Path E2 7

							Gastrointestinal System

Diseases of the GI tract can be classified as
    Developmental disorders
    Inflammatory diseases
    Functional disorders
    Circulatory disturbances
    Neoplastic diseases
    Esophagus
          o Hiatal hernia
          o Reflux esophagitis
          o Barrett esophagus
          o Achalasia
          o Esophageal varices
          o Esophageal cancer
    Stomach
          o Acute gastritis
          o Chronic gastritis
          o Peptic ulcer disease
          o Stomach cancer
    Small intestine
          o Meckel diverticulum
          o Bowel obstruction
          o Herniation
          o Adhesions
          o Intussusception
          o Volvulus
          o Adenocardinoma
          o Carcinoid tumor
    Large intestines
          o Pseudomembraneous colitis
          o Diverticulosis
          o Crohn disease
          o Ulcerative colitis
          o Adenomatous polyps
          o Colon cancer

Layers
    Mucosa
        o Epithelium
        o Lamina propria
        o Muscularis mucosae
    Submucosa
    Muscularis
        o Circumferential
          o Longitudinal
      Adventitia or serosa
      Vasculature

Most important clinical symptoms and signs relating to the GI system
   Dysphagia – difficulty in swallowing
   Vomiting – expulsion of stomach contents through the mouth
   Hematemesis – vomiting of fresh, red blood
   Hematochezia – bright, red blood in stool
   Melena – black, tarry feces; from blood that’s been digested higher in system
   Diarrhea – frequent, loose, watery bowel movements
   Constipation – hard feces that are difficult to eliminate
   Odynophagia – painful swallowing

Esophagus
    Mucosa
        o Epithelium
        o Lamina propria
        o Muscularis mucosae
    Submucosa
    Muscularis
        o Skeletal muscle
    Main clinical signs and symptoms of esophageal disease
        o Dysphagia
        o Odynophagia
        o Heartburn – a burning behind the sternum (GERD)
        o Acid regurgitation into the mouth – a sign of GERD
    Achalasia
        o A functional (motor) disorder of swallowing
        o Dysfunction of ganglion cells of myenteric plexus (Auerbach plexus) prevents
            proper relaxation of lower esophageal sphincter
        o Dysphagia, regurgitation, halitosis, and proximal dilation
    Plummer Vinson syndrome
        o Scandinavian, northern European women
        o Severs FE deficiency anemia
        o Mucosal atrophy – atrophic glossitis
        o Esophageal webs – dysphagia
        o Increased risk for squamous cell carcinoma
                 Esophagus
                 Oropharynx
                 Posterior oral cavity
    Esophageal varices
        o Portal hypertension produces venous dilation
        o Important cause of death in alcholoics
        o Rupture leads to hematemesis and massive upper GI bleed
          o Rupture of a varix is associated with high mortality
          o Rupture of a varix accounts for half of the deaths in advanced cirrhosis
      Mallory weiss syndrome
          o Mallory-weiss tears are seen in chronic alcoholics, where violent retching
              causes esophageal lacerations and hemorrhage
      Hiatal hernia
          o Diaphragmatic hernia – widened diaphragmatic hiatus allows protrusion of
              the stomach through the diaphragm
          o Gastroesophageal junction pulled into thorax causing GERD, heartburn and
              dysphagia
      GERD
          o Reflux of gastric contents into esophagus due to incompetence of lower
              esophageal sphincter
          o Complications of GERD include chemical esophagitis, Barrett esophagus ad
              peptic ulceration
                   Metaplasia of epithelium to glandular like stomach for protection.
      Barrett esophagus
          o Gastric metaplasia of lower esophageal mucosa – columnar epithelium
              replaces stratified squamous epithelium
          o Odynophagia, ulceration, hemorrhage
          o Adenocarcinoma
      Esophageal neoplasia
          o Squamous cell carcinoma
          o Adenocarcinoma – barrett esophagus
          o Dysphagia due to narrowing of lumen or interference with peristalsis
      Esophageal squamous cell carcinoma
          o Older adults, geographical variation, poor prognosis
          o Squamous cell carcinoma most common world-wide, but adenocarcinoma of
              esophagus is more common in the US
          o Most common in the middle third
          o Alcohol and tobacco, plummer-vinson syndrome, and diet influence
              incidence
          o Rolled border with middle put ulcer
      Esophageal adenocarcinoma
          o Lower segment
          o Barrett esophagus is a risk factor
          o More common that squamous carcinoma in US
          o Beneath glandular mucosa

Stomach
    Epithelial cells of the stomach
        o Mucous cells
        o Parietal cells – HCL, intrinsic factor (for absorption of B12)
        o Chief cells – pepsin
        o Endocrine cells – G-cells (secrete gastrin)
   Gastritis
       o Inflammation of the gastric mucosa
       o Acute gastritis – erosive, due to irritants and NSAIDs
       o Chronic gastritis – erosive or non-erosive
   Chronic gastritis
       o Infectious – the most common form of chronic gastritis is due to infection by
           helicobacter pylori
       o Autoimmune – autoantibodies to parietal cells
       o Helicobacter pylori gastritis
                Peptic ulcer disease
                Adenocarcinoma
                MALT lymphoma
                H. Pylori
                       Gram negative, S-shaped rods
                       Biopsy and silver stain
                       Urea breath test
                       Antibody test to H. pylori
                       Is a potential human carcinogen
       o Autoimmune (atrophic) gastritis
                Autoantibodies against gastric parietal cells
                Gastric mucosal atrophy
                No intrinsic factor, low serum vitamin B12, pernicious anemia
   Acute gastritis
       o Erosive
                Epigastric burning, pain, nausea, vomiting
                Shallow erosions
                Asprin, NSAIDs, alcohol, stress, shock, sepsis
                One of the major causes of hematemsis (blood in vomit) in alcoholics
       o Gastric stress ulcers
                Deeper than erosions, may extend to muscularis
                Severe stress – ICU patients (shock, trauma, burns, sepsis)
   Peptic ulcer disease
       o Most peptic ulcers are generally solitary lesions
       o Most occur in the duodenum – 98% are located in the duodenum and
           stomach
       o No rolled borders
       o Sharply-demarcated ulcer with a clean, smooth base
                Because all acid cleans it out
       o Chronic lesions may exhibit puckering due to fibrosis
       o Acute-chronic blood loss
       o Nausea, vomiting, hematemesis, melena
       o Perforation – major cause of death in PUD
                Ulcer erodes through the wall of the organ it’s in and causes
                   peritonitis
       o Immediate pain – gastric ulcer
        o Delayed pain – duodenal ulcer
        o Etiology
                Multifactorial disease, decreased mucosal resistance
                Infection by H. pylori
                Drugs – aspirin, NSAIDs
                Neuroendocrine – hormonal hypersecretion syndromes
                        Cushing syndrome – corticosteroids
                        Zollinger-Ellison syndrome – gastrin
        o Complications of PUD
                Minor hemorrhage – melena, iron deficiency anemia
                Major hemorrhage – hematemesis
                Perforation – peritonitis
                Stenosis and obstruction
                Penetration into pancreas
   Zollinger Ellison syndrome
        o Gastrin-secreting tumor in pancreas or duodenum (“gastrinoma”)
        o Hypergastrinemia causes hypersecretion of gastric acid
        o Severe peptic ulcer disease with multiple ulcers in unusual locations
        o Triad of gastrinoma, gastric acid, and peptic ulcers
   Adenocarcinoma of stomach
        o Older individuals, poor prognosis
        o Smoked fish – nitrosamines
        o Predisposition to gastric cancer
                H. Pylori infection
                Chronic atrophic gastritis
                Gastric adenomatous polyps
        o In lesser curve of antro-pyloric region
        o Intestinal type – bulky tumors composed of glandular structures
        o Diffuse type – infiltrative growth of poorly-differentiated cells (linitis
           plastica)
                Thickens the organ walls
   Krukenberg tumor
        o Metastatic adenocarcinoma to ovaries
        o Bilateral ovarian metastasis
        o Frequently of gastric origin – mucus-producing cells
                Filled with mucin
   Lymphoma of GI tract
        o Non-hodgkin lymphoma
                Primary lymphomas – MALT-omas and other NHLs; low grade
                Secondary lymphomas – extranodal spread
        o Gastric MALT lymphoma
                Stomach is the most common site for extranodal lymphomas
                MALT lymphomas – B cell lymphomas of mucosa-associated lymphoid
                   tissue
                    Associated with H. pylori infection – may regress with H. pylori
                     treatment

Small Intestine
   Meckel diverticulum
          o Developmental defect of ileum – a blind pouch containing all layers
          o “Left-sided appendix” – may produce symptoms similar to appendicitis
   Bowel obstruction
          o Herniation: weakness in peritoneum; inguinal, femoral, umbilicus, incisional
          o Adhesions : fibrotic bridges of peritoneum; may trap and kink bowel
             segments; they are usually sequelae of prior surgery or infection
          o Intussusception: small intestine invaginates into itself and becomes necrotic
             unless everted; small pedunculated tumors carried by peristalsis may pull
             forward the loop to which it is attached
          o Volvulus: rotation of a loop of intestine about its own mesenteric root; most
             common in small intestine and sigmoid colon; volvulus undergoes necrosis
             from no oxygen
   Adenocarcinoma of small intestine
          o Rare
   Carcinoid tumor
          o A low-grade malignancy of neuroendocrine cells, appearing as mucosal
             nodules
          o May occur throughout GI tract but are most common in appendix
          o May produce hormones such as serotonin
          o Carcinoid syndrome
                 Caused by a serotonin-producing carcinoid tumor that is
                    asymptomatic until metastasis to the liver
                 The serotonin that is no longer metabolized by the liver causes
                    cramping, diarrhea, flushing, and bronchospasm
                 In appendix, can be a cause of appendicitis
   Ischemic bowel disease
          o Mucosal infarction - little mucosa
          o Mural infarction – pretty much all mucosa
          o Transmural infarction – mucosa and muscularis propria

Large Intestines
    Colon
          o Enteric nervous system – myenteric and submucosal plexus
          o Colonized by non-pathogenic strains of bacteria
          o Crypts (small intestine has villi)
    Hirschprung disease – congenital magacolon
          o Developmental defect of enteric nervous system – agangliosis of ternimal
             colon (myenteric plexus)
          o Chronic constipation, proximal dilation
          o Resection of aganglionic segment
   Appendicitis
        o An acute bacterial infection of appendix
        o Complication may include rupture and peritonitis
        o Swelling and erythema
        o If ruptures, colon contents go into peritoneum (bad) and could cause
           peritonitis
        o Obstruction of lumen
                Fecalith – inspissated fecal material
                Reactive lymphoid hyperplasia – response to viral infection
                Neoplasm – carcinoid tumor
        o Acute appendicitis
                Acute inflammation, mucosal ulceration
                Transmural inflammation
                Serositis
                Peritonitis
                Can be necrotic
                Pus can come out
                Right lower quadrant pain, rebound tenderness
                Leukocytosis, fever, nausea, vomiting
   Hemorrhoids
        o Varicose dilation of hemorroidal venous plexus at anorectal junction
        o Increased venous pressure may be associated with pregnancy, chronic
           constipation, portal hypertension
        o Internal and external
   Diverticulosis
        o Consists of out-pouchings og mucosa and submucosa through muscular layer
           of colon
        o Associated with a low bulk diet, straining during defecation
        o May become inflamed and makes it easy to get stuff caught in there
   Intestinal polyps
        o Neoplastic polyps (adenomatous polyps, adenomas)
                Precursors to colon cancer
                Tubular adenoma – tubular glands, frequently pedunculated, most
                   common neoplastic polyp, <5% malignant transformation, endoscopic
                   polypectomy curvatire
                Villous adenoma – villous projections, frequently sessile, least
                   common neoplastic polyp, 50% malignant transformation, endoscopic
                   removal often not possible (because you would have to take out part
                   of the colon too)
        o Non-neoplastic polyps
                Hyperplastic polyp – most common; hyperplasia of epithelium; not
                   pre-malignant
                Hamartomatous polyp – Peutz-Jeghers syndrome
                        Autosomal dominant
                        Affects all layers of mucosa
                          Pigmented macules of oral mucosa and perioral skin
                          Hamartomatous polyps of bowel
                          Increased risk for adenocarcinoma outside GI tract – pancreas,
                           breast, lung, ovary, uterus
                        The polyp: large, pedunculated, risk for intussusception, no
                           malignant change
   Colonic adenocarcinoma
        o Third most common cause of cancer death – lung, breast/prostate, colon
        o Older adults, unless predisposing condition (ulcerative colitis, hereditary
           colon cancer syndrome – gardner syndrome)
               Almost 100% of patients with gardner syndrome have this
        o Dietary risk factors – high caloric intake, high fat, red meat, high refined
           carbohydrates, low fiber
        o Accumulation of mutations in tumor suppressor genes and proto-oncogenes
        o Sigmoid colon most common site
        o Left side – circumferential, napkin-ring lesion producing narrowing of lumen
        o Right side – exophytic, polypoid, crater-like ulcerations with rolled borders
        o Stage is most important prognosti indicator
        o Hereditary colonic cancer syndromes – autosomal dominant
               Familial adenomatous polyposis coli (FAP) – multipe adenomas,
                   100% malignant transformation
               Gardner syndrome – a variant of FAP with multiple supernumerary
                   teeth, jaw bone densities, multiple osteomas, fibromatosis, epidermal
                   inclusion cysts
               Hereditary non-polyposis colorectal cancer (HNPCC) – colonic cancer
                   unrelated to adenomas, also endometrial and ovarian cancers
   Fecal occult blood test
        o Screening test for occult bleeding in GI tract
   Colostomy
        o Cut off end part of colon and attach it to an external bag where the contents
           go
   Inflammatory bowel disease
        o Two chronic, relapsing inflammatory disorders or unknown etiology
        o Crohn disease
        o Ulcerative colitis
        o Exaggerated and unregulated local immune response in genetically
           susceptible individuals
   Crohn disease
        o Any level of GI tract, esophagus to anus, most often distal ileum and colon
        o Transmural inflammation, thickened intestinal wall, like cobblstones
               Granulomatous inflammation
        o Sarcoid-like non-caseating granulomas
        o Pain, diarrhea, fissure and fistula formation
               Fistula – an abnormal channel between two hollow organs or between
                   a hollow organ and the skin surface
                           Enteroenteric, enterocutaneous, enterovesical, enterovaginal
          o Oral manifestations
                   Aphthous-like lesions
                   Granulomatous nodules
                   Malabsorption, vitamin K-dependent clotting factor deficiency,
                      bleeding diathesis
      Ulcerative colitis
          o Chronic inflammatory disease with increased risk of malignancy
          o Thinning of intestinal wall, limited to colon and rectum
          o Relapsing diarrhea and pain
          o Inflammation limited to mucosa – not transmural
          o Crypt abscesses – accumulation of neutrophils within colonic crypts are signs
              of active inflammation
          o Pseudopolyps
                   Remnants of colonic mucosa surrounded by ulceration
          o Pyostomatitis vegetans
                   Oral lesions of ulcerative colitis
                   Small, yellow superficial pustules

Crohn Disease vs Ulcerative Colitis

                              Crohn Disease                 Ulcerative Colitis
Region                        Ileum and colon               Colon only
Distribution                  Skip lesions                  Diffuse, continuous
Wall                          Thickened                     Thin
Inflammation                  Transmural                    Mucosa
Ulcers                        Deep, linear                  Superficial
Granulomas                    Yes                           No
Fistulae                      Yes                           No
Malabsorption                 Yes                           No
Malignant risk                Low                           High