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The Pathology of Intestines I. Developmental anomalies Atresia (bowel): complete failure of development of the intestinal lumen (imperforate anus) Atresia.

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Presentation on theme: "The Pathology of Intestines I. Developmental anomalies Atresia (bowel): complete failure of development of the intestinal lumen (imperforate anus) Atresia."— Presentation transcript:

1 The Pathology of Intestines I

2 Developmental anomalies Atresia (bowel): complete failure of development of the intestinal lumen (imperforate anus) Atresia (bowel): complete failure of development of the intestinal lumen (imperforate anus) Stenosis (bowel): narrowing of the intestinal lumen 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). Duplication (small intestine): well-formed saccular-tubular cystic spaces (may or may not communicate with the lumen). Omphalocele (small intestine): a membranous sac; herniation. Omphalocele (small intestine): a membranous sac; herniation. Malrotation (bowel): malposition of the large intestinal components (caecum in the left upper quadrant). Malrotation (bowel): malposition of the large intestinal components (caecum in the left upper quadrant).

4 Meckel diverticulum: (small intestine) Meckel diverticulum: (small intestine) Common; in ileum; Common; in ileum; Failure of involution of the omphalomesenteric (vitelline) duct which connects the lumen of the developing gut to the yolk sac ; 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); Persistent blind-ended tubular protrusion (5-6 cm long); Contains all three layers of the normal bowel wall: mucosa, submucosa, and muscularis propria; Contains all three layers of the normal bowel wall: mucosa, submucosa, and muscularis propria; Asymptomatic Asymptomatic Pernicious anemia-like syndromes (bacteria  B 12 depletion); Pernicious anemia-like syndromes (bacteria  B 12 depletion); Acute appendicitis-like syndrome (heterotopic rests of gastric mucosa  Peptic ulceration  bleeding). Acute appendicitis-like syndrome (heterotopic rests of gastric mucosa  Peptic ulceration  bleeding).

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6 Hirschsprung’s Disease (Congenital Megacolon) Hirschsprung’s Disease (Congenital Megacolon) Pathogenesis: 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 births Occurs in approximately 1 out of 5000 to 8000 live births M/F : 4/1 M/F : 4/1

7 Hirschsprung’s disease is characterized by the absence of Hirschsprung’s disease is characterized by the absence of ganglion cells, ganglion cells, ganglia, ganglia, in the muscle wall and submucosa of the affected segment. The rectum is always affected, (most cases involve the rectum and sigmoid only), 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. 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) 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. 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. Mucosal inflammation or shallow stercoral ulcers produced by impacted feces may appear. Enterocolitis. Enterocolitis.

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9 Acquired megacolon (1) Chagas’ disease (in which the trypanosomes directly invade the bowel wall to destroy the enteric plexuses); (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; (2) obstruction of the bowel as by a neoplasm or inflammatory stricture; (3) toxic megacolon complicating ulcerative colitis or Crohn’s disease (3) toxic megacolon complicating ulcerative colitis or Crohn’s disease (4) a functional psychosomatic disorder. (4) a functional psychosomatic disorder.

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11 Vascular disorders Ischemic Bowel Disease Ischemic Bowel Disease Arterial thrombosis Arterial thrombosis Arterial embolism Arterial embolism Venous thrombosis Venous thrombosis Nonocclusive ischemia Nonocclusive ischemia Miscellaneous: radiation injury, volvulus, stricture, and internal or external herniation. Miscellaneous: radiation injury, volvulus, stricture, and internal or external herniation. Angiodysplasia Angiodysplasia Hemorrhoids Hemorrhoids

12 Ischemic Bowel Disease R estricted to the small or large intestine or may affect both, R estricted 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. 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. Lesions within the end-arteries, which penetrate the gut wall, produce small, focal ischemic lesions.

13 The severity of injury ranges from The severity of injury ranges from (1) transmural infarction of the gut, involving all visceral layers (acute occlusion of a major artery); (1) transmural infarction of the gut, involving all visceral layers (acute occlusion of a major artery); (2) mural infarction of the mucosa and submucosa; (2) mural infarction of the mucosa and submucosa; (3) mucosal infarction (erosions), if the lesion extends no deeper than the muscularis mucosa. (3) mucosal infarction (erosions), if the lesion extends no deeper than the muscularis mucosa.

14 Arterial embolism: Arterial embolism: cardiac vegetations, cardiac vegetations, angiographic procedures, angiographic procedures, aortic thromboembolism. aortic thromboembolism. Arterial thrombosis: Arterial thrombosis: severe atherosclerosis (a.mesenterica), severe atherosclerosis (a.mesenterica), systemic vasculitis (polyarteritis nodosa), systemic vasculitis (polyarteritis nodosa), dissecting aneurysm, dissecting aneurysm, angiographic procedures, angiographic procedures, aortic reconstructive surgery, aortic reconstructive surgery, surgical accidents, surgical accidents, hypercoagulable states, hypercoagulable states, oral contraceptives. oral contraceptives.

15 Venous thrombosis: Venous thrombosis: hypercoagulable states, hypercoagulable states, oral contraceptives, oral contraceptives, antithrombin III deficiency, antithrombin III deficiency, intraperitoneal sepsis, intraperitoneal sepsis, the postoperative state, the postoperative state, invasive neoplasms (particularly hepatocellular carcinoma), invasive neoplasms (particularly hepatocellular carcinoma), cirrhosis, cirrhosis, abdominal trauma. abdominal trauma. Nonocclusive ischemia: Nonocclusive ischemia: cardiac failure, cardiac failure, shock, shock, dehydration, dehydration, vasoconstrictive drugs (digitalis, vasopressin, cocaine, heroin). vasoconstrictive drugs (digitalis, vasopressin, cocaine, heroin). Miscellaneous: -Radiation -Volvulus -Stricture -herniation

16 Morphology Transmural Infarction: Transmural Infarction: Sudden and total occlusion of mesenteric arterial blood  intestinal infarction. Sudden and total occlusion of mesenteric arterial blood  intestinal infarction. Arterial or venous occlusion  hemorrhagic infarct, Arterial or venous occlusion  hemorrhagic infarct, ischemic injury  mucosal necrosis  h  fibrinous exudate over the serosa ischemic injury  mucosal necrosis  h  fibrinous exudate over the serosa Margins of the infarct: Margins of the infarct: in arterial occlusions : distinct (demarcation) in arterial occlusions : distinct (demarcation) in venous occlusions : less distinct in venous occlusions : less distinct Microscopy: edema, interstitial hemorrhage, necrosis Microscopy: edema, interstitial hemorrhage, necrosis (24 h)  gangrene  perforation  peritonitis !!! (24 h)  gangrene  perforation  peritonitis !!!

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18 Mural & Mucosal Infarction: Mural & Mucosal Infarction: In any level of the gut from the stomach to anus In any level of the gut from the stomach to anus lesions may be multifocal-scattered or continuous-widely distributed (depends on the level of the arterial narrowing), lesions 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), 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. on opening the bowel, there is hemorrhagic, edematous thickening of the mucosa. Superficial ulcerations with Superficial ulcerations with edema, edema, hemorrhage, hemorrhage, fibrinous inflammation (psedomembrane due to superinfection). fibrinous inflammation (psedomembrane due to superinfection).

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20 Chronic Ischemia: Chronic Ischemia: Chronic vascular insufficiency  mucosal inflammation and ulceration Chronic vascular insufficiency  mucosal inflammation and ulceration Submucosal chronic inflammation and fibrosis  stricture. Submucosal chronic inflammation and fibrosis  stricture. Segmental and patchy. Segmental and patchy.

21 Angiodysplasia Tortuous dilatations of submucosal and mucosal blood vessels Tortuous dilatations of submucosal and mucosal blood vessels most often in the cecum or right colon most often in the cecum or right colon after the sixth decade of life after the sixth decade of life intestinal bleeding: intestinal bleeding: chronic and intermittent (  anemia) chronic and intermittent (  anemia) acute and massive. acute and massive.

22 Hemorrhoids Variceal dilatations of the anal and perianal venous plexuses Variceal dilatations of the anal and perianal venous plexuses Persitently elevated venous pressure within the hemorrhoidal plexus Persitently elevated venous pressure within the hemorrhoidal plexus Predispositions: Predispositions: chronic constipation, chronic constipation, pregnancy. pregnancy. Thin-walled, dilated vessels Thin-walled, dilated vessels Complications: Bleeding, prolapsing. Complications: Bleeding, prolapsing.

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24 Diarrheal diseases Diarrhea is an increase in stool: Diarrhea is an increase in stool: Mass Mass Frequency Frequency Fludity Fludity Disentery is a kind of diarrhea with: Disentery is a kind of diarrhea with: Low-volume Low-volume Pain Pain Hemorrhage Hemorrhage

25 Diarrhea 1. Secretory diarrhea 1. Secretory diarrhea 2. Osmotic diarrhea 2. Osmotic diarrhea 3. Exudative diarrhea 3. Exudative diarrhea 4. Malabsorption 4. Malabsorption 5. Deranged motility 5. Deranged motility

26 1. Secretory diarrhea Intestinal fluid secretion (catarrh) Intestinal fluid secretion (catarrh) Serous Serous Causes: Causes: Infection (bacteria, virus) Infection (bacteria, virus) Neoplastic (secretion of peptides and serotonin) Neoplastic (secretion of peptides and serotonin) Excessice laxative use Excessice laxative use

27 2. Osmotic diarrhea Excessive osmotic forces Excessive osmotic forces Causes: Causes: Lactulose therapy (hepatic encephalopathy, constipation) Lactulose therapy (hepatic encephalopathy, constipation) Gut lavage Gut lavage Antacids (magnesium salts) Antacids (magnesium salts)

28 3. Exudative diarrhea Purulent/bloody stool Purulent/bloody stool Causes: Causes: Infections Infections escherichia, escherichia, campylobacter, campylobacter, shigella, shigella, salmonella, salmonella, Entamoeba histolytica, Entamoeba histolytica, Idiopathic inflammatory bowel disease Idiopathic inflammatory bowel disease

29 4. Malabsorption Voluminous, bulky stool Voluminous, bulky stool Causes: Causes: Defective intraluminal digestion Defective intraluminal digestion Defective mucosal cell absorption Defective mucosal cell absorption Reduced small intestinal surface area Reduced small intestinal surface area Lymphatic obstruction Lymphatic obstruction Infection (Giardia) Infection (Giardia)

30 5. Deranged motility Decreased intestinal retention time Decreased intestinal retention time Surgical reduction of gut length Surgical reduction of gut length Neural dysfunction (irritable bowel syndrome) Neural dysfunction (irritable bowel syndrome) Hyperthyroidism Hyperthyroidism Decreased motility Decreased motility Surgery Surgery Bacterial overgrowth in the small intestine Bacterial overgrowth in the small intestine

31 Infectious enterocolitis Intestinal diseases of microbial origin Intestinal diseases of microbial origin Diarrhea and sometimes ulceroinflammatory changes Diarrhea and sometimes ulceroinflammatory changes Most common offenders Most common offenders rotavirus rotavirus Norwalk virus Norwalk virus Enterotoxigenic Escherichia coli Enterotoxigenic Escherichia coli

32 Offenders vary with the Offenders vary with the age, age, nutrition, nutrition, immune status of the host, immune status of the host, environment (living conditions, public health measures), environment (living conditions, public health measures), Special predispositions: Special predispositions: hospitalization, hospitalization, wartime dislocation, wartime dislocation, foreign travel. foreign travel.

33 Viral Gastroenterocolitis The small intestinal mucosa usually exhibits The small intestinal mucosa usually exhibits shortened villi shortened villi infiltration of the lamina propria by lymphocytes infiltration of the lamina propria by lymphocytes vacuolization and loss of the microvillus brush border in surface epithelial cells vacuolization and loss of the microvillus brush border in surface epithelial cells crypts appear hypertrophied crypts appear hypertrophied viral particles within surface epithelial cells by electron microscopy and in stool. viral particles within surface epithelial cells by electron microscopy and in stool.

34 Bacterial Gastroenterocolitis Numerous bacteria and several pathogenic mechanisms: Numerous bacteria and several pathogenic mechanisms: Ingestion of preformed toxin, present in contaminated food (major offenders are Staphylococcus aureus, Vibrios, and Clostridium perfringens) 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 toxigenic organisms (which proliferate within the gut lumen and elaborate an enterotoxin) Infection by enteroinvasive organisms (which proliferate, invade, and destroy mucosal epithelial cells) Infection by enteroinvasive organisms (which proliferate, invade, and destroy mucosal epithelial cells)

35 Most bacterial infections exhibit a general nonspecific pattern: Most bacterial infections exhibit a general nonspecific pattern: damage of the surface epithelium damage of the surface epithelium decreased epithelial cell maturation decreased epithelial cell maturation an increased mitotic rate (“regenerative change”) an increased mitotic rate (“regenerative change”) hyperemia and edema of the lamina propria hyperemia and edema of the lamina propria variable neutrophilic infiltration into the lamina propria and epithelial layer. variable neutrophilic infiltration into the lamina propria and epithelial layer.

36 Salmonella (multiple species, including S. typhimurium and S. paratyphi): Salmonella (multiple species, including S. typhimurium and S. paratyphi): primarily ileum and colon primarily ileum and colon blunted villi, blunted villi, vascular congestion, vascular congestion, Peyer’s patch involvement with swelling, Peyer’s patch involvement with swelling, congestion, congestion, ulceration (linear ulcers) ulceration (linear ulcers) Typhoid fever : may result in chronic infection of Typhoid fever : may result in chronic infection of biliary tree, biliary tree, joints, joints, bones, bones, meninges. meninges.

37 Shigella Shigella primarily distal colon primarily distal colon acute mucosal inflammation and erosion acute mucosal inflammation and erosion purulent exudate purulent exudate Campylobacter Campylobacter small intestine, appendix, colon small intestine, appendix, colon villus blunting villus blunting multiple superficial ulcers multiple superficial ulcers mucosal inflammation mucosal inflammation purulent exudate purulent exudate

38 Yersinia enterocolitica and Y. pseudotuberculosis: Yersinia enterocolitica and Y. pseudotuberculosis: ileum, appendix, and colon ileum, appendix, and colon mucosal hemorrhage and ulceration mucosal hemorrhage and ulceration bowel wall thickening bowel wall thickening Peyer’s patch and mesenteric lymph node hypertrophy with necrotizing granulomas Peyer’s patch and mesenteric lymph node hypertrophy with necrotizing granulomas systemic spread (with peritonitis, pharyngitis, pericarditis  3-Ps) systemic spread (with peritonitis, pharyngitis, pericarditis  3-Ps) V. cholerae: V. cholerae: essentially intact small intestinal mucosa, essentially intact small intestinal mucosa, with mucus-depleted crypts with mucus-depleted crypts C. perfringens: C. perfringens: similar to V. cholerae but with some epithelial damage; similar to V. cholerae but with some epithelial damage; some strains produce a severe necrotizing enterocolitis with perforation. some strains produce a severe necrotizing enterocolitis with perforation.

39 Necrotizing Enterocolitis Neonates (premature or of low birth weight) Neonates (premature or of low birth weight) acute, necrotizing inflammation. acute, necrotizing inflammation. A combination of A combination of ischemic injury, ischemic injury, colonization by pathogenic organisms, colonization by pathogenic organisms, excess protein substrate in the intestinal lumen, excess protein substrate in the intestinal lumen, functional immaturity of the neonatal gut. functional immaturity of the neonatal gut.

40 The disease may present as a mild gastrointestinal disturbance or as a fulminant illness with The disease may present as a mild gastrointestinal disturbance or as a fulminant illness with intestinal gangrene, intestinal gangrene, perforation, perforation, sepsis, sepsis, shock. shock. Terminal ileum and ascending colon, Terminal ileum and ascending colon, although in severe cases, the entire small and large bowel may be involved. although in severe cases, the entire small and large bowel may be involved.

41 In early phases, the mucosa exhibits In early phases, the mucosa exhibits edema, edema, hemorrhage, hemorrhage, necrosis necrosis As the disease progresses, the full thickness of the bowel wall becomes As the disease progresses, the full thickness of the bowel wall becomes hemorrhagic, hemorrhagic, inflamed, inflamed, gangrenous gangrenous frank intraluminal hemorrhage frank intraluminal hemorrhage mural gas formation mural gas formation Reparative changes Reparative changes epithelial regeneration epithelial regeneration granulation tissue formation granulation tissue formation fibrosis. fibrosis.

42 Antibiotic-Associated Colitis (Pseudomembranous Colitis) C. difficile (a normal gut commensal) C. difficile (a normal gut commensal) acute colitis acute colitis plaque-like adhesion of fibrinopurulent-necrotic debris and mucus to damaged colonic mucosa plaque-like adhesion of fibrinopurulent-necrotic debris and mucus to damaged colonic mucosa

43 following a course of broad-spectrum antibiotic therapy following a course of broad-spectrum antibiotic therapy also may occur following any severe mucosal injury, also may occur following any severe mucosal injury, ischemic colitis, ischemic colitis, volvulus, volvulus, necrotizing infections (staphylococci, shigella, candida, necrotizing enterocolitis) necrotizing infections (staphylococci, shigella, candida, necrotizing enterocolitis)

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46 Malabsorption Syndromes Malabsorption Syndromes Malabsorption is characterized by suboptimal absorption of fats, fat-soluble and other vitamins, proteins, carbohydrates, electrolytes and minerals, and water. 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. The consequences of malabsorption affect many organ systems.

47 Etiology Mal-digestion: Mal-digestion: Exocrine pancreatic disease Exocrine pancreatic disease Lack of bile salts Lack of bile salts Disaccharidase (lactase, etc.) deficiency Disaccharidase (lactase, etc.) deficiency Problems with the small bowel mucosa: Problems with the small bowel mucosa: Sprue Sprue Crohn's disease Crohn's disease Whipple's disease Whipple's disease Acute infections Acute infections Parasites (Giardia) Parasites (Giardia) Allergic gastroenteritis Allergic gastroenteritis Amyloidosis Amyloidosis Lymphomas Lymphomas Radiation sickness / B 12 / folate deficiency Radiation sickness / B 12 / folate deficiency Super-fast transit time: Laxatives Laxatives Cholera Cholera Vasoactive intestinal polypeptide-producing tumors Vasoactive intestinal polypeptide-producing tumors Mechanical problems: Blocked lymphatics (cancer, TB) Blocked lymphatics (cancer, TB) After re-routing surgery (gastrectomy, bypass) After re-routing surgery (gastrectomy, bypass)

48 Clinicopathology Alimentary tract: Alimentary tract: diarrhea diarrhea abdominal pain abdominal pain weight loss weight loss vitamin deficiencies vitamin deficiencies Hematopoietic system: Hematopoietic system: anemia (iron, pyridoxine, folate, or vitamin B12 deficiency) anemia (iron, pyridoxine, folate, or vitamin B12 deficiency) bleeding (vitamin K deficiency) bleeding (vitamin K deficiency) Nervous system: Nervous system: peripheral neuropathy peripheral neuropathy Skin: Skin: purpura and petechiae edema dermatitis hyperkeratosis Musculoskeletal system: Musculoskeletal system: osteoporosis tetany Endocrine system: Endocrine system: amenorrhea impotence infertility hyperparathyroidism

49 Celiac sprue Small intestine Small intestine idiosyncratic reaction to gliadin, a protein in the gluten of wheat, rye, and barley idiosyncratic reaction to gliadin, a protein in the gluten of wheat, rye, and barley an antibody against the transglutaminase an antibody against the transglutaminase activated cytotoxic killer-T cells invade the epithelium activated cytotoxic killer-T cells invade the epithelium Microscopy: Microscopy: villi disappear villi disappear crypts deepen crypts deepen

50 Whipple's disease Small intestine & systemic Small intestine & systemic lipid pools in the mucosa lipid pools in the mucosa Tropheryma whippelii (~actinomyces) Tropheryma whippelii (~actinomyces) bacilli-laden macrophages in: bacilli-laden macrophages in: gut mucosa gut mucosa lymph nodes, lymph nodes, joints, joints, endocardium endocardium brain. brain.

51 IDIOPATHIC INFLAMMATORY BOWEL DISEASES

52 Crohn’s Disease Idiopathic Idiopathic Western developed populations Western developed populations limited to the terminal ileum (terminal ileitis) limited to the terminal ileum (terminal ileitis) segmental lesions with intervening unaffected (“skip”) areas (regional enteritis) segmental lesions with intervening unaffected (“skip”) areas (regional enteritis) any level of the alimentary tract with systemic manifestations any level of the alimentary tract with systemic manifestations

53 Early disease: Early disease: focal mucosal ulcers focal mucosal ulcers Progressive disease: Progressive disease: mucosal ulcers coalesce  long, serpentine “linear ulcers” mucosal ulcers coalesce  long, serpentine “linear ulcers” tend to be oriented along the axis of the bowel tend to be oriented along the axis of the bowel mucosa acquires a coarsely textured, “cobblestone” appearance mucosa acquires a coarsely textured, “cobblestone” appearance narrow fissures  penetrating deeply through the bowel wall perforation or localized abscesses Hallmark: sharp demarcation of diseased bowel segments from adjacent uninvolved bowel. Crohn’s disease: Morphology

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55 Serosa: granular and dull gray Serosa: granular and dull gray Mesentery: thickened, edematous, and sometimes fibrotic Mesentery: thickened, edematous, and sometimes fibrotic Intestinal wall: rubbery and thick (edema, inflammation, fibrosis, hypertrophy of the muscularis) Intestinal wall: rubbery and thick (edema, inflammation, fibrosis, hypertrophy of the muscularis) Lumen: narrowed (x-ray film of small intestine shows “string sign” ) Lumen: narrowed (x-ray film of small intestine shows “string sign” ) Segmental disease: sharp demarcation of diseased bowel segments from adjacent uninvolved bowel. Segmental disease: sharp demarcation of diseased bowel segments from adjacent uninvolved bowel. Crohn’s disease: Morphology

56 Microscopic Characteristics: Transmural involvement of the bowel by Transmural involvement of the bowel by inflammatory process inflammatory process mucosal damage mucosal damage noncaseating granulomas(50%) noncaseating granulomas(50%) lymphoid aggregates lymphoid aggregates fibrosis  strictures fibrosis  strictures Fissuring and formation of fistulas Fissuring and formation of fistulas Crypt destruction Crypt destruction progressive atrophy progressive atrophy Paneth cell metaplasia Paneth cell metaplasia

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58 Ulcerative colitis An ulceroinflammatory disease An ulceroinflammatory disease limited to the colon limited to the colon affecting only the mucosa and submucosa affecting only the mucosa and submucosa extends in a continuous fashion proximally from the rectum (in contrast to Crohn’s disease) extends in a continuous fashion proximally from the rectum (in contrast to Crohn’s disease) granulomas are absent granulomas are absent Systemic disorder (similar to Crohn’s disease) Systemic disorder (similar to Crohn’s disease) migratory polyarthritis, sacroiliitis, ankylosing spondylitis, uveitis, hepatic involvement (pericholangitis and primary sclerosing cholangitis), skin lesions.

59 Involves the rectum and extends proximally in a retrograde fashion to involve the entire colon (“pancolitis”) in the more severe cases. 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 It is a disease of continuity “skip” lesions such as occur in CD are not found “skip” lesions such as occur in CD are not found In 10% of patients with severe pancolitis, the distal ileum may develop mild mucosal inflammation (“backwash ileitis”). In 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 appendix may be involved with both CD and UC. The mucosa exhibits The mucosa exhibits slight reddening granularity friability easy bleeding

60 Fully developed severe, active inflammation: Fully developed severe, active inflammation: extensive and broad- based ulceration of the mucosa in the distal colon or throughout its length extensive and broad- based ulceration of the mucosa in the distal colon or throughout its length Isolated islands of regenerating mucosa bulge upward to create “pseudopolyps.” Isolated 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. Often the undermined edges of adjacent ulcers interconnect to create tunnels covered by tenuous mucosal bridges. The ulcers are frequently aligned along the axis of the colon (as with CD) The ulcers are frequently aligned along the axis of the colon (as with CD) In contrast to Crohn’s disease: In contrast to Crohn’s disease: rarely do the linear serpentine ulcers mural thickening does not occur Progressive mucosal atrophy in chronic cases Progressive mucosal atrophy in chronic cases Microscopy: Microscopy: diffuse mononuclear inflammatory infiltrate in the lamina propria, admixed with neutrophils occasional eosinophils and mast cells.

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62 Diffuse mononuclear cell infitration Pseudopolyps (carpet-like mucosa) ulcer pseudopolyp

63 Crypt abscess

64 Long-term complication of UC : cancer. Long-term complication of UC : cancer. Particular attention to: Particular attention to: epithelial changes signifying dysplasia and epithelial changes signifying dysplasia and the progression to frank carcinoma the progression to frank carcinoma Underlying inflammatory disease may mask the symptoms and signs of carcinoma Underlying inflammatory disease may mask the symptoms and signs of carcinoma The 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. The 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 Celiac sprue Gluten (gladin) Small intestine villi disappear crypts deepen Whipple's disease Tropherhyma whipplii Small intestine (lymph nodes, joints, endocardium and/or brain) bacilli-laden macrophages Bacterial Overgrowth Syndrome Aerobic and anaerobic organisms Proximal small bowel luminal stasis, hypochlorhydria, immunedeficiencies Disaccharidase deficiency Less intestinal lactase Small intestine osmotic diarrhea Abetalipo- proteinemia Inability to synthesize All enterocytes loaded with dietary fat Crohn’s Disease Idiopathic Terminal ileum noncaseating granulomas and ulcers with perforation Ulcerative Colitis IdiopathicColon Severe active inflammation, ulcers & pseudopolyps Malabsorption Syndromes

66 Location Location Bowel Bowel Terminal ileum Terminal ileum Colon Colon Anal troubles Anal troubles Oral lesions Oral lesions Skip lesions Skip lesions Layers Layers Ulcers Ulcers Pseudopolyps Pseudopolyps Fibrosis Fibrosis Fistulas Fistulas Granulomas Granulomas Bleeding Bleeding Carcinoma risk Carcinoma risk Crohn's disease VariableSmall Favorite site Right more than left CommonMaybe+ All three Linear fissures Subtle+ Ulcerative colitis Rectum and upwards Large"Backwash" Left more than right -- No; continuous Mucosa only Broad / 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 gut A diverticulum is a blind pouch leading off the alimentary tract, lined by mucosa that communicates with the lumen of the gut Acquired diverticula may occur in the esophagus, stomach, and duodenum; duodenal diverticula occur in more than 1% of adults Acquired diverticula may occur in the esophagus, stomach, and duodenum; duodenal diverticula occur in more than 1% of adults Congenital diverticula (Meckel’s diverticulum) have all three layers of the bowel wall; Congenital 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. all other diverticula are acquired and either lack or have an attenuated muscularis propria.

68 Most colonic diverticula are small flask-like or spherical outpouchings, usually 0.5 to 1 cm in diameter and located in the sigmoid colon Most colonic diverticula are small flask-like or spherical outpouchings, usually 0.5 to 1 cm in diameter and located in the sigmoid colon descending colon or entire colon, however, may be affected descending colon or entire colon, however, may be affected Pathogenesis Pathogenesis (1) focal weakness in the colonic wall (1) focal weakness in the colonic wall (2) increased intraluminal pressure. (2) increased intraluminal pressure. Histology: Histology: a thin wall composed of a flattened or atrophic mucosa, a thin wall composed of a flattened or atrophic mucosa, compressed submucosa, compressed submucosa, attenuated or totally absent muscularis propria attenuated or totally absent muscularis propria hypertrophy of the circular layer of the muscularis propria in the affected bowel segment is usually seen. hypertrophy of the circular layer of the muscularis propria in the affected bowel segment is usually seen.

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70 Complications Obstruction Obstruction Perforation Perforation Marked fibrotic thickening due to the inflammation Marked fibrotic thickening due to the inflammation Narrowing (resembles colonic cancer) Narrowing (resembles colonic cancer) Diverticular infection Diverticular infection pericolic abscesses sinus tracts pelvic or generalized peritonitis.

71 Mechanical obstruction Mechanical obstruction Adhesions (post-op, Crohn's) Adhesions (post-op, Crohn's) Hernias Hernias Volvulus Volvulus Intussusception Intussusception Tumors Tumors Inflammatory strictures Inflammatory strictures Obstructive material (gallstone, fecalith, foreign body) Obstructive material (gallstone, fecalith, foreign body) Congenital Congenital Atresia of the anus / imperforate anus Atresia of the anus / imperforate anus Congenital atresia / strictures Congenital atresia / strictures Meconium ileus (cystic fibrosis) Meconium ileus (cystic fibrosis) Pseudo-obstruction Pseudo-obstruction Paralytic ileus Vascular bowel infarction Myopathies & neuropathies (Hirschsprung’s disease ) Bowel Obstruction Bowel Obstruction

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. 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: The usual sites: anteriorly at the inguinal and femoral canals, anteriorly at the inguinal and femoral canals, umbilicus, umbilicus, surgical scars. surgical scars. Intruders : Intruders : small bowel loops, omentum, large bowel. Pathology: Pathology: impair venous drainage of the trapped viscus stasis and edema compromise of arterial supply and venous drainage (strangulation) infarction of the trapped segment.

73 Bowel Obstruction : Adhesions Peritonitis: Peritonitis: surgical procedures, surgical procedures, infection, infection, endometriosis. endometriosis. As the peritonitis heals: As the peritonitis heals: adhesions (between bowel segments or the abdominal wall and operative site) adhesions (between bowel segments or the abdominal wall and operative site) fibrous bridges  closed loops  trapped intestine (internal herniation). fibrous bridges  closed loops  trapped intestine (internal herniation). The sequence of events following herniation: The sequence of events following herniation: obstruction strangulation.

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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. 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. Once trapped, the invaginated segment is propelled by peristalsis farther into the distal segment, pulling its mesentery along behind it. Clinical: Clinical: intraluminal mass or tumor as the point of traction. Complications: Complications: intestinal obstruction infarction.

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77 Bowel Obstruction : Volvulus Complete twisting of a loop of bowel about its mesenteric base of attachment Complete twisting of a loop of bowel about its mesenteric base of attachment produces intestinal obstruction and infarction. produces intestinal obstruction and infarction. Sigmoid, Sigmoid, cecum, cecum, small bowel (all or portions), small bowel (all or portions), stomach, stomach, transverse colon (rarely). transverse colon (rarely).

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