DISEASES OF SMALL AND LARGE INTESTINE

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DISEASES OF SMALL AND LARGE INTESTINE
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Diseases of small and large intestine

• Disease of bowel caused by
• Developmental anomalies (Hirschsprung Disease)
• Vascular Disorders
• Diarrheal diseases
• Idiopathic inflammatory bowel disease
• Tumors
• Others.

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Developmental anomalies

• Meckel diverticulum
• is the most common and innocuous of the
  anomalies. It results from failure of involution
  of the omphalomesenteric duct, leaving a
  persistent blind-ended 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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Developmental anomalies (Hirschsprung Disease)

• during development, the migration of neural
  crest-derived 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.

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Diarrheal diseases

• Diarrheal diseases including
• Acute inflammation caused by infectious organism
• Malabsorption disorder.
• Idiopathic inflammatory bowel disease.

• Symptoms diarrhea, dysentery and pain.

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Diarrheal diseases

• 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

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Principal mechanisms of diarrhea

• Secretory
• isotonic to plasma, occur in infectious
  conditions, neoplastic conditions and in
  excessive laxatives used
• Osmotic
• excessive osmotic forces as Lactulose therapy
  and antiacids
• Exudative
• output of purulent, bloody stool, occur in
  infectious conditions and Idiopathic inflammatory
  bowel disease
• Malabsorption
• voluminous stool, occur in defective absorption
  and intraluminal digestion or lymphatic
  obstruction
• Deranged motility

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Infectious Enterocolitis

• 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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Infectious Enterocolitis

• 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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Infectious EnterocolitisViral gastroenterocolitis

• 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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Viral gastroenterocolitis

• 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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Viral gastroenterocolitis

• Caliciviruses most common virus of nonbacterial
  foodborne epidemic in older children and adult.
• Adenovirus and astrovirus

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Infectious Enterocolitis

• Bacterial enterocolitis
• 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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Infectious EnterocolitisBacterial enterocolitis

• In enteroinvasive organism and toxigenic
  organisms bacterial replication occur
• This depend on
• The ability to adhere to mucosa ( adhesins )
• The ability to elaborate toxins
• The capacity to invade

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Bacterial Enterocolitis

• Morphology
• Pathologic manifestations are variable normal
  (v. cholerae) to non specific inflammation and
  severe ulceration
• E.coli - different subtypes
• Entertoxigenic
• The Shiga toxin - producing strain
• Enteropathogenic strains
• Enteroinvasive strains
• Enteroaggregating strains
• Shigella distal colon, acute mucosal
  inflammation and erosion.
• C. Jejuni small and large intestine villus
  blunting, ulceration.

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Bacterial Enterocolitis

• 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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Antibiotic Associated Colitis (Pseudomembranous
colitis)

• 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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Bacterial EnterocolitisClinical manifestation

• 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.

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Protozoal Infection

• Amebiasis
• 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
  (flask-shaped ulcer).

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Amebiasis

• Gross multiple ulcers separated by
  healthy-appearing 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.

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Giardia Lamblia
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Malabsorption Syndrome
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Malabsorption Syndrome

• 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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Mechanism of Malabsorption

• It result from disturbance of one of these normal
  digestive functions
• Intraluminal digestion
• Terminal digestion
• Transepithelial transport

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Disease Causing Malabsorption

• Defective intraluminal digestion e.g. pancreatic
  insufficiency.
• Mucosal cell abnormality e.g. lactose
  intolerance, abetalipoproteinemia.
• Reduced intestinal surface e.g. celiac disease
  and Crohns disease.
• Lymphatic obstruction e.g. lymphoma.
• Infection e.g. tropical sprue.
• Iatrogenic e.g. gastrectomy.

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Diseases Causing Malabsorption

• Celiac disease
• Synonyms nontropical sprue gluten-induced
  enteropathy, gluten-sensitive enteropathy
• 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 (1300 in Europe).

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Malabsorption Syndrome Celiac disease

• 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 8T 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

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Cl
Normal
Celiac disease
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Malabsorption SyndromeCeliac 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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Malabsorption SyndromeCeliac Disease

• 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.

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Malabsorption Syndrome Celiac Disease

• Clinical features
• Infants Failure to thrive, diarrhea.
• Adults Diarrhea, flatulence, weight loss
• and fatigue.

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Malabsorption Syndrome Celiac Disease

• Diagnosis
• Clinical documentations of malabsorption.
• Small intestine biopsy demonstrate intestinal
  lesion.
• Improvement of symptom and mucosal histology on
  gluten withdrawal from diet.
• Challenge test.

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Malabsorption Syndrome

• 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.

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Malabsorption Syndrome

• 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.

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Malabsorption SyndromeClinical features

• Malabosortion affect many organs
• Hematopiotic system, anemia and bleeding
• Musculoskeletal system, osteopenia and tetany
• Endocrine system, amenorrhea, infertility,
  hyperparathyridism
• Skin, purpura dermatitis hyperkeratosis
• Nervous system system, neuropathy