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					Diseases of the Gastrointestinal Tract



Condition          Pathology                           Clinical features                    Morphology
Esophagus
Anatomic Anomalies
Atresia & Fistulas  Uncommon & incompatible            Artesia: a segment of the          
                      with life.                          esophagus is only a thin,
                    Associated with congenital heart     noncanalized cord, with blind
                      disease & other gastrointestinal    pouches on either side.
                      tract malformations.              Fistula: connects one of the
                                                          pouches with the trachea or
                                                          bronchus.
Stenosis, Webs &    Stenosis: congenital or acquired  Progressive dypshagia               
Rings                 in adult life after severe
                      esophageal injury.
                    Mucosal rings: smooth ledges of
                      mucosa & a vascularized
                      fibrous core.
Motor Dysfunction
Achalasia           Present in young adulthood.        Aperistalsis of the esophagus.        Dilated esophagus above
                                                        Partial or incomplete relaxation       LES.
                   Secondary achalasia occurs in:         of the lower esophageal              Thickened or thinned
                    Chagas disease                       sphincter (LES) with                  muscular wall.
                    Polio                                swallowing.                          Diminished myenteric
                    Diabetic autonomic neuropathy  Increased resting tone of (LES).           ganglia.
                    Malignancy, amyloidosis,           Esophageal dilation.                  Secondary mucosal damage.
                      sarcoidosis.                      Dysphagia & regurgitation.

                                                        Complications:
                                                         Candidal esophagitis
                                                         Diverticula
                                                         Aspiration pneumonia.



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Diseases of the Gastrointestinal Tract



Hiatal Hernia          A saclike dilation of stomach       Reported in 1-20% of normal        
                        with protrusion above the            adults.
                        diaphragm.                          Retrosternal chest pain.
                                                            Regurgitation of gastric juices.
                    Sliding hiatal hernia:                  A hiatal hernia may ulcerate or
                     90% of cases.                          strangulate, causing bleeding or
                     Shortened esophagus.                   perforation.
                     Traction of upper stomach into
                        thorax.
                     Bell-like dilation of stomach
                        within thoracic cavity.

                    Paraesophageal hiatal hernia:
                     <10% of cases.
                     Cardia of stomach dissects
                       alongside esophagus into
                       thorax.
                     Vulnerable to strangulation &
                       infarction.
Diverticula          An outpouching of the                                                    
                       alimentary tract that contains
                       one or more layers of the wall,
                       result of motor dysfunction.
                     Pharyngeal: upper esophagus.
                     Traction: more distal location,
                       attributed to fibrosing
                       mediastinal processes or
                       abnormal motility.
                     Epiphrenic: immediately above
                       esophageal sphincter, unknown




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Diseases of the Gastrointestinal Tract



                         cause.
Lacerations             Longitudinal tears in the            Potentially massive                
(Mallory-Weiss           esophagus at the                      hematemesis.
Syndrome)                esophagogastric junction.            Inflammation
                        Caused by episodes of excessive      Residual ulcer
                         vomiting in toxic gastritis.         Mediastinitis
                        Seen most frequently in              Peritonitis
                         alcoholics.                          Not usually fatal &healing
                                                               tends to be prompt.
Esophagitis
Reflux Esophagitis      Foremost cause of esophagitis.       Occurs usually in adults.             Hyperemia & edema
                        Decreased efficacy of                Dysphagia                             Thickening of basal zone &
                         esophageal antireflux                Heartburn                              thinning of superficial layers
                         mechanisms                           Regurgitation of sour brash            of stratified squamous
                        Presence of a sliding hiatal         Hematemesis                            epithelium
                         hernia.                              Melena                                Polymorphonuclear or
                                                              Can lead to stricture or Barrett       eosinophilic leukocyte
                                                               esophagus.                             infiltrate.
                                                                                                     Superficial necrosis &
                                                                                                      ulceration.
Barrett Esophagus       Replacement of distal                Risk of ulceration & stricture.       Gross: red, velvety mucosa as
                         esophageal squamous                  Risk of adenocarcinoma is 30           irregular circumferential band
                         epithelium by a metaplastic           times normal.                          at gastroesophageal junction,
                         columnar epithelium, in                                                      linear streaks or patches in
                         response to prolonged injury.                                                distal esophagus.
                        Inflammation & ulceration of                                                Histology: mixture of gastric-
                         squamous mucosa.                                                             type & intestinal-type
                        Healing is by re-epithelization                                              columnar epithelial cells.
                         by pluripotent stem cells.
Infectious &            Prolonged gastric intubation                                            



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Diseases of the Gastrointestinal Tract



Chemical               Ingestion of irritants: alcohol,
Esophagitis             excessive hot fluids, smoking.
                       Uremia
                       Bacteremia or viremia:
                        herpesvirus, CMV
                       Fungal infection: candidiasis,
                        mucormycosis, aspergillosis
                       Radiation
                       Cytotoxic anticancer therapy
Varices                Occur in 90% of cirrhotic             Clinically silent until rupture,       Tortuous dilated veins lying
                        patients.                              with hematemesis –fatality rate         within submucosa of distal
                       Hepatic schistosomiasis is a           is 40%.                                 esophagus & proximal
                        common cause worldwide.               90% chance of recurrence                stomach.
                       Portal hypertension induce             within a year in survivors.            Irregular protrusion of
                        formation of collateral bypass                                                 overlying mucosa into lumen.
                        channels through the coronary                                                 Superficial ulceration,
                        veins of stomach into                                                          inflammation, or adherent
                        eosphageal subepithelial &                                                     blood clot.
                        submucosal veins.
Squamous cell          Occurs in adults older than age       Insidious in onset, symptoms           Being as in-situ lesions: gray-
carcinoma               50, more often in men.                 develop late in the course.             white, plaquelike thickenings
                       Pathogenesis is multifactorial.       Dysphagia                               or elevations of mucosa.
                                                              Obstruction                            With progression, the lesions
                    Dietary:                                  Weight loss                             extend longitudinally along
                     Vitamin deficiency                      Hemorrhage                              axis, circumferentially, &
                     Deficiency of trace metals              Sepsis, secondary to ulceration         deep with invasion.
                     Fungal contamination of                 Fistula formation into
                       foodstuffs                              respiratory tree with aspiration.
                     High content of                         5-year survival: 75%
                       nitrites/nitrosamines                   (superficial), 25% (advanced)



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Diseases of the Gastrointestinal Tract



                       Betel chewing

                    Lifestyle:
                     Alcohol consumption
                     Tobacco use

                    Esophageal disorders:
                     Long-standing esophagitis
                     Achalasia
                     Long-standing celiac disease.
Adenocarcinoma       One half of esophageal cancers.      Arise in patients older than age   Gross:
                     Evolve through dysplastic             40, more commonly in men            Exophytic nodule
                       change in Barrett mucosa.            than in women.                      Excavated & deeply
                                                           Overall 5-year survival is less       infiltrative.
                    Genetic alterations:                    than 30%; screening programs
                     Overexpression of p53 protein.        detect disease earlier.            Histology:
                     Allelic losses at 17p.                                                    Mucin-producing glandular
                                                                                                  tumors.
                                                                                                Diffusely infiltrative signet
                                                                                                  ring cells.
Stomach
Pyloric Stenosis    Congenital pyloric stenosis:           Visible peristalsis
                     Hypertrophy & hyperplasia of         Firm ovoid palpable mass by
                       circular muscle of muscularis        physical examination.
                       propria of pyloris.                 Mucosal edema &
                     Occurs in 1:300-1:900 live            inflammation.
                       births.                             Regurgitation & vomiting by
                     Male-female ratio is 4:1.             third week of life.

                    Acquired pyloric stenosis:



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Diseases of the Gastrointestinal Tract



                       Long term complication of
                        chronic antral gastritis.
                       Peptic ulcers close to pylorus &
                        malignancy.
Acute Gastritis        Chronic use of NSAIDs.                Asymptomatic or minor          Moderate edema &
                       Excessive alcohol consumption.         abdominal pain.                 hyperemia
                       Heavy smoking                         Acute abdominal pain with      Entry of neutrophils into
                       Cancer chemotherapy                    hematemesis.                    epithelial layer
                       Ischemic & shock                                                      Sloughing of superficial
                                                                                               epithelium
                    Mechanism of action:                                                      Hemorrhage
                     Increased acid production
                     Decreased production of surface
                      bicarbonate buffer
                     Reduced mucosal blood flow,
                      disruption of mucus layer.
                     Direct damage to mucosal
                      epithelium.
Chronic Gastritis    Presence of chronic mucosal                                         
                      inflammatory changes leading
                      to mucosal atrophy & epithelial
                      metaplasia.
                     Chronic infection with
                      Helicobacter pylori.
                     Antibodies to parietal cells.
                     Toxic: alcohol & tobacco
                     Postsurgical: reflux of bile.
                     Granulomatous conditions:
                      Crohn disease
Autoimmune           Antibodies to gastric parietal          Few symptoms                   Reddened, coarse-textured



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Diseases of the Gastrointestinal Tract



Gastritis                  cells.                                Nausea & vomiting                     mucosa.
                          Associated with Hashimoto             Upper abdominal discomfort           Inflammatory infiltrate of
                           thyroiditis & Addison disease.        Overt pernicious anemia is rare       lymphocyte & plasma cells in
                                                                 Long-term risk of cancer: 2-4%        lamina propria.
                                                                                                       Variable atrophy.
                                                                                                       Metaplasia to intestinal-type
                                                                                                        epithelium.
                                                                                                       Dysplasia
Peptic Ulcer disease      A breach in the mucosa of the         Epigastric burning, gnawing or       98% of ulcers found in
                           alimentary tract that extends          aching pain which is worse at         duodenum & stomach in a
                           through the muscularis mucosa          night & 1-3 hours after meals.        ratio of 4:1.
                           into the submucosa or deeper.         Nausea & vomiting.                   Gross: a sharply punched-out
                          Produced by an imbalance              Bloating & belching                   defect with overhanging
                           between gastroduodenal                Weight loss                           mucosal borders & smooth
                           mucosal defenses & damaging                                                  clean ulcer base.
                           forces of gastric acid & pepsin.   Complications:
                          No genetic tendencies.              Anemia                              Histology:
                                                               Hemorrhage                           Thin superficial layer of
                       Duodenal ulcer is more frequent in      Perforation                            necrotic debris.
                       patients with:                          Obstruction                          Zone of inflammation
                        Alcoholic cirrhosis                                                         Granulation tissue
                        Chronic obstructive pulmonary                                               Scar
                           disease                                                                   Chronic gastritis in
                        Chronic renal failure                                                         surrounding mucosa.

                       Promotors:
                        Gastric hyperacidity
                        Chronic use of NSAIDs
                        Cigarette smoking
                        Alcoholic cirrhosis



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Diseases of the Gastrointestinal Tract



                       Corticosteroids
                       Hypercalcemia
Acute gastric          Focal, acutely developing             Acute gastric erosions or ulcers      Ulcers are <1cm in diameter,
ulceration              gastric mucosal defects.                                                      multiple & shallow.
                       Encountered in shock, extensive                                              Ulcer base is brown.
                        burns or severe trauma.

Hypertrophic          Giant cerebriform enlargement          Patients are at risk for peptic
Gastropathy            of gastric rugal folds, caused by       ulceration.
                       hyperplasia of mucosal                 Excess secreted proteins may
                       epithelial cells.                       cause hypoalbuminemia &
                     Menetrier disease: surface               protein-losing
                       mucosal cells.                          gastroenteropathy.
                     Hypertrophic-hypersecretory             Hyperplastic mucosa may
                       gastropathy: parietal & chief           become dysplastic, with risk of
                       cells.                                  adenocarcinoma.
                     Gastric gland: secondary to
                       excessive gastrin secretion in
                       Zollinger-Ellison syndrome.
Benign Tumors       Gastric polyps (90%):                  
                     Nodule or mass that projects
                       above level of surrounding
                       mucosa.
                     Majority are hyperplastic or
                       inflammatory.
                     Smooth surfaced, sessile or
                       pedunculated with epithelial
                       tubules & cysts.
                     Multiple & are seen in chronic
                       gastritis.




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Diseases of the Gastrointestinal Tract




                    Gastric adenomas (5-10%):
                     Single & maybe sessile or
                       pedunculated.
                     True neoplasm with
                       proliferative dysplastic
                       epithelium.
                     Incidence increases with age.
Gastric Carcinoma   Contributing factors:                   Insidious disease, initially   Gross locations:
                     Diet: lack of refrigeration, use       asymptomatic.                   Pylorus & antrum: 50-60%
                       of preservatives, lack of fresh      Weight loss                     Cardia: 25%
                       fruit & vegetable.                   Abdominal pain                  Body & fundus: 15-25%
                     Cigarette smoking                     Anorexia                        Lesser curvature: 40%
                     Infection by H.pylori leading to      Vomiting                        Greater curvature: 12%
                       chronic gastritis.                   Altered bowel habits
                     Autoimmune gastritis                  Dysphagia                      Features:
                     Partial gastrectomy                   Anemia                          Early gastric carcinoma is
                                                            Hemorrhage                        confined to mucosa &
                    Genetic alterations:                    Dissemination to ovaries          submucosa.
                     Lead to dysplasia of gastric           generate Krukenberg tumors.     Advanced gastric carcinoma
                       mucosa.                                                                 extends beyond submucosa.
                     Genetic instability in DNA         Prognosis:                          Tumors are exophytic, flat,
                       repair genes                       Resected early: 90-95% 5-year       depressed, or excavated.
                     Expression of telomerase              survival.
                                                          Advanced: 15% 5-year             Intestinal subtype:
                                                            survival.                        Gland-forming columnar
                                                                                                epithelium.
                                                                                             Mucin-producing.
                                                                                             Polypoid expansile growth
                                                                                                pattern.



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Diseases of the Gastrointestinal Tract



                                                                                                  Mean age: 55
                                                                                                  Male-female ratio: 2:1

                                                                                               Diffuse subtype:
                                                                                                Poorly differentiated
                                                                                                Single signet-ring cells
                                                                                                Mucin-producing
                                                                                                Infiltrative growth patterh
                                                                                                Mean age: 48
                                                                                                Male-female ratio: 1:1
Small and Large Intestines
Congenital Anomalies
Meckel Diverticulum  A blind pouch leading off the           Usually asymptomatic
                         alimentary tract, lined by           May intussuscept, incarcerate
                         mucosa.                               or perforate.
                      Persistence of the vitelline duct
                         leaves a solitary diverticulum
                         30cm from the ileocecal valve.
Hirschsprung          Arrested migration of neural           Failure to pass meconium in        Absence of ganglion cells &
Disease                  crest cells into gut.                 neonate.                            ganglia in muscle wall &
                      Functional obstruction &               Abdominal distention.               submucosa of affected
                         dilation proximal to affected        Risk of perforation, sepsis &       segment.
                         segment.                              enterocolitis with fluid           Rectum is always affected.
                      Male-female ratio: 4:1                  derangement.                       Progressive dilation &
                      Associated with Down                                                        hypertrophy of unaffected
                         syndrome                                                                  proximal colon.

                      Acquired megacolon:
                       Chagas disease
                       Bowel obstruction



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Diseases of the Gastrointestinal Tract



                       Inflammatory bowel disease
                       Psychosomatic disorders

Enterocolitis
Diarrhea &             Diarrhea: daily stool production   
Dysentery               in excess of 250gm, containing
                        70-95% water.
                       Dysentery: low-volume, painful
                        diarrhea.

                    Secretory:
                     Infectious
                     Neoplastic

                    Osmotic:
                     Disaccharidase deficiencies
                     Prescribed gut lavage
                     Latulose therapy
                     Antacids

                    Exudative:
                     Infectious: bacterial damage to
                       mucosal epithelium
                     Idiopathic inflammatory bowel
                       disease

                    Malabsorption:
                     Defective intraluminal digestion
                     Infectious: Giardia lamblia
                     Lymphatic obstruction



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Diseases of the Gastrointestinal Tract




                      Deranged motility:
                       Decreased intestinal transit time
                       Decreased motility
Viral                  Rotavirus                              Incubation period ranges from
Gastroenterocolitis    Enteric adenoviruses                    hours to several days.
                       Astroviruses                           Acute illness occurs from 1-7
                       Norwalk virus                           days.
                                                               Anorexia, headache & fever.
Bacterial                Ingestion of preformed toxin in      Ingestion of toxins: explosive        Salmonella: ileum & colon
enterocolitis             contaminated food: S.aureus,          diarrhea & abdominal pain              with Peyer patch
                          Vibrios, Clostridium                  within hours.                          involvement.
                          perfringens.                         Infection with enteric                Shigella: colonic
                         Infection by toxigenic                pathogens: incubation period of        inflammation, erosion &
                          organisms                             hours to days, followed by             exudate.
                         Infection by enteroinvasive           diarrhea, dehydration or              Campylobacter jejuni: small
                          organisms.                            dysentery.                             intestine, appendix, colon,
                                                               Insidious infection: Yersinial &       ulcers, inflammation &
                      Mechanism:                                mycobacterial infection.               exudate.
                       Bacterial adhesion & replication                                              Y.enterocolitica: ileum Peyer
                       Enterotoxins: secretagogues &                                                  patches, appendix, colon, &
                        cytotoxins                                                                     mesenteric lymph nodes with
                       Invasion: E.coli, Shigella,                                                    necrotizing granulomas &
                        Salmonella & Yersinia                                                          systemic spread.
                        enterocolitis
Necrotizing            Acute, necrotizing inflammation        Mild gastrointestinal illness         Mucosal edema
enterocolitis           of small intestine & colon in          Fulminant illness with                Hemorrhage
                        low-birth-weight or premature           gangrene, perforation, sepsis &       Necrosis
                        neonates.                               shock.
                       Result of immaturity of immune



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Diseases of the Gastrointestinal Tract



                        system, initiation of oral
                        feeding, mucosal injury &
                        impaired intestinal blood flow.

Pseudomembranous     Acute colitis caused by toxins of                                           Plaquelike adhesion of
Colitis               C.difficile in setting of antibiotic                                          fibrinopurulent necrotic
                      therapy.                                                                      debris & mucus to damaged
                     Formation of an adherent                                                      colonic mucosa.
                      inflammatory membrane.
Parasite-caused     Nematodes:                                                                
Inflammatory         Strongyloides
disorders            Ascaris
                     Hookworms

                    Flatworms:
                     Tapeworms
                     Flukes

                    Protozoa:
                     Entamoeba histolytica
                     Giardia lamblia

                    AIDS patients:
                     Microsporidia
                     Crytosporidia
Malabsorption        Characterized by suboptimal             Diarrhea                         
                       absorption of fats, fat-soluble &      Flatus
                       other vitamins, proteins,              Pain
                       carbohydrates & electrolytes.          Weight loss
                     Result of disturbed intraluminal        Passage of bulky, frothy, greasy



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Diseases of the Gastrointestinal Tract



                        & terminal digestion,                   stools
                        transepithelial transport through      Anemia & bleeding
                        enterocyte.                            Osteopenia & tetany
                                                               Ameorrhea, impotence &
                                                                infertility
                                                               Purpura & petechia, edema,
                                                                dermatitis
                                                               Peripheral neuropathy
                                                               Hyperparathyroidism
Celiac Spruce          A chronic disease with small           Diarrhea                     
                        intestinal mucosal lesion &            Flatulence
                        impaired nutrient absorption.          Weight loss
                                                               Fatigue
                    Pathogenesis:
                     Sensitivity to gluten, which          Complications:
                       contains the gliadin protein          Iron & vitamin deficiencies
                       component shared by wheat,            10-15% of gastrointestinal
                       oat, barley & rye.                     lymphoma, usually T-cell.
                     Genetic susceptibility: 90-95%
                       of patients express DQw1 &
                       HLA-B8.
                     Immune-mediated: cross
                       reactivity with type 12
                       adenovirus.
Tropical Spruce      Occurs almost exclusively in                                             Lamina propria has abundant
                       people living in tropics.                                                 lymphocytes & more
                     Responds to long-term board-                                               eosinophils than celiac
                       spectrum antibiotic therapy.                                              disease.
                                                                                                Brunt of injury is distal in
                                                                                                 contrast to celiac disease




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Diseases of the Gastrointestinal Tract



Whiple disease           Rare, systemic condition            Diarrhea                  Small intestine mucosa is
                          involving intestine, CNS &          Steatorrhea                laden with distended
                          joints.                             Abdominal cramps           macrophages in lamina
                         Due to infection by Tropheryma      Fever                      propria & in lymphatics,
                          whippelii, a gram-positive          Weight loss                joints & brain.
                          actinomycete.                       Migratory arthritis       Rod-shaped bacilli.
                                                                                         Inflammation is absent.
Disaccharidase            An apical membrane enzyme of  Diarrhea                       No abnormalities of mucosa.
deficiency                 surface absorptive cells.        Malabsorption
                         Deficiency: lactose remains in
                           lumen & exerts osmotic effect.
Abetalipoproteinemia  Familial autosomal recessive         Failure to thrive        
                           inheritance.                     Diarrhea
                         Inability to synthesize           Steatorrhea
                           apoproteins required for
                           lipoprotein export from mucosal
                           cells – lipid vacuolation
                         Depressed levels of
                           chylomicrons VLDL & LDL.
Idiopathic Inflammatory Bowel Disease:
 Crohn disease: granulomatous disease affecting any portion of gut.
 Ulcerative colitis: colonic disease, no granulomas
Crohn Disease            Sharply delimited & transmural Intermittent attacks of:     Gross:
                           involvement of the bowel by      Diarrhea                  Granular serosa with adherent
                           inflammatory processes with      Fever                       creeping mesenteric fat.
                           mucosal damage.                  Abdominal pain            Rubbery thick intestinal wall
                         Presence of noncaseating          Anorexia & weight loss      with edema, inflammation,
                           granulomas.                                                   fibrosis, muscular
                         Fissuring & fistula formation.   Complications:                hypertrophy & stricture.
                                                            Fibrotic strictures       Mucosal punched-out ulcers.



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Diseases of the Gastrointestinal Tract



                                                             Fistulas to adjacent viscera          Tendency to fistula & sinus
                                                             Abdominal & perianal skin              tract formation.
                                                             Loss of abdumin                       Skip lesions: affected areas
                                                             Vitamin B12 deficiency with            with intervening normal
                                                              pernicious anemia                      areas.
                                                             Malabsorption of bile salts with
                                                              steatorrhea.                       Histology:
                                                                                                  Mucosal inflammation with
                                                         Systemic manifestations:                   intraepithelial neutrophils &
                                                          Migratory polyarthritis                  crypt abscesses, laminar
                                                          Sacroilitis                              propria mononuclear
                                                          Ankylosing spondylitis                   inflammation.
                                                          Erythema nodosum                       Ulceration.
                                                          Uveitis                                Chronic mucosal damage:
                                                          Cholangitis                              villus blunting, atrophy,
                                                                                                    metaplasia.
                                                          Amyloidosis
                                                                                                  Transmural inflammation
                                                          Risk of bowel cancer
                                                                                                    with lymphoid aggregates.
                                                                                                  Noncaseating granulomas
                                                                                                  Fibrosis, muscle & neural
                                                                                                    hypertrophy, vasculitis.
Ulcerative Colitis      Affects only mucosa &               Intermittent attacks of bloody     Gross:
                         submucosa of colon.                  mucoid diarrhea.                    Extends retrograde from
                        Extends in a continuous fashion.    Migratory polyarthritis               rectum to involve entire colon
                        Granulomas are absent.              Sacroilitis                           in a continuous fashion.
                                                             Ankylosing spondylitis              Mucosa may be reddened,
                                                             Uveitis                               granular or friable with
                                                             Cholangitis                           inflammatory pseudopolyps.
                                                             Primary sclerosing cholangitis      No mural thickening or
                                                             Skin lesions                          stricture.




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Diseases of the Gastrointestinal Tract



                                                           Risk of carcinoma higher in
                                                            patients with colitis > 10 years.   Histology:
                                                                                                 Crypt abscesses
                                                                                                 Ulceration
                                                                                                 Chronic mucosal damage &
                                                                                                   atrophy
                                                                                                 Epithelial dysplasia may
                                                                                                   progress to carcinoma.
Vascular Disorders
Ischemic Bowel       Predisposing conditions:              Total infarction: 50-75% death      Transmural infarction:
Disease               Arterial thrombosis:                 rate.                                Infarction of all bowel layers.
                        atherosclerosis, vasculitis,       Occurs in severely ill patients.     Bowel segment in
                        dissecting aneurysm.               Severe abdominal pain &                hemorrhagic.
                      Arterial embolism: cardiac           tenderness.                          Bowel appears rubbery &
                        vegetations.                       Bloody diarrhea                        dusky.
                      Venous thrombosis:                  Nausea & vomiting                    Bacteria produce gangrene.
                        hypercoagulable states,            Bloating & abdominal wall            Perforation develops within
                        cirrhosis, sepsis                   rigidity                               days.
                      Nonocclusive ischemia: cardiac
                        failure, shock, dehydration.                                            Mural & mucosal infarction:
                                                                                                 Incomplete necrosis or
                                                                                                  necrosis of mucosa only.
                                                                                                 Mucosa appears hemorrhagic.
                                                                                                 Distribution is patchy.

                                                                                                Chronic ischemia:
                                                                                                 Cause mucosal inflammation,
                                                                                                   ulceration, fibrosis &
                                                                                                   stricture.
                                                                                                 Segmental patchy



                                                                                                                               17
Diseases of the Gastrointestinal Tract



                                                                                                    distribution.
Angiodysplasia            Tortuous, abnormal dilations of                                     Range from small, focal ectasias
                           submucosal veins that dilate                                         to large, dilated, tortuous venous
                           into lamina propria, cecum &                                         formation.
                           ascending colon.
                          Tend to bleed.
                          Due to partial, intermittent
                           occlusion of submucosal veins
                           in the cecum & ascending
                           colon.
Hemorrhoids               Variceal dilation of anal &                                            Ectasia of inferior
                           perianal submucosal venous                                               hemorrhoidal plexus below
                           plexuses.                                                                anorectal line.
                          Associated with constipation,                                           Secondary thrombosis,
                           venous stasis of pregnancy &                                             strangulation or ulceration
                           cirrhosis.                                                               with fissure.
Diverticular Disease      Acquired diverticula may occur         Usually asymptomatic.           Multiple flasklike
                           anywhere in gut.                       Cramping, abdominal              outpouchings 0.5-1cm in
                          Focal weakness in bowel wall at         discomfort & constipation.       diameter in distal colon.
                           sites of penetrating blood             Diverticulitis: pericolic       Occur alongside taeniae coli
                           vessels.                                abscesses, sinus tracts &        & dissect into appendices
                          Increased intralaminal pressure         peritonitis.                     epiploicae.
                           from exaggerated peristaltic                                            Muscularis of intervening
                           contractions.                                                            bowel wall is hypertrophic.
                          Diverticulitis: inflammation of
                           diverticulum after obstruction or
                           perforation.
Intestinal Obstruction
Hernias                   Weakness or a defect in wall of        Stasis & edema leads to      
                           peritoneal cavity permits               incarceration.




                                                                                                                                 18
Diseases of the Gastrointestinal Tract



                        protrusion of a peritoneal sac.        Vascular compromise leads to
                      Segments of viscera become               strangulation.
                        trapped in them.
                      Sites: inguinal & femoral
                        canals, umbilicus, surgical
                        scars, retroperitoneal
Adhesions             Localized peritoneal                 Complications:                     
                        inflammation after surgery,          Internal herniation
                        infection, endometriosis or          Obstruction & strangulation of
                        radiation.                            viscera.
                      Healing leads to fibrous bridges
                        between viscera.
Intussusception       Telescoping of one segment of                                           
                        intestine into immediately distal
                        segment.
                      Children: spontaneous &
                        reversible.
Volvulus              Complete twisting of a bowel                                            
                        loop about its mesenteric base.
                      Obstruction & infarction.
                      Occurs in small bowel or
                        redundant loops of sigmoid
                        colon.
Tumors of the Small and Large Intestine
Small intestinal      3-6% of tumors                          Adenomas are silent, unless    
neoplasms             Benign lesions: leiomyomas,              they obstruct the intestinal
                        adenomas, lipomas, neuromas &           lumen or common bile duct.
                        hamartomas.                            Cramping pain
                      Adenomas frequently occur in            Nausea & vomiting
                        the region of ampulla of Vater,        Bleeding



                                                                                                   19
Diseases of the Gastrointestinal Tract



                        especially in patients with          Spread of mesentery, regional
                        polyposis syndromes.                  lymph nodes & liver.
                                                             5-year survival is 70% with
                                                              wide en bloc excision.
Non-neoplastic         90% of epithelial polyps in                                          
polyps                  colon.

                    Hyperplastic polyp:
                     Found in more than one half of
                       persons older than 60 years.
                     Nipple-like protrusions less than
                       5mm in diameter.
                     Composed of well-formed
                       mature glands & scant lamina
                       propria.

                    Juvenile polyp:
                     Focal hamartomatous
                       malformations of small intestine
                       & colon mucosa, usually
                       sporadic.
                     Occur in children less than 5
                       years old.
                     Rare juvenile polyposis
                       syndrome: large (1-3cm) &
                       numerous, autosomal
                       dominance, pedunculated with
                       cystically dialated glands &
                       increased risk of
                       adenocarcinomas.




                                                                                                  20
Diseases of the Gastrointestinal Tract




                    Peutz-Jeghers polyp:
                     Hamartomatous mucosal polyps
                       of small intestine & colon, often
                       sporadic.
                     Rare Peutz-Jeghers syndrome
                       exhibits autosomal dominance,
                       melanotic pigmentation of
                       mucosal & skin surfaces, &
                       increased risk of carcinoma.
                     Large, pedunculated, lobulated
                       polyps with arborizing smooth
                       muscle surrounding normal
                       abundant glands.
Adenomas             Prevalence: 50% after age 60.           May be asymptomatic or cause         90% of adenomas are in the
                     Frequently multiple.                     anemia & occult bleeding.             colon.
                     Arise as the result of epithelial       Small intestine: adenomas may
                       dysplasia.                              cause obstruction &               All adenomas exhibit:
                     Histologic subtype: tubular,             intussusception.                   Dysplastic epithelium
                       villous & tubulovillous                Severe dysplasia                   Tall hyperchromatic
                     Large villous adenomas are              Intramucosal carcinoma is still       disorderly cells with
                       more likely to harbor severe            confined to mucosa; has little        increased nuclear-cytoplasmic
                       dysplasia or carcinoma.                 or no metastatic potential.           ratio, cigar-shaped nuclei.
                     Adenomas are slow growing.              Invasive adenocarcinoma is a
                                                               malignant lesion with                All adenomas may harbor
                    Risk of malignancy is correlated           metastatic potential as it has        intramural or intramucosal
                    with:                                      crossed into submucosa.               carcinoma.
                     Polyp size                              Only adequate treatment for
                     Histologic architecture                  any adenoma is resection.         Tubular adenomas:
                     Severity of dysplasia                                                       Involve only a few adjacent
                                                                                                    crypts.



                                                                                                                                  21
Diseases of the Gastrointestinal Tract



                                                                Become bulky neoplasms
                                                                 with growth & protrude into
                                                                 lumen.
                                                                Branching dysplastic glands
                                                                 are embedded in lamina
                                                                 propria.

                                                             Villous adenomas:
                                                              Larger than tubular
                                                                 adenomas.
                                                              May carpet up to 10cm of
                                                                 colonic mucosa.
                                                              Finger-like projections are
                                                                 lined by dysplastic epithelium
                                                                 with a lamina propria core.
Familial syndromes   Familial adenomatous polyposis:        
                      Innumerable adenomatous
                        polyps in colon.
                      Risk of progression to
                        adenocarcinoma is 100%.
                      Minimum of 100 colon
                        adenomas required for
                        diagnosis.
                      Prophylactic colectomy is
                        curative.
                      Average age of onset: teens to
                        20s.
                      Progression to cancer occurs in
                        10-15 more years without
                        surgery.




                                                                                             22
Diseases of the Gastrointestinal Tract




                    Gardner syndrome:
                     A familial adenomatous
                       polyposis variant.
                     Exhibits multiple osteomas,
                       epidermal cysts, fibromatosis,
                       abnormal dentition & higher
                       frequency of duodenal &
                       thyroid cancer.

                    Genetic alterations:
                     Somatic mutation in tumor-
                       suppressor APC gene.
                     Inherited mutations in DNA
                       mismatch repair genes in
                       hereditary nonpolyposis
                       colorectal cancer syndrome.
                     DNA methylation: loss of DNA
                       methyl groups occurs early in
                       colonic cancer.
                     Mutations of K-ras gene & other
                       oncogenes.
                     Losses on 18q & 17p.
                     Expression of telomerase.
Colorectal           Arise in polypoid adenomas          Asymptomatic for years.         Sites of occurrence:
Carcinoma            Hereditary nonpolyposis             Fatigue                          Cecum/ascending colon: 38%
                       colorectal syndrome.               Weakness                         Transverse colon: 18%
                                                          Iron deficiency anemia           Descending colon: 8%
                    Risk of cancer is associated with:    Abdominal discomfort             Rectosigmoid: 35%
                     Excess energy intake.               Progressive bowel obstruction    Multiple sites: 1%




                                                                                                                     23
Diseases of the Gastrointestinal Tract



                       Low vegetable fiber intake.          Liver enlargement
                       High content of refined              Prognosis is based on extent of   Presentation:
                        carbohydrates.                        invasion at diagnosis              Polypoid, fungating masses
                       High intake of red meat.             5-ear survival depends on depth    Annular, encircling masses.
                       Decreased intake of vitamins A,       of penetration & lymph node        Poorly differentiated
                        C, E.                                 involvement; 100% for lesions        neoplastic cells.
                                                              limited to mucosa & 25% of         Tumors incite inflammation
                                                              extensively invasive tumors.         & fibrosis of mesenchyme.
                                                             Surgery is only hope for cure.     Minority produces copious
                                                                                                   mucin.
                                                                                                 Foci of neuroendocrine
                                                                                                   differentiation, signet-ring
                                                                                                   features or squamous
                                                                                                   differentiation.
Carcinoid Tumors       Tumors of gut endocrine cells.       Usually asymptomatic               Intramural or submucosal
                       Peak incidence: 50s                  Symptoms occur from                  masses: small, firm & yellow-
                       Appendiceal, rectal carcinoids        obstruction & bleeding.              tan.
                        seldom metastasize.                  Inconstant secretory products:     Appendix & rectum: solitary
                       Ileal, gastric, & colonic             gastrin, ACTH & insulin.             masses; elsewhere, there tend
                        carcioids are often aggressive.      Carcinoid syndrome arises            to be multiple nodules.
                                                              from tumor secretion of            Nodules may cause kinking &
                                                              serotonin & seen only with           obstruction of intestine.
                                                              metastases or with carcinoids      Metastases tend to be small &
                                                              outside of gut.                      dispersed.

                                                          Features of Carcinoid syndrome:       Histology:
                                                           Vasomotor: flushing, cyanosis        Discrete islands, trabeculae,
                                                           Intestinal hypermotility:              glands.
                                                             diarrhea, cramps, nausea &          Sheets of monotonou uniform
                                                             vomiting                              cells with scant, pink,




                                                                                                                              24
Diseases of the Gastrointestinal Tract



                                                            Asthmatic bronchoconstriction:        granular cytoplasm.
                                                             cough, wheezing, dyspnea             Oval, stippled nuclei,
                                                            Hepatomegaly: hepatic                 separated by a fibrous stroma.
                                                             metastases.
                                                            Systemic fibrosis: pulmonic &
                                                             tricuspid valve thickening &
                                                             stenosis, endocardial fibrosis.
                                                            Diagnosed by excess 5-
                                                             hydroxyindoleacetic acid.
Gastrointestinal       Gut is most common location:        Sporadic lymphomas are               Early lesions are plaquelike
Lymphoma                40% of lymphomas other than          amenable to surgical resection        expansions of mucosa &
                        lymph nodes.                         & are chemoresponsive.                submucosa.
                                                            Lymphomas associated with            Advanced lesions are full-
                    Predisposing factors:                    H.pylori infection may be             thickness mural lesions or
                     Chronic spruelike                      treatable by eradication of           polypoid, fungating masses
                       malabsorption syndromes               H.pylori.                             protruding into lumen.
                     Natives of Mediterranean region                                             Atypical lymphocytes
                     Immunodeficiency states.                                                     infiltrate mucosa & wall.

                    Sporadic lymphomas:
                     Stomach: 55-60%
                     Small intestine: 25-30%
                     Colon: 20-25%

                    Spruce-associated lymphomas:
                     Affects younger individuals (30-
                       40 years).
                     Long duration of malabsorption
                       disorders.
                     Usually T-cell lymphoma.



                                                                                                                                  25
Diseases of the Gastrointestinal Tract



                        Poor prognosis

                     Mediterranean lymphoma:
                      B-cell lymphoma in children &
                       young adults of Mediterranean
                       ancestry.
                      Background of chronic diffuse
                       mucosal plasmacytosis.
                      Prognosis is poor.
Appendix
Acute Appendicitis      Most common cause of                 Mainly a disease of adolescents     Early acute appendicitis:
                         abdominal condition requiring         & young adults.                      Scant neutrophil exudations
                         surgery.                             Periumbilical pain, then               throughout mucosa,
                                                               localizing to right lower              submucosa & muscularis.
                     Obstruction of lumen:                     quadrant.                            Congestion of subserosal
                      Due to fecalith, calculus, tumor,      Nausea or vomiting                     vessels
                        worms                                 Abdominal tenderness                 Perivascular neutrophil
                      Predisposes to buildup of              Mild fever                             emigration.
                        intraluminal pressure, ischemic       Leukocytosis                         Serosa is dull, granular & red.
                        injury & bacterial invasion.          False-positive clinical diagnosis
                                                               rate of 20-25%.                     Advanced acute appendicitis:
                                                                                                    More severe neutrophilic
                                                           Complications:                             infiltration.
                                                            Perforation                            Fibrinopurulent serosal
                                                            Pyelophlebitis                           exudate
                                                            Thrombosis of portal venous            Luminal abscess formation
                                                             drainage                                 with ulceration & suppurative
                                                            Liver abscess                            necrosis
                                                            Bacteremia                             Further worsening leads to
                                                                                                      gangrenous necrosis followed




                                                                                                                                  26
Diseases of the Gastrointestinal Tract



                                                          Mimics:                      by rupture.
                                                           Enterocolitis
                                                           Mesenteric lymphadenitis
                                                           Acute salpingitis
                                                           Ectopic pregnancy
                                                           Cystic fibrosis
                                                           Meckel diverticulitis
Tumors of Appendix   Mucocele:                            
                      Dilation of appendiceal lumen
                       by mucinous secretions.
                      Caused by mucosal hyperplasia.
                      Nonneoplastic elongated
                       columnar mucous cells produce
                       copious mucin.

                     Mucinous cystadenoma:
                      Neoplastic mucin-producing
                       columnar epithelium.
                      Mechanical distention leads to
                       appendiceal rupture & spillage
                       of mucin & neoplastic cells into
                       abdomen.

                     Mucinous cystadenocarcinoma:
                      Invasion of appendiceal wall by
                       non-malignant neoplastic cells.
                      Spread beyond appendix as
                       peritoneal implants.
                      Peritoneal cavity becomes
                       distended with semisolid,



                                                                                                     27
Diseases of the Gastrointestinal Tract



                           mucin-containing anaplastic
                           adenocarcinoma cells.
Peritoneum
Inflammation             Sterile peritonitis: result from   
                          spillage of bile or pancreatic
                          enzymes.
                        Surgical procedures: incite
                          foreign body reaction followed
                          by development of adhesions.
                        Endometriosis: introduce irritant
                          blood into peritoneal cavity.
Peritoneal Infection   Causes:                                  Infection may heal                    Dull, gray transformation of
                        Appendicitis                            spontaneously or with therapy.         normally glistening peritoneal
                        Ruptured peptic ulcer                  Residual, walled off abscess           membranes.
                        Cholecystitis                           may persist, serving as foci for      Development of exudate &
                        Diverticulitis                          new infection.                         outright suppuration.
                        Bowel strangulation                    Exudate may organize, leaving         Localized abscesses
                        Acute salpingitis                       fibrous adhesions.                    Inflammation remains
                        Abdominal trauma                                                               superficial
                        Peritoneal dialysis                                                           Tuberculous peritonitis:
                        Perforated inflammatory                                                        plastic exudate with myriad
                          conditions of intestines                                                      minute granulomas.
                        Ascites
                        Nephrotic syndrome in children
                        Cirrhosis in adults
Sclerosing              Dense fibromatous overgrowth           Overgrowth may encroach on            Fibrous overgrowth is
Retroperitonitis          of retroperitoneal tissues.            ureters (leading to                    infiltrative accompanied by
                                                                 hydronephrosis) or bowel               inflammatory cells.
                                                                 segments.




                                                                                                                                      28

				
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