Gastrointestinal Diseases

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Gastrointestinal Diseases

• Sherif Tawfic, MD, Ph.D.
• Surgical Pathology
• Fairview University Medical Center
• tawfi001_at_umn.edu

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Esophagus

• Normal esophageal mucosa appears white to tan

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• Esophageal mucosa is lined by non-keratinized
  stratified squamous epithelium
• Gastric mucosa is lined by columnar glandular
  epithelium

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Selected disorders of the esophagus

• Motor disorders Achalasia
• Mechanical injury Lacerations (Mallory-Weiss
  syndrome)
• Varices
• Esophagitis Reflux, infections, drugs,
  irradiation
• Barretts esophagus
• Malignant neoplasms

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Achalasia (failure to relax)

• Incomplete relaxation of lower sphincter during
  swallowing leading to functional obstruction and
  proximal dilatation
• Aperistalsis, incomplete relaxation, increased
  resting tone
• Ganglion cells of the myenteric plexus are
  diminished or absent
• Clinical picture dysphagia, regurgitation and
  aspiration
• Histology Inflammation in the area of M. plexus
• Hypotheses autoimmune, viral infections
• May occur secondary to Trypanosoma cruzi
  infection (Chagas disease)
• 5 develop squamous cell carcinoma, at younger
  age

Loss of inhibitory innervation to the sphincter
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Esophageal lacerations (Mallory- Weiss syndrome)

• Longitudinal tears at the gastroesophageal
  junction
• Clinical setting chronic alcoholics after a bout
  of severe vomiting
• Tear may be superficial or deep affecting all
  layers
• Clinical picture Pain, bleeding, superimposed
  infection
• Hiatal hernia is found in 75 of patients
• Most often bleeding stops w/o intervention, but
  life-threatening hematemesis may occur.
• Supportive therapy and balloon tamponade.
  Healing is prompt with minimal or no residue

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Hiatal hernia
Dilatation of the space between the diaphragmatic
muscles which permits a dilated segment of the
stomach to protrude above the diaphragm.
95
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1-20 of adult subjects only 9 of those
affected suffer from heartburn and reflux
esophagitis complications may include ulceration
and bleeding
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Esophagitis

• Reflux esophagitis
• Infections
• Crohn disease, acute graft versus host disease
• Prolonged gastric intubation
• Ingestion of irritant substance
• Chemotherapy and irradiation

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Reflux esophagitis

• Reflux of gastric contents into esophagus
• Possible etiologies inadequate function of lower
  sphincter sliding hiatal hernia
• CP heart burn
• Complications ulceration, bleeding, stricture,
  Barrett esophagus

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Infection-induced esophagitis

• More common in patients with impaired immunity
• Fungal Candida
• Viruses Herpes and Cytomegalovirus

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Barrett esophagus

• A complication of long standing reflux
  esophagitis
• Replacement of squamous epithelium by columnar
  epithelium with goblet cells
• 30- to 40-fold greater risk to develop
  adenocarcinoma

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Esophageal varices

• Tortuous dilated veins in the submucosa of distal
  esophagus

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Esophageal varices

• Etiology portal hypertension secondary to liver
  cirrhosis
• Asymptomatic until they rupture leading to
  massive hemorrhage
• 50 subsides spontaneously
• 20-30 die during the first episode
• Rebleeding occurs in 70 of cases within one year
  

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Esophageal carcinoma

• Squamous cell carcinoma
• More prevalent worldwide
• Risk factors long-standing esophagitis,
  achalasia, smoking, alcohol, diet (low vitamins
  and zinc), genetics
• 50 in middle 1/3

• Adenocarcinoma
• More common in USA
• Occurs on top of Barrett esophagus
• More in distal 1/3

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Stomach
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1
3

• 1) Cardia
• 2) Body Parietal and Chief cells
• 3) Antrum Mucin secretion and G-cells that
  secrete gastrin

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Selected disorders of the stomach

• Gastritis
• Gastropathy
• Gastric cancer

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Gastritis

• Inflammation of the mucosa
• Causes
• Helicobacter pylori G-ve bacilli
• Autoimmune rare in USA, autoantibodies to
  parietal cells (decreased acid and intrinsic
  factor)
• Helicobacter pylori is present in 70-90 of
  patients with gastric and duodenal ulcers,
  respectively
• Look for intestinal (goblet cell) metaplasia as a
  precancerous lesion

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Helicobacter pylori and associated disorders
H. pylori
Gastric ulcer

• Gastritis (chronic and acute), gastric and
  duodenal ulcers
• Gastric adenocarcinoma, intestinal type
• Gastric lymphoma

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Mechanisms of H. pylori-induced pathology

• Although the organism is not invasive, it induces
  intense inflammatory and immune response
  cytokines and B-cell activation
• Enhances gastric acid secretion
• Bacterial products such as urease, lipases and
  proteases that induce epithelial injury

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Gastropathy

• Injury to the gastric mucosa with no
  participation of inflammatory cells
• Causes
• Non-steroidal antiinflammatory drugs
• Alcohol
• Hypovolemia
• Shock
• Stress
• Uremia
• Enterogastric reflux

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Gastric cancer

• Intestinal-type
• Risk factors diet (nitrites, smoked food,
  increased salt), chronic gastritis (H. pylori),
  altered anatomy after resection
• On top of intestinal metaplasia
• Decreasing in incidence
• Glandular morphology

• Diffuse-type
• Undefined risk factors
• ( no known relation to H. pylori)
• Signet cell morphology

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Macroscopic growth patterns of gastric
adenocarcinoma
Mass
Ulcer
Lintis plastica
Clinical picture asymptomatic or abdominal
discomfort, weight loss, anemia
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Small and large bowel

• Developmental
• Infections
• Vascular
• Idiopathic inflammatory bowel disease
• Malabsorption
• Diverticular disease
• Tumors

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Infectious enterocolitis
Viruses Bacteria Parasites

• Viral destroy the absorptive epithelium leading
  to diarrhea
• Rotavirus children 6-24 M of age, 130 million
  cases per year, fecal oral mode of transmission
• Caliciviruses older children and adults

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Bacteria

• Mechanisms of injury
• Preformed toxins Staphylococcus aureus
• Toxigenic organisms require proliferation within
  bowel Vibrio cholerae, E. coli (Shiga toxin
  leading to hemorrhagic colitis and hemolytic
  uremic syndrome)
• Enteroinvasive organisms Shigella, Salmonella
  typhi
• Both invasive and toxin Clostridium difficile
  with antibiotic therapy, leading to
  pseudomembranous colitis

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Pseudomembranous colitis

• Membranes made of neutrophils and fibrin
• Seen in Cl. Difficile infection and in ischemia

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Parasites

• Entamoeba histolytica Invasive, amebic colitis
  and amebic liver abscesses
• Giardia lamblia duodenum and jejunum, diarrhea
  and malabsorption
• Cryptosporidium self-limited diarrhea in
  immunocompetent individuals long course in AIDS
  patients
• Worms uncommon in USA

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Idiopathic inflammatory bowel disease

• Ulcerative colitis
• Colon only
• Continuous involvement
• Superficial inflammation
• No granulomas
• Good response to surgery
• Increased risk for cancer

• Crohn disease
• Small bowel and colon (mostly right side)
• Patchy involvement
• Transmural inflammation, fistulas, strictures,
  serositis
• Non-caseating granulomas
• Poor response to surgery
• Increased risk for cancer

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Malabsorption syndromes

• Defective intraluminal digestion
• pancreatic insufficiency
• Defective bile secretion
• Mucosal abnormalities
• Disaccharide deficiency
• Reduced surface area
• Celiac disease hypersensitivity to gliadin, a
  component of gluten (present in wheat flour)
  leading to blunted villi and increased
  intraepithelial lymphocytes
• Surgical resection
• Crohn disease

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Diverticulosis

• Herniation of the mucosa and submucosa through
  the muscle wall
• 50 after age 50
• Related to low-fiber diet, increased intraluminal
  pressure and focal defects in muscular layer
• Mostly in sigmoid colon
• Asymptomatic unless infected

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Tumors of the large bowel

• Hyperplastic polyps not precancerous
• Adenomatous polyps precancerous
• Familial polyposis syndrome Autosomal dominant
  500-2500 polyps, 100 risk for developing cancer
  mutations in APC gene

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Colonic adenocarcinoma

• Almost always arises from adenomatous polyp
• Risk factors low fiber, high fat, decreased vit
  A, C, E, idiopathic inflammatory bowel disease,
  familial adenomatous polyposis
• Several hits to different genes APC, k-ras,
  p53 or DNA mismatch repair genes
• Survival depends on stage (depth of invasion and
  node metastasis)

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Colonic adenocarcinoma
Exophytic tumor leading to partial obstruction

• Clinical picture Asymptomatic or fatigue,
  weakness and iron deficiency anemia in tumors of
  right side. Left sided tumors may produce
  bleeding, change in bowel habits and crampy pain

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Colonic adenocarcinoma

• Course tumor invades bowel wall and
  lymphatics/blood vessels with metastasis to lymph
  nodes, liver, lungs, and bones. 25 of patients
  have metastatic disease at presentation
• Diagnosis is based on endoscopy and biopsy
• Prognosis depends on stage (depth of invasion,
  nodal and distant metastasis), and 5-year
  survival varies from gt90 in stage I, to 4 with
  distant metastasis.