פתולוגיה של מערכת העיכול

1. פתולוגיה של מערכת העיכול הרצאה 10

2. מבנה עקרוני של GIT • מערכת "צינורות" של אברים חלולים • הדופן בנוי מרירית, תת רירית, שריר, נסיובית • רירית: אפיתל (שטוח רב שכבתי או עמודי) +למינה פרופריה Lamina propria - • תת רירית Submucosa - • שריר • נסיובית(סרוזה) או אדבנטיציה

3. Normal Esophagus and Stomach (Gross) Normal stomach Normal esophagus

4. Normal Esophagus (Microscopic) Squamous Epithelium Muscularis mucosa Submucosa Muscular Wall (muscularis propria)

5. Normal esophagus (Micro – high power) Stratified squamous epithelium Basal cell layer (1-3 cells thick)

6. Esophageal (and gastric) varices

7. Vascular Disorders • Esophageal Varices • Dilated submucosal veins due to portal hypertension and shunting of blood from the portal to systemic venous system (collateral circulation) • Increased pressure causes the tortuous esophageal veins to bulge into the lumen (varices) • The overlying mucosa may ulcerate and bleed • Clinically: Can cause massive GI bleeding and hematemesis and lead to death

8. Infectious / Chemical (Acute) Esophagitis • Infections tend to occur in the immunocompromised, but can occur in healthy individuals • Herpes, Cytomegalovirus (CMV), Candida • Chemical injury is either accidental (“stuck” pill) or intentional (suicide attempt) • Severely caustic agents (lye, acids) can cause sloughing of the entire mucosa and necrosis of the wall • Other causes: Radiation, GVHD • Reflux (GERD)

9. “Generic” Acute Esophagitis • Numerous • neutrophils in the • epithelium • Reactive squamous • cells • Inflamed lamina • propria (chronic • inflammation)

10. Herpes Esophagitis (Gross) Punched-out ulcers

11. (See next slide) Herpes Esophagitis (Micro) Edge of ulcer

12. Herpes Esophagitis (Micro – high power) - The virus is present within the cherry-red nuclear inclusions - Multinucleation is also a feature

13. Barrett’s Esophagus • Single most important risk factor for esophageal adenocarcinoma • Patients with >3cm of Barrett mucosa have a 30x-40x increased risk of developing cancer • A complication of longstanding GERD • Chronic mucosal injury causes the squamous mucosa to change into intestinal-type mucosa with goblet cells (“intestinal metaplasia”)

14. Barrett Esophagus (Gross) Gastric mucosa Velvety tan Barrett mucosa Normal white squamous mucosa Anatomic GE junction Squamocolumnar junction

15. Barrett’s Esophagus (Micro) Glandular mucosa with goblet cells Squamous mucosa

16. Barrett Esophagus w/High Grade Dysplasia - High nuclear-to-cytoplasmic ratios - Loss of nuclear polarity with pseudostratification - Loss of goblet cells - Glandular crowding (back-to-back or cribriforming glands)

17. ADENOCARCINOMA

18. Adenocarcinoma (Gross) Gastric mucosa Barrett mucosa Ulcerated mass at the GEJ with heaped-up edges

19. Adenocarcinoma (Micro – low power) “Normal” • Moderately differentiated adenocarcinoma • Malignant glandular structures infiltrate into submucosa • The surface is ulcerated • The adenocarcinoma undermines normal mucosa • A residual precursor lesion (BE with dyspalsia) is no longer present MP

20. SQUAMOUS CARCINOMA • DYSPLASIAIN-SITUINFILTRATION

22. The normal gastric mucosa • Cardia – mainly mucus-secreting cells • Fundus (body) – acid producing parietal cells, pepsin producing chief cells • Pylorus – hormone (gastrin) production

23. CELLS MUCOUS: MUCUS, PEPSINOGEN II CHIEF: PEPSINOGEN I, II PARIETAL: ACID ENTEROENDOCRINE: HISTAMINE, SOMATOSTATIN, ENDOTHELIN

24. Gastritis • Acute gastritis often due to chemical injury (alcohol drugs) • Chronic gastritis: • Helicobacter pylori infection • Chemical damage (bile reflux, drugs) • Autoimmune (associated with vitamin B12 malabsorption (pernicious anaemia)

25. GASTRITIS ACUTE, HEMORRHAGIC HISTOLOGY: Erosion, Hemorrage, NEUTROPHILS

26. Acute gastritis • Drugs (non-steroidal anti-inflammatory drugs NSAID), alcohol cause acute erosion (loss of mucosa superficial to muscularis mucosae). Can result in severe haemorrhage • Acute Helicobacter infection has a prominent neutrophil infiltrate

27. Morphology of chronic gastritis • Chronic inflammatory cell infiltration • Mucosal atrophy • Intestinal (goblet cell) metaplasia Seen in Helicobacter and autoimmune gastritis (not chemical)

28. Helicobacter pylori • Adapted to live in association with surface epithelium beneath mucus barrier • Causes cell damage and inflammatory cell infiltration • In most countries the majority of adults are infected

29. PEPTIC ULCER DISEASE • In normal acid/pepsin attack is balanced by mucosal defences • Increased attack by hyperacidity • Weakened mucosal defence – the major factor (H. pylori related)

30. Morphology of peptic ulcers • Clean, non-elevated edge • Granulation tissue base (floor) • Underlying fibrosis

31. Complications of peptic ulcer • Perforation leading to peritonitis • Haemorrhage by erosion of vessel in base • Penetration of surrounding organ (liver/pancreas) • Obstruction (by scarring) – pyloric stenosis • (Cancer – rare event in true peptic ulcer)

32. ADENOCARCINOMAGROWTH PATTERNS

33. Macroscopic Pathology • Gross types • Polypoid • Ulcerative • Infiltrative (extreme is linitis plastica – “leather bottle stomach)

34. Microscopy • Intestinal type (forms glands – like cancers of colon and oesophagus) • Diffuse type – dissociated tumour cells often containing a mucinous “blob” – signet ring cells

35. Gastrointestinal stromal tumours (GIST) • Mesenchymal neoplasms • Derived from interstitial cells of Cajal (pacemaker cells controlling peristalsis) • Overexpress c-kit oncogene • Used as diagnostic aid on tissue • A target for therapy with tyrosine kinase inhibitor imatinib (also used in CML)

36. GIST-spindle cell neoplasm of GI tract

37. Normal small and large intestine • SI: ABSORPTIVE, MUCUS, PANETH (apical granules) • VILLI • LI: MUCUS, ABSORPTIVE, ENTEROENDOCRINE (basal granules) • CRYPTS

38. CELIAC DISEASE • Also called SPRUE • Also called NON-tropical SPRUE • Also called GLUTEN-SENSITIVE ENTEROPATHY • Sensitivity to GLUTEN, a wheat protein, gliadin • Immobilizes T-cells • Also in oat, barley, rye • Progressive mucosal “atrophy”, i.e. villous flattening • Relieved by gluten withdrawal

39. CELIAC DISEASE

40. Inflammatory bowel disease (IBD) • מחלות דלקתיות של מעי – מחלות כרוניות חוזרות • מבדילים 2 סוגים לפי מעורבות מעי ולפי עומק דלקת בדופן • מחלת קרוהןCrohn’s disease - • קוליטיס כיבית Ulcerative colitis – • נשארים מקרים לא ברורים -Undeterminate colitis • עלול לגרום Colitis associated dysplasia - ובמחלה ממושכת לגידולים

43. מחלת קרוהן • מעורבות של כל איבר במע' העיכול מפה - לפי הטבעת, הכי שכיח מעי דק סופי-terminal ileum • Skip lesions- קטע חולה לסרוגין עם קטע תקין • כל עובי דופן המעי: רירית, שריר,שומן, קשרי לימפה • כיבים, פיסורות, פיסטולות, היצרויות, הדבקויות • רירית במראה אבני מרצפת cobblestone - • שומן זוחל creeping fat - • GRANULOMA

44. קוליטיס כיבית • רקטום ומעי גס המשכי ברצף עד לפנקוליטיס • כיבים, פסאודופוליפים • מעורבות שטחית של דופן מעי – רק רירית • Cryptitis, crypt abscesses • NOT GRANULOMAS

45. CROHN-CD /ULCERATIVE-UC _ TRANSMURAL, THICK WALL • NOT LIMITED to COLON • GRANULOMAS • FISTULAE COMMON • TERMINAL ILEUM OFTEN • SKIP AREAS • “CRYPT” ABSCESSES NOT COMMON • NO PSEUDOPOLYPS • MALABSORPTION • MUCOSAL, THICK MUCOSA • LIMITED to COLON • NO GRANULOMAS • FISTULAE RARE • TERMINAL ILEUM NEVER • NO SKIP AREAS • “CRYPT” ABSCESSES COMMON • PSEUDOPOLYPS • NO MALABSORPTION

46. Complications Strictures which can lead to obstruction Fistulas & abscesses (more common in CD, but also 20% UC) Fistula types: enterovesical, enteroenteric, enteromesenteric, enterocutaneous, rectovaginal & perianal Stenosis and obstruction In CD, obstructive hydronephrosis (RLQ compressing rt. ureter) Sepsis, malnutrition in Crohn’s

47. Extraintestinal complications Arthritis Ankylosing spondylitis (HLA-B27) Episcleritis (3-4%)-parallels course of disease Iritis Erythema nodosum (often at disease onset)-esp. anterior tibia Pyoderma gangrenosum Aphthous ulcers

50. DIVERTICULOSIS