1. Non-Neoplastic Colon Disorders Randolph K Peterson, MD Department of Laboratory Medicine and Pathology

2. Colon Disorders: Review The colon is retroperitoneal for most of it’s length. Vascular supply: – Superior mesenteric artery: cecum, right colon, transverse colon – Inferior mesenteric: descending colon, sigmoid colon, proximal rectum – Hemorrhoidal branches of internal iliac: distal rectum

3. Colon Disorders: Review (2) This vascular distribution produces “Watershed Areas,” at the points they meet: – Splenic Flexure – Rectum What this means is that during times of systemic ischemia/shock/hypovolemia/etc. these areas have a compromised vascular supply and may infarct!

4. Colon Disorders: Review (3) The colon has an intrinsic nervous supply: Auerbach’s plexus (within the muscularis), and Meissner’s plexus (submucosa).

5. Colon Disorders: Malformations Hirschsprung’s Disease – Failure of nueroblasts to migrate to the end of the bowel: the distal portion is aganglionic. – ALWAYS involves the rectum (90% restricted to rectum) and extends proximally to a varying degree. – 80 % are male; 10 % have Down Syndrome; 4 % risk in siblings of affected individuals. – Histo: no ganglion cells with patchy nerve hyperplasia in submucosa.

6. Colon Disorders: Malformations (2) – Lack of peristalsis forms a functional obstruction – The distal portion dilates; “Megacolon.” – Surgical correction is required. 5-10 % mortality rate due to electrolyte imbalances and infection. Diverticula: – Outpouchings of Mucosa through a weakened area of the muscularis – Symptomatic in only 20%

7. Colon Disorders: Malformations (3) – Symptoms: abdominal discomfort and pain are variable. If inflamed/infected may fibrose, or form an abscess/perf/fistula. Hemorrhoids – Variceal dilations of the anal and perianal venous plexus – 5 % of population affected. Unusual under 30 except for pregnant females. – Types: External: below anorectal line; inferior hemorrhoidal plexus Internal: above; superior

8. Colon Disorders: Malformations (4) Angiodysplasia – Dilation and increased tortuosity of the submucosal veins in the cecum and ascending colon. – Probably acquired. – May cause bleeding in elderly. Misc.: Malrotation Duplication Imperforate anus

9. Colon Disorders: Inflammation Necrotizing Enterocolitis – Acute necrotizing inflammation of the small and large intestine. – Affects INFANTS! Supossedly 10% of full term babies (????). Most common in premies. – Peaks at 2-3 days of life following initiation of oral feeding. – More common in formula fed babes. – Symptoms: Vary from mild tenderness to bleeding, perf., sepsis. – Most common in terminal Ilium, cecum, ascending colon.

10. Colon Disorders: Inflammation Inflammatory Bowel Disease Etiology: Unknown, Probably multifactorial ?Genetic? (Families = 10x risk  ) – NOD2 = product of candidate gene at IBD1 locus on chromosome 16 – used by immune system cells to detect bacterial products through activation of cytokines – Recently: IL23R mutation prevents cell from binding proinflammatory protein

11. INFLAMMATORY BOWEL DISEASE: ETIOLOGY (2) Infectious: – Virus: rota, EBV, CMV – Bacteria: Pseudomonas, M. Kansasii, Chlamydia, Yersinia Current concept: Disease is product of overly-aggressive immune response to commensal bacteria in genetically predisposed person

12. INFLAMMATORY BOWEL DISEASE: ETIOLOGY (3) Immunologic: – Antibodies + immune complexes (1°? 2°?) – Cell-mediated: tissue lymphs (2°?) Other: vasculitis

13. IBD: CROHN DISEASE Chronic enteritis with recurrent acute relapses Granulomatous inflammation Fibrosing Enteritis (any level) Idiopathic

14. CROHN DISEASE: PATHOLOGY Transmural inflammation –  wall thick, rigid, scarred –  granulomatous –  mucosal ulcers long, thin “Skip areas” common

23. CROHN DISEASE: LOCATION 40% ileum only 30% terminal ileum + colon 30% colon only

25. CROHN DISEASE: PATHOLOGY Transmural inflammation –  wall thick, rigid, scarred –  granulomatous –  mucosal ulcers long, thin “Skip areas” common

28. CROHN DISEASE: COMPLICATIONS Stenosis Fistulae (bowel, bladder, perineum) Protein-losing enteropathy Malabsorption Systemic: – arthritis, uveitis, gallstones –  cancer (local; distant) 3%

30. CROHN DISEASE: COMPLICATIONS Stenosis Fistulae (bowel, bladder, perineum) Protein-losing enteropathy Malabsorption Systemic: – arthritis, uveitis, gallstones –  cancer (local; distant) 3%

34. CROHN DISEASE: COMPLICATIONS Stenosis Fistulae (bowel, bladder, perineum) Protein-losing enteropathy Malabsorption Systemic: – arthritis, uveitis, gallstones –  cancer (local; distant) 3%

35. CROHN DISEASE: THERAPY (1) Reduce antigenic load: – anti-inflammatory agents: 5-aminosalicylates (mesalamine) sulfasalazine antibodies against tumor necrosis factor (infliximab)—but serious side effects (activation of latent tb, lymphoma) – total parenteral nutrition – surgical diversion

36. CROHN DISEASE: THERAPY (2) Immunosuppression: – Steroids (budesonide = local effect but minimal systemic: rapid liver metabolize) – Immunosuppressives — azathioprine, methotrexate, cyclosporine – T-cell apheresis – Anti-tumor necrosis factor alpha (TNF-  ) monoclonal antibody (cA2)—only for severe disease or fistulae. 60% improve. Other: fish oil diet; smoking 

37. Ulcerative Colitis Begins in rectum; progresses proximally Limited to mucosa and submucosa Nongranulomatous No skip areas ("backwash ileitis") Scarring mild Ulcers: crypt abscess, irregular pseudopolyps p-ANCA (peripheral-antineutrophile cytoplasmic antibody) + 75% - 80% (only 8% in Crohn's)

47. CrohnsUC SiteAll of GI, extra GIColon InflammationGranulomatousNon-granulomatous Skip areasPresentAbsent Wall DepthFull ThicknessMucosa Fistula formationYesNo ObstructionYesNo Cancer3%30% +

48. CUC: COMPLICATIONS Stenosis: none Fistulae: none Protein-losing enteropathy: few Malabsorption: rare Systemic: primary sclerosing cholangitis  obstructive jaundice Cancer:  (duration & degree): – 10 yrs <1%, 30 yrs 30% Toxic megacolon

50. CUC: COMPLICATIONS Stenosis: none Fistulae: none Protein-losing enteropathy: few Malabsorption: rare Systemic: as in Crohn disease, plus primary sclerosing cholangitis  obstructive jaundice Cancer:  (duration & degree): – 10 yrs <1%, 30 yrs 30% Toxic megacolon

52. CUC: THERAPY Medical: – Sulfasalazine – Antigen-processing inhibitor (chloroquine) – Steroids – I.V. cyclosporine (T lymphs  Surgical: colectomy with ileoanal anastomosis

53. Colon Disorders: Inflammation Non IBD Ischemic Colitis – Most common in elderly in distal colon and watershed areas. – Early: edema, hemorrhage – Late (Chronic): fibrosis, psuedomembranes, psudopolyps Infectious: – Acute self-limited Colitis Numerous organisms.

54. Colon Disorders: Inflammation Non IBD (2) – Pseudomembranous Colitis Caused by Clostridium difficile. A pseudomembrane of fibrin and inflammatory cells Most often involves the right colon TEST for toxin in lab – Other infections that may involve the colon: Amebic, TB, CMV, Cryptosporidiosis