2 Developmental anomalies Atresia (bowel): complete failure of development of the intestinal lumen (imperforate anus)Stenosis (bowel): narrowing of the intestinal lumen
3 Duplication (small intestine): well-formed saccular-tubular cystic spaces (may or may not communicate with the lumen).Omphalocele (small intestine): a membranous sac; herniation.Malrotation (bowel): malposition of the large intestinal components (caecum in the left upper quadrant).
4 Meckel diverticulum: (small intestine) Common; in ileum;Failure of involution of the omphalomesenteric (vitelline) duct which connects the lumen of the developing gut to the yolk sac ;Persistent blind-ended tubular protrusion (5-6 cm long);Contains all three layers of the normal bowel wall: mucosa, submucosa, and muscularis propria;AsymptomaticPernicious anemia-like syndromes (bacteria B12 depletion);Acute appendicitis-like syndrome (heterotopic rests of gastric mucosa Peptic ulcerationbleeding).
6 Hirschsprung’s Disease (Congenital Megacolon) Pathogenesis:The enteric neuronal plexus develops from neural crest cells which must migrate into the bowel wall during development mostly in a cephalad-to-caudad direction.Congenital megacolon, or Hirschsprung’s disease, results when the migration of neural crest cells arrests at some point before reaching the anus.Hence a segment remains that lacks both Meissner’s submucosal and Auerbach’s myenteric plexuses.Loss of enteric neuronal coordination leads to(1) functional obstruction(2) colonic dilatation proximal to the affected segment.Occurs in approximately 1 out of 5000 to 8000 live birthsM/F : 4/1
7 Hirschsprung’s disease is characterized by the absence of ganglion cells,ganglia,in the muscle wall and submucosa of the affected segment.The rectum is always affected, (most cases involve the rectum and sigmoid only),Proximal to the aganglionic segment, the colon undergoes progressive dilatation and hypertrophy.With time, the colon may become massively distended, sometimes achieving a diameter of 15 to 20 cm (megacolon)The colonic wall becomes markedly thinned and may rupture, usually near the caecum.Mucosal inflammation or shallow stercoral ulcers produced by impacted feces may appear.Enterocolitis.
9 Acquired megacolon(1) Chagas’ disease (in which the trypanosomes directly invade the bowel wall to destroy the enteric plexuses);(2) obstruction of the bowel as by a neoplasm or inflammatory stricture;(3) toxic megacolon complicating ulcerative colitis or Crohn’s disease(4) a functional psychosomatic disorder.
12 Ischemic Bowel Disease Restricted to the small or large intestine or may affect both,Acute occlusion of one of the three major supply trunks of the intestines (celiac and superior and inferior mesenteric arteries) infarction.Lesions within the end-arteries, which penetrate the gut wall, produce small, focal ischemic lesions.
13 The severity of injury ranges from (1) transmural infarction of the gut, involving all visceral layers (acute occlusion of a major artery);(2) mural infarction of the mucosa and submucosa;(3) mucosal infarction (erosions), if the lesion extends no deeper than the muscularis mucosa.
16 Transmural Infarction: MorphologyTransmural Infarction:Sudden and total occlusion of mesenteric arterial blood intestinal infarction.Arterial or venous occlusionhemorrhagic infarct,ischemic injury mucosal necrosis h fibrinous exudate over the serosaMargins of the infarct:in arterial occlusions : distinct (demarcation)in venous occlusions : less distinctMicroscopy: edema, interstitial hemorrhage, necrosis(24 h)gangreneperforationperitonitis !!!
18 Mural & Mucosal Infarction: In any level of the gut from the stomach to anuslesions may be multifocal-scattered or continuous-widely distributed (depends on the level of the arterial narrowing),does not affect the entire thickness (may not be visible from the serosal surface),on opening the bowel, there is hemorrhagic, edematous thickening of the mucosa.Superficial ulcerations withedema,hemorrhage,fibrinous inflammation (psedomembrane due to superinfection).
20 Chronic Ischemia:Chronic vascular insufficiency mucosal inflammation and ulcerationSubmucosal chronic inflammation and fibrosis stricture.Segmental and patchy.
21 Tortuous dilatations of submucosal and mucosal blood vessels AngiodysplasiaTortuous dilatations of submucosal and mucosal blood vesselsmost often in the cecum or right colonafter the sixth decade of lifeintestinal bleeding:chronic and intermittent (anemia)acute and massive.
22 Variceal dilatations of the anal and perianal venous plexuses HemorrhoidsVariceal dilatations of the anal and perianal venous plexusesPersitently elevated venous pressure within the hemorrhoidal plexusPredispositions:chronic constipation,pregnancy.Thin-walled, dilated vesselsComplications: Bleeding, prolapsing.
30 5. Deranged motility Decreased intestinal retention time Surgical reduction of gut lengthNeural dysfunction (irritable bowel syndrome)HyperthyroidismDecreased motilitySurgeryBacterial overgrowth in the small intestine
31 Infectious enterocolitis Intestinal diseases of microbial originDiarrhea and sometimes ulceroinflammatory changesMost common offendersrotavirusNorwalk virusEnterotoxigenic Escherichia coli
32 Offenders vary with the age,nutrition,immune status of the host,environment (living conditions, public health measures),Special predispositions:hospitalization,wartime dislocation,foreign travel.
33 Viral Gastroenterocolitis The small intestinal mucosa usually exhibitsshortened villiinfiltration of the lamina propria by lymphocytesvacuolization and loss of the microvillus brush border in surface epithelial cellscrypts appear hypertrophiedviral particles within surface epithelial cells by electron microscopy and in stool.
34 Bacterial Gastroenterocolitis Numerous bacteria and several pathogenic mechanisms:Ingestion of preformed toxin, present in contaminated food (major offenders are Staphylococcus aureus, Vibrios, and Clostridium perfringens)Infection by toxigenic organisms (which proliferate within the gut lumen and elaborate an enterotoxin)Infection by enteroinvasive organisms (which proliferate, invade, and destroy mucosal epithelial cells)
35 Most bacterial infections exhibit a general nonspecific pattern: damage of the surface epitheliumdecreased epithelial cell maturationan increased mitotic rate (“regenerative change”)hyperemia and edema of the lamina propriavariable neutrophilic infiltration into the lamina propria and epithelial layer.
36 Typhoid fever : may result in chronic infection of Salmonella (multiple species, including S. typhimurium and S. paratyphi):primarily ileum and colonblunted villi,vascular congestion,Peyer’s patch involvement with swelling,congestion,ulceration (linear ulcers)Typhoid fever : may result in chronic infection ofbiliary tree,joints,bones,meninges.
38 Yersinia enterocolitica and Y. pseudotuberculosis: ileum, appendix, and colonmucosal hemorrhage and ulcerationbowel wall thickeningPeyer’s patch and mesenteric lymph node hypertrophy with necrotizing granulomassystemic spread (with peritonitis, pharyngitis, pericarditis 3-Ps)V. cholerae:essentially intact small intestinal mucosa,with mucus-depleted cryptsC. perfringens:similar to V. cholerae but with some epithelial damage;some strains produce a severe necrotizing enterocolitis with perforation.
39 Necrotizing Enterocolitis Neonates (premature or of low birth weight)acute, necrotizing inflammation.A combination ofischemic injury,colonization by pathogenic organisms,excess protein substrate in the intestinal lumen,functional immaturity of the neonatal gut.
40 Terminal ileum and ascending colon, The disease may present as a mild gastrointestinal disturbance or as a fulminant illness withintestinal gangrene,perforation,sepsis,shock.Terminal ileum and ascending colon,although in severe cases, the entire small and large bowel may be involved.
41 In early phases, the mucosa exhibits edema,hemorrhage,necrosisAs the disease progresses, the full thickness of the bowel wall becomeshemorrhagic,inflamed,gangrenousfrank intraluminal hemorrhagemural gas formationReparative changesepithelial regenerationgranulation tissue formationfibrosis.
42 Antibiotic-Associated Colitis (Pseudomembranous Colitis) C. difficile (a normal gut commensal)acute colitisplaque-like adhesion of fibrinopurulent-necrotic debris and mucus to damaged colonic mucosa
43 following a course of broad-spectrum antibiotic therapy also may occur following any severe mucosal injury,ischemic colitis,volvulus,necrotizing infections (staphylococci, shigella, candida, necrotizing enterocolitis)
46 Malabsorption Syndromes Malabsorption is characterized by suboptimal absorption of fats, fat-soluble and other vitamins, proteins, carbohydrates, electrolytes and minerals, and water.The consequences of malabsorption affect many organ systems.
47 Problems with the small bowel mucosa: EtiologyMal-digestion:Exocrine pancreatic diseaseLack of bile saltsDisaccharidase (lactase, etc.) deficiencyProblems with the small bowel mucosa:SprueCrohn's diseaseWhipple's diseaseAcute infectionsParasites (Giardia)Allergic gastroenteritisAmyloidosisLymphomasRadiation sickness / B12 / folate deficiencySuper-fast transit time:LaxativesCholeraVasoactive intestinal polypeptide-producing tumorsMechanical problems:Blocked lymphatics (cancer, TB)After re-routing surgery (gastrectomy, bypass)
48 Hematopoietic system: ClinicopathologyAlimentary tract:diarrheaabdominal painweight lossvitamin deficienciesHematopoietic system:anemia (iron, pyridoxine, folate, or vitamin B12 deficiency)bleeding (vitamin K deficiency)Nervous system:peripheral neuropathySkin:purpura and petechiaeedemadermatitishyperkeratosisMusculoskeletal system:osteoporosistetanyEndocrine system:amenorrheaimpotenceinfertilityhyperparathyroidism
49 Celiac sprue Small intestine idiosyncratic reaction to gliadin, a protein in the gluten of wheat, rye, and barleyan antibody against the transglutaminaseactivated cytotoxic killer-T cells invade the epitheliumMicroscopy:villi disappearcrypts deepen
50 Whipple's disease Small intestine & systemic lipid pools in the mucosa Tropheryma whippelii (~actinomyces)bacilli-laden macrophages in:gut mucosalymph nodes,joints,endocardiumbrain.
52 Crohn’s Disease Idiopathic Western developed populations limited to the terminal ileum (terminal ileitis)segmental lesions with intervening unaffected (“skip”) areas (regional enteritis)any level of the alimentary tract with systemic manifestations
53 Crohn’s disease: Morphology Early disease:focal mucosal ulcersProgressive disease:mucosal ulcers coalescelong, serpentine “linear ulcers”tend to be oriented along the axis of the bowelmucosa acquires a coarsely textured, “cobblestone” appearancenarrow fissures penetrating deeply through the bowel wallperforation or localized abscessesHallmark: sharp demarcation of diseased bowel segments from adjacent uninvolved bowel.
55 Crohn’s disease: Morphology Serosa: granular and dull grayMesentery: thickened, edematous, and sometimes fibroticIntestinal wall: rubbery and thick (edema, inflammation, fibrosis, hypertrophy of the muscularis)Lumen: narrowed (x-ray film of small intestine shows “string sign” )Segmental disease: sharp demarcation of diseased bowel segments from adjacent uninvolved bowel.
56 Crohn’s disease: Morphology Microscopic Characteristics:Transmural involvement of the bowel byinflammatory processmucosal damagenoncaseating granulomas(50%)lymphoid aggregatesfibrosisstricturesFissuring and formation of fistulasCrypt destructionprogressive atrophyPaneth cell metaplasia
58 Ulcerative colitis Systemic disorder (similar to Crohn’s disease) migratory polyarthritis,sacroiliitis,ankylosing spondylitis,uveitis,hepatic involvement (pericholangitis and primary sclerosing cholangitis),skin lesions.An ulceroinflammatory diseaselimited to the colonaffecting only the mucosa and submucosaextends in a continuous fashion proximally from the rectum (in contrast to Crohn’s disease)granulomas are absent
59 It is a disease of continuity Involves the rectum and extends proximally in a retrograde fashion to involve the entire colon (“pancolitis”) in the more severe cases.It is a disease of continuity“skip” lesions such as occur in CD are not foundIn 10% of patients with severe pancolitis, the distal ileum may develop mild mucosal inflammation (“backwash ileitis”).The appendix may be involved with both CD and UC.The mucosa exhibitsslight reddeninggranularityfriabilityeasy bleeding
60 Fully developed severe, active inflammation: The ulcers are frequently aligned along the axis of the colon (as with CD)In contrast to Crohn’s disease:rarely do the linear serpentine ulcersmural thickening does not occurProgressive mucosal atrophy in chronic casesMicroscopy:diffuse mononuclear inflammatory infiltrate in the lamina propria, admixed withneutrophilsoccasional eosinophils and mast cells.Fully developed severe, active inflammation:extensive and broad-based ulceration of the mucosa in the distal colon or throughout its lengthIsolated islands of regenerating mucosa bulge upward to create “pseudopolyps.”Often the undermined edges of adjacent ulcers interconnect to create tunnels covered by tenuous mucosal bridges.
64 Long-term complication of UC : cancer. Particular attention to: epithelial changes signifying dysplasia andthe progression to frank carcinomaUnderlying inflammatory disease may mask the symptoms and signs of carcinomaThe risk of cancer is highest in patients with pancolitis of 10 or more years’ duration, in whom it exceeds by 20-fold to 30-fold that in a control population.
65 Malabsorption Syndromes Celiac sprueGluten (gladin)Small intestinevilli disappearcrypts deepenWhipple's diseaseTropherhyma whipplii(lymph nodes, joints, endocardium and/or brain)bacilli-laden macrophagesBacterial Overgrowth SyndromeAerobic and anaerobic organismsProximal small bowelluminal stasis, hypochlorhydria, immunedeficienciesDisaccharidase deficiencyLess intestinal lactaseosmotic diarrheaAbetalipo-proteinemiaInability to synthesizeAllenterocytes loaded with dietary fatCrohn’s DiseaseIdiopathicTerminal ileumnoncaseating granulomas and ulcers with perforationUlcerative ColitisColonSevere active inflammation, ulcers & pseudopolyps
66 LocationBowelTerminal ileumColonAnal troublesOral lesionsSkip lesionsLayersUlcersPseudopolypsFibrosisFistulasGranulomasBleedingCarcinoma riskCrohn's diseaseVariableSmallFavorite siteRight more than leftCommonMaybe+All threeLinear fissures+++SubtleUlcerative colitisRectum and upwardsLarge"Backwash"Left more than right-No; continuousMucosa onlyBroad / irregular++Heavy-duty+++
67 Colonic Diverticulosis A diverticulum is a blind pouch leading off the alimentary tract, lined by mucosa that communicates with the lumen of the gutAcquired diverticula may occur in the esophagus, stomach, and duodenum; duodenal diverticula occur in more than 1% of adultsCongenital diverticula (Meckel’s diverticulum) have all three layers of the bowel wall;all other diverticula are acquired and either lack or have an attenuated muscularis propria.
68 a thin wall composed of a flattened or atrophic mucosa, Most colonic diverticula are small flask-like or spherical outpouchings, usually 0.5 to 1 cm in diameter and located in the sigmoid colondescending colon or entire colon, however, may be affectedPathogenesis(1) focal weakness in the colonic wall(2) increased intraluminal pressure.Histology:a thin wall composed of a flattened or atrophic mucosa,compressed submucosa,attenuated or totally absent muscularis propriahypertrophy of the circular layer of the muscularis propria in the affected bowel segment is usually seen.
70 Marked fibrotic thickening due to the inflammation ComplicationsObstructionPerforationMarked fibrotic thickening due to the inflammationNarrowing (resembles colonic cancer)Diverticular infectionpericolic abscessessinus tractspelvic or generalized peritonitis.
71 Bowel Obstruction Mechanical obstruction Pseudo-obstruction Adhesions (post-op, Crohn's)HerniasVolvulusIntussusceptionTumorsInflammatory stricturesObstructive material (gallstone, fecalith, foreign body)CongenitalAtresia of the anus / imperforate anusCongenital atresia / stricturesMeconium ileus (cystic fibrosis)Pseudo-obstructionParalytic ileusVascular bowel infarctionMyopathies & neuropathies (Hirschsprung’s disease)
72 Bowel Obstruction : Hernias A weakness or defect in the wall of the peritoneal cavity may permit protrusion of a pouch-like, serosa-lined sac of peritoneum, called a hernial sac.The usual sites:anteriorly at the inguinal and femoral canals,umbilicus,surgical scars.Intruders :small bowel loops,omentum,large bowel.Pathology:impair venous drainage of the trapped viscusstasis and edemacompromise of arterial supply and venous drainage (strangulation)infarction of the trapped segment.
73 Bowel Obstruction : Adhesions Peritonitis:surgical procedures,infection,endometriosis.As the peritonitis heals:adhesions (between bowel segments or the abdominal wall and operative site)fibrous bridges closed loops trapped intestine (internal herniation).The sequence of events following herniation:obstructionstrangulation.
75 Bowel Obstruction : Intussusception Intussusception occurs when one segment of the small intestine, constricted by a wave of peristalsis, suddenly becomes telescoped into the immediately distal segment of bowel.Once trapped, the invaginated segment is propelled by peristalsis farther into the distal segment, pulling its mesentery along behind it.Clinical:intraluminal mass or tumor as the point of traction.Complications:intestinal obstructioninfarction.
77 Bowel Obstruction : Volvulus Complete twisting of a loop of bowel about its mesenteric base of attachmentproduces intestinal obstruction and infarction.Sigmoid,cecum,small bowel (all or portions),stomach,transverse colon (rarely).