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CONGENITAL DISORDERS
Atresia
• Complete occlusion of the
intestinal lumen, may manifest
as:
– Thin intraluminal diaphragm
– Blind proximal and distal sacs
joined by a cord
– Disconnected blind ends
Stenosis
• Incomplete stricture narrows
the lumen, but does not occlude
• Usually symptomatic in infancy
Atresia and stenosis
• Diagnosed on the basis of:
1. Persistent vomiting of bile-containing fluid within the first day
of life
2. Meconium is not passed
3. Obstructed intestine is dilated and filled with fluid (xray)
• Most common and most clinically significant congenital anomaly of the small
intestine
Meckel diverticulum
• True diverticulum
• Most are asymptomatic
• If symptomatic, about ½ has ectopic
gastric, duodenal, pancreatic,
biliary, or colonic tissue
• Complications:
– Hemorrhage
– Perforation
– Obstruction
– Diverticulitis
Meconium ileus
• Accumulation of tenacious
meconium in the small intestine
– Neonatal intestinal obstruction in
cystic fibrosis
• In half of patients, it is
complicated by
– Volvulus
– Perforation with meconium
peritonitis
– Intestinal atresia
INFECTIONS OF THE
SMALL INTESTINE
Bacterial diarrhea
• Most significant factor in infectious diarrhea is increased
intestinal secretion
– Stimulated by bacterial toxins and enteric hormones
• Agents:
– Toxigenic organisms
• V. cholera, some E. coli strains
– Adherent or invasive bacteria
• Shigella, Salmonella, some E. coli strains, Yersinia, and Campylobacter
Viral gastroenteritis
• Most common causes:
• ROTAVIRUS
– Common cause of infantile diarrhea
– Hospitalized children <2y/o
– Injury to surface epithelium of duodenum (for up to 2 months)
• NORWALK VIRUS
– 1/3 of viral gastroenteritis epidemics in US
– Targets upper small intestine
– Causes patchy mucosal lesions and malabsorption
– Vomiting and diarrhea resolve w/in 2 days
Decreased intestinal blood flow can lead to ISCHEMIC BOWEL DISEASE
VASCULAR DISEASES
Acute intestinal ischemia
ARTERIAL OCCLUSION
• Occlusion of the superior mesenteric artery (SMA) is the most
common cause
• Infarct may be segmental or may lead to gangrene of entire SI
• Less commonly, caused by vasculitis w/c involves small arteries
• Other causes: volvulus, intussusception, incarceration in
hernial sac
Acute intestinal ischemia
NONOCCLUSIVE INTESTINAL ISCHEMIA
• May be extensive
• Seen in hypoxic patients w/ reduced cardiac output sec. to
shock
– Hemorrhage
– Sepsis
– AMI
Acute intestinal ischemia
THROMBOSIS OF MESENTERIC VEINS
• Causes:
– Hypercoagulable state
– Stasis
– Inflammation (pylephlebitis)
• Almost all affect superior mesenteric vein
Acute intestinal ischemia
MALABSORPTION
• Only absorption from the small intestine, mainly the proximal
portion, is clinically important
• INTESTINAL PHASE
– Processes that occur in cells and transport channels
Luminal phase malabsorption
• Interruption of the normal continuity of the distal stomach and
duodenum – i.e. gastroduodenal surgery
• Pancreatic dysfunction – chronic pancreatitis, cancer, cystic
fibrosis
• Deficient or ineffective bile salts, causes:
1. Impaired excretion of bile – liver disease
2. Bacterial overgrowth – blind-loop syndrome, multiple diverticula,
muscular/neurogenic defects
• Defective GI motility causes deconjugation of bile salts by excess bacterial
flora cannot form micelles cannot be absorbed
Intestinal phase malabsorption
• Reflects specific enzyme defects or impaired transport
PATHOGENESIS:
• Microvilli – binds disaccharidases and oligopeptidases
– Disaccharidases – essential for sugar absorption only
monosaccharides can be absorbed by intestinal epithelial cells
– Abnormal function:
• Primary – disaccharidase deficiency
• Secondary – damage to villi (celiac disease/sprue)
Intestinal phase malabsorption
PATHOGENESIS:
• Absorptive area – Severe diminution of small bowel surface
area
1. Small bowel resection (short bowel syndrome)
2. Gastrocolic fistula – SI is bypassed
3. Mucosal damage – celiac disease, tropical sprue, Whipple dse
Intestinal phase malabsorption
PATHOGENESIS:
• Metabolic function of the absorptive cells – monoglycerides
and FFAs are reassembled into TG and coated with apoproteins
form chylomicrons and lipoproteins
– Abetalipoproteinemia – absorptive cells cannot synthesize the
apoprotein required for the assembly of lipoproteins and
chylomicrons
– Nonspecific damage – celiac dse, tropical sprue, Whipple dse,
hyperacidity due to gastrinoma
Intestinal phase malabsorption
PATHOGENESIS:
• Transport – impaired transport through conduits like blood
capillaries and lymphatic vessels
– Whipple dse, intestinal lymphomas, congenital lymphangiectasia
Clinical features
• Specific or isolated malabsorption
– Identifiable molecular defect that causes malabsorption of a single
nutrient
• Disaccharidase deficiency – i.e. Lactase deficiency
• Deficiency of gastric intrinsic factor – vitamin B12 malabsorption
pernicious anemia
– Generalized malabsorption – several or all nutrient classes
malnutrition
Lactase deficiency
• Intolerance to milk products
• Abdominal distention, flatulence, and diarrhea
• Injury to intestinal mucosa acquired lactase deficiency
Celiac disease
• Aka celiac sprue, gluten-sensitive enteropathy
• Characterized by:
1. Generalized malabsorption
2. Small intestinal mucosal lesions
3. Prompt clinical and histopathologic response to the withdrawal of
gluten-containing foods from the diet
• M:F = 1:1.3
• Dx during childhood – seen after introducing cereals into the
diet
PATHOGENESIS (Celiac disease)
• Cereals (wheat, barley, rye flour), and Gliadin (alcohol soluble
fraction of gluten) active dse
• Genetics: 90% of px w/ celiac dse carry HLA-B8, HLA DQ2 and
DQ8
• Immunologic factors:
– Characterized by:
• damage to epithelial cells
• marked increase in CD8+ T lymphocytes in w/in epithelium and plasma cells
in lamina propria
– Diagnostic HALLMARK of celiac dse serum IgA antibodies to gluten
PATHOGENESIS (Celiac disease)
• Association with dermatitis
herpetiformis
– Vesicular skin dse – affects extensor
surfaces and exposed parts of the body
– IgA deposits in BM and autoantibodies
to tissue transglutaminase
MECHANICAL OBSTRUCTION
Intussusception
NEOPLASMS
BENIGN
Adenomas
• Resemble those of the colon
– Tubular, villous, tubulovillous
• Villous adenoma is rare in SI – usually in duodenum
(periampullary region); may undergo malignant transformation
Peutz-Jeghers syndrome
• Autosomal dominant hereditary disorder
• Characterized by:
– intestinal hamartomatous polyps – occur mostly in proximal SI
– mucocutaneous melanin pigmentation – face, buccal mucosa, hands,
feet, perianal and genital areas; usually fade at puberty (except
buccal)
• Associated with inactivating mutations of a gene (LKB1) on
chromosome 19p
– Increased risk for cancers of the breast, pancreas, testis, ovary
Peutz-Jeghers syndrome
• Hamartomas
• Branching networks of smooth
muscle fibers continuous with
the muscularis mucosae that
support glandular epithelium
Gastrointestinal stromal tumors (GIST)
• Occur mostly in jejunum
• Intramural mass covered by
intact mucosa
• Behave more aggressively than
their gastric counterparts
(benign)
Uncommon in small intestine
MALIGNANT
Adenocarcinoma
• Minute proportion of all GI tumors
• But account for half of all malignant small bowel tumors
• Mostly in duodenum and jejunum
• Middle-age; male predominance
• Crohn disease of SI is a risk factor
• FAP, HNPCC/Lynch syndrome, celiac disease
Adenocarcinoma
• Polypoid, ulcerative, annular, stenosing
• Originate from crypt epithelium resemble colorectal cancers
• By the time px becomes symptomatic
– Most have metastasized to local lymph nodes
– Overall 5-year survival rate - <20%
Neuroendocrine tumor (carcinoid tumor)
• All considered MALIGNANT; with LOW metastatic potential
• 20% of all small intestinal malignancies
• Sites of origin;
1. Appendix – most common
2. Rectum
• #1&2 – small, rarely aggressive
3. Ileum – often multiple, more aggressive
CONGENITAL DISORDERS
Hirschsprung disease (congenital megacolon)
INFECTIONS
Pseudomembranous colitis
• Generic term for an inflammatory disease of the colon,
characterized by exudative plaques on the mucosa
• Clostridium difficile – usually the offending organism
– Also implicated in neonatal necrotizing enterocolitis (NEC)
– Associated with antibiotic therapy
– Not invasive; produces toxins damage the colonic mucosa
Pathology
DIVERTICULAR DISEASE
Diverticulosis
• Acquired herniation of mucosa and submucosa through the
muscular layer of colon
– Pseudodiverticula
• Sigmoid colon – 95% of cases
• Most appear in parallel rows between the mesenteric and
lateral taeniae
• Flask-like structure – extends from lumen through the muscle
layers
• Episodic abdominal pain, alternating constipation and diarrhea
Diverticulitis
• Irritation caused by retained fecal material
• Inflammation of wall of diverticulum
• Most common symptoms:
– Persistent lower abdominal pain
– Fever
– Changes in bowel habit
– Leukocytosis
Crohn disease
Ulcerative colitis
INFLAMMATORY
BOWEL DISEASE
Crohn disease
• Most common sites involved – terminal ileum, ileocecal valve,
and cecum
• Cause: unknown
• Adolescents or young adults
• M:F = 1:1.6
• Multiple, separate, sharply delineated areas of disease SKIP
LESIONS (characteristic)
Crohn disease
Two major characteristics:
1. Inflammation involves ALL LAYERS of the
bowel wall Transmural inflammatory
disease
2. Discontinuous involvement of the
intestine – alternating normal and
inflamed tissue
• Macroscopic patterns:
1. Ileum and cecum – 50%
2. Small intestine only – 15%
3. Colon only – 20%
4. Anorectal region – 15%
Crohn disease
• Earliest lesion – aphthous ulcer/s coalesce into elongated,
serpentine ulcers along the axis of the bowel
• Sparing of interspersed mucosa COBBLESTONE
APPEARANCE
• Fissures may lead to fistula form’n
• Bowel wall – thick and rubbery
– Transmural edema, inflammation, submucosal fibrosis, muscularis
propria hypertrophy stricture form’n
– Mesenteric fat extends around serosal surface – creeping fat
Crohn disease
• 60-70 y/o
• these lesions are without malignant
potential.
• Most commonly found in left colon
• <5mm
• Histo: composed of mature goblet
and absorptive cells.
• crowding creates the serrated
surface architecture that is the
morphologic hallmark of these
lesions
Juvenile polyps
• focal malformations of the mucosal epithelium and lamina
propria
• sporadic or syndromic
– Sporadic – solitary, retention polyp
– Syndromic – autosomal dominant; 3-100 hamartomatous polyps
colectomy
• children less than 5 years of age
• Majority in rectum rectal bleeding
Juvenile polyps
• <3cm
• Pedunculated, smooth-surfaced
• Char.: cystic spaces at sectioning
• Histo: cysts are dilated glands filled
with mucin and inflammatory
debris
Inflammatory polyps
• Elevated nodules of inflamed regenerating epithelium
• Commonly found in Crohn and UC
• Histo: distorted and inflamed mucosal glands, intermixed with
granulation tissue
MALIGNANT TUMORS
Colorectal adenocarcinoma
• Most common cause of cancer deaths that are not directly
attributable to tobacco use (western countries)
• Peak – 60-70y/o
• M>F
• Dietary factors: low intake of unabsorbable vegetable fiber,
high intake of refined carbohydrates and fat (i.e. fastfood)
Pathogenesis
• Multistep carcinogenesis
• APC/β-catenin pathway – associated with WNT and classic
adenocarcinoma sequence
• Microsatellite instability pathway – defects in DNA mismatch
repair
Molecular genetics
• APC gene – germline mutations in APC (adenomatous
polyposis coli) lead to FAP
– Normal APC is a negative regulator of β-catenin
– Mutant APC β-catenin accumulation in nucleus activate
proliferation genes (cyclin D1, MYC)
– APC is mutated in most SPORADIC colorectal cancers
• TX: resection
Hereditary nonpolyposis colon cancer
• HNPCC or Warthin-Lynch syndrome
• Autosomal dominant; 3-5% of all colorectal cancers
• Characterized by:
1. Young age at onset
2. Few adenomas (hence, nonpolyposis)
3. High frequency of Ca proximal to splenic flexure
4. Multiple synchronous or metachronous Ca
5. Extracolonic cancers – endometrial, ovarian, stomach, SI,
hepatobiliary tract, renal pelvis and ureters (TCC)
Pathology
• Germline mutation followed by somatic mutation (LOH) in DNA
mismatch repair genes
– hMSH2 on chromosome 2p
– hMLH1 on chromosome 3p
• Microsatellite instability
• High frequency of mucinous signet ring cell and solid
(medullary) carcinomas
ANAL CANAL
Anal canal
APPENDIX
Acute appendicitis
• M>F
• Commonly confused clinically with acute salpingitis, ectopic
pregnancy, Meckel’s etc
• Progressive increase in intraluminal pressure venous
outflow compromise
• 50-80% - cause by fecalith
Morphology
• Early: congestion, perivascular neutrophilic infiltrate
• Histologic hallmark: neutrophilic infiltration of the muscularis
propria
• Acute suppurative appendicitis – focal abscesses w/in the wall
• Acute gangrenous appendicitis - large areas of hemorrhagic
ulceration and gangrenous necrosis that extends to the serosa
– Followed by rupture peritonitis
Clinical features
• Periumbilical pain RLQ pain
• Nausea, vomiting, low-grade fever, mildly elevated WBC count
• McBurney’s sign – deep tenderness at McBurney’s point
Tumors of the appendix
SALAMAT!