestion, dental enamel defects
Labs: 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
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
Diagnosis: antitransglutaminase or antigliadin or antiendomysial antibodies plus clinical malabsorption plus typical histologic findings plus improvement in symptoms and histology after gluten withdrawal
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
Gross: usually flat, scalloped mucosa; may be normal
Micro: increase in intraepithelial lymphocytes (initial and most sensitive marker, 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); 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; neutrophils, if present, are not prominent
Note: pathology report can only say consistent with celiac sprue
DD: severe tropical sprue (no antiendomysial antibodies, responds to antibiotics and folate), dermatitis herpetiformis (associated with gluten-sensitive enteropathy but also has skin lesions), infectious enteritis (prominent neutrophils, normal intraepithelial lymphocytes), kwashiorkor, common variable immunodeficiency (no plasma cells, marked lymphoid hyperplasia, often Giardia infection), other protein allergies (sprue symptoms with disappearance and reappearance if offending substance is withdrawn / reintroduced), Crohn’s disease, autoimmune enteropathy (crypt injury or destruction, anti-enterocyte antibodies, typically within first 6 months of life)
References: Mod Path 2003;16:342
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 lesion symmetrically distributed on scalp, buttocks, extremities, with granular deposition of IgG at epidermal-dermal junctional
Micro: severe mucosal lesion on small bowel biopsy; may be patchy with variable villus abnormality
Disaccharidase (lactase) deficiency
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
Diagnosis: increased hydrogen in breath test due to bacterial fermentation of undigested lactose
Treatment: terminate milk and milk products
Dilated lymphatic channels cause protein-rich fluid in lamina propria and then into gut lumen, causing protein-losing enteropathy
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 Path 2000;31:1404
Treatment: small bowel transplant
Micro: severe villous abnormality with crypt hypoplasia, resembling celiac sprue but without lymphocytosis; increased enterocyte apoptosis and proliferation
Positive stains: CD10, PAS, polyclonal CEA, alkaline phosphatase (cytoplasmic staining vs. linear brush border staining in normals); vacuoles - PAS, CEA
EM: abnormal microvillus structures at luminal border of enterocytes; apical intracytoplasmic inclusions lined by microvilli
References: AJSP 2002;26:902
Also called unclassified sprue
Celiac sprue that does not respond to gluten free diet; may be due to lymphoma
Note: wheat is present in many foods, so must ensure that diet is really gluten free
Associated with cavitation of mesenteric lymph nodes and hyposplenism
Collagenous sprue: patchy, excessive subepithelial collagen deposit in some of these patients (5/10 in one study); may eventually respond to gluten-free diet, but disease may also be fatal
DD: lymphoma
References: AJSP 2000;24:676
Also called post-infectious sprue
Affects people living in or visiting the tropics, particularly Caribbean (not Jamaica), Africa, India, SE Asia, Central/South America
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: variable villous atrophy (none, partial, total); injury to entire small bowel (not proximal as in celiac sprue), inflammatory infiltrate, crypt hyperplasia
Ulcers
Decreasing incidence, but still common
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
Gross: 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: 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 metaplasia and chronic duodenitis common; various villus abnormality in proximal duodenum with active duodenitis; also Brunner’s gland hyperplasia; Helicobacter pylori often present
Associated with gastrojejunostomy opening, usually in jejunum distal to stoma
Almost always related to other gastroduodenal disease
Associated with obstruction, perforation, hemorrhage
Causes: congenital anomalies, mechanical disorders, vascular occlusions, radiation, celiac disease, endometriosis, tumors, specific inflammations, medication (NSAIDs, enteric-coated potassium and hydrochlorothiazide)
Gross: ulcer with adjacent hemorrhage, congestion, edema
Micro: nonspecific changes
Inflammatory disorders
Intractable watery diarrhea syndrome in infants
Associated with antibodies to intestinal epithelial cells
Usually severe and intractable, requiring total parenteral nutrition
Similar condition in adults associated with variable immunodeficiency and type I diabetes, rheumatoid arthritis, hemolytic anemia
Treatment: immunosuppressive agents
Micro: variable villus abnormality, few intraepithelial lymphocytes; may have colitis
GI involvement in 10% of cases, usually ileum and cecum
Punched out ulcers that may perforate; perivascular inflammation and necrotizing vasculitis often present
Also aphthous stomatitis, genital ulcers, relapsing iritis
High intraepithelial lymphocyte count in terminal ileum biopsies of affected patients, Mod Path 2003;16:115, AJSP 2002;26:1484
Lymphocytes are mostly suppressor T cells
Symptoms: chronic nonbloody diarrhea, relatively normal endoscopy
Positive stains: trichrome
Also called terminal ileitis, regional enteritis, granulomatous colitis
Relapsing, discontinuous, transmural granulomatous disease from oral cavity to anus, usually involves small intestine and colon
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
Cause unknown, although recent study found Yersinia DNA in 30% of cases by PCR, AJSP 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
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
Carcinoma: small bowel - mean 20 years after onset of Crohn’s, usually ileum or site of active disease; often in strictures, poorly differentiated, poor prognosis; 25% in bypassed bowel loops; 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
Sites: small bowel only (particularly terminal ileum)-40%, colon only-30%; rarely other sites in GI tract
Course: progressive, only rarely regresses
Treatment: medical (immunosuppressive therapy), surgical
Gross: 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
Micro: 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); 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”, Archives 2001;125:1331
DD: Crohn’s disease of colon resembles ulcerative colitis (Crohn’s: skip lesions, transmural involvement, deep ulcerations, marked lymphocytic infiltrate, serositis, granulomas, fissures, fistulas, malabsorption if ileum involved); sigmoid colon diverticular disease; tuberculosis, ischemic bowel disease
Associated with dyspepsia
Micro: increased plasma cells, edema, intraepithelial neutrophils; severe cases have villous atrophy, more neutrophils but fewer plasma cells; gastric metaplasia, Helicobacter pylori may be present
Enterocolic (lymphocytic) phlebitis
Also called lymphocytic or granulomatous or necrotizing phlebitis, myointimal venous hyperplasia
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
References: AJSP 2000;24:824
Eosinophilic enteritis / gastroenteritis
Associated with peripheral eosinophilia and allergic symptoms in children or young adults
Nausea, vomiting, diarrhea, steatorrhea, protein-losing enteropathy
Symptoms are related to site of infiltration - mucosa of stomach/small bowel with diarrhea and malabsorption, submucosa and muscularis propria with obstruction, subserosa with ascites
Micro: marked eosinophilic infiltration of bowel wall, prominent vessels, occasionally necrotizing granulomas and vasculitis; eosinophils typically not associated with other inflammatory cells; infiltration may be patchy
DD: Ancylostoma caninum infection, Sarcocystis infection, collagen vascular disease, inflammatory bowel disease, non-Hodgkin’s lymphoma
Associated with bone marrow transplants
Severe watery diarrhea, also changes in skin and liver
Micro: epithelial crypt apoptosis with minimal inflammation; severe cases have sloughing of mucosa
Formed from connecting loops of terminal ileum; for patients requiring total colectomy 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
Micro: decreased epithelial cell mucin, few/no lymphoid follicles; ulcers with granulation tissue, cryptitis, crypt abscesses and patchy neutrophils; rarely dysplasia
Treatment: antibiotics, pouch excision
Also called acute phlegmonous jejunitis
Rare, men and women age 55+
Gross: sharply demarcated bowel mucosal inflammation, often with serosal pus; edematous bowel wall, glassy mesentery, enlarged lymph nodes
Micro: lymphangitis, regional lymphadenitis, abscesses within mesentery
Spruelike condition
Refractory spruelike condition associated with colonic mucosal abnormalities
Lymphocytic colitis related
High intraepithelial lymphocyte count in terminal ileum biopsies of affected patients, Mod Path 2003;16:115, AJSP 2002;26:1484
Lymphocytes are mostly suppressor T cells
Symptoms: chronic nonbloody diarrhea, relatively normal endoscopy
Most likely secondary to bacterial infection
Rare in small bowel
Micro: histiocytes contain calcospherites (Michaelis-Gutmann bodies)
Acute, necrotizing inflammation of small bowel and colon
Most common acquired GI emergency of neonates; common in premature or low birth weight infants, particularly when they start on oral foods at 2-4 days
Cause: feeding with immature gut immune system causes release of proinflammatory cytokines; bacteria in food produce more cytokines and injure mucosa; may also be due to deranged intestinal blood flow
Affects terminal ileum, ascending colon
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
Micro: early-mucosal edema, hemorrhage, necrosis; late-hemorrhagic and gangrenous bowel wall, fibrous strictures; pneumatosis cystoides intestinalis often present
Acute - anorexia, cramps, diarrhea due to mucosal injury and malabsorption
Chronic - may present as inflammatory colitis or indolent; vascular injury, ischemic fibrosis, stricture
Micro (chronic): atrophic mucosa, ectatic blood vessels, fibrosis, vascular wall thickening, vascular stenosis
Usually does NOT involve the small bowel
Should rule out Crohn’s disease before making this diagnosis
Autosomal dominant trait in Mennonites in Canada
Early childhood diarrhea and dehydration may be fatal
May have common variable immunodeficiency but no malabsorption
Micro: lamina propria edema, shortened and broadened villi, focal acute inflammatory changes
Backwash ileitis and involvement of appendix occurs in continuity with severe colitis; also postcolectomy pouchitis
Rarely diffuse duodenitis is associated with ulcerative colitis, but it does not behave as Crohn’s disease, AJSP 2000;24:1407
Infectious disorders
Usual intestinal fluid input 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
Dysentery: low volume, painful, bloody diarrhea
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
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
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: patchy lesions with variable villus abnormality, rarely severe; increased chronic and acute inflammatory infiltrate in epithelium and lamina propria
Due to 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
Bacterial adhere to mucosal epithelial cells, elaborate enterotoxins, have capacity to invade
Adherence by plasmid-mediated adhesins in E. coli and V. cholera; may be via fimbriae or pili; adhesion destroys microvilli brush border
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
Cytotoxins: Shiga toxin, enterohemorrhagic E. coli
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
Salmonella: invades via transcytosis with minimal epithelial damage
Yersinia enterocolitica: penetrates ileal mucosa, multiplies in Peyer’s patches and regional lymph nodes
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
Insidious infection: Yersinia and Mycobacterium tuberculosis
Complications due to massive fluid loss and loss of mucosal barrier include dehydration, sepsis, perforation
Micro: 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
DD: inflammatory bowel disease
AIDS / HIV
Associated with Kaposi’s sarcoma, lymphoma, smooth muscle tumors; also infectious disorders (see below)
30-60% with HIV infection historically had diarrhea and either malabsorptive symptoms with villus atrophy or colitis resembling ulcerative colitis
Must rule out presence of other infectious organisms
Case report of patient with abdominal pain and peripheral eosinophilia after eating raw salmon from Pacific Ocean, AJSP 2003;27:1167
Micro: 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
Campylobacter jejuni and others invade small bowel or colon
Bacteria found in milk or poultry or transmitted from animal contact
Causes dysentery or diarrhea
Micro: villus blunting, purulent exudate
Infection by nematode Capillaria philippinensis; described in Philippines, Thailand, Iran, Korea, Egypt
May cause protein-losing enteropathy
Worms infest jejunum and upper ileum; resemble trichuriasis
Diagnosis: worms, eggs, larvae in stool
Clostridium difficile
Produces cytotoxin; locally invasive only
Nosocomial environmental spread
Produces bloody diarrhea after antibiotics (antibiotic associated colitis)
Clostridium perfringens
Produces enterotoxin; usually noninvasive
Transmitted from meat, poultry, fish
Causes watery diarrhea
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
Usually associated with severe protein malnutrition in parts of Asia, Africa, South Pacific
Rarely occurs in developed countries in patients with diabetes
Case report of 66 year old black woman with Type 2 diabetes mellitus who developed severe abdominal pain and bloody diarrhea after eating cooked turkey sausage prepared in Illinois, Mod Path 2002;15:66
Occurred after World War II in previously starved children/adults after eating large meals of meat and vegetables
High mortality rate unless diagnose early and treat with antibiotics or surgical excision of necrotic bowel; preventative vaccine is available for toxin
Gross: segmental necrosis of proximal jejunum
CMV duodenitis may present with bleeding or ulceration
Associated with immunosuppression, HIV; usually reflects disseminated infection if present in gut
May cause necrotizing injury and perforation
Micro: inclusions in endothelial cells, fibroblasts, smooth muscle cells
Cryptosporidium parvum
Associated with immunosuppression, HIV; rarely with contaminated water
Self-limited disease in immunocompetent; in immunocompromised, causes severe, watery diarrhea resistant to most therapy
Diagnosis: acid-fast infective oocyst in stool
Micro: 2-5 micron basophilic spherical structures attached to microvillus surface of epithelium; variable villus abnormality, may have eosinophils infiltrating mucosa
Positive stains: Giemsa, silver stains, PAS
DD: mucin, cellular debris
Diagnosis: oocyst in stool with modified acid-fast stain
Micro: resembles isospora
EM: helpful for diagnosis
Dysentery causing protozoa
Increased incidence in homosexual men and AIDS patients; can cause fulminant colitis
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
Rare abscesses in lung, heart, kidneys, brain
Causes traveler’s diarrhea (watery diarrhea, hemorrhagic colitis / hemolytic-uremic syndrome)
Different types of E. coli infection:
Enterotoxigenic: cholera like, not invasive, from food, water
Enterohemorrhagic: Shiga-like toxin, not invasive, from undercooked beef
Enteropathogenic: enterocyte effacement, no invasion, from weaning foods, water
Enteroinvasive: invasion and local spread, from cheese, water, person-to-person spread
Associated with malabsorption, chronic diarrhea
Spread by fecally contaminated water, common in underdeveloped countries
Affects 1/3 of homosexual men in urban communities
Attaches to mucosa but does not invade
Diagnosis: detect cysts, trophozoites or antigens in stool
Micro: 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
Positive stains: trichrome with iron hematoxylin counterstain, Giemsa stain
Ovoid developmental forms in and beneath epithelial cells near villus tip
Causes chronic diarrhea and acalculous cholecystitis in AIDS patients
Diagnosis: cysts in stool, biopsy (H&E or EM)
Micro: cysts present in parasitophorous vacuole in lamina propria
Positive stains: Giemsa
References: Hum Path 2001;32:500
Intracellular protozoa that infects macrophages and may disseminate throughout reticuloendothelial system
Case report of visceral leishmaniasis and mycobacterial infection in same lesion in AIDS patient, Archives 1999;123:835
Associated with immunosuppression, HIV
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 AIDS patients
Diagnosis: stool examination, PCR
Treatment: albendozole for E. intestinalis, nothing for E. bieneusi
Micro: 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
Positive stains: Giemsa
EM: often helpful for diagnosis
Atypical mycobacteria
May resemble Whipple’s disease; associated with immunosuppression, HIV
Usually part of disseminated infection
Micro: foamy macrophages fill lamina propria; usually patchy, no fat vacuoles
Positive stains: PAS (faintly positive bacillary forms), acid-fast stains
DD: Whipple’s disease
Mycobacteria tuberculosis
Common in some parts of world
Invasive bacteria transmitted via contaminated milk
Symptoms: abdominal pain, malabsorption, strictures, perforation, fistula
Sites: terminal ileum, cecum, appendix
Gross: multiple and circumferential ulcers and strictures
Micro: confluent granulomas with central necrosis and peripheral lymphocytosis; destruction of muscularis propria, scarring
Positive stains: acid-fast stains
DD: Crohn’s disease (linear and serpiginous ulcers)
Symptoms vary from food poisoning to typhoid fever (S. typhi)
Typhoid fever: bacteremia, fever, systemic dissemination, chronic infection of joints, biliary tree, bones, meninges
From contaminated milk, eggs, beef, poultry
Usually affects terminal ileum
Micro: ulcers overlying Peyer’s patches with minimal inflammatory cells; often histiocytes with erythrophagocytosis
Stronglyoides stercoralis
Nematode that buries into mucosa of duodenum and jejunum; females lay eggs, which develop into lavae that pass in stool; larvae mature and become infective, and can penetrate intact skin
If larvae become infective before passed in stool, may invade intestinal mucosa or perianal skin, causing autoinfection
Symptoms: none, diarrhea, malabsorption; severe/fatal infections in immunocompromised
Diagnosis: larvae in stool; adult female or eggs in small bowel mucosa, often with eosinophilic or granulomatous inflammation
Noninvasive bacteria, produces enterotoxin
Transmitted via water, shellfish, person-to-person; spreads via pandemics
Produces water diarrhea, cholera
Also called intestinal lipodystrophy
Rare systemic condition, usually affects proximal intestine, mesenteric lymph nodes
Caused by Tropheryma whippelii, a gram positive intracellular actinomycete
Affects whites, age 30-49, 90% males
Symptoms: malabsorption with diarrhea, weight loss, abdominal pain; occasionally polyarthritis, CNS complaints, lymphadenopathy, hyperpigmentation; cardiac involvement less common