small and large intestine pathology

SMALL AND LARGE INTESTINESSMALL AND LARGE INTESTINES

• Congenital anomaliesa) Meckel diverticulum

i) blind pouch located on antimesenteric side of

small bowel- within 2 feet on ileocecal valve

ii) true diverticulum- contains all 3 layers

iii) usually asymptomaticwww.freelivedoctor.comwww.freelivedoctor.com

www.freelivedoctor.comwww.freelivedoctor.com

• Hirschsprung disease (aganglionic megacolon)

a) lack of neural connectioni) devoid of Meisnner and Auerbach myenteric plexus

b) functional obstructioni) dilation proximal to affected

segmentii) normal ganglia in dilated

segmentiii) loss of ganglia in

contracted segmentwww.freelivedoctor.comwww.freelivedoctor.com

iv) rectum always affectedv) “short disease” involves rectum and sigmoidvi) “long disease” involves

rectum and entire colonvii) male 4:1

- 10% with Down’s syndrome

viii) enterocolitis, perforations with peritonitis are major causes of deathwww.freelivedoctor.comwww.freelivedoctor.com

c) acquired Hirschsprungi) Chagas diseaseii) organic obstruction

- neoplasm- inflammatory stricture- toxic (UC or Crohn’s)

ENTEROCOLITISENTEROCOLITIS• Diarrheal diseases

a) infectionsb) malabsorptionc) inflammatory bowel diseasewww.freelivedoctor.comwww.freelivedoctor.com

• Diarrhea and dysentery a) diarrhea > 250 grams

stool/dayi) 70-95% water

b) dysentery low volume, painful, bloody diarrhea

c) causes: see table 17-6i) 5 categories

- secretorysecretory: > 500 ml fluid stool, isotonic, with

fasting- osmoticosmotic: > 500 ml fluid

stool, stops with fasting, Osm > plasma (50 mOsm)


- exudativeexudative: bacterial damage, bloody, persist

with fasting- motility diseasemotility disease:

increased- malabsorptionmalabsorption: bulky

stool, Osm, steatorrhea, stops with fasting

• Infectious enterocolitisa) > 12,000 deaths/day in children in developing countriesb) 50% of all deaths worldwide

i) children < 5 yrs.


ii) self-limited diarrhea mostly caused by viruses

c) 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 diarrheawww.freelivedoctor.comwww.freelivedoctor.com

iv) calicivirus - Sapporo-like (rare)- Norwalk-like (common);

majority of nonbacterial food-borne epidemic gastroenteritis in all age groups

v) astrovirus- 1o children

d) necrotizing enterocolitisi) neonates, premature, low

birth weight (sm intest) www.freelivedoctor.comwww.freelivedoctor.com

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 SYNDROMESMALABSORPTION 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”, Celiac disease (“celiac sprue”, “gluten sensitive enteropathy”)“gluten sensitive enteropathy”)

a) chronic diseasei) T-cell inflammatory reaction with autoimmune

componentb) mucosal lesions

i) 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) familial

i) class II HLA-DQ2 or HLA- DQ8

f) clinical:i) characteristic skin blisters

- dermatitis herpetiformisii) neurologic disordersiii) Dx:

- history of malabsorption- lesion present via biopsy- improve without glutenwww.freelivedoctor.comwww.freelivedoctor.com

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

Tropical sprueTropical spruea) same characteristics as celiacb) Caribbean (not Jamaica), India, Africa, Asia c) NO specific causal agent found

i) bacterial overgrowth ?- E. coli; Hemophilus www.freelivedoctor.comwww.freelivedoctor.com

d) injury seen at all levels of small intestinee) usually folate/B12 deficiencyf) broad spectrum antibiotics

i) bacterial origin ?g) no carcinoma susceptibility

Whipple diseaseWhipple diseasea) rare

i) bacterium - Tropheryma whippelii

b) systemic conditionwww.freelivedoctor.comwww.freelivedoctor.com

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 dystrophy”

iv) Caucasians; 10:1 male v) Dx = PAS+ macrophages

- with rod shaped organisms


PASBacilli withinmacrophage

Arthritis(often)

Steatorrhea

Encephalopathy(occasionally)

MalabsorptionAnd diarrhea

lymphadenopathyLipid pools in mucosa


Disaccharidase (lactase) Disaccharidase (lactase) deficiencydeficiency

a) rare (congenital form)b) acquired is commonc) lactose glucose + galactose

i) osmotic diarrhea

IDIOPATHIC INFLAMMATORY IDIOPATHIC INFLAMMATORY BOWEL DISEASE (IBD) 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 DiseaseCrohn Disease• any level of alimentary tract

a) 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)www.freelivedoctor.comwww.freelivedoctor.com

• clinical:a) more subtle than UCb) diarrhea, fever, abdominal pain

i) lower right pain- mimic appendicitis or- perforation

c) colonic involvement bloodi) anemia over time

d) bimodal age distributioni) 10-30 and 50-70 yrs

e) Caucasians 5:1 vs. noncaucasians www.freelivedoctor.comwww.freelivedoctor.com

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 colitisUlcerative colitis

• inflammatory disease limited to colon• affecting mucosa and submucosa

a) 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 colon

a) “pancolitis”b) disease of continuity

i) NO skip lesionsc) more common than CDd) NO mural thickening vs. CDe) with severe cases toxic megacolon

i) 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 CA

i) 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 DISORDERSVASCULAR DISORDERS

• Ischemic bowel disease a) small and/or large intestine

i) depending on vessel(s)- superior mesenteric- celiac- inferior mesenteric

• Types:a) transmural infarcts

i) mechanical compromise - major mesenteric vesselswww.freelivedoctor.comwww.freelivedoctor.com

b) mucosal (i.e., mural) infarcts

i) hypoperfusionc) venous compromise is a less frequent cause of

infarcts

• Causes:a) arterial thrombosis

i) 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 drugs

d) venous thrombosisi) BC pillsii) hypercoagulable statesiii) peritonitisiv) invasive neoplasmsv) cirrhosisvi) abdominal trauma

e) other (radiation, herniation, etc.)


• clinical:a) embolic injury mainly affects

i) SMAb) injury

i) initial hypoxic insultii) reperfusion injury

- most of intestinal injuryc) bowel infarction is uncommon

i) 50-75% lethalityii) older population (disease)

d) abdominal paine) bloody diarrheawww.freelivedoctor.comwww.freelivedoctor.com

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

• Hemorrhoidsa) vertical dilations of anal and perianal venous plexuses

i) causes:- straining with

constipation- venous stasis of

pregnancywww.freelivedoctor.comwww.freelivedoctor.com

DIVERTICULAR DISEASEDIVERTICULAR DISEASE

•Blind poucha) congenital

i) involve all 3 layers- Meckel diverticulum

b) 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 pressure

i) lack of fiber in dietii) causes “sequestration”

• clinical:a) cramping; feeling “not able to empty”; blood losswww.freelivedoctor.comwww.freelivedoctor.com

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 OBSTRUCTIONINTESTINAL OBSTRUCTION occur at any level

a) small intestine most ofteni) narrow lumen

• causes:a) see table 17-11

i) hernias, volvulus, adhesions and intussusception > 80% of cases

b) hernias:i) weakness or defect in wall

of peritoneal cavity- protrusion hernial sac


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


NEOPLASMSNEOPLASMS

• 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 sarcomas

ii) most in the duodenumiii) near ampulla of Vater may

cause obstructive jaundice

iv) 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”)- lymphoid

iii) 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) asymptomatic

i) evaluation of anemia/bleed

b) 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 CA

i) FAP ~100% riskc) FAP (familial adenomatous

polyposi)i) caused by mutation on

chromosome 5q21- APC gene (adenomatous polyposi coli)


Familial polyposisThe colon is covered in a carpet of adenomatous polyps.


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

1.- attenuated1.- attenuateda) fewer polyps (avg. ~ 30)b) most in proximal colonc) lifetime risk of CA ~ 50%


2. – Gardner syndrome2. – Gardner syndromea) # polyps same as classical FAPb) multiple osteomas

i) skull, mandible and long bones

c) 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 syndrome3.- 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 endometriumwww.freelivedoctor.comwww.freelivedoctor.com

COLORECTAL CARCINOMACOLORECTAL CARCINOMA• most occur sporadically•Well defined sequence

a) 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/APC/ββ-caterin-caterin – (“first hit”)

i) chromosomal instability- loss of APC gene 5q21 (FAP)

b) 80% of colorectal CA patients have APC inactivation

c) 50% of CA without APC mutations have β-caterin mutations

d) APC function:i) cell adhesions & regulates

proliferationwww.freelivedoctor.comwww.freelivedoctor.com

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 polyps

b) peak age 60-80 yrs.i) if occurs < 50 yrs – other

factors (UC, FAP, etc.)www.freelivedoctor.comwww.freelivedoctor.com

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 meatwww.freelivedoctor.comwww.freelivedoctor.com

•clinical:a) in proximal colon

i) polypoid lesion- obstruction uncommon- bleeding

b) in distal coloni) encircling ring

- “napkin ring” constriction- constipation & reduced

caliber of stool- dx earlier vs. proximal

c) 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 indicator

i) 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 tumorsCarcinoid tumorsa) possess endocrine cells

i) lung also had endocrine cells

ii) most carcinoids are from gut

b) ~ 2% of colorectal CAi) ~ 50% of small intestine CA

c) 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 circulation

i) Zollinger-Ellison syndrome- gastrin from pancreatic carcinoid many peptic ulcers

g) “carcinoid” syndrome (see table 17-15)

i) serotonin (5-HT) and its metabolite (5-HIAA) hydroxyindoleacetic

acid www.freelivedoctor.comwww.freelivedoctor.com

• GI Lymphomaa) secondary involvement by NHL

i) gut 1o siteb) primary GI lymphoma show NO:

i) liverii) spleeniii) bone marrowiv) mediastinal lymph node

involvement !!c) B- or T-cell lymphoma

i) B-cell MALT or IPSID and Burkitt lymphoma (NHL)www.freelivedoctor.comwww.freelivedoctor.com

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 rolewww.freelivedoctor.comwww.freelivedoctor.com

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


PERITONEUMPERITONEUM

• Inflammation (peritonitis)a) sterile

i) mild leakage of bile or pancreatic enzymes

b) acute hemorrhagic pancreatitisi) fat necrosis

c) perforations of biliary systemd) surgical procedures

i) adhesionsii) granulomas (talc)www.freelivedoctor.comwww.freelivedoctor.com

• 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

malignancywww.freelivedoctor.comwww.freelivedoctor.com

small and large intestine pathology

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