Non-Neoplastic Colon Disorders

Randolph K Peterson, MDDepartment of Laboratory Medicine

and Pathology

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

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!

Colon Disorders: Review (3)

• The colon has an intrinsic nervous supply: Auerbach’s plexus (within the muscularis), and Meissner’s plexus (submucosa).

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.

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%

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

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

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.

Colon Disorders: InflammationInflammatory 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

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

INFLAMMATORY BOWEL DISEASE: ETIOLOGY (3)

• Immunologic:– Antibodies + immune complexes (1°? 2°?)– Cell-mediated: tissue lymphs (2°?)

• Other: vasculitis

IBD: CROHN DISEASE

• Chronic enteritis with recurrent acute

relapses

• Granulomatous inflammation

• Fibrosing

• Enteritis (any level)

• Idiopathic

CROHN DISEASE: PATHOLOGY

• Transmural inflammation– wall thick, rigid, scarred

– granulomatous

– mucosal ulcers long, thin

• “Skip areas” common

CROHN DISEASE: LOCATION

• 40% ileum only

• 30% terminal ileum + colon

• 30% colon only

CROHN DISEASE: PATHOLOGY

• Transmural inflammation– wall thick, rigid, scarred

– granulomatous

– mucosal ulcers long, thin

• “Skip areas” common

CROHN DISEASE: COMPLICATIONS

• Stenosis• Fistulae (bowel, bladder, perineum)• Protein-losing enteropathy• Malabsorption• Systemic:– arthritis, uveitis, gallstones– cancer (local; distant) 3%

CROHN DISEASE: COMPLICATIONS

• Stenosis• Fistulae (bowel, bladder, perineum)• Protein-losing enteropathy• Malabsorption• Systemic:– arthritis, uveitis, gallstones– cancer (local; distant) 3%

CROHN DISEASE: COMPLICATIONS

• Stenosis• Fistulae (bowel, bladder, perineum)• Protein-losing enteropathy• Malabsorption• Systemic:– arthritis, uveitis, gallstones– cancer (local; distant) 3%

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

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-a) monoclonal

antibody (cA2)—only for severe disease or fistulae. 60% improve.

• Other: fish oil diet; smoking ¯

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)

Crohns UC

Site All of GI, extra GI Colon

Inflammation Granulomatous Non-granulomatous

Skip areas Present Absent

Wall Depth Full Thickness Mucosa

Fistula formation Yes No

Obstruction Yes No

Cancer 3% 30% +

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

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

CUC: THERAPY

• Medical: – Sulfasalazine– Antigen-processing inhibitor (chloroquine)– Steroids– I.V. cyclosporine (T lymphs

• Surgical: colectomy with ileoanal anastomosis

Colon Disorders: InflammationNon 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.

Colon Disorders: InflammationNon 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