Transcript DISEASES OF SMALL AND LARGE INTESTINE

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Disease of bowel caused by:
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Developmental anomalies (Hirschsprung Disease)
Vascular Disorders
Diarrheal diseases
Idiopathic inflammatory bowel disease
Tumors
Others.
Meckel diverticulum
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is the most common and innocuous of the anomalies. It
results from failure of involution of the
omphalomesenteric duct, leaving a persistent blindended tubular protrusion as long as 5 to 6 cm
in the ileum, about 80cm proximal to the ileocecal
valve
Peptic ulceration in the adjacent intestinal mucosa
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during development, the migration of neural crestderived cells along the alimentary tract arrests at some
point before reaching the anus.
an aganglionic segment is formed that lacks both the
Meissner submucosal and Auerbach myenteric
plexuses.
This causes functional obstruction and progressive
distention of the colon proximal to the affected
segment.
Ganglia are absent from the muscle wall and
submucosa of the constricted segment but may be
present in the dilated portion.
Diarrheal diseases including
Acute
inflammation caused by
infectious organism
Malabsorption
Idiopathic
disorder.
inflammatory bowel
disease.
Symptoms: diarrhea, dysentery and pain.
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Diarrhea consists of daily stool production in
excess of 250 g, containing 70% to 90% water.
Often accompanied by pain, discomfort,
urgency and incontinence.
Dysentery is low volume painful, bloody
diarrhea
Secretory:
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Osmotic:
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excessive osmotic forces as Lactulose therapy and antiacids
Exudative:
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output of purulent, bloody stool, occur in infectious conditions and
Idiopathic inflammatory bowel disease
Malabsorption:
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isotonic to plasma, occur in infectious conditions, neoplastic
conditions and in excessive laxatives used
voluminous stool, occur in defective absorption and intraluminal
digestion or lymphatic obstruction
Deranged motility
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A global problem, 2.9 million death per year
Account for 1/2 of death in children younger
than 5 years in some countries
In USA, about 500 infants and young children
die each year because of diarrheal disease
Most common problem in traveler
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Direct invasion of microbe with ulceration.
Production of enterotoxin.
Ability to adhere to mucosal lining.
Major causative agents: bacteria (E.coli),
virus (calcivirus, rotavirus and Norwalk
virus), fungus and protozoa.
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Viral infection destroy superficial epithelium in small
intestine & their absorptive function
Repair by immature enterocytes with secretory function
Rotavirus: 130 million cases per year and 0.9 million
deaths worldwide per year, mainly children (6-24
month)
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Rotavirus is the most common agent (140 million cases and 1
million death 1 year).
Affect children 6-24 months.
Incubation period is 2 days followed by vomiting and watery
diarrhea.
Affect epithelium of the small intestine leading to secretion of
water and electrolytes
May produce a flat mucosa in small intestine.
Rotavirus have intrinsic viral factor, nonstuctural protein 4
(NSP4) that induce direct diarrhea
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Caliciviruses most common virus of nonbacterial
foodborne epidemic in older children and adult.
Adenovirus and astrovirus
Bacterial enterocolitis
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Caused by a variety of bacterial species e.g. E.coli,
salmonella, shigella, campylobacter, vibrio cholerae and
others.
Pathogenic mechanism:
1. Ingestion of preformed toxin e.g.
C. botulism and S. aureus.
2. Infection by toxigenic organisms, e.g.
E. coli, V. cholerae.
3. Infection by enteroinvasive organism e.g.
salmonella, shigella or E. coli.
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In enteroinvasive organism and toxigenic organisms
bacterial replication occur
This depend on:
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The ability to adhere to mucosa ( adhesins )
The ability to elaborate toxins
The capacity to invade
Morphology
 Pathologic manifestations are variable – normal (v.
cholerae) to non specific inflammation and severe
ulceration
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E.coli - different subtypes
 Entertoxigenic
 The Shiga toxin - producing strain
 Enteropathogenic strains
 Enteroinvasive strains
 Enteroaggregating strains
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Shigella – distal colon, acute mucosal inflammation and erosion.
C. Jejuni – small and large intestine; villus blunting, ulceration.
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Y enterocolitis – ileum, appendix and colon;
hemorrhage. and necrosis, invade Peyer patches and
lymph node leading to necrotizing granulomas
Salmonella – ileum and colon; invade Peyer patches and
produce linear ulceration, serosa may be normal or
covered by serous, fibrinous or hemorrhagic exudate,
regional lymph node may be enlarged, systemic
infection (Typhoid fever)
Mycobacterium tuberculosis
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Acute colitis with formation of adherent
inflammtory exudate.
Caused by C. difficile (produce two protein
exotoxins A & B).
Occur after a coarse of broad spectrum
antibiotic.
Can occur after severe necrotizing
enterocolitis or in ischemic colitis.
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Ingestion of preformed toxin: diarrhea, acute
abdominal pain.
Infection with enteric pathogens:
- Secretory enterotoxin: diarrhea
- Cytotoxin or enteroinvasive process: dysentery.
Insidious infection: Yersenia and TB – subacute
diarrheal illness.
Amebiasis
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Entamoeba histiolytica is a common pathogen of colon.
Ingestion of cysts in the contaminated food and water.
Cysts release active amebas (trophozoites), invade large
bowel mucosa and enter the submucosa (site of
maximum involvement), enzymatic necrosis (flaskshaped ulcer).
Gross:
multiple ulcers separated by healthyappearing mucosa, undermined by
submucosal abscesses.
Micro:
mucosal ulcers covered by a necrotic
base. Amebas are found in the wall of the
ulcer.
Complication:
perforation, haemorrhage,
toxic megacolon, amebic abscess.
Giardia Lamblia
Malabsorption Syndrome
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There is increased fecal excretion of fat
(steatorrhea) and the systemic effects of
deficiency of vitamins, minerals, protein and
carbohydrates.
Steatorrhea is passage of soft, yellowish, greasy
stools containing an increased amount of fat.
Fat excretion exceeding 6 g/d is demonstrated in
a 72-hour stool sample.
Disturbance of normal digestive function.
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It result from disturbance of one of these
normal digestive functions
Intraluminal digestion
 Terminal digestion
 Transepithelial transport
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Defective intraluminal digestion e.g. pancreatic
insufficiency.
Mucosal cell abnormality e.g. lactose intolerance,
abetalipoproteinemia.
Reduced intestinal surface e.g. celiac disease and
Crohn’s disease.
Lymphatic obstruction e.g. lymphoma.
Infection – e.g. tropical sprue.
Iatrogenic – e.g. gastrectomy.
Celiac disease
 Synonyms: nontropical sprue; gluten-induced
enteropathy, gluten-sensitive enteropathy
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Is a chronic disease
characteristic mucosal lesion of the small intestine with
impaired nutrient absorption, which improves on
withdrawal of wheat gliadins.
Occurs largely in whites (1:300 in Europe).
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Most likely an immune reaction to gliadin
Usually diagnosed in childhood – mid adult.
Genetic background: 95% of patient have HLA-DQ2- and the
remainder have HLA-DQ8-positive antigen presenting cells
in the lamina properia of small intestine to CD4+ t cells
CD 8+T cells the NK cell-associated NKG2D receptor, which
recognizes stress-induced molecules on epithelial cells
virus (type 12 adenovirus)
Patients have raised antibodies to gluten and IgA
antiendomysial autoantibodies
Normal
Celiac disease
Malabsorption Syndrome
Celiac Disease
Morphology
•Mucosa
is flattened with marked villous
atrophy.
•Crypts
are elongated and hyperplastic.
•Lamina
propria: increase in chronic
inflammatory cells.
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Immunoperoxidase shows immunocytes with IgA
antigliadin antibodies.
Changes are more marked in the proximal than in the
distal small intestine.
There is a 10 to 15% risk of developing GI lymphoma.
Clinical features
Infants :
Adults :
Failure to thrive, diarrhea.
Diarrhea, flatulence, weight loss
and fatigue.
Diagnosis
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Clinical documentations of malabsorption.
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Small intestine biopsy demonstrate intestinal lesion.
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Improvement of symptom and mucosal histology on
gluten withdrawal from diet.
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Challenge test.
Tropical Sprue (post-infectious sprue)
 Occurs in people living in or visiting tropical or
semitropical locales.
 Of unknown etiology, perhaps enterotoxigenic
E.coli or haemophilus.
 Most patients improve or are cured with long-term
broad spectrum antibiotic therapy.
Tropical Sprue (post-infectious sprue)
Morphology
 Variable ranging from normal to those of celiac disease.
 Unlike celiac disease, injury of small intestine occur at
all levels.
 Deficiency of folic acid and vit. B12 – megaloblastic
changes.
Malabosortion affect many organs
 Hematopiotic system, anemia and bleeding
 Musculoskeletal system, osteopenia and tetany
 Endocrine system, amenorrhea, infertility,
hyperparathyridism
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Skin, purpura dermatitis hyperkeratosis
Nervous system system, neuropathy