SMALL AND LARGE INTESTINES

Congenital anomaliesa) Meckel diverticulumi) blind pouch located on antimesenteric side of small bowel- within 2 feet on ileocecal valveii) true diverticulum- contains all 3 layersiii) usually asymptomatic

Hirschsprung disease (aganglionic megacolon)a) lack of neural connectioni) devoid of Meisnner and Auerbach myenteric plexusb) functional obstructioni) dilation proximal to affected segmentii) normal ganglia in dilated segmentiii) loss of ganglia in contracted segment

iv) rectum always affectedv) short disease involves rectum and sigmoidvi) long disease involves rectum and entire colonvii) male 4:1- 10% with Downs syndromeviii) enterocolitis, perforations with peritonitis are major causes of death

c) acquired Hirschsprungi) Chagas diseaseii) organic obstruction- neoplasm- inflammatory stricture- toxic (UC or Crohns)ENTEROCOLITIS Diarrheal diseasesa) infectionsb) malabsorptionc) inflammatory bowel disease

Diarrhea and dysentery a) diarrhea > 250 grams stool/dayi) 70-95% waterb) dysentery low volume, painful, bloody diarrheac) causes: see table 17-6i) 5 categories- secretory: > 500 ml fluid stool, isotonic, with fasting- osmotic: > 500 ml fluid stool, stops with fasting, Osm > plasma (50 mOsm)

- exudative: bacterial damage, bloody, persist with fasting- motility disease: increased- malabsorption: bulky stool, Osm, steatorrhea, stops with fasting Infectious enterocolitisa) > 12,000 deaths/day in children in developing countriesb) 50% of all deaths worldwidei) children < 5 yrs.

ii) self-limited diarrhea mostly caused by virusesc) viral gastroenteritisi) see table 17-7ii) rotavirus - children 6-24 months- young children & debilitated adults- selectively destroys enterocytes in small intestine malabsorption, secretory and Osm diarrhea

- peds. in hospitals and day- care centers- Ab in moms milk infections seen at time of weaningiii) adenovirus - Ad31, Ad40 & Ad41 most common diarrhea in children- malabsorption and secretory diarrhea

iv) calicivirus - Sapporo-like (rare)- Norwalk-like (common); majority of nonbacterial food-borne epidemic gastroenteritis in all age groups v) astrovirus- 1o childrend) necrotizing enterocolitisi) neonates, premature, low birth weight (sm intest)

Necrotizing enterocolitis (NEC). Left picture shows an abdominal X-ray of a preterm infant with NEC. The presence of gas in the wall of the intestines (pneumatosis intestinalis) proves the diagnosis. Right picture on the top shows multifocal necrosis of the bowel, marked by the segmental dusky, hemorrhagic appearance. The most common sites of involvement are the terminal ileum and proximal colon. Right picture on the bottom shows a distended, congested, necrotic bowel (Compare the involved segment of intestine below with the more normal segment above.)

MALABSORPTION SYNDROMES defective absorption:a) fats (hallmark)b) CHOc) proteind) H2Oe) mineralsf) vitamins chronic diarrhea and steatorrhea see table 17-9 most common in USA:a) celiac disease,Crohn's & Pancreatic

Celiac disease (celiac sprue, gluten sensitive enteropathy)a) chronic diseasei) T-cell inflammatory reaction with autoimmune componentb) mucosal lesionsi) small intestine (duod-jejunum)c) improves with removal of gluten and related grain proteins from diet (i.e., wheat, oats, barley, rye)i) CD8+ in mucosa when gluten present (IL-15 sensitive)

d) Caucasianse) familiali) class II HLA-DQ2 or HLA- DQ8f) clinical:i) characteristic skin blisters- dermatitis herpetiformisii) neurologic disordersiii) Dx:- history of malabsorption- lesion present via biopsy- improve without gluten

g) long term risk:i) NHLii) adenocarcinomaiii) esophageal carcinoma

Tropical spruea) same characteristics as celiacb) Caribbean (not Jamaica), India, Africa, Asia c) NO specific causal agent foundi) bacterial overgrowth ?- E. coli; Hemophilus

d) injury seen at all levels of small intestinee) usually folate/B12 deficiencyf) broad spectrum antibioticsi) bacterial origin ?g) no carcinoma susceptibility

Whipple diseasea) rarei) bacterium - Tropheryma whippeliib) systemic condition

Fluorescent in situ hybridisation of a small intestinal biopsy in a case of Whipple's disease (confocal laser scanning microscopy). Tropheryma whipplei rRNA is blue, nuclei of human cells are green and the intracellular cytoskeletal protein vimentin is red. Magnification approximately 200 x.

i) affect any body partii) mainly intestines, CNS and joints (1o presentation)iii) small intestines:- distended macrophages- mucosal edema- lymphatic distension: lipid deposition in villi lipid dystrophyiv) Caucasians; 10:1 male v) Dx = PAS+ macrophages- with rod shaped organisms

PASBacilli withinmacrophageArthritis(often)Steatorrhea Encephalopathy(occasionally) MalabsorptionAnd diarrhealymphadenopathyLipid pools in mucosa

Disaccharidase (lactase) deficiencya) rare (congenital form)b) acquired is commonc) lactose glucose + galactosei) osmotic diarrheaIDIOPATHIC INFLAMMATORY BOWEL DISEASE (IBD) Chronic relapsing diseases Crohn disease & Ulcerative colitis activation of mucosal immune system

Dx of IBD:a) clinical historyb) lab and path findingsc) NO single test to Dx IBD nor to differentiate CD from UCd) p-ANCA + is 75% with UC and only 11% with CD

Crohn Disease any level of alimentary tracta) small intestine alone 40%b) sm. Intestine + colon 30%c) colon alone 30% skip lesions pathological characteristics:a) mucosal damage (transmural)b) well demarcated regionsc) noncaseating granulomasd) formation of fissures e) narrowed lumen (obstruction)

clinical:a) more subtle than UCb) diarrhea, fever, abdominal paini) lower right pain- mimic appendicitis or- perforation c) colonic involvement bloodi) anemia over timed) bimodal age distributioni) 10-30 and 50-70 yrse) Caucasians 5:1 vs. noncaucasians

f) chronic course may lead to:i) fibrosing strictures- terminal ileum- fistulas other areas ii) protein lossiii) Vit B12 lossiv) bile salt loss- steatorrhea v) linear serpentine ulcers

e) extraintestinal: (altered immunity)i) polyarthritis ii) erythema nodosumiii) clubbing of fingersiv) ankylosing spondylitis v) risk of GI carcinoma- less than UC

Ulcerative colitis

inflammatory disease limited to colon affecting mucosa and submucosaa) except in most severe casesi) transmural extends in continuous fashiona) from rectum well formed granulomas are absent as with CD, UC is systemic disease incidence vs. CD age peak 20-30 yrs

involves rectum and extends retrograde to involve entire colona) pancolitisb) disease of continuityi) NO skip lesionsc) more common than CDd) NO mural thickening vs. CDe) with severe cases toxic megacoloni) muscularis and neural plexus involvement - neuromuscular failure

f) ulceration of distal colon or throughout its length g) evolution of UC dysplasia carcinoma clinical:a) relapsing bloody mucoid diarrheai) relieved by defecation- 1st initial signsb) long term complication CAi) with pancolitis (25X normal)c) see table 17-10 i) Crohn vs. UC

Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue, lips, palate and pharynx Endoscopic image of ulcerative colitis showing loss of vascular pattern of the sigmoid colon, granularity and some friability of the mucosa.

VASCULAR DISORDERS

Ischemic bowel disease a) small and/or large intestinei) depending on vessel(s)- superior mesenteric- celiac- inferior mesenteric Types:a) transmural infarctsi) mechanical compromise - major mesenteric vessels

b) mucosal (i.e., mural) infarctsi) hypoperfusionc) venous compromise is a less frequent cause of infarcts

Causes:a) arterial thrombosisi) atheroma (origin of vessel), angiography (i.e., Ca++), BC pillsb) arterial embolismi) atheroemboli (i.e., plaques), cardiac vegetations

c) nonocclusive ischemiai) cardiac failureii) shockiii) vasoconstrictive drugsd) venous thrombosisi) BC pillsii) hypercoagulable statesiii) peritonitisiv) invasive neoplasmsv) cirrhosisvi) abdominal traumae) other (radiation, herniation, etc.)

clinical:a) embolic injury mainly affects i) SMAb) injuryi) initial hypoxic insultii) reperfusion injury- most of intestinal injuryc) bowel infarction is uncommoni) 50-75% lethalityii) older population (disease)d) abdominal paine) bloody diarrhea

f) vasculitides:i) PANii) WGiii) Henoch-Schnlein disease

Hemorrhoidsa) vertical dilations of anal and perianal venous plexusesi) causes:- straining with constipation- venous stasis of pregnancy

DIVERTICULAR DISEASE

Blind poucha) congenitali) involve all 3 layers- Meckel diverticulumb) acquiredi) lack or attenuated muscularis ii) most common location- left side of colon- majority in sigmoid

iii) rare < 30 yrsiv) > 60 yrs common (~ 50%)v) occur in multiples- diverticulosis pathogenesis:a) focal weakness in colonic wallb) intraluminal pressurei) lack of fiber in dietii) causes sequestration clinical:a) cramping; feeling not able to empty; blood loss

Colonic diverticula are acquired herniations in which the mucosa and submucosa protrude through weak spots in the muscular layer of the colon wall. They are usually multiple (can vary from a few to hundreds) and are referred to as diverticulosis. The sigmoid colon is the location of most cases of diverticulosis (95%), although any part of the colon can be involved. They often appear on the serosal surface in parallel rows between the teniae as seen in the gross specimen across

Histologically, colonic diverticula have a thin wall composed of a flattened mucosa and submucosa, and a markedly attenuated and often totally absent muscularis propria layer. In most diverticula, the base of the structure consists only of a thin serosal connective tissue layer. The adjacent bowel wall surrounding diverticula shows prominent hypertrophy and thickening of the muscularis propria.

INTESTINAL OBSTRUCTION occur at any levela) small intestine most ofteni) narrow lumen causes:a) see table 17-11i) hernias, volvulus, adhesions and intussusception > 80% of casesb) hernias:i) weakness or defect in wall of peritoneal cavity- protrusion hernial sac

ii) inguinal, umbilical and scar areas- most are small bowel

NEOPLASMS

small intestinea) uncommon hereb) benign:i) adenomas and mesenchymal are most common benign- near ampulla of Vater- occult blood loss- CA precursor ii) others are lipomas, angiomas and harmartomas

c) malignant:i) adenocarcinoma, carcinoid, lymphomas and sarcomasii) most in the duodenumiii) near ampulla of Vater may cause obstructive jaundiceiv) obstruction major complaint- pain, cramping, nausea, vomiting, weight loss, tired (due to blood loss)v) risk from IBD (e.g., CD) and celiac disease, etc.

large intestine (colon and rectum)a) colorectal CA very common malignancies in Western countriesb) benign:i) polyps- tumorous mass protruding into lumen- sessile (without stalk) or- pedunculated (stalk)

Tubular adenoma of the colon. This lesion was removed with snare-electrocautery during colonoscopy. Note the stalk of normal tan mucosa and the multilobulated head of the polyp. The stalk is formed when the polyp grows to a size that allows it to be pulled on by peristaltic forces.

ii) nonneoplastic polyps- hyperplastic (~ 95%)NO malignant potential- harmartomous (juvenile)RISK of CA- harmatomous (Peutz-Jeghers) AD genetics. Multiple scattered throughout GI tract. Melanin color around lips, face, palms. NO risk of polyp CA. Risk of intussusceptions. CA risk of breast, lungs, ovary and uterus.

Enterography: Lobulated polyps in the small bowel (arrows) cause intermitting obstruction (arrows).

- inflammatory (pseudo)- lymphoidiii) adenomas- polyp types: 1.- tubular (most common) 2.- villous 3.- tubulovillous - arise from dysplasia, low grade to high grade (CA in situ)- precursor to invasive colorectal CA- slow growing (10 yrs. to 2x)

clinical (adenomas):a) asymptomatici) evaluation of anemia/bleedb) evolution to malignancy:i) high grade dysplasiaii) penetration through muscularis into submucosa- invasive CA- polypectomy Tx if:1-CA not invasive of stalk; 2-no vascular invasion; 3-not poorly differentiated

Familial syndromes (familial polyposis)a) AD geneticsb) risk of CAi) FAP ~100% riskc) FAP (familial adenomatous polyposi)i) caused by mutation on chromosome 5q21- APC gene (adenomatous polyposi coli)

Familial polyposis The colon is covered in a carpet of adenomatous polyps.

ii) further classified:- 1) attenuated- 2) Gardner syndrome- 3) Turcot syndrome

1.- attenuateda) fewer polyps (avg. ~ 30)b) most in proximal colonc) lifetime risk of CA ~ 50%

2. Gardner syndromea) # polyps same as classical FAPb) multiple osteomasi) skull, mandible and long bonesc) epidermal cystsd) fibromatosise) risk of duodenal and thyroid CA

Dental panoramic tomogram shows a sharply defined, large radiopaque lesion consisting of several clumped toothlets on the right mandibular corpus.

3.- Turcot syndromea) rareb) colonic polyposisc) CNS tumors (medulloblastoma APC mutations - ~67%; glioblastoma other gene (HNPCC) mutations 33% HNPCC (hereditary nonpolyposi colorectal cancer)a) AD genetics; DNA repair geneb) risk of colorectal CA and endometrium

COLORECTAL CARCINOMA most occur sporadicallyWell defined sequencea) adenoma carcinomai) populations with incidence of adenoma have risk of carcinomaii) distribution similar to adenomasiii) some dysplastic lesions can evolve CA w/out polyp (adenoma) phase

pathways:a) APC/-caterin (first hit)i) chromosomal instability- loss of APC gene 5q21 (FAP)b) 80% of colorectal CA patients have APC inactivationc) 50% of CA without APC mutations have -caterin mutationsd) APC function:i) cell adhesions & regulates proliferation

e) other genetic factors:i) K-RAS mutationsii) loss of SMAD (2 and 4)- tumorogenesisf) loss of p53g) activation of telomerase CAa) 98% in colon are adenocarcinomasi) usually arise in polypsb) peak age 60-80 yrs.i) if occurs < 50 yrs other factors (UC, FAP, etc.)

c) environmental factorsi) diet !!- immigrants from low risk CA countries coming to USA develop increased risk of CA- implicated are:1. fiber intake2. caloric intake vs. requirement3. unrefined CHO4. red meat

clinical:a) in proximal coloni) polypoid lesion- obstruction uncommon- bleedingb) in distal coloni) encircling ring- napkin ring constriction- constipation & reduced caliber of stool- dx earlier vs. proximalc) asymptomatic for years

Figure 17-61 Carcinoma of the cecum. The fungating carcinoma projects into the lumen but has not caused obstruction. Figure 17-62 Carcinoma of the descending colon. This circumferential tumor has heaped-up edges and an ulcerated central portion. The arrows identify separate mucosal polyps.

d) iron deficiency anemia in older male means GI CA until disproved ! e) metastasize to regional lymph nodes, liver, bone etc.f) Most important prognostic indicatori) extent or STAGE of tumor at time of diagnosis- TNM classificationsee Table 17-14

Figure 17-64 Pathologic staging of colorectal cancer. Staging is based on the depth of tumor invasion

Carcinoid tumorsa) possess endocrine cellsi) lung also had endocrine cellsii) most carcinoids are from gutb) ~ 2% of colorectal CAi) ~ 50% of small intestine CAc) most common site is appendix, followed by small intestine (ileum)i) appendix and rectal carcinoids rarely metastasize !d) solid, yellow-tan appearancee) rarely produce local symptoms

f) can release hormones directly into circulationi) Zollinger-Ellison syndrome- gastrin from pancreatic carcinoid many peptic ulcersg) carcinoid syndrome (see table 17-15)i) serotonin (5-HT) and its metabolite (5-HIAA) hydroxyindoleacetic acid

GI Lymphomaa) secondary involvement by NHLi) gut 1o siteb) primary GI lymphoma show NO:i) liverii) spleeniii) bone marrowiv) mediastinal lymph node involvement !!c) B- or T-cell lymphomai) B-cell MALT or IPSID and Burkitt lymphoma (NHL)

ii) MALT most common in USA- adults- no gender preference- CD5 and CD10 negative- anywhere in gut- H. pylori may be driving force (e.g., gastric MALT lymphoma)iii) IPSID (Mediterranean lymphoma) - B-cell (plasmacytosis)- infection plays a role

iv) T-cell lymphoma- long term malabsorption syndrome (i.e., celiac disease)- 30-40 yrs. (10-20 yr symptoms)- proximal bowel- poor prognosis vs. B-cell

PERITONEUM

Inflammation (peritonitis)a) sterile i) mild leakage of bile or pancreatic enzymesb) acute hemorrhagic pancreatitisi) fat necrosisc) perforations of biliary systemd) surgical proceduresi) adhesionsii) granulomas (talc)

tumorsa) all are malignant (rare)i) primary:- mesothelioma- desmoplastic small round cell tumor t(11,22)b) secondary:i) common- ovarian- pancreatic- any intra-abdominal malignancy