SMALL AND LARGE INTESTINES

Congenital anomalies
a) 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 asymptomatic
 megacolon)
Hirschsprung disease (aganglionic

a) lack of neural connection

i) devoid of Meisnner and
Auerbach myenteric plexus
b) functional obstruction
i) dilation proximal to affected
segment
ii) normal ganglia in dilated
segment
iii) loss of ganglia in contracted
segment
iv) rectum always affected
v) short disease involves
rectum and sigmoid
vi) long disease involves rectum
and entire colon
vii) male 4:1
- 10% with Downs syndrome
viii) enterocolitis, perforations
with peritonitis are major
causes of death
 c) acquired Hirschsprung
i) Chagas disease
ii) organic obstruction
- neoplasm
- inflammatory stricture
- toxic (UC or Crohns)

ENTEROCOLITIS
Diarrheal diseases
a) infections
b) malabsorption
c) inflammatory bowel disease
 Diarrhea and dysentery
a) diarrhea > 250 grams stool/day
i) 70-95% water
b) dysentery low volume, painful,
bloody diarrhea
c) causes: see table 17-6
i) 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 enterocolitis
a) > 12,000 deaths/day in children
in developing countries
b) 50% of all deaths worldwide
i) children < 5 yrs.
 ii) self-limited diarrhea mostly
caused by viruses
c) viral gastroenteritis
i) see table 17-7
ii) 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
weaning
iii) 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 children
d) necrotizing enterocolitis
i) 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) CHO
c) protein
d) H2O
e) minerals
f) 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 disease
i) T-cell inflammatory reaction
with autoimmune component
b) 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) Caucasians
e) familial
i) class II HLA-DQ2 or HLA-
DQ8
f) clinical:
i) characteristic skin blisters
- dermatitis herpetiformis
ii) neurologic disorders
iii) Dx:
- history of malabsorption
- lesion present via biopsy
- improve without gluten
 g) long term risk:
i) NHL
ii) adenocarcinoma
iii) esophageal carcinoma

Tropical sprue
a) same characteristics as celiac
b) Caribbean (not Jamaica), India,
Africa, Asia
c) NO specific causal agent found
i) bacterial overgrowth ?
- E. coli; Hemophilus
 d) injury seen at all levels of small
intestine
e) usually folate/B12 deficiency
f) broad spectrum antibiotics
i) bacterial origin ?
g) no carcinoma susceptibility

Whipple disease
a) rare
i) bacterium
- Tropheryma whippelii
b) 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 part
ii) 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
 Encephalopathy
(occasionally)

Lipid pools in mucosa

lymphadenopathy

Malabsorption
And diarrhea

Arthritis
(often)

Bacilli within PAS Steatorrhea

macrophage
Disaccharidase (lactase) deficiency
a) rare (congenital form)
b) acquired is common
c) lactose glucose + galactose
i) osmotic diarrhea

IDIOPATHIC INFLAMMATORY BOWEL

DISEASE (IBD)
Chronic relapsing diseases
Crohn disease & Ulcerative colitis
activation of mucosal immune system
 Dxa)ofclinical
IBD:
history
b) lab and path findings
c) NO single test to Dx IBD nor to
differentiate CD from UC
d) p-ANCA + is 75% with UC and only
11% with CD
Crohn 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 regions
c) noncaseating granulomas
d) formation of fissures
e) narrowed lumen (obstruction)
 clinical:
a) more subtle than UC
b) diarrhea, fever, abdominal pain
i) lower right pain
- mimic appendicitis or
- perforation
c) colonic involvement blood
i) anemia over time
d) bimodal age distribution
i) 10-30 and 50-70 yrs
e) Caucasians 5:1 vs. noncaucasians
f) chronic course may lead to:
i) fibrosing strictures
- terminal ileum
- fistulas other areas
ii) protein loss
iii) Vit B12 loss
iv) bile salt loss
- steatorrhea
v) linear serpentine ulcers
e) extraintestinal:
(altered immunity)
i) polyarthritis
ii) erythema nodosum
iii) clubbing of fingers
iv) ankylosing spondylitis
v) risk of GI carcinoma
- less than UC
Ulcerative colitis

inflammatory disease limited to colon

affecting mucosa and submucosa
a) except in most severe cases
i) transmural
extends in continuous fashion
a) from rectum
well formed granulomas are absent
as with CD, UC is systemic disease
incidence vs. CD
age peak 20-30 yrs
 retrograde
involves rectum and extends
to involve entire colon
a) pancolitis
b) disease of continuity
i) NO skip lesions
c) more common than CD
d) NO mural thickening vs. CD
e) 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 diarrhea
i) relieved by defecation
- 1st initial signs
b) long term complication CA
i) with pancolitis (25X normal)
c) see table 17-10
i) Crohn vs. UC
 Patients with ulcerative
Endoscopic image of ulcerative
colitis can occasionally
colitis showing loss of vascular
have aphthous ulcers
pattern of the sigmoid colon,
involving the tongue, lips,
granularity and some friability of
palate and pharynx
the mucosa.
 VASCULAR 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 vessels
 b) mucosal (i.e., mural) infarcts
i) hypoperfusion
c) venous compromise is a less
frequent cause of infarcts

Causes:
a) arterial thrombosis
i) atheroma (origin of vessel),
angiography (i.e., Ca++), BC pills
b) arterial embolism
i) atheroemboli (i.e., plaques),
cardiac vegetations
c) nonocclusive ischemia
i) cardiac failure
ii) shock
iii) vasoconstrictive drugs
d) venous thrombosis
i) BC pills
ii) hypercoagulable states
iii) peritonitis
iv) invasive neoplasms
v) cirrhosis
vi) abdominal trauma
e) other (radiation, herniation, etc.)
 clinical:
a) embolic injury mainly affects
i) SMA
b) injury
i) initial hypoxic insult
ii) reperfusion injury
- most of intestinal injury
c) bowel infarction is uncommon
i) 50-75% lethality
ii) older population (disease)
d) abdominal pain
e) bloody diarrhea
 f) vasculitides:
i) PAN
ii) WG
iii) Henoch-Schnlein disease

Hemorrhoids
a) vertical dilations of anal and
perianal venous plexuses
i) causes:
- straining with constipation
- venous stasis of pregnancy
 DIVERTICULAR DISEASE

Blind pouch
a) congenital
i) involve all 3 layers
- Meckel diverticulum
b) acquired
i) lack or attenuated muscularis
ii) most common location
- left side of colon
- majority in sigmoid
 iii) rare < 30 yrs
iv) > 60 yrs common (~ 50%)
v) occur in multiples
- diverticulosis
pathogenesis:
a) focal weakness in colonic wall
b) intraluminal pressure
i) lack of fiber in diet
ii) 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 level
a) small intestine most often
i) 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
 NEOPLASMS

small intestine
a) uncommon here
b) 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 duodenum
iii) 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 countries
b) 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 dysplasia
ii) 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 genetics
b) risk of CA
i) FAP ~100% risk
c) 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.- attenuated
a) fewer polyps (avg. ~ 30)
b) most in proximal colon
c) lifetime risk of CA ~ 50%
2. Gardner syndrome
a) # polyps same as classical FAP
b) multiple osteomas
i) skull, mandible and long bones
c) epidermal cysts
d) fibromatosis
e) 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 syndrome
a) rare
b) colonic polyposis
c) CNS tumors (medulloblastoma
APC mutations - ~67%;
glioblastoma other gene (HNPCC)
mutations 33%
HNPCC (hereditary nonpolyposi
colorectal cancer)
a) AD genetics; DNA repair gene
b) risk of colorectal CA and
endometrium
 COLORECTAL CARCINOMA

most occur sporadically

Well defined sequence

a) adenoma carcinoma
i) populations with incidence of
adenoma have risk of
carcinoma
ii) distribution similar to
adenomas
iii) some dysplastic lesions can
evolve CA w/out polyp
(adenoma) phase
 pathways:
a) APC/-caterin (first hit)
APC/-caterin
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 -caterin mutations
d) APC function:
i) cell adhesions & regulates
proliferation
 e) other genetic factors:
i) K-RAS mutations
ii) loss of SMAD (2 and 4)
- tumorogenesis
f) loss of p53
g) activation of telomerase
CA
a) 98% in colon are adenocarcinomas
i) usually arise in polyps
b) peak age 60-80 yrs.
i) if occurs < 50 yrs other
factors (UC, FAP, etc.)
c) environmental factors
i) diet !!
- immigrants from low risk
CA countries coming to
USA develop increased risk
of CA
- implicated are:
1. fiber intake
2. caloric intake vs.
requirement
3. unrefined CHO
4. red meat
clinical:
a) in proximal colon
i) polypoid lesion
- obstruction uncommon
- bleeding
b) in distal colon
i) encircling ring
- napkin ring constriction
- constipation & reduced
caliber of stool
- dx earlier vs. proximal
c) asymptomatic for years
Figure 17-61 Carcinoma of the
Figure 17-62 Carcinoma of the
cecum. The fungating carcinoma
descending colon. This
projects into the lumen but has
circumferential tumor has
not caused obstruction.
heaped-up edges and an ulcerate
central portion. The arrows
identify separate mucosal polyp
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 classification
see Table 17-14
Figure 17-64 Pathologic staging of
colorectal cancer. Staging is based on the
depth of tumor invasion
 Carcinoid tumors
a) possess endocrine cells
i) lung also had endocrine cells
ii) most carcinoids are from gut
b) ~ 2% of colorectal CA
i) ~ 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 appearance
e) 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
 GIa)Lymphoma
secondary involvement by NHL
i) gut 1o site
b) primary GI lymphoma show NO:
i) liver
ii) spleen
iii) bone marrow
iv) mediastinal lymph node
involvement !!
c) B- or T-cell lymphoma
i) 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
a) sterile
(peritonitis)

i) mild leakage of bile or

pancreatic enzymes
b) acute hemorrhagic pancreatitis
i) fat necrosis
c) perforations of biliary system
d) surgical procedures
i) adhesions
ii) granulomas (talc)
 tumors
a) 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